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23,165 results on '"German Cancer Research Center"'

251. Dietary intake and plasma phospholipid concentrations of saturated, monounsaturated and trans fatty acids and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Author: Joseph A. Rothwell, Giovanna Masala, José María Huerta, Aurora Perez-Cornago, Elisabete Weiderpass, Anja Olsen, Magritt Brustad, Claudia Agnoli, Corinne Casagrande, Guri Skeie, Ulrika Ericson, Verena Katzke, Mazda Jenab, Christina C. Dahm, Anne Tjønneland, Geneviève Nicolas, Rudolf Kaaks, Inge Huybrechts, Veronika Fedirko, Carlotta Sacerdote, Neil Murphy, Maria Wennberg, Veronique Chajes, Jeroen W.G. Derksen, Matthias B. Schulze, Elom K. Aglago, Bas Bueno-de-Mesquita, Alicia K Heath, Pilar Amiano, Salvatore Panico, Paula Jakszyn, Rosario Tumino, Marc J. Gunter, Inger T. Gram, María José Sánchez, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 1000143, MR/M012190/1, Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, National Research Council, NRC, University of Maryland School of Public Health, SPH, Cancer Research UK, CRUK: 14136, C8221/A29017, World Cancer Research Fund, WCRF, Imperial College London, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Rijksinstituut voor Volksgezondheid en Milieu, RIVM, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, World Cancer Research Fund, Grant/Award Number: WCRF 2013/1002 Funding information trans, The authors would like to thank the EPIC study participants and staff for their valuable contribution to this research. The authors would also like to thank Ms Beatrice Vozar, Mr Bertrand Hemon and Ms Carine Biessy for the analysis of plasma samples, and the preparation of the databases. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC‐Norfolk, C8221/A29017 to EPIC‐Oxford), MedicalResearch Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford). (United Kingdom), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. The EPIC‐Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1, MC‐PC_13048 and MC‐UU_12015/1). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. The authors would like to acknowledge the use of data and samples from EPIC centres in Cambridge, France, Asturias, and Navarro. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Our study was funded by a grant from the World Cancer Research Fund to Marc Gunter (Grant number: WCRF 2013/1002)., Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Health Research Fund (FIS)?Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology?ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), MedicalResearch Council (1000143 to EPIC-Norfolk, and MR/M012190/1 to EPIC-Oxford). (United Kingdom), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1, MC-PC_13048 and MC-UU_12015/1). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. The authors would like to acknowledge the use of data and samples from EPIC centres in Cambridge, France, Asturias, and Navarro. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Our study was funded by a grant from the World Cancer Research Fund to Marc Gunter (Grant number: WCRF 2013/1002).
Subjects: Cancer Research, medicine.medical_specialty, Colorectal cancer, Myristic acid, [SDV.CAN]Life Sciences [q-bio]/Cancer, colorectal cancer, Gastroenterology, fatty acids, DISEASE, Palmitic acid, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, COLON, medicine, 2 SIDES, 2. Zero hunger, chemistry.chemical_classification, business.industry, Fatty acid, Odds ratio, ASSOCIATION, medicine.disease, Elaidic acid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Oncology, chemistry, 030220 oncology & carcinogenesis, biomarker, Stearic acid, business, dietary intake, LIPIDS
Abstract: International audience; Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial-processed trans (iTFA), and ruminant-sourced trans (rTFA) fatty acids, and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Baseline fatty acid intakes were estimated in 450 112 participants (6162 developed CRC, median follow-up = 15 years). In a nested case-control study, plasma phospholipid fatty acids were determined by gas chromatography in 433 colon cancer cases and 433 matched controls. Multivariable-adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Cox and conditional logistic regression, respectively. Dietary total SFA (highest vs lowest quintile, HRQ5vsQ1 = 0.80; 95%CI:0.69-0.92), myristic acid (HRQ5vsQ1 = 0.83, 95%CI:0.74-0.93) and palmitic acid (HRQ5vsQ1 = 0.81, 95%CI:0.70-0.93) were inversely associated with CRC risk. Plasma myristic acid was also inversely associated with colon cancer risk (highest vs lowest quartile, ORQ4vsQ1 = 0.51; 95%CI:0.32-0.83), whereas a borderline positive association was found for plasma stearic acid (ORQ4vsQ1 = 1.63; 95%CI:1.00-2.64). Dietary total MUFA was inversely associated with colon cancer (per 1-SD increment, HR1-SD = 0.92, 95%CI: 0.85-0.98), but not rectal cancer (HR1-SD = 1.04, 95%CI:0.95-1.15, Pheterogeneity = 0.027). Dietary iTFA, and particularly elaidic acid, was positively associated with rectal cancer (HR1-SD = 1.07, 95%CI:1.02-1.13). Our results suggest that total and individual saturated fatty acids and fatty acids of industrial origin may be relevant to the aetiology of CRC. Both dietary and plasma myristic acid levels were inversely associated with colon cancer risk, which warrants further investigation.
Published: 2021
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252. Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1

Author: Luisa Ladel, Anna Rita Redavid, Erik Zwart, Leonid Bystrykh, Patrick Mehlen, Benjamin Gibert, Jasper Panten, Maik Brune, Mathias Heikenwalder, Bertien Dethmers-Ausema, Katharina Schönberger, Dachuan Zhang, Maria Maryanovich, Pia Sommerkamp, Simon Renders, Simón Méndez-Ferrer, Andreas Narr, Markus Sohn, Manon Tourbez, Claudia Korn, Petra Zeisberger, Seka Lazare, Andreas Trumpp, Agnes Hotz-Wagenblatt, Benjamin Ducarouge, Gerald de Haan, Paul S. Frenette, Adriana Przybylla, Arthur Flohr Svendsen, Nina Cabezas-Wallscheid, Nicolas Rama, Daniel Klimmeck, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Heidelberg University Hospital [Heidelberg], University of Groningen [Groningen], Heidelberg University, Développement Cancer et Thérapies Ciblées [Lyon] (LabEx DEVweCAN), Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Albert Einstein College of Medicine [New York], Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, University of Cambridge [UK] (CAM), NHS Blood and Transplant [London, UK], German Cancer Consortium [Heidelberg] (DKTK), Stem Cell Aging Leukemia and Lymphoma (SALL), Rama, Nicolas [0000-0003-1614-7755], Maryanovich, Maria [0000-0002-2015-0538], Gibert, Benjamin [0000-0002-5295-3124], Zwart, Erik [0000-0002-4552-003X], Zhang, Dachuan [0000-0002-1746-275X], Mendez-Ferrer, Simon [0000-0002-9805-9988], Heikenwälder, Mathias [0000-0002-3135-2274], Bystrykh, Leonid [0000-0001-6924-5602], Frenette, Paul S [0000-0003-0862-9922], de Haan, Gerald [0000-0001-9706-0138], Cabezas-Wallscheid, Nina [0000-0003-0870-0530], Trumpp, Andreas [0000-0002-6212-3466], Apollo - University of Cambridge Repository, and Frenette, Paul S. [0000-0003-0862-9922]
Subjects: 0301 basic medicine, Cellular differentiation, [SDV]Life Sciences [q-bio], General Physics and Astronomy, 631/532/2441, Transgenic, Mice, 0302 clinical medicine, Netrin, Hematopoietic Stem Cells/metabolism, 14/19, Stem Cell Niche, Cellular Senescence, Multidisciplinary, Haematopoietic stem cells, Arterioles/metabolism, Hematopoietic Stem Cell Transplantation, Hematopoietic stem cell, Cell Differentiation, Netrin-1, 3. Good health, Cell biology, 13/31, Mutant Strains, Haematopoiesis, Arterioles, medicine.anatomical_structure, Self-renewal, 64/60, Stem cell, Signal Transduction, Stromal cell, Science, 13/106, Mice, Transgenic, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 38/91, 631/532/2139, 03 medical and health sciences, 13/100, Downregulation and upregulation, medicine, Animals, Cell Proliferation, 631/443/7, Membrane Proteins, General Chemistry, Hematopoietic Stem Cells, 631/532/1542, Mice, Mutant Strains, Ageing, 030104 developmental biology, 13/51, Netrin-1/metabolism, Membrane Proteins/metabolism, Bone marrow, 030217 neurology & neurosurgery, Stem-cell niche, Gene Deletion
Abstract: Haematopoietic stem cells (HSCs) are characterized by their self-renewal potential associated to dormancy. Here we identify the cell surface receptor neogenin-1 as specifically expressed in dormant HSCs. Loss of neogenin-1 initially leads to increased HSC expansion but subsequently to loss of self-renewal and premature exhaustion in vivo. Its ligand netrin-1 induces Egr1 expression and maintains quiescence and function of cultured HSCs in a Neo1 dependent manner. Produced by arteriolar endothelial and periarteriolar stromal cells, conditional netrin-1 deletion in the bone marrow niche reduces HSC numbers, quiescence and self-renewal, while overexpression increases quiescence in vivo. Ageing associated bone marrow remodelling leads to the decline of netrin-1 expression in niches and a compensatory but reversible upregulation of neogenin-1 on HSCs. Our study suggests that niche produced netrin-1 preserves HSC quiescence and self-renewal via neogenin-1 function. Decline of netrin-1 production during ageing leads to the gradual decrease of Neo1 mediated HSC self-renewal., Haematopoietic stem cells (HSCs) are characterized by their self-renewal potential and associated dormancy. Here the authors show that niche produced netrin-1 preserves HSC quiescence and self-renewal via neogenin-1, and that decline of netrin-1 production during ageing leads to decreased Neo1 mediated HSC self-renewal.
Published: 2021
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253. Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

Author: Mirjam Lutz, Ekaterina Friebel, Roland S. Liblau, Antoine Roquilly, Guillaume Martin-Blondel, Manfred Claassen, Benjamin Gaborit, Manuel Kauffmann, Sepideh Babaei, Donatella De Feo, Nicolás Gonzalo Núñez, Nisar P. Malek, Chiara Alberti, Sally Al-Hajj, Susanne Unger, Siri Goepel, Ikram Ayoub, Helene A. Häberle, Jakob Nilsson, Nicole Puertas Jurado, Peter Rosenberger, Stefanie Kreutmair, Sinduya Krishnarajah, Burkhard Becher, Michael Bitzer, Florian Ingelfinger, Pistre, Karine, Universität Zürich [Zürich] = University of Zurich (UZH), German Cancer Consortium [Heidelberg] (DKTK), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institute of Experimental Immunology [Zurich], Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), German Center for Infectious Research - partner site Tübingen [Tübingen, Allemagne] (DZIF), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University hospital of Zurich [Zurich], University of Zurich, and Becher, Burkhard
Subjects: 0301 basic medicine, CD4-Positive T-Lymphocytes, Male, MESH: CD4-Positive T-Lymphocytes / immunology, MESH: Biomarkers / blood, [SDV]Life Sciences [q-bio], MESH: HLA Antigens / genetics, MESH: COVID-19 / pathology, 10263 Institute of Experimental Immunology, Hospital-acquired pneumonia, Severity of Illness Index, 0302 clinical medicine, MESH: Pneumonia / immunology, HLA Antigens, T-Lymphocyte Subsets, peptide binding strength, Immunopathology, Immunology and Allergy, MESH: Pneumonia / pathology, MESH: T-Lymphocyte Subsets / metabolism, COVID, high-dimensional single cell analysis, Antigen Presentation, MESH: Middle Aged, spectral flow cytometry, immune profiling, MESH: SARS-CoV-2 / immunology, Middle Aged, Acquired immune system, MESH: HLA Antigens / immunology, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, HLA typing, 030220 oncology & carcinogenesis, MESH: T-Lymphocyte Subsets / immunology, 2723 Immunology and Allergy, MESH: SARS-CoV-2 / pathogenicity, Biomarker (medicine), Cytokines, biomarker, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Immunity, Innate, Angiotensin-Converting Enzyme 2, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Immunophenotyping, Immunology, Antigen presentation, 610 Medicine & health, Human leukocyte antigen, Biology, Article, 03 medical and health sciences, MESH: Natural Killer T-Cells / immunology, Immune system, immunophenotyping, MESH: CD4-Positive T-Lymphocytes / metabolism, MESH: Angiotensin-Converting Enzyme 2 / metabolism, MESH: Severity of Illness Index, medicine, Humans, 2403 Immunology, SARS-CoV-2, COVID-19, GM-CSF, 2725 Infectious Diseases, Pneumonia, biochemical phenomena, metabolism, and nutrition, medicine.disease, MESH: COVID-19 / immunology, Immunity, Innate, 030104 developmental biology, MESH: Antigen Presentation, 10033 Clinic for Immunology, 570 Life sciences, biology, Natural Killer T-Cells, Biomarkers
Abstract: Immune profiling of COVID-19 patients has identified numerous alterations in both innate and adaptive immunity. However, whether those changes are specific to SARS-CoV-2 or driven by a general inflammatory response shared across severely ill pneumonia patients remains unknown. Here, we compared the immune profile of severe COVID-19 with non-SARS-CoV-2 pneumonia ICU patients using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided analysis. COVID-19 and non-SARS-CoV-2 pneumonia both showed increased emergency myelopoiesis and displayed features of adaptive immune paralysis. However, pathological immune signatures suggestive of T cell exhaustion were exclusive to COVID-19. The integration of single-cell profiling with a predicted binding capacity of SARS-CoV-2-petides to the patients’ HLA profile further linked the COVID-19 immunopathology to impaired virus recognition. Towards clinical translation, circulating NKT cell frequency was identified as a predictive biomarker for patient outcome. Our comparative immune map serves to delineate treatment strategies to interfere with the immunopathologic cascade exclusive to severe COVID-19., Graphical Abstract, The pathogen-specific immune alterations in severe COVID-19 remain unknown. Using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided comparison of COVID-19 vs. non-SARS-CoV-2-pneumonia patient samples, Kreutmair et al. identify T and NK cell immune signatures specific to SARS-CoV-2. They furthermore reveal NKT cell frequency as a predictive biomarker for COVID-19 outcome prediction and link impaired virus recognition to HLA genetics.
Published: 2021
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254. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. Tulloch-Reid, Seppo Koskinen, James E. Bennett, Marcela González-Gross, Virginija Dulskiene, Idris Guessous, Assembekov Batyrbek, Kamarul Imran Musa, Jeannette Lee, Josep Redon, Bihungum Bista, Luisa M Macieira, Johan Sundström, Andres Metspalu, Lariane M Ono, Flora A. Ukoli, Salar Rahimikazerooni, Andrea Gualtieri, Trevor S. Ferguson, Félicité Tchibindat, Eliza Cinteza, Ha Tp Do, Tajana Zeljkovic Vrkic, Tuyen D Le, Alison J. Hayes, Abdul Basit, Chandini Nekkantti, Teresa Norat, Eunice Ugel, Gulmira Aitmurzaeva, Mariachiara Di Cesare, Abdul Hamid Zargar, Vincenzo Solfrizzi, Garry L. Jennings, Aline Meirhaeghe, Kaare Christensen, Päivi Mäki, Xu Lin, Ali Esmaeili, Joanna Baran, Aneta Grajda, Renata Cifkova, Alexandre C. Pereira, Martin Bobak, Iuliia A Rusakova, Keiu Nelis, Damian K Francis, Guansheng Ma, Axel C. Carlsson, Alejandro Diaz, Alireza Ansari-Moghaddam, N Capkova, Zumin Shi, Maria Turley, Imelda A. Agdeppa, Helena I. S. Nogueira, Marcia Scazufca, Katharina Maruszczak, Natascia Rinaldo, Paulo A. Lotufo, Nuno Lunet, Thor Aspelund, Caroline H.D. Fall, Antonio Cabrera de León, Ahmad Faudzi Yusoff, Holger Theobald, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Mihai Gafencu, Tandi E. Matsha, Ana B. Crujeiras, Ahmad Reza Dorosty, Alain Morejon, Weili Yan, Dominique Hange, Bekbolat Zholdin, Frédéric Gottrand, Jorge Mota, Jana Námešná, Stevo Popovic, Louise Eriksen, Line Lund Kårhus, Cihangir Erem, Juergen Breckenkamp, Mathilde Kersting, Yi Song, Martin McKee, Aleksandra Gomula, Rafaela Rosário, Enzo Manzato, S. Goya Wannamethee, Sounnia Mediene Benchekor, Azim Nejatizadeh, Krishna Kumar Aryal, Juan P. González-Rivas, Vedrana Sember, Stephen T. McGarvey, Jukka T. Salonen, Patrick Pasquet, Patricia Varona-Pérez, Amelia C. Crampin, Ramin Heshmat, Violeta Iotova, Juvenal Soares Dias-da-Costa, Oye Gureje, Aletta E. Schutte, João Luiz Bastos, Anelise Reis Gaya, Konrad Jamrozik, Dalia Luksiene, Amina Barkat, Maria Paula Santos, José Camolas, Azli Baharudin, Diego Vanuzzo, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, Albertino Damasceno, Davood Khalili, Simona Bo, Martina Müller-Nurasyid, Dominique Cottel, Markku Peltonen, Fikru Tullu, Ana Isabel Rito, Angélica Ochoa-Avilés, Annette J. Dobson, Christopher T. Cowell, Charumathi Sabanayagam, Rildo de Souza Wanderley Júnior, Oanh T. H. Trinh, Farahnaz Joukar, Mostafa K. Mohamed, Mostafa Qorbani, Jeongseon Kim, Helmut Schröder, Machi Suka, Natasja M. van Schoor, Jussi Kauhanen, Teresa Haugsgjerd, Goodarz Danaei, M. Fernanda Lima-Costa, Yong Tao, Elisabetta L. Romeo, Grazyna Jasienska, Victor Guillermo Sequera, Kazem Mohammad, Yanina Zócalo, Fernanda Cunha Soares, Jianfeng Wu, Mohammad Esmaeel Motlagh, María Elena Díaz-Sánchez, Monika Zuziak, Eldridge Ferrer, Anette Varbo, Leila Beltrami Moreira, Jeremy M. 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Mini, Viktoria Anna Kovacs, Rosemarie Martin, Nahla Hwalla, Wei Zheng, Hoang Van Minh, Edward D Janus, Laetitia Huiart, Farhad Pourfarzi, Sudha Ramachandra Rao, Fred Paccaud, Marcia Makdisse, Aye Aye Sein, Enrique Gutiérrez-González, Yang Yang, Anneke Blokstra, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Wan Nazaimoon Wan Mohamud, Jesús Ibarluzea, Julio Zuñiga Cisneros, Laura Lauria, Argyro Karakosta, Dragana P Jovic, Jun Hata, Elio Riboli, Piotr Bandosz, Xun Tang, Parvina Mukhtorova, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Aleksandra Piwońska, Dusan Grafnetter, Mette Rasmussen, Daniel Weghuber, Sherali Rakhmatulloev, Martine Vrijheid, Johann Willeit, Motahareh Kheradmand, Małgorzata Mossakowska, Lechaba Tshepo, Dongfeng Gu, Hyeon Chang Kim, Vilmundur Gudnason, Maria Forsner, Peter Bjerregaard, Leon A. Simons, Rachael McLean, Japhet Killewo, Ramón Suárez-Medina, Y Nikitin, Eng Joo Tan, Jean Claude Mbanya, Aroor Bhagyalaxmi, Renata Kuciene, Kairat Davletov, Jose Eugenio Lozano, Afshin Ostovar, Niloofar Peykari, Guy De Backer, Soheir H Ahmed, Nicholas J. Wareham, Sai Yin Ho, Constanta Huidumac Petrescu, Maria Hassapidou, Iris Pigeot, Myriam Galfo, Susana Cararo Confortin, Blanca Sandra Ruiz-Betancourt, W. M. Monique Verschuren, Catterina Ferreccio, Fabio Galvano, Leila Houti, Daniel Bia, Annika Rosengren, Marcin Rutkowski, Biruta Velika, Joana Araújo, Fernando Rigo, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Marie Kunešová, Boban Mugoša, Sania Nishtar, Mangesh S. Pednekar, Shahla AlDhukair, Helle-Mai Loit, Antonis Zampelas, Altan Onat, Maciej Banach, Shohreh Naderimagham, Hajer Aounallah-Skhiri, Maja Bæksgaard Jørgensen, Yin Guo, Ewelina Czenczek-Lewandowska, Parasmani Dasgupta, Elvis Oa Wambiya, Inge Huybrechts, Raimund Erbel, Jari Jokelainen, Ana P. Ortiz, Stefan Kiechl, Emmanuel Cohen, Caleb Ochimana, Shynar Abdrakhmanova, Laura Censi, Iqbal Bata, Geetha R Menon, Snehalatha Chamukuttan, Pedro Plans-Rubio, Domenico Palli, Ana Azevedo, Slawomir Koziel, Benoît Salanave, Parinaz Mehdipour, Shu Ti Chiou, Lela Sturua, Lubica Ticha, Felipe Vogt Cureau, Jin Soo Moon, Ming-Hui Zhao, Urho M. Kujala, Nathalie Michels, Ertugrul Celikcan, Jaakko Tuomilehto, Judith Benedics, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, Andrea Rodriguez-Martinez, Tai Hing Lam, Yn-Tz Sung, Jürgen König, Kodavanti Mallikharjuna Rao, Hazzaa M. Al-Hazzaa, Karen Morgan, Bogdan Wojtyniak, Cynthia M. Pérez, Ilse Khouw, Manoli Garcia-de-la-Hera, Dong Wook Shin, Genc Burazeri, Ausra Petrauskiene, Charles Sossa Jérome, Kenisha Russell Jonsson, José Boggia, Daniela Galeone, Alice Bonilla-Vargas, Han Cg Kemper, Rahman Shiri, Stefaan Demarest, Else Karin Grøholt, San-Lin You, Adelheid Weber, Juha Auvinen, Aida Pilav, Sibel Gogen, Suzanne N Morin, Wan Mohamad Wan Bebakar, Viviane Cunha Cardoso, Kavumpurathu Raman Thankappan, Hana Zamrazilová, Frank Claessens, Karien Stronks, Helen Gonçalves, Tahir Aris, Luis Revilla, Sérgio Viana Peixoto, Zhamilya Battakova, Jing Liu, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Priscilla Duboz, Sandjaja, Tiina Laatikainen, Rafel Ramos, Sareh Eghtesad, Judith Simons, Orn Olafsson, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Aung Soe Htet, Bente Sparboe-Nilsen, Paul Elliott, Soon-Woo Park, Angel R. 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Eriksson, Margarita Samoutian, Andreia N. Pizarro, Mohammed Rasoul Tarawneh, Jean Woo, Kaspar Staub, Maria Teresa Menzano, Mojtaba Farjam, Adroaldo Cesar Araujo Gaya, Mohammad El-khateeb, Zulfiqar A Bhutta, Mukharram M. Bikbov, Hsien-Ho Lin, Oscar Noboa, Thomas Waldhör, Garry Brian, Simona Costanzo, Frank Tanser, Nor Azwany Yaacob, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ioannis Pagkalos, Ivan Pećin, Carlo M. Barbagallo, Abla M. Sibai, Yuna He, Matsuda Fumihiko, Bharathi Viswanathan, Ali Reza Safarpour, Wei Cheng Lo, Abdullatif Husseini, Jiang He, Liv Elin Torheim, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, William R. Tebar, Yingfeng Zheng, Eha Nurk, Bhawesh Koirala, Ana Jelakovic, Suhad Bahijri, Freja B Kampmann, Qi Sheng You, Marika Ferrari, María-Elena González-Villalpando, Aline Wagner, Olfa Saidi, Anwar Batieha, Eduardo Capuano, Coimbatore Subramaniam Shanthirani, Dong Wook Kim, Albina A Fakhretdinova, Tom Wilsgaard, Maria Avdicova, Moesijanti Soekatri, Chiara Donfrancesco, Salim Mohanna, Paola Russo, Uruwan Yamborisut, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Khairil Si-Ramlee, Kirsten Mehlig, Christina Mavrogianni, Raluca Pop, Lèlita Santos, Graziella Bruno, Valentina Peterkova, Iná S. Santos, Georg Lappas, Alberto Palloni, Malay K. Mridha, Andrzej Pajak, Marta García-Solano, Stefaan De Henauw, Daniel Ferrante, Rute Santos, Anders Grøntved, Lucjan Szponar, Mihaela Vladulescu, Chien-An Sun, Jan A. Staessen, Paula Duarte de Oliveira, Norazizah Ibrahim Wong, Maria Nordendahl, Elaine M. Dennison, Jeonghee Lee, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Noushin Mohammadifard, Igor Spiroski, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Valéria Regecová, Cláudia S. Minderico, Johanna A. Otero, Jamila Abubakar Garba, Vesselka Duleva, Rui Ornelas, Ilpo Huhtaniemi, Cesar G. Victora, Lijuan Liu, Rody G. Sy, Mahmood Moosazadeh, Ali Ahmadi, Antonio Pedro Graça, Natalia Nowak-Szczepanska, Miao Li Chee, Michael Sjöström, Charles Agyemang, Shiqi Zhen, Xiu-Hua Guo, Pawel Kurjata, Jardena J. Puder, Mehrdad Azmin, Neil Murphy, Kaosar Afsana, Alireza Sadjadi, Johanna M. Geleijnse, Prashant Mathur, Elysée Claude Bika Lele, Raphael Mendes Ritti-Dias, Yannis Manios, Majid Shirani, Rosemary B. Duda, Liis Nelis, Jurate Klumbiene, Zhengming Chen, Wichai Aekplakorn, Alun Evans, Andrzej Wiecek, Lars Lind, Denise Eldemire-Shearer, Bernardo L. Horta, Macia Enguerran, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Kumiko Ohara, Ursula Kiechl-Kohlendorfer, Hermann Brenner, Przemyslaw Slusarczyk, Espen Bjertness, Jutta Stieber, Augusto Di Castelnuovo, Joel G. R. Roy, Aryeh D. Stein, Ruth Frikke-Schmidt, Vera Musil, Amaneh Shayanrad, Marcel Goldberg, Ramon O. Jimenez, Mohammad Reza Fattahi, Jolanda Hyska, Amir Houshang Mehrparvar, Elin Kolle, Mohamed Bamoshmoosh, Michelle Holdsworth, Felipe F. Casanueva, Børge G. Nordestgaard, Niels Wedderkopp, Eva Corpeleijn, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Larissa Pruner Marques, Slavica Sović, Olli T. Raitakari, Marco Aurélio Peres, Alexandra Cucu, Gregorio Varela-Moreiras, Janine Clarke, Andrea Gazzinelli, Mieczysław Litwin, Sara Schramm, Xenophon Theodoridis, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Dimitrios Papandreou, Peter T. Katzmarzyk, Benjamin Acosta-Cazares, Ben Schöttker, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Sadaf G. Sepanlou, Adolfo Rubinstein, Francis Delpeuch, Julianne Williams, Abbas Dehghan, Leanne M. Riley, Heloisa Bettiol, Gabriele Nagel, Ellisiv B. Mathiesen, Ekaterina Stoyanova, Alisha N. Wade, Zhamyila Usupova, Arnaud Chiolero, Oonagh Markey, Jacqueline Ramke, Elena Bogova, Niveen M E Abu-Rmeileh, Nguyen D Nguyen, Tomasz Zdrojewski, Marjo-Riitta Järvelin, Jose Sanchez-Abanto, Rômulo Araújo Fernandes, Lourdes Ribas-Barba, Nalan Uysal, Mohamad Hasnan Ahmad, Krista Fischer, Maria Wany Louzada Strufaldi, Ramiro Guerrero, Farnam Mohebi, Tran Quoc Bao, Flávio Danni Fuchs, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Farzad Hadaegh, Robert Lundqvist, Saeid Safiri, Iraj Mohebbi, George Luiz Lins Machado-Coelho, Annette Peters, Gonzalo Valdivia, Magdalena Korzycka, Rajiv T Erasmus, Masanori Iwasaki, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Quang Ngoc La, Ricky Eddie, Petra Rust, Daniela Rodrigues, Dirk De Bacquer, Karen Sparrenberger, Agneta Sjöberg, Thet Thet Mu, Katarzyna Dereń, Cora L. Craig, Jorge Motta, Janina Petkeviciene, Boyd Swinburn, Paibul Suriyawongpaisal, Visnja Djordjic, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Daan Kromhout, Marius B. Bjertness, Stefano Marventano, Juel Jarani, Alireza Khosravi, Eva Martos, David De Ridder, Lizzy M. Brewster, Nico Dragano, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Hashem Jaddou, Grzegorz Sobek, Dimitrios Trichopoulos, Marvin Cervantes-Loaiza, Abu Am Hanif, Elaine M. Murtagh, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Kyungwon Oh, Heiner Boeing, Regina Heidinger-Felso, André Luiz Sena Guimarães, Balkish M. Naidu, Avula Laxmaiah, Ana M. B. Menezes, Marie Eliasen, Francesco Pistelli, Yuan He, Dusko Bjelica, José A. Casajús, Guang Ning, Lutgart Braeckman, Dirk Vanderschueren, Jochanan Stessman, Ivana Radic, Yi Zeng, Hans Concin, Damaskini Valvi, Sari Hantunen, Catherine Kyobutungi, Diego Augusto Santos Silva, Wenhua Zhao, Sok King Ong, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Mattias Johansson, Samuel C. Dumith, Magdalena Muc, Sabine Schipf, Idowu O Senbanjo, Jim Mann, Rajaa Al-Raddadi, Yih Chung Tham, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Sahar Saeedi Moghaddam, Reza Mohammadpourhodki, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Camilla T. Damsgaard, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Constance Schultsz, Santiago F. Gomez, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Pierre Traissac, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Eleonora d'Orsi, Irene G. M. van Valkengoed, Anna Fijałkowska, Wen-Harn Pan, Gregor Starc, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Abdullah Alkandari, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Saeed Dastgiri, Lien Braeckevelt, Nasheeta Peer, Radka Taxová Braunerová, Mohamed M. Ali, Steiner Krokstad, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Silvana Donoso, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paola Nardone, Alberto Barceló, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Miquel Porta, Vesna Jureša, Alexander D. Deev, David Faeh, Antonio Bernabe-Ortiz, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Anjani Kumar Jha, Thamara Hubler Figueiró, Jana Kratenova, Claudia M. Hormiga, Maria Tsigga, Zivka Dika, Indrapal I. Meshram, Ei Ei K. Nang, Ian Rouse, Rusidah Selamat, Paul Korrovits, Grethe S. Tell, Julie Taylor, Anabela Mota-Pinto, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Frank J Rühli, Shelly R. McFarlane, Sara Santos Sanz, Edyta Łuszczki, Maria G. Stathopoulou, Tara Coppinger, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. Patel, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Son Thai Pham, Simona Giampaoli, Dong Zhao, Indah Suci Widyahening, Merete Osler, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, Giota Touloumi, Janice Luisa Lukrafka, Adela Chirita-Emandi, Maryam Kavousi, Sanja Musić Milanović, Jean-Michel Gaspoz, Jalila El Ati, Sauli Herrala, Liang Xu, Pilar Guallar-Castillón, Bee Koon Poh, Luis Serra-Majem, Jonathan E. Shaw, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Yuki Fujita, Tiffany K. Gill, Nish Chaturvedi, Erkin M. Mirrakhimov, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Deepak Amarapurkar, Deepa Weerasekera, Diana A. Santos, Marjeta Majer, Herman Schargrodsky, Bruna Gonçalves Cordeiro da Silva, Ebrahim Eftekhar, Jesús Vioque, Marisa K. Sophiea, Teresa Shamah-Levy, María Dolores Chirlaque, Mohd Azahadi Omar, Stefan Söderberg, Isabel O. Oliveira, Joanne Katz, Xingwang Ye, Christophe Tzourio, Marie Zins, Aneta Weres, Ulrich Keil, Haiquan Xu, Akihiro Yoshihara, Rachel Dankner, Gabriella Gruden, Maroje Sorić, Hanspeter Stamm, Kim Overvad, Yanping Li, Carsten Oliver Schmidt, Christa L. Lilly, Veikko Salomaa, Gilad Twig, Senthil K Vasan, Qian Wang, Liufu Cui, Andrzej Galbarczyk, Sylvain Sebert, Wilma M. Hopman, Karl-Heinz Jöckel, Ari Voutilainen, Peter Schnohr, Jerzy Chudek, Katia Vergetti Bloch, Vincenzo Capuano, Jyh Eiin Wong, Torben Jørgensen, Anja Schienkiewitz, Nader Saki, Carolina Tarqui-Mamani, Maria Cecília Formoso Assunção, Kazi M. Jamil, Juraci Almeida Cesar, Pedro J Ortiz, Delphine De Smedt, Luciana Zaccagni, Lynne M. Boddy, Jie Hao, David Alejandro González-Chica, Romana Roccaldo, Sara Magnacca, Peter Stehle, Victoria Farrugia Sant'Angelo, Gry Skodje, Maryam Keramati, Tabara Yasuharu, Ali Ghanbari, Gyulli M. Kazakbaeva, Takuro Furusawa, Felicia Cañete, Kari Kuulasmaa, Justina Vaitkeviciute, (NCD-RisC), NCD Risk Factor Collaboration, Imperial College London, Harvard T.H. Chan School of Public Health, Middlesex University [London], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Wellcome TrustEuropean Commission, Clinical Developmental Psychology, APH - Mental Health, Sociology, The Social Context of Aging (SoCA), Nutrition and Health, Iurilli, Maria LC [0000-0003-0409-1635], Zhou, Bin [0000-0002-1741-8628], Ezzati, Majid [0000-0002-2109-8081], Apollo - University of Cambridge Repository, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Public and occupational health, APH - Health Behaviors & Chronic Diseases, VU University medical center, APH 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Ltd, Orebro University, University of London, Universitas Indonesia, Institute of Food and Nutrition Development of Ministry of Agriculture and Rural Affairs, Children’s Hospital of Fudan University, University of Cyprus, Niigata University, International Medical University, Iran University of Medical Sciences, Center for Diabetes and Endocrine Care, Peking University First Hospital, Jiangsu Provincial Center for Disease Control and Prevention, Sun Yat-sen University, West Kazakhstan Medical University, Inner Mongolia Medical University, University of Ghana, Maria Lc Iurilli , Bin Zhou , James E Bennett , Rodrigo M Carrillo-Larco , Marisa K Sophiea , Andrea Rodriguez-Martinez , Honor Bixby , Bethlehem D Solomon , Cristina Taddei , Goodarz Danaei , Mariachiara Di Cesare , Gretchen A Stevens , Leanne M Riley , Stefan Savin , Melanie J Cowan , Pascal Bovet , Albertino Damasceno , Adela Chirita-Emandi , Alison J Hayes , Nayu Ikeda , Rod T Jackson , Young-Ho Khang , Avula Laxmaiah , Jing 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Chiara Donfrancesco , Silvana P Donoso , Angela Döring , Maria Dorobantu , Ahmad Reza Dorosty , Kouamelan Doua , Nico Dragano , Wojciech Drygas , Jia Li Duan , Charmaine A Duante , Priscilla Duboz , Rosemary B Duda , Vesselka Duleva , Virginija Dulskiene , Samuel C Dumith , Anar Dushpanova , Vilnis Dzerve , Elzbieta Dziankowska-Zaborszczyk , Ricky Eddie , Ebrahim Eftekhar , Eruke E Egbagbe , Robert Eggertsen , Sareh Eghtesad , Gabriele Eiben , Ulf Ekelund , Mohammad El-Khateeb , Jalila El Ati , Denise Eldemire-Shearer , Marie Eliasen , Paul Elliott , Reina Engle-Stone , Macia Enguerran , Rajiv T Erasmus , Raimund Erbel , Cihangir Erem , Louise Eriksen , Johan G Eriksson , Jorge Escobedo-de la Peña , Saeid Eslami , Ali Esmaeili , Alun Evans , David Faeh , Albina A Fakhretdinova , Caroline H Fall , Elnaz Faramarzi , Mojtaba Farjam , Victoria Farrugia Sant'Angelo , Farshad Farzadfar , Mohammad Reza Fattahi , Asher Fawwad , Francisco J Felix-Redondo , Trevor S Ferguson , Romulo A Fernandes , Daniel Fernández-Bergés , Daniel Ferrante , Thomas Ferrao , Marika Ferrari , Marco M Ferrario , Catterina Ferreccio , Eldridge Ferrer , Jean Ferrieres , Thamara Hubler Figueiró , Anna Fijalkowska , Günther Fink , Krista Fischer , Leng Huat Foo , Maria Forsner , Heba M Fouad , Damian K Francis , Maria do Carmo Franco , Ruth Frikke-Schmidt , Guillermo Frontera , Flavio D Fuchs , Sandra C Fuchs , Isti I Fujiati , Yuki Fujita , Matsuda Fumihiko , Takuro Furusawa , Zbigniew Gaciong , Mihai Gafencu , Andrzej Galbarczyk , Henrike Galenkamp , Daniela Galeone , Myriam Galfo , Fabio Galvano , Jingli Gao , Manoli Garcia-de-la-Hera , Marta García-Solano , Dickman Gareta , Sarah P Garnett , Jean-Michel Gaspoz , Magda Gasull , Adroaldo Cesar Araujo Gaya , Anelise Reis Gaya , Andrea Gazzinelli , Ulrike Gehring , Harald Geiger , Johanna M Geleijnse , Ali Ghanbari , Erfan Ghasemi , Oana-Florentina Gheorghe-Fronea , Simona Giampaoli , Francesco Gianfagna , Tiffany K Gill , Jonathan Giovannelli , Glen 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, Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , 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, Luxia Zhang , Zhen-Yu Zhang , Dong Zhao , Ming-Hui Zhao , Wenhua Zhao , Shiqi Zhen , Wei Zheng , Yingfeng Zheng , Bekbolat Zholdin , Maigeng Zhou , Dan Zhu , Marie Zins , Emanuel Zitt , Yanina Zocalo , Julio Zuñiga Cisneros , Monika Zuziak , Majid Ezzati , Sarah Filippi, Epidemiology, Iurilli, Maria LC, Zhou, Bin, Bennett, James E, Carrillo-Larco, Rodrigo M, Sophiea, Marisa K, Rodriguez-Martinez, Andrea, Bixby, Honor, Solomon, Bethlehem D, Taddei, Cristina, Danaei, Goodarz, Di Cesare, Mariachiara, Stevens, Gretchen A, Riley, Leanne M, Savin, Stefan, Cowan, Melanie J, Bovet, Pascal, Damasceno, Albertino, Chirita-Emandi, Adela, Hayes, Alison J, Ikeda, Nayu, Jackson, Rod T, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Miranda, J Jaime, Saidi, Olfa, Sebert, Sylvain, Sorić, Maroje, Starc, Gregor, Gregg, Edward W, Abarca-Gómez, Leandra, Abdeen, Ziad A, Abdrakhmanova, Shynar, Ghaffar, Suhaila Abdul, Rahim, Hanan F Abdul, Abu-Rmeileh, Niveen M, Garba, Jamila Abubakar, Acosta-Cazares, 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Poudyal, Anil, Poulimeneas, Dimitrio, Pouraram, Hamed, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J, Price, Jacqueline F, Providencia, Rui, Puder, Jardena J, Pudule, Iveta, Puhakka, Soile E, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahimikazerooni, Salar, Rahman, Mahfuzar, Rahman, Mahmudur, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina, Rakhmatulloev, Sherali, Rakovac, Ivo, Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramke, Jacqueline, Ramos, Elisabete, Ramos, Rafel, Rampal, Lekhraj, Rampal, Sanjay, Rarra, Vayia, Rascon-Pacheco, Ramon A, Rasmussen, Mette, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M, Regecová, Valéria, Revilla, Lui, Rezaianzadeh, Abba, Ribas-Barba, Lourde, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, Rinaldo, Natascia, de Wit, Tobias F Rinke, Rito, Ana, Ritti-Dias, Raphael M, Rivera, Juan A, Robitaille, Cynthia, Roccaldo, Romana, Rodrigues, Daniela, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Romeo, Elisabetta L, Rosario, Rafaela V, Rosengren, Annika, Rouse, Ian, Roy, Joel GR, Rubinstein, Adolfo, Rühli, Frank J, Ruidavets, Jean-Bernard, Ruiz-Betancourt, Blanca Sandra, Ruiz-Castell, Maria, Moreno, Emma Ruiz, Rusakova, Iuliia A, Jonsson, Kenisha Russell, Russo, Paola, Rust, Petra, Rutkowski, Marcin, Sabanayagam, Charumathi, Sacchini, Elena, Sachdev, Harshpal S, Sadjadi, Alireza, Safarpour, Ali Reza, Safiri, Saeid, Saki, Nader, Salanave, Benoit, Martinez, Eduardo Salazar, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Samoutian, Margarita, Sánchez-Abanto, Jose, Sandjaja, null, Sans, Susana, Marina, Loreto Santa, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Osvaldo, Santos, Rute, Sanz, Sara Santo, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savva, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Victor, Serra-Majem, Lui, Servais, Jennifer, Ševcíková, Ludmila, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed
Published: 2021
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255. Chromatin structure changes in Daphnia populations upon exposure to environmental cues – or – The discovery of Wolterecks 'Matrix'

Author: Emilien Luquet, Silvain Pinaud, Fabien Aubret, Aki Minoda, Vicki A. Thomson, Etienne Danchin, Céline Cosseau, Patrice David, Dominique Joly, David Duval, Ranja Andriantsoa, Mariana Gomes Lima, Jean-François Allienne, Jeremie Vidal-Dupiol, Déborah Federico, Cristian Chaparro, Christoph Grunau, Ronaldo de Carvalho Augusto, Oliver Rey, Mamadou Dia Sow, Sina Tönges, Interactions Hôtes-Pathogènes-Environnements (IHPE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Perpignan Via Domitia (UPVD), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (LEHNA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS), Station d'écologie théorique et expérimentale (SETE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-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), Curtin University [Perth], Planning and Transport Research Centre (PATREC), Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC), Institut National de la Recherche Agronomique (INRA)-Université d'Orléans (UO), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut de Recherche pour le Développement (IRD [France-Sud]), University of Adelaide, Evolution, génomes, comportement et écologie (EGCE), Institut de Recherche pour le Développement (IRD)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratório de Malacologia [Rio de Janeiro], Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Evolution et Diversité Biologique (EDB), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, These experiments were done in the framework of the RTP 3E summer school 'Epigenetics for field ecologists' and received support from the CNRS., Interactions Hôtes-Pathogènes-Environnements [2015-...] (IHPE), Université de Perpignan Via Domitia (UPVD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Parasitologie fonctionnelle et évolutive [2003-2006] (PFE), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Ecologie et évolution des interactions [2011-2014] (2EI), Centre National de la Recherche Scientifique (CNRS), Université de Perpignan Via Domitia (UPVD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.EE]Life Sciences [q-bio]/Ecology, environment, 0303 health sciences, Phenotypic plasticity, biology, [SDV]Life Sciences [q-bio], fungi, ATAC-seq, ATAC-Seq, 010501 environmental sciences, Gene mutation, biology.organism_classification, 01 natural sciences, Daphnia pulex, Daphnia, Chromatin, 03 medical and health sciences, Reaction norm, Evolutionary biology, population epigenetics, norm of reaction, Epigenetics, Adaptation, 030304 developmental biology, 0105 earth and related environmental sciences
Abstract: Phenotypic plasticity is an important feature of biological systems that is likely to play a major role in the future adaptation of organisms to the ongoing global changes. It may allow an organism to produce alternative phenotypes in responses to environmental cues. Modifications in the phenotype can be reversible but are sometimes enduring and can even span over generations. The notion of phenotypic plasticity was conceptualized in the early 20thcentury by Richard Woltereck. He introduced the idea that the combined relations of a phenotypic character and all environmental gradients that influence on it can be defined as “norm of reaction”. Norms of reaction are specific to species and to lineages within species, and they are heritable. He postulated that reaction norms can progressively be shifted over generations depending on the environmental conditions. One of his biological models was the water-fleedaphnia. Woltereck proposed that enduring phenotypic modifications and gene mutations could have similar adaptive effects, and he postulated that their molecular bases would be different. Mutations occurred in genes, while enduring modifications were based on something he called theMatrix. He suggested that this matrix (i) was associated with the chromosomes, (ii) that it was heritable, (iii) it changed during development of the organisms, and (iv) that changes of the matrix could be simple chemical substitutions of an unknown, but probably polymeric molecule. We reasoned that the chromatin has all postulated features of this matrix and revisited Woltereck’s classical experiments withdaphnia. We developed a robust and rapid ATAC-seq technique that allows for analyzing chromatin of individual daphnia and show here (i) that this technique can be used with minimal expertise in molecular biology, and (ii) we used it to identify open chromatin structure in daphnia exposed to different environmental cues. Our result indicates that chromatin structure changes consistently in daphnia upon this exposure confirming Woltereck’s classical postulate.
Published: 2020

256. The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells

Author: Schmezer, Peter [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)]
Published: 2012
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257. Position detection accuracy of a novel linac-mounted intrafractional x-ray imaging system

Author: Nill, Simeon [Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany)]
Published: 2012
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258. DNA bending potentials for loop-mediated nucleosome repositioning

Author: Langowski, Jorg [German Cancer Research Center, Heidelberg]
Published: 2012

259. Electromagnetic Real-Time Tumor Position Monitoring and Dynamic Multileaf Collimator Tracking Using a Siemens 160 MLC: Geometric and Dosimetric Accuracy of an Integrated System

Author: Oelfke, Uwe [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany)]
Published: 2011
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260. Ground-state properties of the retinal molecule: from quantum mechanical to classical mechanical computations of retinal proteins

Author: Suhai, Sandor [German Cancer Research Center, Heidelberg]
Published: 2011

261. Real-time tumor tracking: Automatic compensation of target motion using the Siemens 160 MLC

Author: Oelfke, Uwe [Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany)]
Published: 2010
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262. Differences in Clinical Results After LINAC-Based Single-Dose Radiosurgery Versus Fractionated Stereotactic Radiotherapy for Patients With Vestibular Schwannomas

Author: Debus, Juergen [Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg (Germany) and Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)]
Published: 2010
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263. Introduction to Ion Beam Therapy

Author: Martisikova, Maria [Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Im NeuenheimerFeld 280, D-69120, Heidelberg (Germany)]
Published: 2010
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264. Treatment Planning for Ion Beam Therapy

Author: Jaekel, Oliver [Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Im NeuenheimerFeld 280, D-69120, Heidelberg (Germany)]
Published: 2010
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265. Quantitative Assessment of Image-Guided Radiotherapy for Paraspinal Tumors

Author: Thieke, Christian [Department of Radiation Oncology, German Cancer Research Center and University Clinic Heidelberg, Heidelberg (Germany)]
Published: 2009
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266. Respiratory Displacement of the Thoracic Aorta: Physiological Phenomenon With Potential Implications for Thoracic Endovascular Repair

Author: Tengg-Kobligk, Hendrik [German Cancer Research Center, Department of Radiology (Germany)]
Published: 2009
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267. Peptides Derived From Insulin Granule Proteins Are Targeted by CD8 + T Cells Across MHC Class I Restrictions in Humans and NOD Mice

Author: Joëlle Vinh, Aurore Pais, Sylvaine You, Etienne Larger, Decio L. Eizirik, Maikel Luis Colli, Laure Alexandre-Heymann, Danièle Dubois-Laforgue, Roberto Mallone, Søren Buus, Georgia Afonso, Graziella Bruno, Mahmoud Tarayrah, Cassandra Lavaud, Gonzalez-Duque Sergio, Jean-Paul Beressi, Sheena Pinto, Marie Eliane Azoury, Claire Maillard, Verdier Yann, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Université libre de Bruxelles (ULB), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Spectrométrie de Masse Biologique et Protéomique (USR3149 / FRE2032) (SMBP), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Copenhagen = Københavns Universitet (UCPH), Centre Hospitalier de Versailles André Mignot (CHV), Università degli studi di Torino = University of Turin (UNITO), YOU, Sylvaine, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris (UP), University of Copenhagen = Københavns Universitet (KU), University of Turin, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Diabetes Research and Welbio [Brussels, Belgium] (Medical Faculty), and INSERM U1016, Institut Cochin, Paris, France
Subjects: 0301 basic medicine, biology, Effector, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Human leukocyte antigen, Nod, Epitope, Cell biology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, MHC class I, Internal Medicine, biology.protein, Cytotoxic T cell, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS, CD8, NOD mice
Abstract: The antigenic peptides processed by β cells and presented through surface HLA Class I molecules are poorly characterized. Each HLA variant, e.g. the most common HLA-A2 and HLA-A3, carries some peptide-binding specificity. Hence, features that, despite these specificities, remain shared across variants may reveal factors favoring β-cell immunogenicity. Building on our previous description of the HLA-A2/A3 peptidome of β cells, we analyzed the HLA-A3-restricted peptides targeted by circulating CD8+ T cells. Several peptides were recognized by CD8+ T cells within a narrow frequency (1-50/106), which was similar in donors with and without type 1 diabetes and harbored variable effector/memory fractions. These epitopes could be classified as conventional peptides or neo-epitopes, generated either via peptide cis-splicing or mRNA splicing, e.g. secretogranin-5 (SCG5)-009. As reported for HLA-A2-restricted peptides, several epitopes originated from β-cell granule proteins, e.g. SCG3, SCG5 and urocortin-3. Similarly, H-2Kd-restricted CD8+ T cells recognizing the murine orthologues of SCG5, urocortin-3, and proconvertase-2 infiltrated the islets of NOD mice and transferred diabetes into NOD/scid recipients. The finding of granule proteins targeted in both humans and NOD mice supports their disease relevance and identifies the insulin granule as a rich source of epitopes, possibly reflecting its impaired processing in type 1 diabetes.
Published: 2020
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268. HPV cervical infections and serological status in vaccinated and unvaccinated women

Author: Bastien Reyné, E. Picot, Tim Waterboer, Vanina Boué, Michel Segondy, Sophie Grasset, Carmen Lía Murall, Ignacio G. Bravo, Jacques Reynes, Soraya Groc, Christian Selinger, Claire Bernat, Massilva Rahmoun, Vincent Tribout, Nathalie Boulle, Samuel Alizon, Noemi Bender, Marine Bonneau, Christelle Graf, Marie-Christine Picot, Vincent Foulongne, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Biopathologie [CHRU Montpellier], Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Evolution Théorique et Expérimentale (MIVEGEC-ETE), Perturbations, Evolution, Virulence (PEV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Project: 648963,H2020,ERC-2014-CoG,EVOLPROOF(2015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), and Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)
Subjects: cross-protection, Genital infections, Uterine Cervical Neoplasms, serology, Alphapapillomavirus, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Serology, 0302 clinical medicine, acute infections, Genotype, Prevalence, 030212 general & internal medicine, Papillomaviridae, genital infections, biology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Vaccination, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Infectious Diseases, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, Female, France, Antibody, Cross-protection, Adult, medicine.medical_specialty, HPV, food.ingredient, Adolescent, 030231 tropical medicine, Young Adult, 03 medical and health sciences, food, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Internal medicine, medicine, genital infections 1, Humans, Papillomavirus Vaccines, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], General Veterinary, General Immunology and Microbiology, business.industry, Public health, Papillomavirus Infections, Public Health, Environmental and Occupational Health, Odds ratio, vaccination, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Confidence interval, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business, Body mass index, Acute infections, Demography, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Background Understanding genital infections by Human papillomaviruses (HPVs) remains a major public health issue, especially in countries where vaccine uptake is low. Methods We investigate HPV prevalence and antibody status in 150 women (ages 18 to 25) in Montpellier, France. At inclusion and one month later, cervical swabs, blood samples and questionnaires (for demographics and behavioural variables) were collected. Results Oncogenic, non-vaccine genotypes HPV51, HPV66, HPV53, and HPV52 were the most frequently detected viral genotypes overall. Vaccination status, which was well-balanced in the cohort, showed the strongest (protective) effect against HPV infections, with an associated odds ratio for alphapapillomavirus detection of 0.45 (95% confidence interval: [0.22;0.58]). We also identified significant effects of age, number of partners, body mass index, and contraception status on HPV detection and on coinfections. Type-specific IgG serological status was also largely explained by the vaccination status. IgM seropositivity was best explained by HPV detection at inclusion only. Finally, we identify a strong significant effect of vaccination on genotype prevalence, with a striking under-representation of HPV51 in vaccinated women. Conclusions Variations in HPV prevalence correlate with key demographic and behavioural variables. The cross-protective effect of the vaccine against HPV51 merits further investigation.
Published: 2020
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269. Dose Estimation for the European Epidemiological Study on Pediatric Computed Tomography (EPI-CT)

Author: Choonsik Lee, Jérémie Dabin, Johannes Hermen, Steven L. Simon, Marie-Odile Bernier, Jordi Figuerola, Magda Bosch de Basea, Hilde Merete Olerud, Roman Pokora, Andreas Jahnen, Elisabeth Cardis, Carlo Maccia, Graham Byrnes, Neige Journy, Johanna M. Meulepas, Isabelle Thierry-Chef, Tore S. Istad, Ausrele Kesminiene, Françoise Malchair, Lucian Le Cornet, Gilles Ferro, Richard W Harbron, Monika Moissonnier, Michael Hauptmann, ATHENA, Irsn, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), International Agency for Research on Cancer (IARC), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), SCK CEN, Norwegian Radiation Protection Authority, Luxembourg Institute of Science and Technology (LIST), Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), Centre d'Assurance qualité des Applications Technologiques dans le domaine de la Santé (CAATS), CAATS, Newcastle University, Barcelona Institute for Global Health (ISGlobal), Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Radiation Programme, Institute of Biometry and Registry Research, Brandenburg Medical School Theodor Fontane, U1018, INSERM (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, The Netherlands Cancer Institute [Amsterdam, The Netherlands], Mainz University, and National Cancer Institute - NCI
Subjects: Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Biophysics, Radiation Dosage, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Dosimetry, Humans, Radiology, Nuclear Medicine and imaging, Young adult, Child, Radiation, business.industry, Phantoms, Imaging, Infant, Newborn, Infant, [SDV] Life Sciences [q-bio], Europe, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Absorbed dose, Child, Preschool, Cohort, Abdomen, Body region, Female, Tomography, business, Nuclear medicine, Tomography, X-Ray Computed
Abstract: International audience; Within the European Epidemiological Study to Quantify Risks for Paediatric Computerized Tomography (EPI-CT study), a cohort was assembled comprising nearly one million children, adolescents and young adults who received over 1.4 million computed tomography (CT) examinations before 22 years of age in nine European countries from the late 1970s to 2014. Here we describe the methods used for, and the results of, organ dose estimations from CT scanning for the EPI-CT cohort members. Data on CT machine settings were obtained from national surveys, questionnaire data, and the Digital Imaging and Communications in Medicine (DICOM) headers of 437,249 individual CT scans. Exposure characteristics were reconstructed for patients within specific age groups who received scans of the same body region, based on categories of machines with common technology used over the time period in each of the 276 participating hospitals. A carefully designed method for assessing uncertainty combined with the National Cancer Institute Dosimetry System for CT (NCICT, a CT organ dose calculator), was employed to estimate absorbed dose to individual organs for each CT scan received. The two-dimensional Monte Carlo sampling method, which maintains a separation of shared and unshared error, allowed us to characterize uncertainty both on individual doses as well as for the entire cohort dose distribution. Provided here are summaries of estimated doses from CT imaging per scan and per examination, as well as the overall distribution of estimated doses in the cohort. Doses are provided for five selected tissues (active bone marrow, brain, eye lens, thyroid and female breasts), by body region (i.e., head, chest, abdomen/pelvis), patient age, and time period (1977-1990, 1991-2000, 2001-2014). Relatively high doses were received by the brain from head CTs in the early 1990s, with individual mean doses (mean of 200 simulated values) of up to 66 mGy per scan. Optimization strategies implemented since the late 1990s have resulted in an overall decrease in doses over time, especially at young ages. In chest CTs, active bone marrow doses dropped from over 15 mGy prior to 1991 to approximately 5 mGy per scan after 2001. Our findings illustrate patterns of age-specific doses and their temporal changes, and provide suitable dose estimates for radiation-induced risk estimation in epidemiological studies.
Published: 2020
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270. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Author: Daniel R. Barnes, Matti A. Rookus, Lesley McGuffog, Goska Leslie, Thea M. Mooij, Joe Dennis, Nasim Mavaddat, Julian Adlard, Munaza Ahmed, Kristiina Aittomäki, Nadine Andrieu, Irene L. Andrulis, Norbert Arnold, Banu K. Arun, Jacopo Azzollini, Judith Balmaña, Rosa B. Barkardottir, Daniel Barrowdale, Javier Benitez, Pascaline Berthet, Katarzyna Białkowska, Amie M. Blanco, Marinus J. Blok, Bernardo Bonanni, Susanne E. Boonen, Åke Borg, Aniko Bozsik, Angela R. Bradbury, Paul Brennan, Carole Brewer, Joan Brunet, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Lise Lotte Christensen, Wendy K. Chung, Kathleen B.M. Claes, Chrystelle Colas, Marie-Agnès Collonge-Rame, Capucine Delnatte, Laurence Faivre, Sophie Giraud, Christine Lasset, Véronique Mari, Noura Mebirouk, Emmanuelle Mouret-Fourme, Hélène Schuster, Dominique Stoppa-Lyonnet, Antonis Antoniou, Jackie Cook, Rosemarie Davidson, Douglas Easton, Ros Eeles, D. Gareth Evans, Debra Frost, Helen Hanson, Louise Izatt, Kai-ren Ong, Lucy Side, Aoife O’Shaughnessy-Kirwan, Marc Tischkowitz, Lisa Walker, Mary B. Daly, Miguel de la Hoya, Robin de Putter, Peter Devilee, Orland Diez, Yuan Chun Ding, Susan M. Domchek, Cecilia M. Dorfling, Martine Dumont, Bent Ejlertsen, Christoph Engel, Lenka Foretova, Florentia Fostira, Michael Friedlander, Eitan Friedman, Patricia A. Ganz, Judy Garber, Andrea Gehrig, Anne-Marie Gerdes, Paul Gesta, Gord Glendon, Andrew K. Godwin, David E. Goldgar, Anna González-Neira, Mark H. Greene, Daphne Gschwantler-Kaulich, Eric Hahnen, Ute Hamann, Julia Hentschel, Frans B.L. Hogervorst, Maartje J. Hooning, Judit Horvath, Chunling Hu, Peter J. Hulick, Evgeny N. Imyanitov, Georgia Chenevix-Trench, Kelly-Anne Phillips, Amanda Spurdle, Marinus Blok, Frans Hogervorst, Maartje Hooning, Marco Koudijs, Arjen Mensenkamp, Hanne Meijers-Heijboer, Matti Rookus, Klaartje van Engelen, Catherine Noguès, Claudine Isaacs, Angel Izquierdo, Anna Jakubowska, Paul A. James, Ramunas Janavicius, Esther M. John, Vijai Joseph, Beth Y. Karlan, Karin Kast, Torben A. Kruse, Ava Kwong, Yael Laitman, Conxi Lazaro, Jenny Lester, Fabienne Lesueur, Annelie Liljegren, Jennifer T. Loud, Jan Lubiński, Phuong L. Mai, Siranoush Manoukian, Hanne E.J. Meijers-Heijboer, Alfons Meindl, Arjen R. Mensenkamp, Austin Miller, Marco Montagna, Semanti Mukherjee, Anna Marie Mulligan, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Dieter Niederacher, Finn Cilius Nielsen, Liene Nikitina-Zake, Edith Olah, Olufunmilayo I. Olopade, Ana Osorio, Claus-Eric Ott, Laura Papi, Sue K. Park, Michael T. Parsons, Inge Sokilde Pedersen, Bernard Peissel, Ana Peixoto, Paolo Peterlongo, Georg Pfeiler, Karolina Prajzendanc, Miquel Angel Pujana, Paolo Radice, Juliane Ramser, Susan J. Ramus, Johanna Rantala, Gad Rennert, Harvey A. Risch, Mark Robson, Karina Rønlund, Ritu Salani, Leigha Senter, Payal D. Shah, Priyanka Sharma, Lucy E. Side, Christian F. Singer, Thomas P. Slavin, Penny Soucy, Melissa C. Southey, Amanda B. Spurdle, Doris Steinemann, Zoe Steinsnyder, Christian Sutter, Yen Yen Tan, Manuel R. Teixeira, Soo Hwang Teo, Darcy L. Thull, Silvia Tognazzo, Amanda E. Toland, Alison H. Trainer, Nadine Tung, Elizabeth J. van Rensburg, Ana Vega, Jeroen Vierstraete, Gabriel Wagner, Shan Wang-Gohrke, Barbara Wappenschmidt, Jeffrey N. Weitzel, Siddhartha Yadav, Xin Yang, Drakoulis Yannoukakos, Dario Zimbalatti, Kenneth Offit, Mads Thomassen, Fergus J. Couch, Rita K. Schmutzler, Jacques Simard, Douglas F. Easton, Antonis C. Antoniou, Pediatric surgery, Human genetics, CCA - Cancer biology and immunology, CCA - Cancer Treatment and quality of life, Amsterdam Reproduction & Development (AR&D), Apollo - University of Cambridge Repository, University of Cambridge [UK] (CAM), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Chapel Allerton Hospital, Great Ormond Street Hospital for Children [London] (GOSH), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Mount Sinai Hospital [Toronto, Canada] (MSH), University of Toronto (University of Toronto), Christian-Albrechts University of Kiel, The University of Texas M.D. Anderson Cancer Center [Houston], Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], CIBER de Enfermedades Raras (CIBERER), Spanish National Cancer Research Center (CNIO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Pomeranian Medical University [Szczecin] (PUM), University of California (UC), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], European Institute of Oncology IRCCS [Milan, Italy] (EIO), Zealand University Hospital [Roskilde, Denmark], Lund University [Lund], National Institute of Oncology [Budapest, Hungary], Abramson Cancer Center [philadelphia], University of Pennsylvania-Perelman School of Medicine, University of Pennsylvania, Institute of Genetic Medicine [Newcastle], Newcastle University [Newcastle], Royal Devon & Exeter Hospital, Exeter, UK, Catalan Institute of Oncology [Barcelone, Espagne], Huntsman Cancer Institute [Salt Lake City], University of Utah, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Pisa University Hospital, Peter MacCallum Cancer Centre [Melbourne, Australie], University of Melbourne, Aarhus University Hospital, Columbia University [New York], Ghent University Hospital, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Sheffield Children's NHS Foundation Trust, Fox Chase Cancer Center, Queen Elizabeth University Hospital (Glasgow), Centre hospitalier universitaire de Nantes (CHU Nantes), Leiden University Medical Center (LUMC), Beckman Research Institute of the City of Hope, Abramson Cancer Center, University of Pretoria [South Africa], Centre Hospitalier Universitaire de Québec Research Center [Canada], Royal Marsden NHS Foundation Trust, Copenhagen University Hospital, Leipzig University, University of Manchester [Manchester], Manchester Academic Health Science Centre (MAHSC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Masaryk Memorial Cancer Institute (MMCI), Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research 'Demokritos' (NCSR), NHMRC Clinical Trials Centre [Camperdown NSW 2050, Australie], Chaim Sheba Medical Center, Tel Aviv University (TAU), Jonsson Comprehensive Cancer Center, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Dana-Farber Cancer Institute [Boston], University of Würzburg, Rigshospitalet [Copenhagen], Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Hospices Civils de Lyon (HCL), University of Kansas [Kansas City], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Medizinische Universität Wien = Medical University of Vienna, University of Cologne, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Lancashire NHS Foundation Trust, University Hospital Leipzig, Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Mayo Clinic, NorthShore University HealthSystem [Evanston, IL, USA], The University of Chicago Medicine [Chicago], N. N. Petrov Institute of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Guy's and St Thomas' NHS Foundation Trust [London, UK], Peter MacCallum Cancer Center, East Melbourne, Peter MacCallum Cancer Center, Vilnius University [Vilnius], The State Scientific Research Institute Nature Research Centre, Vilnius, Lithuania, Stanford University School of Medicine [CA, USA], Memorial Sloane Kettering Cancer Center [New York], Cedars-Sinai Medical Center, Technische Universität Dresden = Dresden University of Technology (TU Dresden), University Medical Center [Utrecht], Odense University Hospital [Odense, Denmark], The Hong Kong Hereditary Breast Cancer Family Registry, The University of Hong Kong (HKU), Hong Kong Sanatorium and Hospital [Hong Kong] (HKSH), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), David Geffen School of Medicine [Los Angeles], Fondation MINES ParisTech, Karolinska Institutet [Stockholm], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Amsterdam UMC - Amsterdam University Medical Center, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Radboud University Medical Center [Nijmegen], Roswell Park Cancer Institute [Buffalo], Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], University of Toronto, University Health Network, University Hospital Düsseldorf, Latvian Biomedical Research and Study Centre [Rīga], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), University of Chicago, Birmingham Women's and Children's NHS Foundation Trust, Cambridge University Hospitals - NHS (CUH), Charité Campus Virchow-Klinikum (CVK), Università degli Studi di Firenze = University of Florence (UniFI), Seoul National University College of Medicine [Séoul, Corée du Sud] (SNUCM), Seoul National University [Seoul] (SNU), QIMR Berghofer Medical Research Institute, Aalborg University [Denmark] (AAU), IRCCS Istituto Nazionale dei Tumori [Milano], Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Klinikum rechts der Isar [Munich, Germany], University of New South Wales [Sydney] (UNSW), Garvan Institute of medical research, Technion Faculty of Medicine [Haifa, Israel], Yale School of Medicine [New Haven, Connecticut] (YSM), Vejle Hospital [Danemark], Ohio State University [Columbus] (OSU), Centre de lutte contre le cancer Paul-Strauss, Institut de Cancérologie de Strasbourg Europe (ICANS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Kansas Medical Center [Kansas City, KS, USA], Princess Anne Hospital, City of Hope Comprehensive Cancer Center [Duarte], Monash University [Clayton], Cancer Council Victoria [Melbourne, VIC, Australia], Hannover Medical School [Hannover] (MHH), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Heidelberg University Hospital [Heidelberg], Institute of Biomedical Sciences Abel Salazar - ICBAS [Porto, Portugal], Malaysia and University Malaya Cancer Research Institute, Faculty of Medicine, University of Malaya [Kuala Lumpur, Malaisie], University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), McGill University = Université McGill [Montréal, Canada], Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Fundación Pública Galega Medicina Xenómica - SERGAS [Santiago de Compostela, Spain] (Grupo de Medicina Xenómica), CIBER de Enfermedades Raras (CIBERER)-Universidade de Santiago de Compostela [Spain] (USC ), Instituto de Investigaciones Sanitarias, Universidade de Santiago de Compostela [Spain] (USC ), Universiteit Gent = Ghent University (UGENT), Oxford University Hospitals NHS Trust, University of Oxford, Universitätsklinikum Ulm - University Hospital of Ulm, University Hospital of Cologne [Cologne], Mayo Clinic [Rochester], Collaborators : Pascaline Berthet, Chrystelle Colas, Marie-Agnès Collonge-Rame, Capucine Delnatte, Laurence Faivre, Sophie Giraud, Christine Lasset, Véronique Mari, Noura Mebirouk, Emmanuelle Mouret-Fourme, Hélène Schuster, Dominique Stoppa-Lyonnet, Julian Adlard, Munaza Ahmed, Antonis Antoniou, Daniel Barrowdale, Paul Brennan, Carole Brewer, Jackie Cook, Rosemarie Davidson, Douglas Easton, Ros Eeles, D Gareth Evans, Debra Frost, Helen Hanson, Louise Izatt, Kai-Ren Ong, Lucy Side, Aoife O'Shaughnessy-Kirwan, Marc Tischkowitz, Lisa Walker, Georgia Chenevix-Trench, Kelly-Anne Phillips, Amanda Spurdle, Marinus Blok, Peter Devilee, Frans Hogervorst, Maartje Hooning, Marco Koudijs, Arjen Mensenkamp, Hanne Meijers-Heijboer, Matti Rookus, Klaartje van Engelen, Nadine Andrieu, Catherine Noguès, Dupuis, Christine, Institut Català de la Salut, [Barnes DR, McGuffog L, Leslie G, Dennis J] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Rookus MA, Mooij TM] The Netherlands Cancer Institute, Department of Epidemiology (PSOE), Amsterdam, The Netherlands. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Barnes, Daniel [0000-0002-3781-7570], Leslie, Goska [0000-0001-5756-6222], Dennis, Joe [0000-0003-4591-1214], Mavaddat, Nasim [0000-0003-0307-055X], RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), Universiteit Leiden, Roswell Park Cancer Institute [Buffalo] (RPCI), Medical Oncology, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, Helsinki University Hospital Area, Department of Obstetrics and Gynecology, Biosciences, HUS Gynecology and Obstetrics, University of Helsinki, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), MINES ParisTech - École nationale supérieure des mines de Paris, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Pomeranian Medical University, University of California, University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Pennsylvania [Philadelphia], University of Leipzig [Leipzig, Allemagne], Masaryk Memorial Cancer Institute (RECAMO), Tel Aviv University [Tel Aviv], University of California-University of California, University of Münster, Amsterdam UMC, Technical University of Munich (TUM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Garvan Institute of Medical Research [Sydney, Australia], Yale University School of Medicine, Vejle Hospital, University of Kansas Medical Center [Lawrence], Université Paris Descartes (Paris 5), University of Malaya [Kuala Lumpur, Malaisie], Universiteit Gent = Ghent University [Belgium] (UGENT), and University of Oxford [Oxford]
Subjects: 0301 basic medicine, Oncology, endocrine system diseases, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], [SDV]Life Sciences [q-bio], Càncer d'ovari, Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES], MODIFIERS, Diàtesi, SUSCEPTIBILITY, Carcinoma, Ovarian Epithelial, PRS, 0302 clinical medicine, Breast cancer, 3123 Gynaecology and paediatrics, Risk Factors, Medicine and Health Sciences, Medicine, Genetics(clinical), genetics, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, Genetics (clinical), Ovarian Neoplasms, education.field_of_study, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], BRCA1 Protein, Hazard ratio, Absolute risk reduction, 1184 Genetics, developmental biology, physiology, article, ASSOCIATION, neoplasias::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas::carcinoma epitelial de ovario [ENFERMEDADES], ddc, 3. Good health, [SDV] Life Sciences [q-bio], ovarian cancer, 030220 oncology & carcinogenesis, Female, Cohort study, medicine.medical_specialty, Heterozygote, Population, 3122 Cancers, Single-nucleotide polymorphism, Breast Neoplasms, MUTATION CARRIERS, Ovaris - Càncer - Aspectes genètics, Càncer de mama, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, Ovarian cancer, BRCA1/2, Internal medicine, Humans, Genetic Predisposition to Disease, education, Retrospective Studies, fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS], BRCA2 Protein, IDENTIFICATION, business.industry, Neoplasms::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms::Carcinoma, Ovarian Epithelial [DISEASES], Retrospective cohort study, ALLELES, medicine.disease, BRCA1, BRCA2, MODEL, PATHOLOGY, 030104 developmental biology, Mutation, Mama - Càncer - Aspectes genètics, 3111 Biomedicine, business
Abstract: Contains fulltext : 229292.pdf (Publisher’s version ) (Open Access) PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. METHODS: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. RESULTS: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10(-72)). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10(-22)) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10(-12)) carriers. The associations in the prospective cohort were similar. CONCLUSION: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.
Published: 2020
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271. Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries

Author: Deschasaux, Mélanie, Huybrechts, Inge, Julia, Chantal, Hercberg, Serge, Egnell, Manon, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Murphy, Neil, Jenab, Mazda, Ward, Heather A, Weiderpass, Elisabete, Overvad, Kim, Tjønneland, Anne, Rostgaard-Hansen, Agnetha Linn, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Mahamat-Saleh, Yahya, Kühn, Tilman, Katzke, Verena, Bergmann, Manuela M, Schulze, Matthias B, Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Agnoli, Claudia, De Magistris, Maria Santucci, Tumino, Rosario, Sacerdote, Carlotta, Boer, Jolanda MA, Verschuren, WM Monique, van der Schouw, Yvonne T, Skeie, Guri, Braaten, Tonje, Redondo, M Luisa, Agudo, Antonio, Petrova, Dafina, Colorado-Yohar, Sandra M, Barricarte, Aurelio, Amiano, Pilar, Sonestedt, Emily, Ericson, Ulrika, Otten, Julia, Sundström, Björn, Wareham, Nicholas J, Forouhi, Nita G, Vineis, Paolo, Tsilidis, Konstantinos K, Knuppel, Anika, Papier, Keren, Ferrari, Pietro, Riboli, Elio, Gunter, Marc J, Touvier, Mathilde, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), 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)-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), Réseau National Alimentation Cancer Recherche (réseau NACRe), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Département de Santé Publique [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), School of Public Health, Imperial College London, Aarhus University [Aarhus], Department of Public Health [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Danish Cancer Society Research Center, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Institute of Nutrition Science, University of Potsdam, Hellenic Health Foundation, 'Attikon' University Hospital, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], AOU Federico II, Partenaires INRAE, Provincial Health Services Authority, Center for Cancer Prevention (CPO-Piemonte), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], The Arctic University of Norway (UiT), Public Health Directorate, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Andalusian School of Public Health [Granada], Escuela Andaluza de Salud Publica, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain, parent, CIBER de Epidemiología y Salud Pública (CIBERESP), Murcia Regional Health Council [Murcia], Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Navarra Public Health Institute, Navarra Institute for Health Research, Biodonostia Health Research Institute, Department of Clinical Sciences [Malmö, Suède], Lund University [Malmö, Suède], Department of Public Health and Clinical Medicine [Umeå, Sweden] (Environmental and Occupational Medicine), Umeå University, University of Cambridge School of Clinical Medicine, University of Ioannina School of Medicine, Nuffield Department of Population Health [Oxford], University of Oxford [Oxford], French National Cancer Institute (INCa)-Canceropole Ile-de-France 2017-1-PL SHS-01-INSERM ADR 5-1Fondation Recherche Medicale ARF201809007046European CommissionEuropean Commission Joint Research CentreInternational Agency for Research on CancerDanish Cancer SocietyLigue nationale contre le cancerInstitut Gustave RoussyMutuelle Generale de l'Education NationaleInstitut National de la Sante et de la Recherche Medicale (Inserm)Deutsche KrebshilfeFederal Ministry of Education & Research (BMBF)Hellenic Health Foundation (Greece)Associazione Italiana per la Ricerca sul Cancro (AIRC)Italian National Research CouncilDutch Ministry of Public Health, Welfare, and Sports (the Netherlands)Netherlands Cancer Registry (the Netherlands)Netherlands GovernmentHealth Research Fund (Spain)Instituto de Salud Carlos IIIJunta de Andalucia Regional government of Asturias (Spain) Regional government of Basque Country (Spain) Regional government of Murcia (Spain) Regional government of Navarra (Spain) Catalan Institute of Oncology (Spain)Swedish Cancer Society Swedish Scientific Council (Sweden) County councils of Skane and Vasterbotten (Sweden)Cancer Research UK C864/A14136 C8221/A19170Medical Research Council UK (MRC) MR/N003284/1 - MC-UU_12015/1 - MR/M012190/1 - MC_UU_12015/1 - MC_UU_12015/5 - National Institute for Health Research Biomedical Research Centre, Cambridge: Nutrition, Diet, and Lifestyle Research Theme IS-BRC-1215-20014, Deschasaux, Mélanie [0000-0002-3359-420X], and Apollo - University of Cambridge Repository
Subjects: Adult, Male, 1117 Public Health and Health Services, Cohort Studies, Food Preferences, Food Labeling, General & Internal Medicine, Surveys and Questionnaires, Mortalitat, Humans, Mortality, Nutrició, ComputingMilieux_MISCELLANEOUS, Nutrition, Proportional Hazards Models, Research, Klinisk medicin, 1103 Clinical Sciences, Middle Aged, Europe, Nutrition Assessment, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Clinical Medicine, Nutritive Value, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Objective: To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. Design: Population based cohort study. Setting: European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. Participants: 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. Main outcome measure: Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. Results: After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, PConclusions: In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.
Published: 2020
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272. The DNA methylation landscape of multiple myeloma shows extensive inter- and intrapatient heterogeneity that fuels transcriptomic variability

Author: Jennifer Derrien, Catherine Guérin-Charbonnel, Victor Gaborit, Loïc Campion, Magali Devic, Elise Douillard, Nathalie Roi, Hervé Avet-Loiseau, Olivier Decaux, Thierry Facon, Jan-Philipp Mallm, Roland Eils, Nikhil C. Munshi, Philippe Moreau, Carl Herrmann, Florence Magrangeas, Stéphane Minvielle, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Laboratoire des Sciences du Numérique de Nantes (LS2N), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], CHU Lille, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Bioquant, Universität Heidelberg [Heidelberg], Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Harvard Medical School [Boston] (HMS), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Humboldt University Of Berlin, and Minvielle, Stéphane
Subjects: Epigenomics, Transcriptomic variability, [SDV.CAN]Life Sciences [q-bio]/Cancer, QH426-470, Epigenesis, Genetic, Histones, Genetic Heterogeneity, [SDV.CAN] Life Sciences [q-bio]/Cancer, Genetics, Humans, Promoter Regions, Genetic, Research, Gene Expression Profiling, Computational Biology, Molecular Sequence Annotation, DNA Methylation, Epiallele switching, Inter- and intrapatient heterogeneity, Prognosis, Gene Expression Regulation, Neoplastic, Disordered DNA methylation, Medicine, CpG Islands, Disease Susceptibility, Epipolymorphism, Multiple Myeloma, Transcriptome
Abstract: Background Cancer evolution depends on epigenetic and genetic diversity. Historically, in multiple myeloma (MM), subclonal diversity and tumor evolution have been investigated mostly from a genetic perspective. Methods Here, we performed an analysis of 42 MM samples from 21 patients by using enhanced reduced representation bisulfite sequencing (eRRBS). We combined several metrics of epigenetic heterogeneity to analyze DNA methylation heterogeneity in MM patients. Results We show that MM is characterized by the continuous accumulation of stochastic methylation at the promoters of development-related genes. High combinatorial entropy change is associated with poor outcomes in our pilot study and depends predominantly on partially methylated domains (PMDs). These PMDs, which represent the major source of inter- and intrapatient DNA methylation heterogeneity in MM, are linked to other key epigenetic aberrations, such as CpG island (CGI)/transcription start site (TSS) hypermethylation and H3K27me3 redistribution as well as 3D organization alterations. In addition, transcriptome analysis revealed that intratumor methylation heterogeneity was associated with low-level expression and high variability. Conclusions We propose that disrupted DNA methylation in MM is responsible for high epigenetic and transcriptomic instability allowing tumor cells to adapt to environmental changes by tapping into a pool of evolutionary trajectories. Supplementary Information The online version contains supplementary material available at (10.1186/s13073-021-00938-3).
Published: 2020
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273. Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food

Author: EFSA Panel Contaminants Food Chain, Knutsen, Helle, Alexander, Jan, Barregård, Lars, Bignami, Bruschweiler, Ceccatelli, Cottrill, Dinovi, Edler, Grasl-Kraupp, Hogstrand, Nebbia, Oswald, Petersen, Rose, Roudot, Schwerdtle, Vleminckx, Vollmer, Wallace, Furst, Håkansson, Helen, Halldorsson, Lundebye, Pohjanvirta, Raimo Kalevi, Rylander, Smith, van Loveren, Waalkens-Berendsen, Zeilmaker, Binaglia, Gomez Ruiz, Horvath, Christoph, Ciccolallo, Ramos Bordajandi, Steinkellner, Hoogenboom, Ron, Raimo Pohjanvirta / Principal Investigator, Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, Norwegian Institute of Public Health [Oslo] (NIPH), German Cancer Research Center, Division of Biostatistics, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Novel Foods & Agrochains, TOXIC EQUIVALENCY FACTORS, Breastfeeding, Plant Science, 010501 environmental sciences, Novel Foods & Agroketens, 01 natural sciences, Human health, Epidemiology, TX341-641, European commission, PERSISTENT ORGANIC POLLUTANTS, BU Toxicology, Novel Foods & Agrochains, Mink, 2. Zero hunger, biology, BU Toxicology, feed, risk assessment, DL-PCBs, MINK MUSTELA-VISON, 3. Good health, BU Toxicologie, Novel Foods & Agroketens, Chemical Contaminants, [SDV.TOX]Life Sciences [q-bio]/Toxicology, AIR-FORCE VETERANS, Risk assessment, SALMON SALMO-SALAR, ARYL-HYDROCARBON RECEPTOR, medicine.medical_specialty, BU Toxicologie, Veterinary (miscellaneous), POLYCHLORINATED-BIPHENYLS PCBS, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, TP1-1185, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Dioxins, Microbiology, 03 medical and health sciences, Semen quality, Animal data, Animal science, SDG 3 - Good Health and Well-being, biology.animal, medicine, PCDD/Fs, VLAG, 0105 earth and related environmental sciences, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, DL‐PCBs, Nutrition. Foods and food supply, Chemical technology, food, DIBENZO-P-DIOXINS, LACTATIONAL 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN EXPOSURE, 030104 developmental biology, Scientific Opinion, 416 Food Science, Animal Science and Zoology, Parasitology, IN-UTERO EXPOSURE, transfer, Food Science
Abstract: The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of dioxins (PCDD/Fs) and DL‐PCBs in feed and food. The data from experimental animal and epidemiological studies were reviewed and it was decided to base the human risk assessment on effects observed in humans and to use animal data as supportive evidence. The critical effect was on semen quality, following pre‐ and postnatal exposure. The critical study showed a NOAEL of 7.0 pg WHO2005‐TEQ/g fat in blood sampled at age 9 years based on PCDD/F‐TEQs. No association was observed when including DL‐PCB‐TEQs. Using toxicokinetic modelling and taking into account the exposure from breastfeeding and a twofold higher intake during childhood, it was estimated that daily exposure in adolescents and adults should be below 0.25 pg TEQ/kg bw/day. The CONTAM Panel established a TWI of 2 pg TEQ/kg bw/week. With occurrence and consumption data from European countries, the mean and P95 intake of total TEQ by Adolescents, Adults, Elderly and Very Elderly varied between, respectively, 2.1 to 10.5, and 5.3 to 30.4 pg TEQ/kg bw/week, implying a considerable exceedance of the TWI. Toddlers and Other Children showed a higher exposure than older age groups, but this was accounted for when deriving the TWI. Exposure to PCDD/F‐TEQ only was on average 2.4‐ and 2.7‐fold lower for mean and P95 exposure than for total TEQ. PCDD/Fs and DL‐PCBs are transferred to milk and eggs, and accumulate in fatty tissues and liver. Transfer rates and bioconcentration factors were identified for various species. The CONTAM Panel was not able to identify reference values in most farm and companion animals with the exception of NOAELs for mink, chicken and some fish species. The estimated exposure from feed for these species does not imply a risk., This publication is linked to the following EFSA Supporting Publications articles: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2018.EN-1136/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2018.EN-1137/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2018.EN-1374/full
Published: 2020
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274. Appropriateness to set a group health based guidance value for nivalenol and its modified forms

Author: EFSA Panel on Contaminants in the Food Chain (CONTAM), Helle Katrine Knutsen, Lars Barregård, Margherita Bignami, Beat Brüschweiler, Sandra Ceccatelli, Bruce Cottrill, Michael Dinovi, Lutz Edler, Bettina Grasl‐Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Carlo Stefano Nebbia, Isabelle P Oswald, Annette Petersen, Martin Rose, Alain‐Claude Roudot, Tanja Schwerdtle, Christiane Vleminckx, Günter Vollmer, Heather Wallace, Chiara Dall'Asta, Arno C Gutleb, Manfred Metzler, Dominique Parent‐Massin, Marco Binaglia, Hans Steinkellner, Jan Alexander, German Cancer Research Center, Division of Biostatistics, King‘s College London, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Tolerable daily intake, Veterinary (miscellaneous), Metabolite, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, Physiology, TP1-1185, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Plant Science, Body weight, 01 natural sciences, Microbiology, Toxicology, 03 medical and health sciences, chemistry.chemical_compound, biology.animal, group health based guidance value, Medicine, TX341-641, Mink, nivalenol, Reference dose, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Toxicity data, biology, Nutrition. Foods and food supply, business.industry, Chemical technology, 010401 analytical chemistry, modified forms, 3. Good health, 0104 chemical sciences, 030104 developmental biology, Scientific Opinion, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Animal Science and Zoology, Parasitology, business, Food Science
Abstract: International audience; The EFSA Panel on Contaminants in the Food Chain (CONTAM) reviewed new studies on nivalenol since the previous opinion on nivalenol published in 2013, but as no new relevant data were identified the tolerable daily intake (TDI) for nivalenol (NIV) of 1.2 lg/kg body weight (bw) established on bases of immuno-and haematotoxicity in rats was retained. An acute reference dose (ARfD) of 14 lg/kg bw was established based on acute emetic events in mink. The only phase I metabolite of NIV identified is de-epoxy-nivalenol (DE-NIV) and the only phase II metabolite is nivalenol-3-glucoside (NIV3Glc). DE-NIV is devoid of toxic activity and was thus not further considered. NIV3Glc can occur in cereals amounting up to about 50% of NIV. There are no toxicity data on NIV3Glc, but as it can be assumed that it is hydrolysed to NIV in the intestinal tract it should be included in a group TDI and in a group ARfD with NIV. The uncertainty associated with the present assessment is considered as high and it would rather overestimate than underestimate any risk.
Published: 2020
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275. The role of rare compound heterozygous events in autism spectrum disorder

Author: Thomas Bourgeron, Alistair T. Pagnamenta, Jeremy R. Parr, Louise Gallagher, Christine M. Freitag, Jacob A. S. Vorstman, Sean Ennis, Isaac J. Nijman, Fabrice Colas, Kristel R. van Eijk, Bochao Danae Lin, Jurjen J. Luykx, Jelena Medic, Sabine M. Klauck, Elena Maestrini, Astrid M. Vicente, Richard Anney, Guiomar Oliveira, Elena Bacchelli, Hilary Coon, Andreas G. Chiocchetti, William J. Brands, Utrecht University [Utrecht], Henan University, Kaifeng, Newcastle University [Newcastle], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Goethe-Universität Frankfurt am Main, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University of Utah School of Medicine [Salt Lake City], Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Centro Hospitalar e Universitário [Coimbra], University of Oxford [Oxford], Trinity College Dublin, University College Dublin [Dublin] (UCD), Cardiff University, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), GGNet Mental Health [Apeldoorn, The Netherlands], The Hospital for sick children [Toronto] (SickKids), University of Toronto, This study has been funded by the Dutch Brain Foundation (Hersenstichting Nederland) to JV., Lin B.D., Colas F., Nijman I.J., Medic J., Brands W., Parr J.R., van Eijk K.R., Klauck S.M., Chiocchetti A.G., Freitag C.M., Maestrini E., Bacchelli E., Coon H., Vicente A., Oliveira G., Pagnamenta A.T., Gallagher L., Ennis S., Anney R., Bourgeron T., Luykx J.J., Vorstman J., Henan University, University of Oxford, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Proband, DNA Copy Number Variations, Autism Spectrum Disorder, Autism, Biology, Compound heterozygosity, ASD, Article, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, medicine, Humans, Genetic Predisposition to Disease, Allele, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Gene, Biological Psychiatry, Alleles, MESH: Autism Spectrum Disorder, Genetics, Comparative genomics, MESH: Humans, MESH: Alleles, [SCCO.NEUR]Cognitive science/Neuroscience, MESH: Genetic Predisposition to Disease, Autism spectrum disorders, medicine.disease, Penetrance, Autism Spectrum Disorders, Autism, CNVs, Deletions, SNVs, Compound Heterozygosity, Targeted Sequencing, Psychiatry and Mental health, 030104 developmental biology, Autism spectrum disorder, Perturbações do Desenvolvimento Infantil e Saúde Mental, MESH: DNA Copy Number Variations, 030217 neurology & neurosurgery
Abstract: The identification of genetic variants underlying autism spectrum disorders (ASDs) may contribute to a better understanding of their underlying biology. To examine the possible role of a specific type of compound heterozygosity in ASD, namely, the occurrence of a deletion together with a functional nucleotide variant on the remaining allele, we sequenced 550 genes in 149 individuals with ASD and their deletion-transmitting parents. This approach allowed us to identify additional sequence variants occurring in the remaining allele of the deletion. Our main goal was to compare the rate of sequence variants in remaining alleles of deleted regions between probands and the deletion-transmitting parents. We also examined the predicted functional effect of the identified variants using Combined Annotation-Dependent Depletion (CADD) scores. The single nucleotide variant-deletion co-occurrence was observed in 13.4% of probands, compared with 8.1% of parents. The cumulative burden of sequence variants (n = 68) in pooled proband sequences was higher than the burden in pooled sequences from the deletion-transmitting parents (n = 41, X2 = 6.69, p = 0.0097). After filtering for those variants predicted to be most deleterious, we observed 21 of such variants in probands versus 8 in their deletion-transmitting parents (X2 = 5.82, p = 0.016). Finally, cumulative CADD scores conferred by these variants were significantly higher in probands than in deletion-transmitting parents (burden test, β = 0.13; p = 1.0 × 10−5). Our findings suggest that the compound heterozygosity described in the current study may be one of several mechanisms explaining variable penetrance of CNVs with known pathogenicity for ASD.
Published: 2020
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276. Disassembly of Tau fibrils by the human Hsp70 disaggregation machinery generates small seeding-competent species

Author: Karine Madiona, Axel Mogk, Taxiarchis Katsinelos, Eliana Nachman, Bernd Bukau, Harm H. Kampinga, Luc Bousset, Anne S. Wentink, Kieren Allinson, Ronald Melki, William A. McEwan, Thomas R. Jahn, Carmen Nussbaum-Krammer, Center for Molecular Biology - Zentrum für Molekulare Biologie [Heidelberg, Germany] (ZMBH), Universität Heidelberg [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), 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-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Clinical Neurosciences [Cambridge], University of Cambridge [UK] (CAM), Cambridge University Hospitals - NHS (CUH), University of Groningen [Groningen], Universität Heidelberg [Heidelberg] = Heidelberg University, Institut de Biologie François JACOB (JACOB), Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), University Medical Center Groningen [Groningen] (UMCG), ANR-17-JPCD-0005,Protest-70,Protecting protein homeostasis in synucleinopathies and tauopathies by modulating the Hsp70/co-chaperone network(2017), European Project: (grant No 116060),IMPRiND, and Molecular Neuroscience and Ageing Research (MOLAR)
Subjects: 0301 basic medicine, 70 kilodalton heat shock protein (Hsp70), [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, PROTEIN, Protein aggregation, Biochemistry, Nucleotide exchange factor, neurodegenerative disease, BINDING, PHOSPHORYLATION, biology, Chemistry, Brain, amyloid, Molecular Bases of Disease, ASSOCIATION, JBC Keywords: Tau protein (Tau), molecular chaperone, Cell biology, ALZHEIMERS-DISEASE, chaperone DNAJ (DNAJ), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Tauopathy, Amyloid, Tau protein, tau Proteins, protein aggregation, prion, 03 medical and health sciences, Alzheimer Disease, Heat shock protein, mental disorders, medicine, Humans, HSP70 Heat-Shock Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, proteostasis, 030102 biochemistry & molecular biology, tauopathy, Cell Biology, 70-kilodalton heat shock protein (Hsp70), AGGREGATION, medicine.disease, GENE-EXPRESSION CHANGES, PATHOLOGY, 030104 developmental biology, Proteostasis, HEK293 Cells, Chaperone (protein), biology.protein, Tau, MEDIATE, HSP110
Abstract: International audience; The accumulation of amyloid Tau aggregates is implicated in Alzheimer’s disease (AD) and other tauopathies. Molecular chaperones are known to maintain protein homeostasis. Here, we show that an ATP-dependent human chaperone system disassembles Tau fibrils in vitro. We found that this function is mediated by the core chaperone HSC70, assisted by specific cochaperones, in particular class B J-domain proteins and a heat shock protein 110 (Hsp110)-type nucleotide exchange factor (NEF). The Hsp70 disaggregation machinery processed recombinant fibrils assembled from all six Tau isoforms as well as Sarkosyl-resistant Tau aggregates extracted from cell cultures and human AD brain tissues, demonstrating the ability of the Hsp70 machinery to recognize a broad range of Tau aggregates. However, the chaperone activity released monomeric and small oligomeric Tau species, which induced the aggregation of self-propagating Tau conformers in a Tau cell culture model. We conclude that the activity of the Hsp70 disaggregation machinery is a double-edged sword, as it eliminates Tau amyloids at the cost of generating new seeds.
Published: 2020
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277. Loss of Wasl improves pancreatic cancer outcome

Author: Katharina Schulte, Juliet M. Daniel, Blessing Bassey-Archibong, Zahra Dantes, Clara Lubeseder-Martellato, Jens T. Siveke, Thomas Engleiter, Maximilian Reichert, Ana Hidalgo-Sastre, Henrik Einwächter, Guido von Figura, Roland M. Schmid, Rupert Öllinger, Katia Steiger, Marina Lesina, Hilal Kabadayi Ensarioglu, Ali Sameer Abdulghani Altaee, Roland Rad, Lyndsay G. A. Rayner, Judit Desztics, Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Germany, Department of Histology and Embryology, Manisa Celal Bayar University, Turkey, Department of Biology, McMaster University, Hamilton, Ontario, Canada, Institute of Molecular Oncology and Functional Genomics and, Institute of Pathology, Technical University of Munich, Munich, Germany, Institute for Developmental Cancer Therapeutics, West German Cancer Center, University Hospital Essen, Essen, Germany, Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK) partner site Essen, Essen, Germany, and German Cancer Research Center (DKFZ), Heidelberg, Germany
Subjects: 0301 basic medicine, Senescence, Medizin, Wiskott-Aldrich Syndrome Protein, Neuronal, Mice, Transgenic, macromolecular substances, Biology, medicine.disease_cause, Mice, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Pancreatic cancer, medicine, Animals, Humans, YAP1, Cancer, Neoplasms, Experimental, General Medicine, medicine.disease, WASL, ddc, Pancreatic Neoplasms, 030104 developmental biology, Tumor progression, 030220 oncology & carcinogenesis, Cancer research, KRAS, Tumor Suppressor Protein p53, Research Article
Abstract: Several studies have suggested an oncogenic role for the neural Wiskott-Aldrich syndrome protein (N-WASP, encoded by the Wasl gene), but thus far, little is known about its function in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed in silico analysis of WASL expression in PDAC patients and found a correlation between low WASL expression and prolonged survival. To clarify the role of Wasl in pancreatic carcinogenesis, we used 2 oncogenic Kras-based PDAC mouse models with pancreas-specific Wasl deletion. In line with human data, both mouse models had an increased survival benefit due to either impaired tumor development in the presence of the tumor suppressor Trp53 or the delayed tumor progression and senescent phenotype upon genetic ablation of Trp53. Mechanistically, loss of Wasl resulted in cell-autonomous senescence through displacement of the N-WASP binding partners WASP-interacting protein (WIP) and p120ctn; vesicular accumulation of GSK3β, as well as YAP1 and phosphorylated β-catenin, which are components of the destruction complex; and upregulation of Cdkn1a(p21), a master regulator of senescence. Our findings, thus, indicate that Wasl functions in an oncogenic manner in PDAC by promoting the deregulation of the p120-catenin/β-catenin/p21 pathway. Therefore, strategies to reduce N-WASP activity might improve the survival outcomes of PDAC patients. CA extern
Published: 2020
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278. The 18S ribosomal <scp>RNA</scp> m 6 A methyltransferase Mettl5 is required for normal walking behavior in Drosophila

Author: Pablo Mier, Christof Niehrs, Ludivine Wacheul, Minh Anh Vu, Michael U. Musheev, Marc Graille, Mihika Pradhan, Jean-Yves Roignant, Miguel A. Andrade-Navarro, Mariangela Spagnuolo, Denis L. J. Lafontaine, Jessica Leismann, Institute of Molecular Biology (IMB), Johannes Gutenberg - Universität Mainz (JGU), RNA Molecular Biology, Center for Microscopy and Molecular Imaging, Fonds de la Recherche Nationale, Université Libre de Bruxelles, Charleroi-Gosselies, Belgium, Laboratoire de Biologie Structurale de la Cellule (BIOC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Division of Molecular Embryology - DKFZ-ZMBH Alliance, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), and ANR-16-CE11-0003,m6A,La modification m6A des ANRm: biogenèse et rôle dans la stabilité des ARNm(2016)
Subjects: Adenosine, Biochimie, m 6 A, Mettl5, Walking, Biology, Biochemistry, Ribosome, 18S ribosomal RNA, 03 medical and health sciences, 0302 clinical medicine, Gene expression, RNA, Ribosomal, 18S, Genetics, Animals, Humans, RNA methyltransferase, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Molecular Biology, 030304 developmental biology, Behavior, 0303 health sciences, Messenger RNA, behavior, Biologie moléculaire, RNA, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Methyltransferases, m6A, Ribosomal RNA, Non-coding RNA, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 3. Good health, Cell biology, ribosome, RNA, Ribosomal, Drosophila, Biologie, 030217 neurology & neurosurgery, Small nuclear RNA, Reports
Abstract: RNA modifications have recently emerged as an important layer of gene regulation. N6-methyladenosine (m6A) is the most prominent modification on eukaryotic messenger RNA and has also been found on noncoding RNA, including ribosomal and small nuclear RNA. Recently, several m6A methyltransferases were identified, uncovering the specificity of m6A deposition by structurally distinct enzymes. In order to discover additional m6A enzymes, we performed an RNAi screen to deplete annotated orthologs of human methyltransferase-like proteins (METTLs) in Drosophila cells and identified CG9666, the ortholog of human METTL5. We show that CG9666 is required for specific deposition of m6A on 18S ribosomal RNA via direct interaction with the Drosophila ortholog of human TRMT112, CG12975. Depletion of CG9666 yields a subsequent loss of the 18S rRNA m6A modification, which lies in the vicinity of the ribosome decoding center; however, this does not compromise rRNA maturation. Instead, a loss of CG9666-mediated m6A impacts fly behavior, providing an underlying molecular mechanism for the reported human phenotype in intellectual disability. Thus, our work expands the repertoire of m6A methyltransferases, demonstrates the specialization of these enzymes, and further addresses the significance of ribosomal RNA modifications in gene expression and animal behavior., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020
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279. Hyd ubiquitinates the NF-κB co-factor Akirin to operate an effective immune response in Drosophila

Author: Adrian Acker, Akira Goto, Michael Boutros, Marie-Odile Fauvarque, Alexandre Cammarata-Mouchtouris, Xuan-Hung Nguyen, Jean-Marc Reichhart, François Bonnay, Nicolas Matt, Amir Orian, Modèles Insectes de l'Immunité Innée (M3I), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vietnam National University [Hanoï] (VNU), Austrian Academy of Sciences (OeAW), Technion - Israel Institute of Technology [Haifa], Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université Grenoble Alpes (UGA), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg University, This work was supported by the Centre National de la Recherche Scientifique (http://www.cnrs.fr/fr/page-daccueil) in the frame of the LIA «REL2 and resistance to malaria». This work was performed under the framework of the LABEX: ANR-10- LABX-0036_NETRNA and ANR-17-EURE-0023, through a funding of the state managed by the French National Research Agency (https://anr.fr/) as part of the Investments for the future program and also from a European Research Council (https://erc.europa.eu/) Advanced Grant (AdG_20090506 ‘‘Immudroso,’’ to J.-M.R.). Generation of RNAi reagents by M.B. was supported by DFG DRiC (https://www.dfg.de/). N. M. is a Fellow at the University of Strasbourg Institute for Advanced Study (USIAS-2018-073, ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-17-EURE-0023,IMCBio,Integrative Molecular and Cellular Biology(2017), European Project: 250076,EC:FP7:ERC,ERC-2009-AdG,IMMUDROSO(2010), 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 la Santé et de la Recherche Médicale (INSERM), ANR-10-IDEX-0002,UNISTRA,Network of regulatory RNAs across kingdoms and dynamical responses to biotic and abiotic stresses.(2010), Bodescot, Myriam, Initiative d'excellence - Par-delà les frontières, l'Université de Strasbourg - - UNISTRA2010 - ANR-10-IDEX-0002 - IDEX - VALID, Integrative Molecular and Cellular Biology - - IMCBio2017 - ANR-17-EURE-0023 - EURE - VALID, and Sensing and Signalling in the Innate Immune Response, using Drosophila as a Model. - IMMUDROSO - - EC:FP7:ERC2010-03-01 - 2015-02-28 - 250076 - VALID
Subjects: Biochemistry, Ligases, chemistry.chemical_compound, Ubiquitin, Transcription (biology), Medicine and Health Sciences, Drosophila Proteins, Small interfering RNAs, Biology (General), Immune Response, 0303 health sciences, biology, Drosophila Melanogaster, 030302 biochemistry & molecular biology, Nuclear Proteins, Eukaryota, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Animal Models, Cell biology, Ubiquitin ligase, Enzymes, Insects, Nucleic acids, Experimental Organism Systems, Drosophila, Signal transduction, Drosophila melanogaster, Research Article, Arthropoda, QH301-705.5, Ubiquitin-Protein Ligases, DNA transcription, Immunology, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Model Organisms, Virology, Gram-Negative Bacteria, DNA-binding proteins, Genetics, Animals, Humans, Non-coding RNA, Molecular Biology, Transcription factor, 030304 developmental biology, Innate immune system, Ubiquitination, Organisms, Biology and Life Sciences, Proteins, NF-κB, RC581-607, biology.organism_classification, Ubiquitin Ligases, Invertebrates, Immunity, Innate, Gene regulation, Regulatory Proteins, chemistry, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], biology.protein, Animal Studies, Enzymology, RNA, Parasitology, Gene expression, Immunologic diseases. Allergy, HeLa Cells, Transcription Factors
Abstract: The Immune Deficiency (IMD) pathway in Drosophila melanogaster is activated upon microbial challenge with Gram-negative bacteria to trigger the innate immune response. In order to decipher this nuclear factor κB (NF-κB) signaling pathway, we undertook an in vitro RNAi screen targeting E3 ubiquitin ligases specifically and identified the HECT-type E3 ubiquitin ligase Hyperplastic discs (Hyd) as a new actor in the IMD pathway. Hyd mediated Lys63 (K63)-linked polyubiquitination of the NF-κB cofactor Akirin was required for efficient binding of Akirin to the NF-κB transcription factor Relish. We showed that this Hyd-dependent interaction was required for the transcription of immunity-related genes that are activated by both Relish and Akirin but was dispensable for the transcription of genes that depend solely on Relish. Therefore Hyd is key in NF-κB transcriptional selectivity downstream of the IMD pathway. Drosophila depleted of Akirin or Hyd failed to express the full set of genes encoding immune-induced anti-microbial peptides and succumbed to immune challenges. We showed further that UBR5, the mammalian homolog of Hyd, was also required downstream of the NF-κB pathway for the activation of Interleukin 6 (IL6) transcription by LPS or IL-1β in cultured human cells. Our findings link the action of an E3 ubiquitin ligase to the activation of immune effector genes, deepening our understanding of the involvement of ubiquitination in inflammation and identifying a potential target for the control of inflammatory diseases., Author summary Ubiquitination has been recently identified in pathogenesis and progression of various diseases where inflammation is critical. NF-κB transcription factors are key actors in the transcriptional cascade leading to inflammation as they activate genes with pro- or anti-inflammatory activities. The similarity between the immune pathways in flies and mammals makes Drosophila melanogaster an excellent model to study the innate response. Accordingly, we decided to identify E3 ubiquitin-ligases involved in the regulation of NF-κB pathway, using Drosophila as a model system. A RNAi based screen in immortalized embryonic macrophage-like Drosophila cells points to the HECT-E3 ubiquitin ligase Hyd as a new regulator of the Immune-deficiency (IMD) NF-κB pathway, activated after Gram-negative immune challenge. More precisely, we showed that Hyd acts at the level of Akirin, an evolutionarily conserved player in the NF-κB pathway, required for the transcription of pro-inflammatory genes, but not for the NF-κB-dependent genes contributing to the down-regulation of inflammation. In addition, we could show that the human homologue of Hyd (UBR5) acts genetically at the level of human AKIRIN2, pointing to a unique dichotomy between Hyd/Akirin-dependent and -independent gene activation, allowing for the decoupling activation and resolution of inflammation. These results identified UBR5 as a putative target for anti-inflammatory compounds.
Published: 2020
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280. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions

Author: Patrick Roth, Jill S. Barnholtz-Sloan, Marc Sanson, Jonathan Tsang, Tracy T. Batchelor, Ingo K. Mellinghoff, Minesh P. Mehta, Kenneth Aldape, Martin J B Taphoorn, Floris P. Barthel, Ranjit S. Bindra, Emilie Le Rhun, David Nathanson, Matthias Preusser, David A. Reardon, Michael Platten, Susan M. Chang, Brian M. Alexander, Andreas von Deimling, Martin J. van den Bent, Andrew B. Lassman, Craig Horbinski, Gelareh Zadeh, Roel G.W. Verhaak, E. Antonio Chiocca, Evanthia Galanis, Susan C Short, Eudocia Q. Lee, Patrick Y. Wen, John DeGroot, Raymond Y. Huang, Michael Weller, Mark R. Gilbert, Joerg C. Tonn, Wolfgang Wick, Monika E. Hegi, David Schiff, Michael Lim, Giuseppe Minniti, Timothy F. Cloughesy, INSERM, Université de Lille, Harvard Medical School [Boston] [HMS], University hospital of Zurich [Zurich], Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM], Dana-Farber Cancer Institute [Boston], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Universität Zürich [Zürich] = University of Zurich (UZH), Case Western Reserve University [Cleveland], The Jackson Laboratory [Bar Harbor] (JAX), Yale University School of Medicine, University of California [San Francisco] (UCSF), University of California, University of California [Los Angeles] (UCLA), MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Mayo Clinic [Rochester], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Université de Lausanne (UNIL), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Northwestern University Feinberg School of Medicine, New York Presbyterian Hospital, Columbia University Irving Medical Center (CUIMC), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Johns Hopkins University School of Medicine [Baltimore], Miami Cancer Institute [Florida], Memorial Sloane Kettering Cancer Center [New York], Università degli Studi di Siena = University of Siena (UNISI), Heidelberg University, Medizinische Universität Wien = Medical University of Vienna, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Virginia [Charlottesville], University of Leeds, Leiden University Medical Center (LUMC), Ludwig Maximilian University [Munich] (LMU), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg University Hospital [Heidelberg], Princess Margaret Cancer Centre [Toronto, Canada], Erasmus University Medical Center [Rotterdam] (Erasmus MC), SALZET, Michel, Yale School of Medicine [New Haven, Connecticut] (YSM), University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Lausanne = University of Lausanne (UNIL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille-UNICANCER, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Virginia, Universiteit Leiden, and Neurology
Subjects: Oncology, clinical trials, diagnosis, glioblastoma, therapy, Cancer Research, medicine.medical_specialty, Consensus, Neuro oncology, [SDV]Life Sciences [q-bio], Oncology and Carcinogenesis, Brain tumor, Review, 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, Internal medicine, medicine, Humans, Oncology & Carcinogenesis, Randomized Controlled Trials as Topic, Cancer, Brain Neoplasms, Molecular pathogenesis, Neurosciences, Chemoradiotherapy, medicine.disease, Isocitrate Dehydrogenase, 3. Good health, Brain Disorders, [SDV] Life Sciences [q-bio], Clinical trial, Phase III as Topic, Brain Cancer, Good Health and Well Being, Current management, 030220 oncology & carcinogenesis, Neurology (clinical), Glioblastoma, Societies, 030217 neurology & neurosurgery
Abstract: Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies, and viral therapies will be reviewed, as well as the current challenges and future directions for research.
Published: 2020
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281. COVID-19 and the Mobilisation of Public Development Banks in the EU

Author: Mertens, Daniel, Rubio, Eulalia, Thiemann, Matthias, Internal Medicine III, Universität Ulm - Ulm University [Ulm, Allemagne], Mechanisms of Leukemogenesis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Centre d'études européennes et de politique comparée (Sciences Po, CNRS) (CEE), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), and Centre d'études européennes et de politique comparée (CEE)
Subjects: [SHS.SCIPO]Humanities and Social Sciences/Political science
Abstract: Introduction: The debate over how Europe should organise solidarity and jointly respond to the COVID induced economic crisis is in full force, with various proposals either agreed or at debate such as the use of the European Stability Mechanism (ESM), the creation of new common debt instruments or the mobilisation of the upcoming Multi-Annual Financial Framework (MFF). So far, however, the prime responses to the economic shock have been located at the national level, not only being proof of the fact that most firefighting is done at the level of Europe’s nation-states but also displaying the inequalities of fiscal capacity that still loom large in the EU’s political economy.There have been various studies and reports comparing governments’ initial fiscal responses to the COVID-19 crisis1. While there are differences in the size and composition of fiscal packages, a common feature that emerges is the strong reliance on credit guarantees and other liquidity support measures. Less appreciated in current debates is the fact that these measures are often administered and distributed by a specific sort of para-fiscal actors: development banks, or national promotional institutions. Even at the European level, significant parts of the common response to the economic impact of the pandemic rest on the European Investment Bank (EIB).This policy brief highlights the key role these para-fiscal institutions play in Europe and reviews the similarities and differences in their responses by focusing on five large institutions (EIB, KfW, Bpifrance, CDP, ICO)2. It explains how these entities have worked as governments’ 'little helpers' in the European context of the past decade and points to key challenges that come with their role in terms of a coordinated and solidarity-based European effort.
Published: 2020

282. Serum levels of hsa‐miR‐16‐5p , hsa‐miR‐29a‐3p , hsa‐miR‐150‐5p , hsa‐miR‐155‐5p and hsa‐miR ‐ 223‐3p and subsequent risk of chronic lymphocytic leukemia in the EPIC study

Author: Heiner Boeing, María Arestin, Aurelio Barricarte, Delphine Casabonne, Elio Riboli, Roel Vermeulen, Carlo La Vecchia, Alexandra Nieters, Federico Canzian, Julie A. Schmidt, Matthias B. Schulze, María Armesto, Rosario Tumino, Yolanda Benavente, Rudolf Kaaks, Salvatore Panico, María José Sánchez, Anna Karakatsani, Pilar Amiano, Caroline Besson, Marc J. Gunter, Giovanna Masala, Carlotta Sacerdote, María Dolores Chirlaque, Silvia de Sanjosé, Valeria Pala, Anne Tjønneland, Charles H. Lawrie, Antonia Trichopoulou, Elisabete Weiderpass, Eric J. Duell, Fatemeh Saberi Hosnijeh, Anja Olsen, Vittorio Perduca, Julia Seifert, Francesca Mancini, Laura Costas, CIBER de Epidemiología y Salud Pública (CIBERESP), Catalan Institute of Oncology (ICO-IDIBELL), Facultat de Medicina [Barcelona], Centre Hospitalier de Versailles André Mignot (CHV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Épidémiologie des radiations, épidémiologie clinique des cancers et survie (U1018 (Équipe 3) ), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Department of Community Medicine, Faculty of Health Sciences, The Arctic University of Norway (UiT), Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Cancer Epidemiology, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Hellenic Health Foundation, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), Civile - M.P.Arezzo Hospital, Nutrition and Metabolism Section, International Agency for Research on Cancer, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, CPO Piemonte, Department of Epidemiology, German Institute of Human Nutrition (DIfE), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Danish Cancer Society Research Center, Danish Cancer Society, Division of Environmental Epidemiology, Utrecht University [Utrecht]-Institute of Risk Assessment Sciences, Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, and Immunology
Subjects: Oncology, Male, DOWN-REGULATION, Cancer Research, PROGNOSIS, Chronic lymphocytic leukemia, ACTIVATION, 0302 clinical medicine, mir-223, Odds Ratio, Prospective Studies, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Area under the curve, Middle Aged, MIR-155, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Up-Regulation, Europe, DIFFERENTIATION, INFECTIONS, 030220 oncology & carcinogenesis, embryonic structures, Monoclonal B-cell lymphocytosis, Female, B-CELL LYMPHOCYTOSIS, Life Sciences & Biomedicine, prospective study, EXPRESSION, medicine.medical_specialty, MICRORNA SIGNATURE, miR-155, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Biomarkers, Tumor, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Liquid biopsy, Science & Technology, business.industry, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, body regions, circulating miRNA, MicroRNAs, Case-Control Studies, chronic lymphocytic leukemia, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, serum, CLL
Abstract: Chronic lymphocytic leukemia (CLL) is an incurable disease accounting for almost one-third of leukemias in the Western world. Aberrant expression of microRNAs (miRNAs) is a well-established characteristic of CLL, and the robust nature of miRNAs makes them eminently suitable liquid biopsy biomarkers. Using a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC), the predictive values of five promising human miRNAs (hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p), identified in a pilot study, were examined in serum of 224 CLL cases (diagnosed 3 months to 18 years after enrollment) and 224 matched controls using Taqman based assays. Conditional logistic regressions were applied to adjust for potential confounders. The median time from blood collection to CLL diagnosis was 10 years (p25–p75: 7–13 years). Overall, the upregulation of hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p was associated with subsequent risk of CLL [OR1∆Ct-unit increase (95%CI) = 1.42 (1.18–1.72), 1.64 (1.31–2.04) and 1.75 (1.31–2.34) for hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p, respectively] and the strongest associations were observed within 10 years of diagnosis. However, the predictive performance of these miRNAs was modest (area under the curve
Published: 2020
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283. Human IgA binds a diverse array of commensal bacteria

Author: Martin R. Larsen, Asok Rajkumar, Carmen Capito, Hela El-Kafsi, Hans Yssel, Guy Gorochov, Delphine Sterlin, Olivia Joan Adams, Catherine Juste, Thomas Candela, Jean-Luc Charuel, Christophe Parizot, Karim Dorgham, Friederike Jönsson, Hedda Wardemann, Hélène Brisson, Stephan von Gunten, Richard D. Cummings, Gaëlle Autaa, Claire Fieschi, Alexandra Aubry, Christophe Trésallet, Jehane Fadlallah, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], University of Bern, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Université Paris Diderot - Paris 7 (UPD7), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, AgroParisTech, Institut National de la Recherche Agronomique (INRA), Université Paris-Saclay, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Bactéries, Pathogènes et Santé (UBaPS), Faculté de Pharmacie, Université Paris-Sud - Paris 11 (UP11)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Université Paris-Saclay, Université Paris-Sud - Paris 11 (UP11), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Harvard Medical School [Boston] (HMS), The study was financed by Inserm, and by Agence Nationale de la Recherche (MetAntibody, ANR-14-CE14-0013) to ML. Research in the laboratory of S. von Gunten is supported by the Swiss National Science Foundation (SNSF) grants 310030_184757 and 310030_162552, and by the Swiss Cancer League/Swiss Cancer Research (grant KFS-3941-08-2016)., ANR-14-CE14-0013,METAntibody,Spécificité des IgA sécrétoires et leur impact sur la composition du microbiote intestinal et sur l'immunité de l'hôte(2014), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Sud - Paris 11 (UP11)-Université Paris-Sud - Paris 11 (UP11), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Immunoglobulin A, Glycan, Immunology, 610 Medicine & health, digestive system, Technical Advances and Resources, Microbiology, Affinity maturation, 03 medical and health sciences, 0302 clinical medicine, fluids and secretions, stomatognathic system, Immunology and Allergy, Secretion, Microbiome, 030304 developmental biology, 0303 health sciences, biology, Mucosal Immunology, Isotype, 3. Good health, Polyclonal antibodies, 030220 oncology & carcinogenesis, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody
Abstract: Intestinal IgA is a key player in host-commensal symbiosis. Sterlin et al. report that human IgAs are microbiota cross-reactive at the clonal level. IgA1 and IgA2 mostly converge toward common gut microbiota targets but possess distinct carbohydrate repertoires., In humans, several grams of IgA are secreted every day in the intestinal lumen. While only one IgA isotype exists in mice, humans secrete IgA1 and IgA2, whose respective relations with the microbiota remain elusive. We compared the binding patterns of both polyclonal IgA subclasses to commensals and glycan arrays and determined the reactivity profile of native human monoclonal IgA antibodies. While most commensals are dually targeted by IgA1 and IgA2 in the small intestine, IgA1+IgA2+ and IgA1−IgA2+ bacteria coexist in the colon lumen, where Bacteroidetes is preferentially targeted by IgA2. We also observed that galactose-α terminated glycans are almost exclusively recognized by IgA2. Although bearing signs of affinity maturation, gut-derived IgA monoclonal antibodies are cross-reactive in the sense that they bind to multiple bacterial targets. Private anticarbohydrate-binding patterns, observed at clonal level as well, could explain these apparently opposing features of IgA, being at the same time cross-reactive and selective in its interactions with the microbiota.
Published: 2020
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284. 2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations

Author: Catherine Leroy, Séverine Amand, Anthony Mouray, David Tulasne, Andreas E. Kulozik, Christine Bailly, Thierry Chassat, Carole Trzaska, David Hannebique, Eric Adriaenssens, Jean-Michel Saliou, Elisabeth Werkmeister, Pierre-Arthur Moreau, Eric Westhof, Evelyne Duvernois-Berthet, Yuri Motorin, Romain Guilbert, Marie-Christine Copin, Virginie Marchand, Sylvie Rebuffat, Fabrice Lejeune, Hana Benhabiles, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Ingénierie, Biologie et Santé en Lorraine (IBSLor), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie moléculaire et adaptation (PhyMA), 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), Réseau International des Instituts Pasteur (RIIP), Laboratoire de Génie civil et Géo-environnement (LGCgE), Ecole nationale supérieure Mines-Télécom Lille Douai (IMT Lille Douai), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Lille-Université d'Artois (UA)-Université catholique de Lille (UCL)-École polytechnique universitaire de Lille (Polytech Lille), Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), F.L. is an Inserm researcher supported by fundings from Vaincre la mucoviscidose, the Association française contre les myopathies, the GIP Cancéropôle Nord Ouest, the Fondation Maladies Rares and the SATT Lutech, Authors would like to thank Dr. Jens Lykke-Andersen, Pr. P.A. Jänne and Pr. Lynne Maquat for reagents, Dr. Clément Carré, Dr. Bruno Lapeyre, Dr. Gabriele Neu-Yilik, Dr. Matthias Hentze, and Dr. Jean-Paul Renaud for helpful discussions. Authors also thank the Bicel facility for technical help, the PLEHTA for technical help on mouse managing and in vivo experiments, Valérie IGEL-BOURGUIGNON and Dr. Lilia AYADI from the Next-Generation Sequencing Core Facility of UMS2008 IBSLor (Université de Lorraine-CNRS-INSERM) for their help in RiboMethSeq library preparation and sequencing., Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers [Lille] (CANTHER), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université Lille Nord (France)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), 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 National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Pediatric Oncology, Alder Hey Children's Hospital, Alder Hey Children's Hospital, Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Médecine cellulaire et molécualire, PRES Université Lille Nord de France-Institut de Biologie de Lille-IFR 142, Université d'Artois (UA)-École polytechnique universitaire de Lille (Polytech Lille)-Université de Lille-Ecole nationale supérieure Mines-Télécom Lille Douai (IMT Lille Douai), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Yncréa Hauts-de-France, and Université catholique de Lille (UCL)-Université catholique de Lille (UCL)
Subjects: 0301 basic medicine, Molecular biology, General Physics and Astronomy, chemistry.chemical_compound, Mice, RNA, Transfer, lcsh:Science, 2-Aminopurine, ComputingMilieux_MISCELLANEOUS, Genetics, Regulation of gene expression, tRNA Methyltransferases, Multidisciplinary, Molecular medicine, Drug discovery, Lepisma, 3. Good health, Gene Expression Regulation, Neoplastic, Drug screening, Codon, Nonsense, Cytosine, Science, Nonsense mutation, Mice, Nude, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, Gene, RNA metabolism, 030102 biochemistry & molecular biology, 2,6-Diaminopurine, HEK 293 cells, fungi, RNA, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Chemistry, Genes, p53, Disease Models, Animal, 030104 developmental biology, HEK293 Cells, chemistry, Cancer cell, Mutation, lcsh:Q, Drug Screening Assays, Antitumor, HeLa Cells
Abstract: Nonsense mutations cause about 10% of genetic disease cases, and no treatments are available. Nonsense mutations can be corrected by molecules with nonsense mutation readthrough activity. An extract of the mushroom Lepista inversa has recently shown high-efficiency correction of UGA and UAA nonsense mutations. One active constituent of this extract is 2,6-diaminopurine (DAP). In Calu-6 cancer cells, in which TP53 gene has a UGA nonsense mutation, DAP treatment increases p53 level. It also decreases the growth of tumors arising from Calu-6 cells injected into immunodeficient nude mice. DAP acts by interfering with the activity of a tRNA-specific 2′-O-methyltransferase (FTSJ1) responsible for cytosine 34 modification in tRNATrp. Low-toxicity and high-efficiency UGA nonsense mutation correction make DAP a good candidate for the development of treatments for genetic diseases caused by nonsense mutations., Nonsense mutations can be corrected by several molecules that activate readthrough of premature termination codon. Here, the authors report that 2,6-diaminopurine efficiently corrects UGA nonsense mutations with no significant toxicity.
Published: 2020
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285. Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Sanikini, Harinakshi, Muller, David C, Sophiea, Marisa, Rinaldi, Sabina, Agudo, Antonio, Duell, Eric J, Weiderpass, Elisabete, Overvad, Kim, Tjønneland, Anne, Halkjaer, Jytte, Boutron-Ruault, Marie-Christine, Carbonnel, Franck, Cervenka, Iris, Boeing, Heiner, Kaaks, Rudolf, Kühn, Tilman, Trichopoulou, Antonia, Martimianaki, Georgia, Karakatsani, Anna, Pala, Valeria, Palli, Domenico, Mattiello, Amalia, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Rylander, Charlotta, López, María Dolores Chirlaque, Sánchez, Maria-Jose, Ardanaz, Eva, Regnér, Sara, Stocks, Tanja, Bueno-de-Mesquita, Bas, Vermeulen, Roel C H, Aune, Dagfinn, Tong, Tammy Y N, Kliemann, Nathalie, Murphy, Neil, Chadeau-Hyam, Marc, Gunter, Marc J, Cross, Amanda J, Cancer Research UK, Department of Medical and Clinical Genetics, University of Helsinki, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre international de Recherche sur le Cancer (CIRC), 6236, PI13/00061, PI13/01162 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, IARC Stand Up To Cancer, SU2C National Research Council, NRC Medical Research Council, MRC: 1000143, MR/M012190/1 Cancer Research UK, CRUK: 14136, C570/A16491, C8221/A19170 World Cancer Research Fund, WCRF European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Vetenskapsrådet, VR Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Fondation Gustave Roussy Hellenic Health Foundation, HHF, This research was funded by the Stand Up to Cancer campaign for Cancer Research UK. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM, France), German Cancer Aid, German Cancer Research Centre (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), National Institute for Public Health and the Environment (Bilthoven, The Netherlands) for their contribution to data collection, Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (no. 6236) and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 to KTK, NJW, and C570/A16491 to RCT and C8221/A19170 to TK [EPIC-Oxford]), Medical Research Council (1000143 to KTK, NJW, MR/M012190/1 to TK [EPIC-Oxford, United Kingdom]).
Subjects: Male, obesity, Esophageal Neoplasms, 3122 Cancers, [SDV.CAN]Life Sciences [q-bio]/Cancer, gastric, Europe/epidemiology, Cohort Studies, Stomach Neoplasms/classification, SDG 3 - Good Health and Well-being, Stomach Neoplasms, esophageal, Risk Factors, cancer, Body Fat Distribution, Humans, VDP::Medisinske Fag: 700, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Prospective Studies, Càncer, Nutrició, Reproductive History, Nutrition, Proportional Hazards Models, reproductive, hormones, Anthropometry, Middle Aged, VDP::Medical disciplines: 700, Europe, Esophageal Neoplasms/classification, Female, Cancer Epidemiology
Abstract: Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow‐up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist‐to‐hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. 98 vs. 0.82 vs. 84 vs. 2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs., What's new? Obesity can change the body's hormone balance, and encourage the onset of cancer. Here, the authors investigated the relationship between obesity, hormones, and esophageal and gastric cancers. Using data from the EPIC cohort, they obtained information about anthropometric and reproductive factors for 476,160 participants. Excess fat around the waist, they found, was associated with esophageal adenocarcinoma and gastric cardia cancer, in women and men. In women, bearing children, as well as younger age at first pregnancy, had an inverse association with certain cancers. Ovariectomy was positively associated with gastric non‐cardia cancer, suggesting involvement of hormone pathways in these malignancies.
Published: 2020
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286. Protein Quality Control Pathways at the Crossroad of Synucleinopathies

Author: Anne S. Wentink, Eduardo Preusser de Mattos, Carmen Nussbaum-Krammer, Steven Bergink, Ronald Melki, Harm H. Kampinga, Christian Hansen, Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, Center for Molecular Biology - Zentrum für Molekulare Biologie [Heidelberg, Germany] (ZMBH), Universität Heidelberg [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), molecular neurobiology, department of experimental medical science [Lund, Sweden], Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), 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-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), European Project: 35311,BIND, Universität Heidelberg [Heidelberg] = Heidelberg University, Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, MULTIPLE SYSTEM ATROPHY, IMPAIRS MACROAUTOPHAGY, autophagy, Parkinson's disease, LYSOSOMAL DEGRADATION, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Review, Biology, Protein aggregation, GLIAL CYTOPLASMIC INCLUSIONS, Protein Aggregation, Pathological, FIBRIL FORMATION, protein aggregation, Alpha-synuclein, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Chaperone-mediated autophagy, PARKINSONS-DISEASE, medicine, Animals, Humans, HEAT-SHOCK PROTEINS, MUTANT ALPHA-SYNUCLEIN, Synucleinopathies, protein homeostasis, Dementia with Lewy bodies, Autophagy, molecular chaperones, synucleinopathies, medicine.disease, nervous system diseases, 030104 developmental biology, chemistry, Proteasome, nervous system, ubiquitin- proteasome system, CHAPERONE-MEDIATED AUTOPHAGY, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), ubiquitin-proteasome system, Neuroscience, 030217 neurology & neurosurgery, Metabolic Networks and Pathways
Abstract: International audience; The pathophysiology of Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and many others converge at alpha-synuclein ($\alpha$-Syn) aggregation. Although it is still not entirely clear what precise biophysical processes act as triggers, cumulative evidence points towards a crucial role for protein quality control (PQC) systems in modulating $\alpha$-Syn aggregation and toxicity. These encompass distinct cellular strategies that tightly balance protein production, stability, and degradation, ultimately regulating $\alpha$-Syn levels. Here, we review the main aspects of $\alpha$-Syn biology, focusing on the cellular PQC components that are at the heart of recognizing and disposing toxic, aggregate-prone $\alpha$-Syn assemblies: molecular chaperones and the ubiquitin-proteasome system and autophagy-lysosome pathway, respectively. A deeper understanding of these basic protein homeostasis mechanisms might contribute to the development of new therapeutic strategies envisioning the prevention and/or enhanced degradation of $\alpha$-Syn aggregates.
Published: 2020
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287. Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses

Author: Elio Riboli, Jochen Hampe, Ruth C. Travis, Andrea N. Burnett-Hartman, Anna H. Wu, Steven Gallinger, Stephen B. Gruber, Christopher I. Li, Bethany Van Guelpen, Kala Visvanathan, Loic Le Marchand, Veronika Vymetalkova, Demetrius Albanes, Jeroen R. Huyghe, Lori C. Sakoda, Jennifer Ose, Daniel D. Buchanan, Kenneth Offit, D. Timothy Bishop, John D. Potter, Sonja I. Berndt, Neil Murphy, Vittorio Perduca, Roger L. Milne, Niki Dimou, Marc J. Gunter, Ulrike Peters, Wen Yi Huang, Sergi Castellví-Bel, Graham Casey, Robert E. Schoen, Martha L. Slattery, Kathryn E. Bradbury, Albert de la Chapelle, Temitope O. Keku, Andrea Gsur, Wei Zheng, Gad Rennert, Hermann Brenner, Tabitha A. Harrison, Claudia Agnoli, Fränzel J.B. Van Duijnhoven, Sabina Rinaldi, Catherine M. Tangen, Jane C. Figueiredo, Ludmila Vodickova, Andrew T. Chan, Tilman Kühn, Hansong Wang, Mingyang Song, Sun-Seog Kweon, Annika Lindblom, Amanda I. Phipps, Cornelia M. Ulrich, Victor Moreno, Mark A. Jenkins, Li Hsu, Emily White, Conghui Qu, Peter T. Campbell, Stéphane Bézieau, Nikos Papadimitriou, Michael O. Woods, Jelena Bešević, Polly A. Newcomb, Pavel Vodicka, Heather Hampel, Barbara L. Banbury, Amanda J. Cross, Robert Carreras-Torres, Alicja Wolk, Graham G. Giles, Michael Hoffmeister, Elizabeth A. Platz, N. Charlotte Onland-Moret, Dallas R. English, Li Li, Jenny Chang-Claude, Vicente Martín, Richard M. Martin, María Dolores Chirlaque, Konstantinos K. Tsilidis, Clemens Schafmayer, Shuji Ogino, Nutrition and Metabolism Section, International Agency for Research on Cancer, Centre international de Recherche sur le Cancer (CIRC), School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Nuffield Department of Population Health - Cancer Epidemiology Unit, University of Oxford [Oxford], International Agency for Cancer Research (IACR), School of Public Health [London, UK] (Faculty of Medicine), Candiolo Cancer Institute (IRCCS), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Interactions récepteurs ligands en immunocancérologie et immunopathologie, IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), St. James's University Hospital, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University Medical Center [Utrecht], The Cancer, Ageing and Somatic Mutation Programme [Cambridgeshire, UK], The Wellcome Trust Sanger Institute [Cambridge], Department of Preventive Medicine, University of Southern California (USC), Division of Cancer Epidemiology, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Ohio State University [Columbus] (OSU), Cancer Epidemiology Centre, Cancer Council Victoria, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medical Department 1 [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), FESTO, Universität Stuttgart [Stuttgart], Division of Cancer Epidemiology and Genetics, Department of Medical Genetics, HMNC Brain Health, University of Hawai‘i [Mānoa] (UHM), Chinese Center for Disease Control and Prevention, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Dell-EMC, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Memorial Sloane Kettering Cancer Center [New York], Department of Pathology, Brigham and Women's Hospital [Boston], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Department of Visceral and Thoracic Surgery [Kiel, Germany], University Hospital Schleswig-Holstein [Kiel, Germany], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Karolinska Institutet [Stockholm], and Center for Astrophysical Sciences [Baltimore]
Subjects: Oncology, Male, Nutrition and Disease, Colorectal cancer, BMI, body mass index, PLASMA-INSULIN, IGFBP3, IGF1, insulin-like growth factor 1, Genome-wide association study, GWAS, genome-wide association studies, MR-PRESSO, Mendelian Randomization Pleiotropy RESidual Sum and Outlier, FACTOR (IGF)-I, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Insulina, Medicine, Insulin, GWAS, Registries, Insulin-Like Growth Factor I, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, ICC, intraclass correlation coefficient, Incidence, Hazard ratio, MR, Mendelian randomization, Gastroenterology, MEN, SNP, single nucleotide polymorphism, Middle Aged, SERUM-LEVELS, 3. Good health, IGF-I, CRC, 030220 oncology & carcinogenesis, CRP, C-reactive protein, Female, Colorectal Neoplasms, Life Sciences & Biomedicine, Medical Genetics, REGRESSION DILUTION, Signal Transduction, medicine.medical_specialty, HbA1c, glycolated hemoglobin, FACTOR-I, Polymorphism, Single Nucleotide, Risk Assessment, Article, C-PEPTIDE, 03 medical and health sciences, Sex Factors, Insulin-Like Growth Factor II, Càncer colorectal, Internal medicine, COLON, Mendelian randomization, Biomarkers, Tumor, Journal Article, Humans, IGFBP3, insulin-like growth factor binding protein 3, 030304 developmental biology, Aged, VLAG, Medicinsk genetik, Cancer och onkologi, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Case-control study, Cancer, IGFBP-3, 1103 Clinical Sciences, Odds ratio, Mendelian Randomization Analysis, medicine.disease, HR, hazard ratio, United Kingdom, CI, confidence interval, OR, odds ratio, Insulin-Like Growth Factor Binding Protein 3, Case-Control Studies, Cancer and Oncology, SHBG, sex hormone binding globulin, 1114 Paediatrics and Reproductive Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, SD, standard deviation, 1109 Neurosciences, Follow-Up Studies
Abstract: Background & Aims Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development. Methods Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) Results After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05–1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03–1.12; P = 3.3 × 10–4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06–1.18; P = 4.2 × 10–5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2. Conclusions In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis., Graphical abstract
Published: 2020
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288. Genetic polymorphisms associated with telomere length and risk of developing myeloproliferative neoplasms

Author: Aleksandra Gołos, Aleksandra Butrym, José Maldonado, Federico Canzian, Daniele Campa, Francesca Tavano, Francisca Hernández Mohedo, Matteo Giaccherini, Manuel Jurado, Federica Gemignani, Nicola Sgherza, Joanna Gora-Tybor, Joaquin Martinez Lopez, Grzegorz Mazur, Raffaele Spadano, Judit Várkonyi, Andres Jerez, Juan Sainz, Angelica Macauda, [Giaccherini,M, Macauda,A, Gemignani,F, Campa,D] Department of Biology, University of Pisa, Pisa, Italy. [Giaccherini,M, Canzian,F] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Sgherza,N] Division of Hematology, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. [Sgherza,N] U.O.C. Ematologia con Trapianto, Azienda Ospedaliero-Universitaria Consorzionale, Policlinico di Bari, Bari, Italy. [Sainz,J, Sanchez Maldonado,JM, Jurado,M] Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government, PTS Granada, Granada, Spain. [Sainz,J, Jurado,M, Hernández Mohedo,F] Monoclonal Gammopathies Unit, University Hospital Virgen de las Nieves, Granada, Spain. [Sainz,J, Hernández Mohedo,F] Pharmacogenetics Unit, Instituto de Investigación Biosanitaria de Granada (Ibs. Granada), Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sainz,J] Department of Medicine, University of Granada, Granada, Spain. [Tavano,F] Division of Gastroenterology and Research Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. [Mazur,G] Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland. [Jerez,A] Hematology and Medical Oncology Department, University Hospital Morales Meseguer-IMIB, CIBERER, Murcia, Spain. [Góra-Tybor,J] Department of Hematology, Medical University of Łódź, Łódź, Poland. [Gołos,A] Department of Clinical Oncology and Chemotherapy, Magodent Hospital, Warsaw, Poland. [Martinez Lopez,J] Hospital 12 de Octubre, H12O-CNIO Hematological Malignancies Clinical Research Unitc Compluntense University, CIBERONC, Madrid, Spain. [Várkonyi,J] Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary. [Spadano,R] Division of Hematology, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. [Butrym,A] Department of Cancer Prevention and Therapy, Wroclaw Medical University, Wroclaw, Poland., and This work was partially supported by intramural funds of Univerity of Pisa and DKFZ, and by the Italian Ministry of Health grants to the Division of Gastroenterology, Fondazione IRCCS 'Casa Sollievo della Sofferenza' Hospital, San Giovanni Rotondo (F.G.), Italy and by the '5 × 1000' voluntary contribution.Open access funding provided by Projekt DEA.
Subjects: Male, Oncology, Polimorfismo de nucleótido simple, Epidemiology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Myeloproliferative neoplasms, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Neoplasms, Medicine, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Predisposición genética a la enfermedad, Hematology, Telomere, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Neoplasias, 030220 oncology & carcinogenesis, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Cell Division::Telomere Homeostasis [Medical Subject Headings], Female, medicine.medical_specialty, Check Tags::Male [Medical Subject Headings], Single-nucleotide polymorphism, Case-control studies, Polymorphism, Single Nucleotide, lcsh:RC254-282, Article, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], 03 medical and health sciences, Internal medicine, Humans, Genetic Predisposition to Disease, Allele, Aged, Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Myeloproliferative Disorders, business.industry, Telomere Homeostasis, Cancer, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], medicine.disease, Increased risk, Check Tags::Female [Medical Subject Headings], Risk factors, Risk allele, business, Telómero, 030215 immunology
Abstract: D.C., F.C., and M.G. conceived and designed the study. A.M. and M.G. performed labwork. A.M., F.C., D.C., and M.G. drafted the manuscript. A.M., F.C., D.C., and M.G. performed data quality control and statistical analyses. All other authors provided samples and data. All authors critically read, commented, and approved the manuscript., Telomere length measured in leukocyte (LTL) has been found to be associated with the risk of developing several cancer types, including myeloproliferative neoplasms (MPNs). LTL is genetically determined by, at least, 11 SNPs previously shown to influence LTL. Their combination in a score has been used as a genetic instrument to measure LTL and evaluate the causative association between LTL and the risk of several cancer types. We tested, for the first time, the “teloscore” in 480 MPN patients and 909 healthy controls in a European multi-center case–control study. We found an increased risk to develop MPNs with longer genetically determined telomeres (OR = 1.82, 95% CI 1.24–2.68, P = 2.21 × 10−3, comparing the highest with the lowest quintile of the teloscore distribution). Analyzing the SNPs individually we confirm the association between TERT-rs2736100-C allele and increased risk of developing MPNs and we report a novel association of the OBFC1-rs9420907-C variant with higher MPN risk (ORallelic= 1.43; 95% CI 1.15–1.77; P = 1.35 × 10−3). Consistently with the results obtained with the teloscore, both risk alleles are also associated with longer LTL. In conclusion, our results suggest that genetically determined longer telomeres could be a risk marker for MPN development
Published: 2020

289. Functional loss of a noncanonical BCOR–PRC1.1 complex accelerates SHH-driven medulloblastoma formation

Author: Norman Mack, Britta Statz, Andrey Korshunov, Norbert Graf, Brian Gudenas, Laura Sieber, Lena M. Kutscher, Micah D. Gearhart, Patricia Benites Goncalves da Silva, Nadja V. Batora, Olivier Ayrault, Brent A. Orr, Marcel Kool, Mikio Hoshino, Sjoerd van Rijn, Kyle S. Smith, Audrey Mercier, Mikaella Vouri, Daisuke Kawauchi, Vivian J. Bardwell, Stefan M. Pfister, Paul A. Northcott, Gudrun Fleischhack, Katja von Hoff, Jessica Clark, Konstantin Okonechnikov, Ryo Shiraishi, Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], Signalisation, radiobiologie et cancer, and Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Carcinogenesis, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Medizin, Polycomb-Group Proteins, medicine.disease_cause, Germline, law.invention, Mice, 0302 clinical medicine, law, Sonic hedgehog, Sequence Deletion, 0303 health sciences, Mutation, biology, Chemistry, Gene Expression Regulation, Neoplastic, Patched-1 Receptor, Histone, 030220 oncology & carcinogenesis, PRC1, brain tumor, Research Paper, animal structures, mouse model, [SDV.CAN]Life Sciences [q-bio]/Cancer, medulloblastoma, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, Animals, Humans, Hedgehog Proteins, PRC1.1 complex, Cerebellar Neoplasms, BCOR, 030304 developmental biology, Medulloblastoma, medicine.disease, Repressor Proteins, Disease Models, Animal, PTCH1, cerebellar granule cells, biology.protein, Cancer research, Suppressor, Developmental Biology
Abstract: Medulloblastoma is a malignant childhood brain tumor arising from the developing cerebellum. In Sonic Hedgehog (SHH) subgroup medulloblastoma, aberrant activation of SHH signaling causes increased proliferation of granule neuron progenitors (GNPs), and predisposes these cells to tumorigenesis. A second, cooperating genetic hit is often required to push these hyperplastic cells to malignancy and confer mutation-specific characteristics associated with oncogenic signaling. Somatic loss-of-function mutations of the transcriptional corepressor BCOR are recurrent and enriched in SHH medulloblastoma. To investigate BCOR as a putative tumor suppressor, we used a genetically engineered mouse model to delete exons 9/10 of Bcor (BcorΔE9–10) in GNPs during development. This mutation leads to reduced expression of C-terminally truncated BCOR (BCORΔE9–10). While BcorΔE9–10 alone did not promote tumorigenesis or affect GNP differentiation, BcorΔE9–10 combined with loss of the SHH receptor gene Ptch1 resulted in fully penetrant medulloblastomas. In Ptch1+/−;BcorΔE9–10 tumors, the growth factor gene Igf2 was aberrantly up-regulated, and ectopic Igf2 overexpression was sufficient to drive tumorigenesis in Ptch1+/− GNPs. BCOR directly regulates Igf2, likely through the PRC1.1 complex; the repressive histone mark H2AK119Ub is decreased at the Igf2 promoter in Ptch1+/−;BcorΔE9–10 tumors. Overall, our data suggests that BCOR–PRC1.1 disruption leads to Igf2 overexpression, which transforms preneoplastic cells to malignant tumors.
Published: 2020
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290. Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations:a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Harms, L.M., Scalbert, A., Zamora-Ros, R., Rinaldi, S., Jenab, M., Murphy, N., Achaintre, D., Tjønneland, A., Olsen, A., Overvad, K., Romana Mancini, F., Mahamat-Saleh, Y., Boutron-Ruault, M.-C., Kühn, T., Katzke, V., Trichopoulou, A., Martimianaki, G., Karakatsani, A., Palli, D., Panico, S., Sieri, S., Tumino, R., Sacerdote, C., Bueno-De-Mesquita, B., Vermeulen, R.C.H., Weiderpass, E., Nøst, T.H., Lasheras, C., Rodríguez-Barranco, M., Huerta, J.M., Barricarte, A., Dorronsoro, M., Hultdin, J., Gunter, M., Riboli, E., Aleksandrova, K., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), PI13/00061, PI13/01162 RD06/0020 6236 KrÃ¦ftens BekÃ¦mpelse, DCS Deutsches Krebsforschungszentrum, DKFZ Centre International de Recherche sur le Cancer, CIRC College of Environmental Science and Forestry, State University of New York, ESF National Research Council, NRC Medical Research Council, MRC: CP15/00100, MR/M012190/1 Cancer Research UK, CRUK: C8221/A19170 World Cancer Research Fund, WCRF: ERC-2009-AdG 232997 European Commission, EC Institut National de la SantÃ© et de la Recherche MÃ©dicale, Inserm Bundesministerium fÃ¼r Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer VetenskapsrÃ¥det, VR Instituto de Salud Carlos III, ISCIII NordForsk European Social Fund, ESF Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Mutuelle GÃ©nÃ©rale de l'Education Nationale, MGEN, The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). R. Z.-R. is supported by the ‘Miguel Servet’ programme (CP15/00100) from the Institute of Health Carlos III and the European Social Fund (ESF).
Subjects: Male, 0301 basic medicine, Medicine (miscellaneous), Gastroenterology, Cohort Studies, chronic diseases, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Neoplasms, Caffeic acid, Medicine, Malalties cròniques, odds ratio, Prospective Studies, Prospective cohort study, Nutrition and Dietetics, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, biology, food and beverages, Full Papers, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Näringslära, Europe, hormone replacement therapy, Polifenols, Cohort, Female, standard deviation, Human and Clinical Nutrition, Cohort study, Adult, Plasma measurements, medicine.medical_specialty, 030209 endocrinology & metabolism, body mass index, Diet Surveys, C-reactive protein, 03 medical and health sciences, Internal medicine, Humans, polyphenols, Aged, Inflammation, 030109 nutrition & dietetics, business.industry, Daidzein, Polyphenols, Diet, cardiovascular diseases, Cross-Sectional Studies, Nutrition Assessment, chemistry, confidence interval, Polyphenol, plasma measurements, inflammation, Chronic diseases, randomized controlled trial, biology.protein, high-sensitivity C-reactive protein, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers
Abstract: Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0 center dot 66, 95 % CI 0 center dot 46, 0 center dot 96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0 center dot 58, 95 % CI 0 center dot 39, 0 center dot 86), 3,4-dihydroxyphenylpropionic acid (OR 0 center dot 63, 95 % CI 0 center dot 46, 0 center dot 87), ferulic acid (OR 0 center dot 65, 95 % CI 0 center dot 44, 0 center dot 96) and caffeic acid (OR 0 center dot 69, 95 % CI 0 center dot 51, 0 center dot 93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0 center dot 67, 95 % CI 0 center dot 48, 0 center dot 93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.
Published: 2020
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291. Retinoic acid synthesis by ALDH1A proteins is dispensable for meiosis initiation in the mouse fetal ovary

Author: Morgane Le Rolle, Isabelle Stévant, Andreas Schedl, Marie-Christine Chaboissier, Norbert B. Ghyselinck, Eric Pailhoux, Fabio Da Silva, Geneviève Jolivet, Anne-Amandine Chassot, Jean-Marie Guigonis, Serge Nef, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), École nationale vétérinaire d'Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Genève (UNIGE), Université Côte d'Azur - Faculté de Médecine (UCA Faculté Médecine), Université Côte d'Azur (UCA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire d'Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Medical School of the University of Geneva, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), French National Research Agency (ANR)ANR-13-BSV2-0017-02 ARGONADSANR-11-LABX-0028-01ANR-18-CE14-0012 SexSpecsLa Ligue Nationale Contre le Cancer (Equipe Labelisée Ligue Nationale Contre le Cancer), ANR-13-BSV2-0017,ARGONADS,Acide rétinoique et devenir des cellules germinales(2013), ANR-18-CE14-0012,Sex-Specs,Homeostasie tissulaire selon le sex et son impact sur les maladies surrénaliennes(2018), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Department of Genetic Medicine and Development [Geneva], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Chaboissier, Marie-Christine, Blanc 2013 - Acide rétinoique et devenir des cellules germinales - - ARGONADS2013 - ANR-13-BSV2-0017 - Blanc 2013 - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Homeostasie tissulaire selon le sex et son impact sur les maladies surrénaliennes - - Sex-Specs2018 - ANR-18-CE14-0012 - AAPG2018 - VALID, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Université Nice Sophia Antipolis (1965 - 2019) (UNS), École nationale vétérinaire - Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), ANR-13-BSV2-0017-02 ARGONADSANR-11-LABX-0028-01ANR-18-CE14-0012 SexSpecsLa Ligue Nationale Contre le Cancer (Equipe Labelisée), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), and COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio], Retinoic acid, Endogeny, Oogenesis, chemistry.chemical_compound, 0302 clinical medicine, CYP26B1, PRIMORDIAL GERM-CELLS, BINDING, ddc:576.5, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, Research Articles, Mammals, 0303 health sciences, Multidisciplinary, integumentary system, SciAdv r-articles, CELL SEX DETERMINATION, LINEAGE, MEIOSIS, OOGENESIS, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, DIFFERENTIATION, Female, Research Article, EXPRESSION, FATE, Ovary, Tretinoin, Biology, ALDH1A2, 03 medical and health sciences, Meiosis, medicine, Animals, Gene, neoplasms, 030304 developmental biology, organic chemicals, Proteins, Cell Biology, GENE, biological factors, ALDH1A1, body regions, MICE, Germ Cells, chemistry, biology.protein, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Retinoic acid synthesis is not essential for meiosis in fetal ovaries, challenging the dogma about the meiosis-inducing factors., In mammals, the timing of meiosis entry is regulated by signals from the gonadal environment. All-trans retinoic acid (ATRA) signaling is considered the key pathway that promotes Stra8 (stimulated by retinoic acid 8) expression and, in turn, meiosis entry. This model, however, is debated because it is based on analyzing the effects of exogenous ATRA on ex vivo gonadal cultures, which not accurately reflects the role of endogenous ATRA. Aldh1a1 and Aldh1a2, two retinaldehyde dehydrogenases synthesizing ATRA, are expressed in the mouse ovaries when meiosis initiates. Contrary to the present view, here, we demonstrate that ATRA-responsive cells are scarce in the ovary. Using three distinct gene deletion models for Aldh1a1;Aldh1a2;Aldh1a3, we show that Stra8 expression is independent of ATRA production by ALDH1A proteins and that germ cells progress through meiosis. Together, these data demonstrate that ATRA signaling is dispensable for instructing meiosis initiation in female germ cells.
Published: 2020
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292. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility

Author: Eduardo Nagore, Caroline Hayward, Christopher I. Amos, Douglas F. Easton, Zaida García-Casado, Julie Lang, Anjali K. Henders, Veronica Höiom, Lisa Bowdler, Kathryn P. Burdon, Laura Del Regno, Nick Orr, Per Arne Andresen, Tongwu Zhang, Rose Yang, Myriam Brossard, Eric K. Moses, Dirk Schadendorf, Laura Cattaneo, Casey Rowe, Essen-Heidelberg Investigators, Hans-Joachim Schulze, Jamie E Craig, D. Timothy Bishop, Anne E. Cust, Johan Hansson, David E. Elder, Nelleke A. Gruis, Donato Calista, Wei V. Chen, Abrar A. Qureshi, Amy Hutchinson, Pilar Galan, Leanne Wallace, Jennifer H. Barrett, Nilesh J. Samani, Maria Teresa Landi, Per Helsing, Andreas Hadjisavvas, Fengju Song, Celia Requena, Elizabeth M. Gillanders, Arantxa Rodriguez, Joan Anton Puig-Butille, Blair H. Smith, Mark Smithers, Michael Malasky, Marianna Sanna, Miriam Potrony, Maria A. Loizidou, Evangelos Evangelou, Richard A. Scolyer, Karen A. Pooley, Rachel E. Neale, Mario Falchi, Adèle C. Green, Monica Rodolfo, Ketty Peris, Licia Rivoltini, Mark M. Iles, Catherine M. Olsen, Alexander J. Stratigos, Tadeusz Dębniak, Weiyin Zhou, H. Peter Soyer, Xin Li, Margaret A. Tucker, Rajesh Kumar, Håkan Olsson, Anders Molven, Nicholas G. Martin, Anthony J. Swerdlow, Aurelie Vogt, Lars A. Akslen, Stuart MacGregor, Sarah V. Ward, Hamida Mohamdi, Bruna Dalmasso, Grant W. Montgomery, Rona M. MacKie, Esther Azizi, Gonçalo R. Abecasis, Chiara Menin, Alison M. Dunning, Ibd investigators, Kevin M. Brown, Jiali Han, Veryan Codd, Graham J. Mann, Nicholas K. Hayward, Marko Hočevar, Eitan Friedman, Richard A. Sturm, Paola Queirolo, Qtwin Investigators, Lawrie Wheeler, Lars G. Fritsche, Shenying Fang, Kiarash Khosrotehrani, Nicole A Kukutsch, Pol Gimenez-Xavier, Belynda Hicks, Matthew Zawistowski, Alessia Visconti, Jessica Harris, Chad M. Brummett, Paola Ghiorzo, andMe, David G. Hunter, Veronique Bataille, Julia Newton-Bishop, Srdjan Novaković, Amfs Investigators, Siranoush Manoukian, Jianxin Shi, Mitchell J. Machiela, G. Mark Lathrop, Josep Malvehy, Katerina P. Kypreou, Susana Puig, Dale R. Nyholt, I. Stefanaki, Maria Concetta Fargnoli, Lisa A. Simms, Kerrie McAloney, M. Malt, Adam J. Trower, Matthew Law, Lei Song, Paul D.P. Pharoah, Christian Ingvar, Jiyeon Choi, Alisa M. Goldstein, Jeffrey E. Lee, Mark Harland, Cristina Pellegrini, Daniela Massi, Sarah Simi, Scott D. Gordon, Jacobo Martinez, Florence Demenais, Kristine Jones, Graham L. Radford-Smith, David C. Whiteman, Lorenza Pastorino, Lisa Elefanti, Arcangela De Nicolo, Mario Mandalà, Juliette Randerson-Moor, Q-Mega, Jan Lubinski, Stephen J. Chanock, Marie-Françoise Avril, David L. Duffy, Helen Gogas, Nienke van der Stoep, Peter A. Kanetsky, Georgina V. Long, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), University of Leeds, QIMR Berghofer Medical Research Institute, National and Kapodistrian University of Athens (NKUA), Ospedale Policlinico San Martino [Genoa], Universita degli studi di Genova, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Maurizio Bufalini Hospital, University of L'Aquila [Italy] (UNIVAQ), Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Cyprus Institute of Neurology and Genetics, University of Athens Medical School [Athens], The University of Sydney, Universitat de Barcelona (UB), Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], University of Michigan [Ann Arbor], University of Michigan System, Instituto Valenciano de Oncologia, Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], IRCCS Istituto Nazionale dei Tumori [Milano], Ninewells Hospital and Medical School [Dundee], Cyprus Institute (CyI), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Queensland [Brisbane], Haukeland University Hospital, University of Bergen (UiB), Geisel School of Medicine at Dartmouth, Oslo University Hospital [Oslo], Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], King‘s College London, Menzies School of Health Research [Australia], Charles Darwin University, The University of Texas M.D. Anderson Cancer Center [Houston], University of Leicester, Flinders University [Adelaide, Australia], West Pomeranian University of Technology Szczecin, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), 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)-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), National Human Genome Research Institute (NHGRI), Leiden University Medical Center (LUMC), Karolinska Institutet [Stockholm], Queensland University of Technology [Brisbane] (QUT), Institute of Oncology Ljubljana, Harvard T.H. Chan School of Public Health, Lund University [Lund], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Glasgow, Statistical Genetics, and Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH) United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USAU19CA148112SEARCH team (Cancer Research UK) C490/A16561AOCS (US Army Medical Research and Material Command) DAMD17-01-1-0729Canadian Institutes of Health Research (CIHR)Cancer Council Victoria Queensland Cancer Fund Cancer Council New South Wales Cancer Council South Australia Cancer Council Western Australia Cancer Council Tasmania National Health and Medical Research Council of AustraliaID400413ID400281National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia National Health and Medical Research Council of Australia Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS Ministry of Health, Italy Associazione Italiana per la Ricerca sul Cancro (AIRC)IG 15460Spanish Fondo de Investigaciones Sanitarias grant - FEDER 'Una manera de hacer Europa' PI15/00716PI15/00956CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Spain - European Development Regional Fund 'A way to achieve Europe' ERDF AGAUR of the Catalan Government, Spain 2014_SGR_603European CommissionEuropean Commission Joint Research CentreLSHC-CT-2006-018702European Union (EU) 'Fundacio La Marato de TV3', Catalonia, Spain 201331-30'Fundacion Cientifica de la Asociacion Espanola Contra el Cancer', Spain GCB15152978SOENCERCA Programme/Generalitat de Catalunya Italian Ministry of the University and Scientific Research (PRIN-2012 grant) 2012JJX494Melanoma Research Alliance United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI)CA88363CA83115CA122838CA87969CA055075CA100264CA133996CA49449National Health and Medical Research Council of Australia200071241944339462380385389927389875389891389892389938443036442915442981496610496675496739552485552498APP1049894Cancer Council Queensland Cancer Institute New South Wales Australian GovernmentDepartment of Industry, Innovation and ScienceCooperative Research Centres (CRC) Programme Australian Cancer Research Foundation Wellcome TrustWT084766/Z/08/ZNational Health and Medical Research Council of Australia Australian Research Council Department of Health and Human Services (DHHS)
Subjects: Sequence Variants, Male, medicine.medical_specialty, Skin Neoplasms, Genotype, Medizin, Identifies 3, Genome-wide association study, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Malignant-melanoma, 0302 clinical medicine, Genetics, medicine, Genetic predisposition, Nevus, Humans, Hla Class-i, Genetic Predisposition to Disease, Polymorphism, Melanoma, 030304 developmental biology, Telomere Length, Cancer, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Loci, Pigmentation, E-cadherin, Single Nucleotide, medicine.disease, Genetic architecture, Attributable Fraction, 3. Good health, Phenotype, Female, Genetic Loci, Genome-Wide Association Study, Cutaneous melanoma, Medical genetics, Settore MED/35 - MALATTIE CUTANEE E VENEREE, 030217 neurology & neurosurgery, Familial Melanoma
Abstract: Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma.Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 x 10(-8)) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.
Published: 2020
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293. Chronic Low-Dose Exposure to Xenoestrogen Ambient Air Pollutants and Breast Cancer Risk: XENAIR Protocol for a Case-Control Study Nested Within the French E3N Cohort

Author: Amadou, Amina, Coudon, Thomas, Praud, Delphine, Salizzoni, Pietro, Leffondre, Karen, Lévêque, Emilie, Boutron-Ruault, Marie-Christine, Danjou, Aurélie M N, Morelli, Xavier, Le Cornet, Charlotte, Perrier, Lionel, Couvidat, Florian, Bessagnet, Bertrand, Caudeville, Julien, Faure, Elodie, Mancini, Francesca Romana, Gulliver, John, Severi, Gianluca, Fervers, Béatrice, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mecanique des Fluides et d'Acoustique (LMFA), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Centre Léon Bérard [Lyon], Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Institut National de l'Environnement Industriel et des Risques (INERIS), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: hormone receptor status, multipollutant, air pollution, Computer applications to medicine. Medical informatics, R858-859.7, land use regression, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, gene-environment interaction, breast cancer, endocrine disruptors, Protocol, Medicine, geographic information system, chemistry-transport model, epigenetic, ComputingMilieux_MISCELLANEOUS, prospective study
Abstract: BackgroundBreast cancer is the most frequent cancer in women in industrialized countries. Lifestyle and environmental factors, particularly endocrine-disrupting pollutants, have been suggested to play a role in breast cancer risk. Current epidemiological studies, although not fully consistent, suggest a positive association of breast cancer risk with exposure to several International Agency for Research on Cancer Group 1 air-pollutant carcinogens, such as particulate matter, polychlorinated biphenyls (PCB), dioxins, Benzo[a]pyrene (BaP), and cadmium. However, epidemiological studies remain scarce and inconsistent. It has been proposed that the menopausal status could modify the relationship between pollutants and breast cancer and that the association varies with hormone receptor status. ObjectiveThe XENAIR project will investigate the association of breast cancer risk (overall and by hormone receptor status) with chronic exposure to selected air pollutants, including particulate matter, nitrogen dioxide (NO2), ozone (O3), BaP, dioxins, PCB-153, and cadmium. MethodsOur research is based on a case-control study nested within the French national E3N cohort of 5222 invasive breast cancer cases identified during follow-up from 1990 to 2011, and 5222 matched controls. A questionnaire was sent to all participants to collect their lifetime residential addresses and information on indoor pollution. We will assess these exposures using complementary models of land-use regression, atmospheric dispersion, and regional chemistry-transport (CHIMERE) models, via a Geographic Information System. Associations with breast cancer risk will be modeled using conditional logistic regression models. We will also study the impact of exposure on DNA methylation and interactions with genetic polymorphisms. Appropriate statistical methods, including Bayesian modeling, principal component analysis, and cluster analysis, will be used to assess the impact of multipollutant exposure. The fraction of breast cancer cases attributable to air pollution will be estimated. ResultsThe XENAIR project will contribute to current knowledge on the health effects of air pollution and identify and understand environmental modifiable risk factors related to breast cancer risk. ConclusionsThe results will provide relevant evidence to governments and policy-makers to improve effective public health prevention strategies on air pollution. The XENAIR dataset can be used in future efforts to study the effects of exposure to air pollution associated with other chronic conditions. International Registered Report Identifier (IRRID)DERR1-10.2196/15167
Published: 2020
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294. Vitamin E: an overview

Author: Mourad Akdad, Farid Khallouki, Marc Poirot, Bachir El Bouhali, Sandrine Silvente-Poirot, Robert W. Owen, Faculté des Sciences et Techniques - Errachidia (FSTE Errachidia), Université Moulay Ismail (UMI), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Poirot, Marc
Subjects: 2. Zero hunger, 0303 health sciences, Antioxidant, Vitamin E, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Cancer, Nutritional status, medicine.disease, Bioinformatics, Treatment failure, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, Human health, 0302 clinical medicine, Functional food, 030220 oncology & carcinogenesis, medicine, Tamoxifen, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, medicine.drug
Abstract: Vitamin E refers to a functional food and dietary nutrient that plays an important role in maintaining human health and nutritional status. Vitamin E is mainly known as an antioxidant, which attacks free radicals and thus protects cells against damage and the human body against aging. Vitamin E components were proposed to prevent some chronic diseases, such as cardiovascular, cancer, and neurodegenerative diseases, by acting either as an antioxidant or through other molecular mechanisms. Importantly, vitamin E has been shown to block the pharmacological action of several drugs revealing a risk of treatment failure, which suggests that diet enrichment in vitamin E must be avoided in these cases. We will present a brief history of the discovery of vitamin E, its chemistry, and we will give an overview of its molecular properties with an emphasis on its impairment of the anticancer action of tamoxifen in breast cancers.
Published: 2020
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295. SBML Level 3: an extensible format for the exchange and reuse of biological models

Author: Edda Klipp, Marco Antoniotti, Frank Bergmann, James C. Schaff, Peter D. Karp, Daniel Lucio, Kedar Nath Natarajan, Thomas M. Hamm, Leandro Watanabe, Henning Hermjakob, David Tolnay, John Wagner, Joerg Stelling, Alida Palmisano, Falk Schreiber, Yukiko Matsuoka, Harold F. Gómez, Huaiyu Mi, Carole J. Proctor, Ulrike Wittig, Neil Swainston, Jan Červený, Denis Thieffry, Piero Dalle Pezze, Julio Saez-Rodriguez, Maciej J. Swat, Bin Hu, Martina Kutmon, Thomas Pfau, Bas Teusink, Sarah M. Keating, Fedor A. Kolpakov, Andreas Dräger, Pedro Mendes, Martin Scharm, Emek Demir, Ioannis Xenarios, Christoph Flamm, Axel von Kamp, Darren J. Wilkinson, Nick Juty, Fengkai Zhang, Leonard A. Harris, Michael Schubert, Dagmar Waltemath, Lucian P. Smith, Steffen Klamt, Herbert M. Sauro, Ali Ebrahim, Wolfram Liebermeister, Christian Knüpfer, Nicolas Rodriguez, Tramy Nguyen, Naoki Tanimura, Christopher Cox, Stuart C. Sealfon, Nicholas Alexander Allen, Clemens Wrzodek, Bastian R. Angermann, Martin Meier-Schellersheim, Anna Zhukova, Jean-Baptiste Pettit, Hovakim Grabski, Devin P. Sullivan, Claudine Chaouiya, Michael L. Blinov, John Doyle, Ilya Kiselev, Roman Schulte, Alex Gutteridge, Mélanie Courtot, Eric Mjolsness, Finja Wrzodek, Rahuman S Malik-Sheriff, Ronan M. T. Fleming, Bruce E. Shapiro, Kimberly Begley, Leslie M. Loew, Colin S. Gillespie, Ibrahim Vazirabad, Michael Hucka, Akira Funahashi, Bernhard O. Palsson, Hamid Bolouri, Tomáš Helikar, Camille Laibe, William S. Denney, Chris T. Evelo, Florian Mittag, William S. Hlavacek, Ron Henkel, Harish Dharuri, Julien Dorier, Karthik Raman, Martina Fröhlich, Conor Lawless, Rainer Machné, Falko Krause, Damon Hachmeister, Matthias König, Clifford A. Shaffer, Benjamin D. Heavner, Douglas B. Kell, Jonathan R. Karr, Mihai Glont, Lukas Endler, Melanie I. Stefan, Robert Phair, Lu Li, Henning Schmidt, Dirk Drasdo, Johan Elf, Allyson L. Lister, Hiroaki Kitano, Richard R. Adams, Oliver A. Ruebenacker, Roland Keller, Sven Sahle, Ion I. Moraru, Gary D. Bader, Poul M. F. Nielsen, Johann M. Rohwer, Johannes Eichner, Daniel R. Hyduke, James R. Faeder, Stefan Hoops, Emanuel Gonçalves, Yuichiro Inagaki, Aurélien Naldi, Koichi Takahashi, Sylvain Soliman, Brett G. Olivier, Kieran Smallbone, Stuart L. Moodie, Pedro T. Monteiro, Chris J. Myers, Martin Golebiewski, Tomas Radivoyevitch, Jeremy Zucker, Hidde de Jong, Andrew Finney, Keating, S, Waltemath, D, König, M, Zhang, F, Dräger, A, Chaouiya, C, Bergmann, F, Finney, A, Gillespie, C, Helikar, T, Hoops, S, Malik-Sheriff, R, Moodie, S, Moraru, I, Myers, C, Naldi, A, Olivier, B, Sahle, S, Schaff, J, Smith, L, Swat, M, Thieffry, D, Watanabe, L, Wilkinson, D, Blinov, M, Begley, K, Faeder, J, Gómez, H, Hamm, T, Inagaki, Y, Liebermeister, W, Lister, A, Lucio, D, Mjolsness, E, Proctor, C, Raman, K, Rodriguez, N, Shaffer, C, Shapiro, B, Stelling, J, Swainston, N, Tanimura, N, Wagner, J, Meier-Schellersheim, M, Sauro, H, Palsson, B, Bolouri, H, Kitano, H, Funahashi, A, Hermjakob, H, Doyle, J, Hucka, M, Adams, R, Allen, N, Angermann, B, Antoniotti, M, Bader, G, Červený, J, Courtot, M, Cox, C, Dalle Pezze, P, Demir, E, Denney, W, Dharuri, H, Dorier, J, Drasdo, D, Ebrahim, A, Eichner, J, Elf, J, Endler, L, Evelo, C, Flamm, C, Fleming, R, Fröhlich, M, Glont, M, Gonçalves, E, Golebiewski, M, Grabski, H, Gutteridge, A, Hachmeister, D, Harris, L, Heavner, B, Henkel, R, Hlavacek, W, Hu, B, Hyduke, D, Jong, H, Juty, N, Karp, P, Karr, J, Kell, D, Keller, R, Kiselev, I, Klamt, S, Klipp, E, Knüpfer, C, Kolpakov, F, Krause, F, Kutmon, M, Laibe, C, Lawless, C, Li, L, Loew, L, Machne, R, Matsuoka, Y, Mendes, P, Mi, H, Mittag, F, Monteiro, P, Natarajan, K, Nielsen, P, Nguyen, T, Palmisano, A, Jean-Baptiste, P, Pfau, T, Phair, R, Radivoyevitch, T, Rohwer, J, Ruebenacker, O, Saez-Rodriguez, J, Scharm, M, Schmidt, H, Schreiber, F, Schubert, M, Schulte, R, Sealfon, S, Smallbone, K, Soliman, S, Stefan, M, Sullivan, D, Takahashi, K, Teusink, B, Tolnay, D, Vazirabad, I, Kamp, A, Wittig, U, Wrzodek, C, Wrzodek, F, Xenarios, I, Zhukova, A, Zucker, J, European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Heidelberg University Hospital [Heidelberg], Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), European Molecular Biology Laboratory (EMBL), University of Connecticut (UCONN), National Institutes of Health [Bethesda] (NIH), Chercheur indépendant, Amazon Web Services [Seattle] (AWS), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), University of Toronto, Masaryk University [Brno] (MUNI), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, The University of Tennessee [Knoxville], The Babraham Institute [Cambridge, UK], Oregon Health and Science University [Portland] (OHSU), Human Predictions LLC, Illumina, Swiss-Prot Group, Swiss Institute of Bioinformatics [Genève] (SIB), Modelling and Analysis for Medical and Biological Applications (MAMBA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California [San Diego] (UC San Diego), University of California (UC), Center for Bioinformatics (ZBIT), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Uppsala University, Institut für Populationsgenetik [Vienna], Veterinärmedizinische Universität Wien, Maastricht University [Maastricht], Alpen-Adria-Universität Klagenfurt [Klagenfurt, Austria], Medizinische Universität Wien = Medical University of Vienna, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg Institute for Theoretical Studies (HITS ), Russian-Armenian University (RAU), GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Microsoft Technology Licensing (MTL), Microsoft Corporation [Redmond, Wash.], Vanderbilt University School of Medicine [Nashville], University of Washington [Seattle], University of Rostock, Los Alamos National Laboratory (LANL), Lorentz Institute, Universiteit Leiden, Tegmine Therapeutics, Modeling, simulation, measurement, and control of bacterial regulatory networks (IBIS), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Jean Roget, SRI International [Menlo Park] (SRI), Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Liverpool, Universitätsklinikum Tübingen - University Hospital of Tübingen, Institute of Information and Computational Technologies (IICT), Max Planck Institute for Dynamics of Complex Technical Systems, Max-Planck-Gesellschaft, Max-Planck-Institut für Molekulare Genetik (MPIMG), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Humboldt University Of Berlin, Newcastle University [Newcastle], École polytechnique (X), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], The Systems Biology Institute [Tokyo] (SBI), Centro de Quimica Estrutural (CQE), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST), University of Southern California (USC), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, University of Southern Denmark (SDU), University of Auckland [Auckland], University of Utah, Virginia Tech [Blacksburg], University of Luxembourg [Luxembourg], Integrative Bioinformatics Inc [Mountain View], Cleveland Clinic, Stellenbosch University, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Universität Heidelberg [Heidelberg] = Heidelberg University, Leibniz Institute of Plant Genetics and Crop Plant Research [Gatersleben] (IPK-Gatersleben), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Manchester [Manchester], Computational systems biology and optimization (Lifeware), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), California Institute of Technology (CALTECH), Encodia Inc [San Diego], Shinshu University [Nagano], University of Amsterdam [Amsterdam] (UvA), Versiti Blood Center of Wisconsin, Greifswald University Hospital, Bioinformatique évolutive - Evolutionary Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Pacific Northwest National Laboratory (PNNL), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), Department of Bioengineering, University of California (UC)-University of California (UC), ANSYS, Virginia Polytechnic Institute and State University [Blacksburg], Eight Pillars Ltd, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Universität Heidelberg, Bioquant, Applied Biomathematics [New York], SimCYP Ltd, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Utah School of Medicine [Salt Lake City], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Mizuho Information and Research Institute, Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Oxford, Computer Science (North Carolina State University), North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of California [Irvine] (UC Irvine), Indian Institute of Technology Madras (IIT Madras), California State University [Northridge] (CSUN), Biotechnology and Biological Sciences Research Council (BBSRC), IBM Research [Melbourne], Benaroya Research Institute [Seattle] (BRI), Okinawa Institute of Science and Technology Graduate University, Keio University, Department of Computing and Mathematical sciences, members, SBML Level 3 Community, Université de Lausanne (UNIL), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of California, Universiteit Leiden [Leiden], Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Inria Grenoble - Rhône-Alpes, Humboldt University of Berlin, Universität Heidelberg [Heidelberg], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Humboldt-Universität zu Berlin, University of California-University of California, Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], University of California [Irvine] (UCI), Biotechnology and Biological Sciences Research Council, Computer Science, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)
Subjects: computational modeling, Medicine (General), Markup language, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, INFORMATION, Interoperability, interoperability, Review, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], ANNOTATION, 0302 clinical medicine, Software, file forma, Models, Biology (General), 0303 health sciences, Computational model, Applied Mathematics, Systems Biology, systems biology, File format, 3. Good health, Networking and Information Technology R&D, Networking and Information Technology R&D (NITRD), Computational Theory and Mathematics, SIMULATION, General Agricultural and Biological Sciences, STANDARDS, REPOSITORY, Information Systems, QH301-705.5, Bioinformatics, Systems biology, Software ecosystem, Reviews, Bioengineering, Methods & Resources, Biology, MARKUP LANGUAGE, Models, Biological, SBML Level 3 Community members, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, R5-920, Animals, Humans, SBML, reproducibility, 030304 developmental biology, ENVIRONMENT, General Immunology and Microbiology, file format, business.industry, Computational Biology, Biological, ONTOLOGY, Metabolism, Logistic Models, Biochemistry and Cell Biology, Other Biological Sciences, Software engineering, business, 030217 neurology & neurosurgery
Abstract: Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution., Over the past two decades, scientists from different fields have been developing SBML, a standard format for encoding computational models in biology and medicine. This article summarizes recent progress and gives perspectives on emerging challenges.
Published: 2020
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296. National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio : a pooled analysis of 458 population-based studies in Asian and Western countries

Author: NCD Risk Factor Collaboration (NCD-RisC), [missing], Taddei, Cristina, Jackson, Rod, Zhou, Bin, Bixby, Honor, Danaei, Goodarz, Di Cesare, Mariachiara, Kuulasmaa, Kari, Hajifathalian, Kaveh, Bentham, James, Bennett, James E, Aekplakorn, Wichai, Cifkova, Renata, Dallongeville, Jean, DeBacquer, Dirk, Giampaoli, Simona, Gudnason, Vilmundur, Khang, Young-Ho, Laatikainen, Tiina, Mann, JimI, Marques-Vidal, Pedro, Mensah, George A, Müller-Nurasyid, Martina, Ninomiya, Toshiharu, Petkeviciene, Janina, Rodríguez-Artalejo, Fernando, Servais, Jennifer, Söderberg, Stefan, Stavreski, Bill, Wilsgaard, Tom, Zdrojewski, Tomasz, Zhao, Dong, Stevens, Gretchen A, Savin, Stefan, Cowan, Melanie J, Riley, Leanne M, Ezzati, Majid, Adams, Robert J, Ahrens, Wolfgang, Amouyel, Philippe, Amuzu, Antoinette, Anderssen, Sigmund A, Ariansen, Inger, Arveiler, Dominique, Aspelund, Thor, Auvinen, Juha, Avdicová, Mária, Banach, Maciej, Bandosz, Piotr, Banegas, José R, Barbagallo, Carlo M, Bata, Iqbal, Baur, Louise A, Beaglehole, Robert, Bernotiene, Gailute, Bi, Yufang, Bienek, Asako, Björkelund, Cecilia, Bo, Simona, Boehm, Bernhard O, Bonaccio, Marialaura, Bongard, Vanina, Borchini, Rossana, Borghs, Herman, Breckenkamp, Juergen, Brenner, Hermann, Bruno, Graziella, Busch, Markus A, Cabrera de León, Antonio, Capuano, Vincenzo, Casanueva, Felipe F, Casas, Juan-Pablo, Caserta, Carmelo A, Censi, Laura, Chen, Fangfang, Chen, Shuohua, Chirlaque, María-Dolores, Cho, Belong, Cho, Yumi, Chudek, Jerzy, Claessens, Frank, Clarke, Janine, Clays, Els, Cooper, Cyrus, Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Crujeiras, Ana B, Cui, Liufu, D'Arrigo, Graziella, Dauchet, Luc, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, De Smedt, Delphine, Dennison, Elaine, Deschamps, Valérie, DiCastelnuovo, Augusto, Dobson, Annette J, Donfrancesco, Chiara, Döring, Angela, Drygas, Wojciech, Du, Yong, Dziankowska-Zaborszczyk, Elzbieta, Eggertsen, Robert, Ekelund, Ulf, Elosua, Roberto, Eriksson, Johan G, Evans, Alun, Faeh, David, Felix-Redondo, Francisco J, Fernández-Bergés, Daniel, Ferrari, Marika, Ferrieres, Jean, Finn, Joseph D, Forslund, Ann-Sofie, Forsner, Maria, Frontera, Guillermo, Fujita, Yuki, Gaciong, Zbigniew, Galvano, Fabio, Gao, Jingli, Garcia-de-la-Hera, Manoli, Garnett, Sarah P, Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Gianfagna, Francesco, Gill, Tiffany K, Giovannelli, Jonathan, Goltzman, David, GonzalezGross, Marcela, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dušan, Gregor, Ronald D, Grodzicki, Tomasz, Grosso, Giuseppe, Gruden, Grabriella, Gu, Dongfeng, Guallar-Castillón, Pilar, Gudmundsson, Elias F, Guessous, Idris, Gunnlaugsdottir, Johanna, Gutzwiller, Felix, Hardy, Rebecca, Hata, Jun, Haugsgjerd, Teresa, Hayes, Alison J, He, Jiang, He, Yuna, Herrala, Sauli, TapaniHihtaniemi, Ilpo, Hobbs, Michael, Hopman, Wilma M, MaríaHuerta, José, Huybrechts, Inge, Iacoviello, Licia, Iannone, Anna G, Ikeda, Nayu, Iwasaki, Masanori, Jamrozik, Konrad, Janszky, Imre, Jarvelin, Marjo-Riitta, Jasienska, Grazyna, Jennings, Garry, Jeong, Seung-lyeal, QiangJiang, Chao, Joffres, Michel, Jokelainen, Jari J, Jonas, Jost B, Jóźwiak, Jacek, Kajantie, Eero O, Kauhanen, Jussi, Keil, Ulrich, Keinänen-Kiukaanniemi, Sirkka, Kersting, Mathilde, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Kim, Jeongseon, Kim, Yeon-Yong, Klumbiene, Jurate, Knoflach, Michael, Ko, Stephanie, Kolle, Elin, Korpelainen, Raija, Koskinen, Seppo, Kouda, Katsuyasu, Kratzer, Wolfgang, Kriemler, Susi, Krokstad, Steinar, Kujala, Urho M, Kurjata, Pawel, HingLam, Tai, Lanska, Vera, Lappas, Georg, Laugsand, Lars E, Lee, Jeonghee, Lehtimäki, Terho, Li, Yanping, Lilly, Christa L, Lin, Xu, Lind, Lars, Lissner, Lauren, Liu, Jing, Lopez-Garcia, Esther, Lorbeer, Roberto, EugenioLozano, José, Luksiene, Dalia, Lundqvist, Annamari, Lundqvist, Robert, Lytsy, Per, Ma, Guansheng, Machi, Suka, Maggi, Stefania, Magliano, Dianna J, Manzato, Enzo, Mathiesen, Ellisiv B, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, Meirhaeghe, Aline, Meisinger, Christa, Metcalf, Patricia, Mi, Jie, Miller, Jody C, Moreno, Luis A, Morin, Suzanne, Mossakowska, Malgorzata, Muiesan, Maria L, Mursu, Jaakko, Nakamura, Harunobu, Námešná, Jana, Nauck, Matthias, MariaNavarrete-Muñoz, Eva, Neal, William A, Nenko, Ilona, Niiranen, Teemu J, Ning, Guang, Noale, Marianna, Norie, Sawada, Noto, Davide, O'Neill, Terence, O'Reilly, Dermot, Oh, Kyungwon, Olafsson, Örn, MichelPaccaud, Fred, Pajak, Andrzej, Palmieri, Luigi, Panza, Francesco, Parnell, Winsome R, Peltonen, Markku, Peters, Annette, Petersmann, Astrid, Pigeot, Iris, Pilotto, Lorenza, Piwonska, Aleksandra, Plans-Rubió, Pedro, Porta, Miquel, Price, Jacqueline F, Puder, Jardena J, Puhakka, Soile E, Radisauskas, Ricardas, Raitakari, Olli, Ramos, Rafel, Redon, Josep, Rigo, Fernando, Rodriguez-Perez, MaríadelCristo, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G R, Ruidavets, Jean-Bernard, Rutkowski, Marcin, Salanave, Benoit, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Sans, Susana, Saramies, Jouko L, Saum, Kai-Uwe, Scheidt-Nave, Christa, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schöttker, Ben, Sebert, Sylvain, Sen, Abhijit, Shaw, Jonathan E, Shibuya, Kenji, WookShin, Dong, Shiri, Rahman, Simons, Judith, Simons, Leon A, Sjöström, Michael, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Solfrizzi, Vincenzo, Sonestedt, Emily, Soumare, Aicha, Staessen, Jan A, Stathopoulou, Maria G, Steene-Johannessen, Jostein, Stehle, Peter, Stieber, Jutta, Stöckl, Doris, Stokwiszewski, Jakub, Sundström, Johan, Suriyawongpaisal, Paibul, Tamosiunas, Abdonas, JooTan, Eng, Taylor, Anne, Tell, Grethe, Thijs, Lutgarde, Tolonen, HannaK, Topór-Madry, Roman, JoséTormo, María, Torrent, Maties, Tsugane, Shoichiro, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Tzourio, Christophe, Uusitalo, Hannu M T, Van Herck, Koen, Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lars, Vega, Tomas, Veronesi, Giovanni, Vioque, Jesus, Virtanen, JyrkiK, Visvikis-Siest, Sophie, Vollenweider, Peter, Voutilainen, Sari, Vrijheid, Martine, Wagner, Aline, Wagner, Anne, Wang, Ming-Dong, Wang, Qian, XingWang, Ya, Wannamethee, S Goya, Wei, Wenbin, Whincup, Peter H, Wiecek, Andrzej, Willeit, Johann, Willeit, Peter, Wojtyniak, Bogdan, Wong, Andrew, Woodward, Mark, GiwercmanWu, Aleksander, Wu, Frederick C, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yan, Weili, Yang, Xiaoguang, Ye, Xingwang, Yoshihara, Akihiro, Zambon, Sabina, Zhao, Wenhua, Imperial College London, University of Auckland [Auckland], Harvard T.H. Chan School of Public Health, Middlesex University, National Institute for Health and Welfare [Helsinki], Weill Medical College of Cornell University [New York], University of Kent [Canterbury], Mahidol University [Bangkok], Charles University [Prague] (CU), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, 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, Droit et Santé, Universiteit Gent = Ghent University [Belgium] (UGENT), Istituto Superiore di Sanita [Rome], Icelandic Heart Association [Kopavogur, Iceland] (IHA), Seoul National University [Seoul] (SNU), University of Otago [Dunedin, Nouvelle-Zélande], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Helmholtz-Zentrum München (HZM), Kyushu University [Fukuoka], Universidad Autonoma de Madrid (UAM), CIBER de Epidemiología y Salud Pública (CIBERESP), Umeå University, The Arctic University of Norway (UiT), Medical University of Gdańsk, Capital University of Medical Sciences [Beijing] (CUMS), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Adelaide, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), London School of Hygiene and Tropical Medicine (LSHTM), Norwegian School of Sport Sciences = Norges idrettshøgskole [Oslo] (NIH), Norwegian Institute of Public Health [Oslo] (NIPH), Université de Strasbourg (UNISTRA), University of Iceland [Reykjavik], University of Oulu, Regional Authority of Public Health [Slovaquia] (RAPH), Ministry of Health of the Slovak Republic [Slovaquia], Medical University of Łódź (MUL), Università degli studi di Palermo - University of Palermo, Dalhousie University [Halifax], The University of Sydney, Public Health Agency of Canada, University of Gothenburg (GU), University of Turin, Nanyang Technological University [Singapour], Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Università degli studi di Napoli Federico II, Faculté de Médecine [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Universität Bielefeld = Bielefeld University, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Robert Koch Institute [Berlin] (RKI), Universidad de La Laguna [Tenerife - SP] (ULL), Universidade de Santiago de Compostela [Spain] (USC ), University College of London [London] (UCL), University of Silesia in Katowice, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Southampton, Biomolécules et inflammation pulmonaire, Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Santé publique France - French National Public Health Agency [Saint-Maurice, France], University of Queensland [Brisbane], IMIM-Hospital del Mar, Generalitat de Catalunya, Queen's University [Belfast] (QUB), Universität Zürich [Zürich] = University of Zurich (UZH), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Manchester [Manchester], Kindai University, Medical University of Warsaw - Poland, Università degli studi di Catania [Catania], Geneva University Hospital (HUG), Universitá degli Studi dell’Insubria, McGill University = Université McGill [Montréal, Canada], Universidad Politécnica de Madrid (UPM), Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institute for Clinical and Experimental Medicine (IKEM), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Bergen (UiB), Tulane University, Chinese Center for Disease Control and Prevention, Oulu University Hospital [Oulu], The University of Western Australia (UWA), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Niigata University, Norwegian University of Science and Technology (NTNU), Simon Fraser University (SFU.ca), University of Eastern Finland, Westfälische Wilhelms-Universität Münster (WWU), Innsbruck Medical University [Austria] (IMU), Universitätsklinikum Ulm - University Hospital of Ulm, University of Jyväskylä (JYU), The University of Hong Kong (HKU), Sahlgrenska Academy at University of Gothenburg [Göteborg], Tampere University Hospital, University of Tampere [Finland], West Virginia University [Morgantown], University of Chinese Academy of Sciences [Beijing] (UCAS), Uppsala Universitet [Uppsala], Universität Greifswald - University of Greifswald, Peking University [Shenzhen], The Jikei University School of Medicine, Baker Heart and Diabetes Institute (AUSTRALIA), Universita degli Studi di Padova, University of Edinburgh, University of Zaragoza - Universidad de Zaragoza [Zaragoza], International Institute of Molecular and Cell Biology [Warsaw] (IIMCB), Università degli Studi di Brescia [Brescia], Konan University [Kobe, Japan], University of Turku, Shanghai Jiao Tong University School of Medicine, Department of Epidemiology and Biostatistics, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, Department of Epidemiology, Health Economics and Public Health, UMR 558 INSERM, Université de Toulouse, Centre Hospitalier Universitaire de Toulouse, Unité de Surveillance et d'Epidémiologie Nutritionnelle (USEN), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut de Veille Sanitaire (INVS)-Université Paris 13 (UP13), Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain, parent, Department of Chronic Disease Prevention, Institute for plasma research, Institute for Plasma Research, Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Department of Reproductive Endocrinology, University of Bari Aldo Moro (UNIBA), Nutritional Epidemiology, Department of Clinical Sciences, Clinical Research Center, Lund University [Lund]-Lund University [Lund], Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Applied Food Science, Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Research Unit Hypertension and Cardiovascular Epidemiology [Louvain, Belgique], Studies Coordinating Centre [Louvain, Belgique], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), National Cancer Center, University of Kuopio, Epidémiologie cardiovasculaire et métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Tampere University, Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Norwegian University of Science and Technology [Trondheim] (NTNU), Departamento de Salud Pública, Universidad Miguel Hernández [Elche] (UMH), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Department of Internal Medicine, School of Public Health and Clinical Nutrition, Epidemiologia Ambiental, Centre for Research in Environmental Epidemiology (CREAL)-Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP) of Pamplona-Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Department of Epidemiology and Public Health, EA 3430, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Medical University of Silesia (SUM), University of Innsbruck, National Institute of Hygiene Warsaw, The Georges Institute for International Health, Naval Research Laboratory (NRL), Grant numbers 101506/Z/13/Z and Research Training Fellowship 203616/Z/16/Z, Ministry of Health of the Czech Republic (grant number 15-27109A), UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología, HUS Children and Adolescents, Department of Public Health, Universidad Autónoma de Madrid (UAM), Università degli studi di Torino = University of Turin (UNITO), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), CHU Toulouse [Toulouse], Université Paris 13 (UP13)-Institut de Veille Sanitaire (INVS)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM), Taddei, C, Zhou, B, Bixby, H, Danaei, G, Di Cesare, M, Kuulasmaa, K, Hajifathalian, K, Bentham, J, Bennett, JE, Aekplakorn, W, Cifkova, R, Dallongeville, J, DeBacquer, D, Giampaoli, S, Gudnason, V, Khang, Y-O, Laatikainen, T, Mann, JI, Marques-Vidal, P, Mensah, GA, Müller-Nurasyid, M, Ninomiya, T, Petkeviciene, J, Rodríguez-Artalejo, F, Servais, J, Söderberg, S, Stavreski, B, Wilsgaard, T, Zdrojewski, T, Zhao, D, Stevens, GA, Savin, S, Cowan, Mj, Riley, LM, Ezzati, M, Adams, R, Ahrens, W, Amouyel, P, Amuzu, A, Anderssen, SA, Ariansen, I, Arveiler, D, Aspelund, T, Auvinen, A, Avdicová, M, Banach, M, Bandosz, P, Banegas. JR, Barbagallo, CM, Bata, I, Baur, LA, Beaglehole, R, Bennet, JE, Bernotiene, G, Bi, Y, Bienek, A, Björkelund, C, Bo, S, Boehm, BO, Bonaccio, M, Bongard, V, Borchini, R, Borghs, H, Breckenkamp, J, Brenner, H, Bruno, G, Busch, MA, CabreradeLeón, A, Capuano, V, Casanueva, FF, Casas, J-P, Caserta, CA, Censi, L, Chen, F, Chen, S, Chirlaque, M-D, Cho, B, Cho, Y, Chudek, J, Claessens, F, Clarke, J, Clays, E, Cooper, C, Costanzo, S, Cottel, D, Cowell C, Crujeiras, AB, Cui, L, D'Arrigo, G, Dauchet, L, De Backer, G, De Bacquer, D, de Gaetano, G, De Henauw, S, De Smedt, D, Dennison, E, Desschamps, V, Di Castelnuovo, A, Dobson, AJ, Donfrancesco, C, Döring, A, Doua, K, Drygas, W, Du, Y, Dziankowska-Zaborszczyk, E, Eggertsen, R, Ekelund, U, Elousa, R, Eriksson, JG, Evans, A, Faeh, D, Felix-Redondo, FJ, Fernández-Bergés, D, Ferrari, M, Ferrieres, J, Finn, JD, Forslund, A-S, Forsner, M, Frontera, G, Fujita, Y, Gaciong, Z, Galvano, F, Gao, J, Garcia-de-la-Hera, M, Garnett, SP, Gaspoz, J-M, Gasul, L, Gates, L, Gianfagna, F, Gill, TK, Giovannelli, J, Goltzman, D, GonzalezGross, M, Gottrand, F, Graff-Iversen, S, Grafnetter, D, Gregor, RD, Grodzicki, T, Grosso, G, Gruden, G, Gu, D, Guallar-Castillón, P, Gudmundsson, EF, Guessous, I, Gunnlaugsdottir J, Gutzwiller, F, Hardy, R, Hata, J, Haugsgjerd, T, Hayes, AJ, He, H, He, Y, Herrala, S, Hihtaniemi, IP, Hobbs, M, Hopman, WM, Huerta, JM, Huybrechts, I, Iacoviello, L, Iannone, AG, Ikeda, N, Iwasaki, M, Jackson, R, Jamrozi, K, Janszky, I, Jarvelin, M-R, Jasienska, G, Jennings, G, Jeong, S-L, Jiang, CQ, Joffres, M, Jokelainen, JJ, Jonas, JB, Jóźwiak, J, Kajantie, EO, Kauhanen, K, Keil, U, Keinänen-Kiukaanniemi, S, Kersting, M, Khang, Y-H, Kiechl-Kohlendorfer, U, Kiechl, S, Kim, J, Kim, Y-Y, Klumbiene, J, Knoflach, M, Ko, S, Kolle, E, Korpelainen, R, Koskinen, S, Kouda, K, Kratzer, W, Kriemler, S, Krokstad, S, Kujala,UM, Kurjata, P, Lam, TH, Lanska, V, Lappas , G, Laugsand, LE, Lee, J, Lehtimäki, T, Li, Y, Lilly, C, Lin, X, Lind, L, Lissner, L, Liu, J, Lopez-Garcia, E, Lorbeer, R, Lozano, JE, Luksiene, D, Lundqvist, A, Lundqvist, R, Lytsy, P, Ma, G, Machi, S, Maggi, S, Magliano, DJ, Manzato, E, Mathiesen, EB, McLachlan, S, McLean, RM, Meirhaeghe, A, Metcalf, P, Mi, JM, Miller, JC, Moreno, LA, Morin, S, Mossakowska, M, Muiesan, ML, Mursu, J, Nakamura, H, Námešná, J, Navarrete-Muñoz, EM, Neal, WA, Nenko, I, Niiranen, T, Ning, G, Noale, M, Norie, S, Noto, Davide, O’Neill, T, O'Reilly, D, Oh, K, Olafsson, O, Paccaud, F, Pajak, A, Palmieri, L, Panza, F, Parnell, WR, Peltonen, M, Peters, A, Petersmann, A, P Pigeot, I, Pilotto, L, Piwonska, A, Pedro Plans-Rubió, P, Porta, M, Price, JF, Puder, JJ, Puhakka, SE, Radisauskas, R, Raitakari, O, Ramos, R, Redon, J, Rigo, F, Rodriguez-Perez, MdC, Romaguera, D, Ronkainen, K, Rosengren, A, Roy, JGR, Ruidavets, JB, Rutkowski, M, Salanave, B, Salmeron, D, Salomaa, V, Salonen, JT, Salvetti, M, Sans, S, Saramies, JL, Saum, K-U, Scheidt-Nave, C, Schienkiewitz, A, Schipf, S, Schmidt, CO, Schottker, B, Sebert S, Sen, A, Shaw, JE, Shibuya, K, Shin, DO, Shiri, R, Simons, J, Simons, LA, Sjostrom, M, Slowikowska-Hilczer, J, Slusarczyk, P, Solfrizzi, V, Sonestedt, E, Soumare, A, Staessen, JA, Stathopoulou, MG, Steene-Johannessen, J, Stehle, P, Stieber, J, Stöckl, D, Stokwiszewski, J, Sundström, J, Suriyawongpaisal, P, Tamosiunas, A, Tan, E, Taylor, A, Tell, G, Thijs, L, Tolonen, HK, Topór-Madry, R, Tormo, MJ, Torrent, M, Tsugane, S, Tuomainen, T-P, Tuomilehto, J, Tzourio, C, Uusitalo, HMT, Van Herck, K, Vanderschueren, D, Vanuzzo, D, Vatten, L, Vega, T, Veronesi, G, Vioque, P, Virtanen, JK, Visvikis-Siest, S, Vollenweider, P, Voutilainen, S, Vrijheid, M, Wagner, A, Wang, M-D, Wang, Q, Wang YX, Wannamethee, SG, Wei, W, Whincup, PH, Wiecek, A, Willeit, J, Willeit, P, Wojtyniak, B, Wong, A, Woodward, M, Wu, FC, JianFeng Wu, JF, Wu, SL, Xu, H, Xu, L, Yan, W, Yang, X, Ye, X, Yoshihara, A, Zambon, S, Zhao, W, NCD Risk Factor Collaboration (NCD-RisC), Jackson, R., Zhou, B., Bixby, H., Danaei, G., Di Cesare, M., Kuulasmaa, K., Hajifathalian, K., Bentham, J., Bennett, J.E., Aekplakorn, W., Cifkova, R., Dallongeville, J., DeBacquer, D., Giampaoli, S., Gudnason, V., Khang, Y.H., Laatikainen, T., Mann, J., Marques-Vidal, P., Mensah, G.A., Müller-Nurasyid, M., Ninomiya, T., Petkeviciene, J., Rodríguez-Artalejo, F., Servais, J., Söderberg, S., Stavreski, B., Wilsgaard, T., Zdrojewski, T., Zhao, D., Stevens, G.A., Savin, S., Cowan, M.J., Riley, L.M., Ezzati, M., Adams, R.J., Ahrens, W., Amouyel, P., Amuzu, A., Anderssen, S.A., Ariansen, I., Arveiler, D., Aspelund, T., Auvinen, J., Avdicová, M., Banach, M., Bandosz, P., Banegas, J.R., Barbagallo, C.M., Bata, I., Baur, L.A., Beaglehole, R., Bernotiene, G., Bi, Y., Bienek, A., Björkelund, C., Bo, S., Boehm, B.O., Bonaccio, M., Bongard, V., Borchini, R., Borghs, H., Breckenkamp, J., Brenner, H., Bruno, G., Busch, M.A., Cabrera de León, A., Capuano, V., Casanueva, F.F., Casas, J.P., Caserta, C.A., Censi, L., Chen, F., Chen, S., Chirlaque, M.D., Cho, B., Cho, Y., Chudek, J., Claessens, F., Clarke, J., Clays, E., Cooper, C., Costanzo, S., Cottel, D., Cowell, C., Crujeiras, A.B., Cui, L., D'Arrigo, G., Dauchet, L., De Backer, G., De Bacquer, D., de Gaetano, G., De Henauw, S., De Smedt, D., Dennison, E., Deschamps, V., DiCastelnuovo, A., Dobson, A.J., Donfrancesco, C., Döring, A., Drygas, W., Du, Y., Dziankowska-Zaborszczyk, E., Eggertsen, R., Ekelund, U., Elosua, R., Eriksson, J.G., Evans, A., Faeh, D., Felix-Redondo, F.J., Fernández-Bergés, D., Ferrari, M., Ferrieres, J., Finn, J.D., Forslund, A.S., Forsner, M., Frontera, G., Fujita, Y., Gaciong, Z., Galvano, F., Gao, J., Garcia-de-la-Hera, M., Garnett, S.P., Gaspoz, J.M., Gasull, M., Gates, L., Gianfagna, F., Gill, T.K., Giovannelli, J., Goltzman, D., GonzalezGross, M., Gottrand, F., Graff-Iversen, S., Grafnetter, D., Gregor, R.D., Grodzicki, T., Grosso, G., Gruden, G., Gu, D., Guallar-Castillón, P., Gudmundsson, E.F., Guessous, I., Gunnlaugsdottir, J., Gutzwiller, F., Hardy, R., Hata, J., Haugsgjerd, T., Hayes, A.J., He, J., He, Y., Herrala, S., TapaniHihtaniemi, I., Hobbs, M., Hopman, W.M., MaríaHuerta, J., Huybrechts, I., Iacoviello, L., Iannone, A.G., Ikeda, N., Iwasaki, M., Jamrozik, K., Janszky, I., Jarvelin, M.R., Jasienska, G., Jennings, G., Jeong, S.L., QiangJiang, C., Joffres, M., Jokelainen, J.J., Jonas, J.B., Jóźwiak, J., Kajantie, E.O., Kauhanen, J., Keil, U., Keinänen-Kiukaanniemi, S., Kersting, M., Kiechl-Kohlendorfer, U., Kiechl, S., Kim, J., Kim, Y.Y., Klumbiene, J., Knoflach, M., Ko, S., Kolle, E., Korpelainen, R., Koskinen, S., Kouda, K., Kratzer, W., Kriemler, S., Krokstad, S., Kujala, U.M., Kurjata, P., HingLam, T., Lanska, V., Lappas, G., Laugsand, L.E., Lee, J., Lehtimäki, T., Li, Y., Lilly, C.L., Lin, X., Lind, L., Lissner, L., Liu, J., Lopez-Garcia, E., Lorbeer, R., EugenioLozano, J., Luksiene, D., Lundqvist, A., Lundqvist, R., Lytsy, P., Ma, G., Machi, S., Maggi, S., Magliano, D.J., Manzato, E., Mathiesen, E.B., McLachlan, S., McLean, R.M., McLean, S.B., Meirhaeghe, A., Meisinger, C., Metcalf, P., Mi, J., Miller, J.C., Moreno, L.A., Morin, S., Mossakowska, M., Muiesan, M.L., Mursu, J., Nakamura, H., Námešná, J., Nauck, M., MariaNavarrete-Muñoz, E., Neal, W.A., Nenko, I., Niiranen, T.J., Ning, G., Noale, M., Norie, S., Noto, D., O'Neill, T., O'Reilly, D., Oh, K., Olafsson, Ö., MichelPaccaud, F., Pajak, A., Palmieri, L., Panza, F., Parnell, W.R., Peltonen, M., Peters, A., Petersmann, A., Pigeot, I., Pilotto, L., Piwonska, A., Plans-Rubió, P., Porta, M., Price, J.F., Puder, J.J., Puhakka, S.E., Radisauskas, R., Raitakari, O., Ramos, R., Redon, J., Rigo, F., Rodriguez-Perez, M., Romaguera, D., Ronkainen, K., Rosengren, A., Ruidavets, J.B., Rutkowski, M., Salanave, B., Salmerón, D., Salomaa, V., Salonen, J.T., Salvetti, M., Sans, S., Saramies, J.L., Saum, K.U., Scheidt-Nave, C., Schienkiewitz, A., Schipf, S., Schmidt, C.O., Schöttker, B., Sebert, S., Sen, A., Shaw, J.E., Shibuya, K., WookShin, D., Shiri, R., Simons, J., Simons, L.A., Sjöström, M., Slowikowska-Hilczer, J., Slusarczyk, P., Solfrizzi, V., Sonestedt, E., Soumare, A., Staessen, J.A., Stathopoulou, M.G., Steene-Johannessen, J., Stehle, P., Stieber, J., Stöckl, D., Stokwiszewski, J., Sundström, J., Suriyawongpaisal, P., Tamosiunas, A., JooTan, E., Taylor, A., Tell, G., Thijs, L., Tolonen, H., Topór-Madry, R., JoséTormo, M., Torrent, M., Tsugane, S., Tuomainen, T.P., Tuomilehto, J., Tzourio, C., Van Herck, K., Vanderschueren, D., Vanuzzo, D., Vatten, L., Vega, T., Veronesi, G., Vioque, J., Virtanen, J., Visvikis-Siest, S., Vollenweider, P., Voutilainen, S., Vrijheid, M., Wagner, A., Wang, M.D., Wang, Q., XingWang, Y., Wannamethee, S.G., Wei, W., Whincup, P.H., Wiecek, A., Willeit, J., Willeit, P., Wojtyniak, B., Wong, A., Woodward, M., GiwercmanWu, A., Wu, F.C., Wu, S., Xu, H., Xu, L., Yan, W., Yang, X., Ye, X., Yoshihara, A., Zambon, S., Zhao, W., Universiteit Gent = Ghent University (UGENT), Istituto Superiore di Sanità (ISS), Helmholtz Zentrum München = German Research Center for Environmental Health, Kyushu University, The Arctic University of Norway [Tromsø, Norway] (UiT), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Catania = University of Catania (Unict), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Università degli Studi di Padova = University of Padua (Unipd), Università degli Studi di Brescia = University of Brescia (UniBs), Service Epidémiologie clinique et santé publique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Laboratoire Chrono-environnement (UMR 6249) (LCE), Leopold Franzens Universität Innsbruck - University of Innsbruck, National Institute of Public Health - National Institute of Hygiene [Poland], 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, Medical University of Silesia, Katowice, University of Helsinki, National Institute for Health and Welfare, University of Helsinki, University of Helsinki, and University of Helsinki, Finnish Institute of Occupational Health
Subjects: Male, gupo de ascendencia continental asiática, Settore MED/09 - Medicina Interna, Total Cholesterol, Ldl Cholesterol, Hdl Cholesterol, Blood Lipids, Multi-country Study, Epidemiology, kolesteroli, humanos, Blood lipids, BLOOD-PRESSURE, 030204 cardiovascular system & hematology, triglicéridos, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, HDL cholesterol, Medicine and Health Sciences, CARDIOVASCULAR RISK-FACTORS, Medicine, 030212 general & internal medicine, mediana edad, lípidos, Public, Environmental & Occupational Health, 2. Zero hunger, anciano, education.field_of_study, Age Factors, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Middle Aged, colesterol, adulto, kansainvälinen vertailu, Lipids, 3142 Public health care science, environmental and occupational health, 3. Good health, Europe, Cholesterol, Population Surveillance, LDL cholesterol, SERUM-LIPIDS, Female, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, Adult, Asian Continental Ancestry Group, Canada, Total cholesterol, blood lipids, multi-country study, medicine.medical_specialty, Asia, Medicina, European Continental Ancestry Group, Population, Nursing, HDL-kolesteroli, White People, DIETARY-FAT, 03 medical and health sciences, Sex Factors, Asian People, kansanterveys, vigilancia de la población, Humans, CORONARY-HEART-DISEASE, ddc:610, LDL-kolesteroli, education, Triglycerides, METAANALYSIS, Aged, INDIVIDUAL DATA, Science & Technology, business.industry, Omvårdnad, blood lipid, Cholesterol, HDL, Ecological study, nutritional and metabolic diseases, Cholesterol, LDL, United States, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Cholesterol/blood, Lipids/blood, Population Surveillance/methods, Triglycerides/blood, chemistry, WORLDWIDE TRENDS, Multi-country study, grupo de ascendencia continental europea, business, HIGH-DENSITY-LIPOPROTEIN, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography, Lipoprotein
Abstract: Artículo con numerosos autores. Sólo quedan reflejados el primero, los pertenecientes a la UAM y el colectivo, Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and non-HDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since ∼1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at ∼0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as ∼0.7 per decade in Swiss men (equivalent to ∼26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol., This work was supported by the Wellcome Trust (grant numbers 101506/Z/13/Z and Research Training Fellowship 203616/Z/16/Z). R.C. acknowledges funding from the Ministry of Health of the Czech Republic (grant number 15-27109A)
Published: 2020
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297. Liposomal Irinotecan + 5-FU/LV in Metastatic Pancreatic Cancer : Subgroup Analyses of Patient, Tumor, and Previous Treatment Characteristics in the Pivotal NAPOLI-1 Trial

Author: Li-Tzong Chen, Andrea Wang-Gillam, Jens T. Siveke, Teresa Macarulla Mercade, Jean-Frédéric Blanc, Bruce Belanger, Kyung-Hun Lee, Chung-Pin Li, David Cunningham, György Bodoky, Andrew Dean, Institut Català de la Salut, [Macarulla Mercadé T] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Chen LT] National Institute of Cancer Research, National Health Research Institutes. Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan. [Li CP] Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital. National Yang-Ming University School of Medicine, Taipei, Taiwan. [Siveke JT] Division of Solid Tumor Translational Oncology, West German Cancer Center, University Hospital Essen. German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany. [Cunningham D] The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom. [Bodoky G] Department of Oncology, Szent László Hospital, Budapest, Hungary, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Oncology, Male, Endocrinology, Diabetes and Metabolism, Leucovorin, Medizin, Phases of clinical research, Kaplan-Meier Estimate, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Deoxycytidine, 0302 clinical medicine, Endocrinology, Antineoplastic Combined Chemotherapy Protocols, Stage (cooking), neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas [ENFERMEDADES], Aged, 80 and over, education.field_of_study, Hazard ratio, Liver Neoplasms, Middle Aged, Pàncrees - Càncer - Prognosi, Treatment Outcome, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Fluorouracil, medicine.drug, Adult, medicine.medical_specialty, Population, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Irinotecan, 03 medical and health sciences, Internal medicine, Pàncrees - Càncer - Tractament, Internal Medicine, medicine, Humans, education, Aged, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms [DISEASES], Hepatology, Errata, business.industry, diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Metastatic Pancreatic Adenocarcinoma, Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Gemcitabine, Clinical trial, Pancreatic Neoplasms, Liposomes, business
Abstract: Càncer de pàncrees metastàtic; Tractament previ; Irinotecan Cáncer de páncreas metastásico; Tratamiento previo; Irinotecan Metastatic Pancreatic Cancer; Previous Treatment; Irinotecan Objectives The NAnoliPOsomaL Irinotecan (NAPOLI-1) study (NCT01494506) was the largest global phase 3 study in a post-gemcitabine metastatic pancreatic adenocarcinoma (mPAC) population (N = 417). The subanalyses reported here investigated the prognostic effect of tumor characteristics and disease stage, prior treatment characteristics, baseline patient characteristics on survival outcomes in NAPOLI-1, and whether liposomal irinotecan (nal-IRI) + 5-fluorouracil/leucovorin (5-FU/LV) benefited patients with mPAC across subgroups. Methods Post hoc analyses were performed in the NAPOLI-1 population (4 across tumor characteristics and disease stage, 6 across prior treatment characteristics, and 4 across patient baseline characteristics). Survival outcomes were estimated by Kaplan-Meier analysis and patient safety data were evaluated. Results Mortality and morbidity risk was lower on nal-IRI+5-FU/LV treatment across subgroups. Exceptions were patients who had received prior nonliposomal irinotecan and those who had undergone prior Whipple procedure (overall survival hazard ratio = 1.25 and 1.23, respectively). Decreased appetite, liver metastases, and number of measurable metastatic lesions seemed to be prognostic of survival in this population. Subgroup safety data were generally comparable with those in the overall NAPOLI-1 safety population. Conclusions A diverse population of patients with mPAC that progressed on gemcitabine-based therapy benefited from nal-IRI+5-FU/LV versus 5-FU/LV, potentially helping guide treatment decisions for challenging cases. The NAPOLI-1 study (ClinicalTrials.gov identifier: NCT01494506) was sponsored by Merrimack Pharmaceuticals, Inc, Cambridge, MA.
Published: 2020

298. BIAS: Transparent reporting of biomedical image analysis challenges

Author: Annika Reinke, Bram van Ginneken, Annette Kopp-Schneider, Tal Arbel, Anne L. Martel, Matthias Eisenmann, Henning Müller, Allan Hanbury, Pierre Jannin, Sinan Onogur, Julio Saez-Rodriguez, Bennett A. Landman, Michal Kozubek, Lena Maier-Hein, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Masaryk University [Brno] (MUNI), University of Toronto, McGill University = Université McGill [Montréal, Canada], Vienna University of Technology (TU Wien), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Applied Sciences and Arts of Western Switzerland (HES-SO), University of Geneva [Switzerland], Heidelberg University, Radboud University Medical Center [Nijmegen], Vanderbilt University [Nashville], ERC-2015-StG-37960, European Research Council, RGPIN-2016-06283, Natural Sciences and Engineering Research Council of Canada, 705772, Canadian Cancer Society, CZ.02.1.01/0.0/0.0/16_013/0001775, Ministerstvo Školství, Mládeže a Tělovýchovy, 1452485, National Science Foundation, R01-EB017230-01A1, NIH Clinical Center, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Genève = University of Geneva (UNIGE), and HAL UR1, Admin
Subjects: FOS: Computer and information sciences, Biomedical Research, Computer science, Computer Vision and Pattern Recognition (cs.CV), media_common.quotation_subject, Computer Science - Computer Vision and Pattern Recognition, Good scientific practice, Biomedical challenges, Health Informatics, Guideline, Biomedical image analysis, Article, Field (computer science), Task (project management), Computer Science - Computers and Society, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Computers and Society (cs.CY), FOS: Electrical engineering, electronic engineering, information engineering, Humans, Radiology, Nuclear Medicine and imaging, Quality (business), Set (psychology), 030304 developmental biology, Interpretability, media_common, [SDV.IB] Life Sciences [q-bio]/Bioengineering, 0303 health sciences, Radiological and Ultrasound Technology, Image and Video Processing (eess.IV), Reproducibility of Results, Benchmarking, Electrical Engineering and Systems Science - Image and Video Processing, Prognosis, Computer Graphics and Computer-Aided Design, Data science, Checklist, 3. Good health, Transparency (graphic), [SDV.IB]Life Sciences [q-bio]/Bioengineering, Computer Vision and Pattern Recognition, 030217 neurology & neurosurgery, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract: Highlights • First guideline for reporting biomedical image analysis challenges • Includes checklist for authors and reviewers, Graphical abstract, The number of biomedical image analysis challenges organized per year is steadily increasing. These international competitions have the purpose of benchmarking algorithms on common data sets, typically to identify the best method for a given problem. Recent research, however, revealed that common practice related to challenge reporting does not allow for adequate interpretation and reproducibility of results. To address the discrepancy between the impact of challenges and the quality (control), the Biomedical Image Analysis ChallengeS (BIAS) initiative developed a set of recommendations for the reporting of challenges. The BIAS statement aims to improve the transparency of the reporting of a biomedical image analysis challenge regardless of field of application, image modality or task category assessed. This article describes how the BIAS statement was developed and presents a checklist which authors of biomedical image analysis challenges are encouraged to include in their submission when giving a paper on a challenge into review. The purpose of the checklist is to standardize and facilitate the review process and raise interpretability and reproducibility of challenge results by making relevant information explicit.
Published: 2020
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299. Predicted basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition

Author: Elisabete Weiderpass, Kim Overvad, Giovanna Masala, Guy Fagherazzi, Rudolf Kaaks, Daniel Redondo-Sánchez, Sabina Rinaldi, Ulrica Ericson, Dagfinn Aune, Pilar Amiano, Therese Haugdahl Nøst, Antonia Trichopoulou, Rosario Tumino, Paula Jakszyn, Neil Murphy, Elio Riboli, Tilman Kühn, Francesca Mancini, Heinz Freisling, Bas Bueno-de-Mesquita, Marie-Christine Boutron-Ruault, Maria Santucci de Magistris, Inge Huybrechts, Marc J. Gunter, Carlotta Sacerdote, Nathalie Kliemann, Christina C. Dahm, Vivian Viallon, Vittorio Krogh, Lena Maria Nilsson, Isabel Drake, Anne M. May, Heiner Boeing, Matthias B. Schulze, Carlo La Vecchia, Anne Tjønneland, Anna Karakatsani, Aurelio Barricarte Gurrea, Konstantinos K. Tsilidis, María Dolores Chirlaque, José Ramón Quirós, Centre international de Recherche sur le Cancer (CIRC), Université de Paris-Saclay [Villejuif], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A19170, 14136, C570/A16491 Ligue Contre le Cancer Bundesministerium für Bildung und Forschung, BMBF Bundesministerium für Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS Research Councils UK, RCUK Health and Medical Research Fund, HMRF: FIS Zorginstituut Nederland, ZIN PI13/01162, PI13/00061 World Cancer Research Fund, WCRF: ERC‐2009‐AdG 232997 Associazione Italiana per la Ricerca sul Cancro, AIRC National Research Council, NRC Ecumenical Project for International Cooperation, EPIC Institut National de la Santé et de la Recherche Médicale, Inserm European Commission, EU Centre International de Recherche sur le Cancer, CIRC Norway Deutsches Krebsforschungszentrum, DKFZ: DKFZ World Cancer Research Fund, WCRF Cancerfonden NordForsk Medical Research Council, MRC: MR/M012190/1, 1000143, The authors would like to thank the EPIC study participants and staff for their valuable contribution to this research. The authors would also like to thank Mr Bertrand Hemon for his support in preparing the databases and Dr Joseph Rothwell for his support in creating the figures. The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM, France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF, Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), ERC‐2009‐AdG 232997 and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS) of the Spanish Ministry of Health (FIS, PI13/00061 to Granada, PI13/01162 to EPIC‐Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, and United Kingdom).
Subjects: Oncology, Adult, Male, metabolic disorder, Cancer Research, medicine.medical_specialty, obesity, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, medicine, Humans, cancer, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Prospective Studies, Risk factor, Càncer, Nutrició, Aged, Cancer, Nutrition, Sex Characteristics, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Metabolic disorder, Middle Aged, medicine.disease, Obesity, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Nutrition Assessment, 030220 oncology & carcinogenesis, Basal metabolic rate, basal metabolic rate, Female, Basal Metabolism, business
Abstract: Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1-standard deviation change in BMR [HR 1-SD]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR 1-SD: 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR 1-SD: 1.16; 95% CI 1.01; 1.35), pancreatic (HR 1-SD: 1.37; 95% CI 1.13; 1.66), thyroid (HR 1-SD: 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR 1-SD: 1.17; 95% CI 1.11; 1.22) and endometrial (HR 1-SD: 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.
Published: 2020
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300. The Image Biomarker Standardization Initiative: standardized quantitative radiomics for highthroughput image-based phenotyping

Author: Olivier Morin, Mahmoud A. Abdalah, Steffen Löck, Sandy Napel, Lisanne V. van Dijk, Arvind Rao, Muhammad Siddique, Jacopo Lenkowicz, Ronald Boellaard, Issam El Naqa, Jairo Socarras Fernandez, Marta Bogowicz, Spyridon Bakas, Jonas Scherer, Are Losnegård, Marie-Charlotte Desseroit, Robert J. Gillies, Gary Cook, Martin Vallières, Vincenzo Valentini, Alex Zwanenburg, Philip Whybra, Sarthak Pati, Sebastian Echegaray, Matthias Guckenberger, Christos Davatzikos, Emiliano Spezi, Roberto Gatta, Nicola Dinapoli, Daniela Thorwarth, Luca Boldrini, Roel J H M Steenbakkers, Esther G.C. Troost, Joost J. M. van Griethuysen, Irène Buvat, Sung Min Ha, Fiona Lippert, Hugo J.W.L. Aerts, Klaus H. Maier-Hein, Fanny Orlhac, Cuong V. Dinh, Stefan Leger, Philippe Lambin, Ralph T.H. Leijenaar, Fabian Isensee, Mathieu Hatt, Vicky Goh, Christian Richter, Roelof J. Beukinga, Henning Müller, Elisabeth Pfaehler, Nanna M. Sijtsema, Floris H. P. van Velden, Aditya Apte, Michael Götz, Arman Rahmim, Vincent Andrearczyk, Stephanie Tanadini-Lang, Adrien Depeursinge, Christophe Nioche, Andriy Fedorov, Saeed Ashrafinia, Taman Upadhaya, University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Helmholtz-Zentrum Dresden-Rossendorf (HZDR), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), McGill University = Université McGill [Montréal, Canada], H. Lee Moffitt Cancer Center and Research Institute, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Dana-Farber Cancer Institute [Boston], University of Applied Sciences of Western Switzerland, Memorial Sloane Kettering Cancer Center [New York], Johns Hopkins University (JHU), University of Pennsylvania [Philadelphia], University Medical Center Groningen [Groningen] (UMCG), Universität Zürich [Zürich] = University of Zurich (UZH), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), King‘s College London, Université de Lausanne (UNIL), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, University of Michigan [Ann Arbor], University of Michigan System, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Tübingen, University of Bergen (UiB), University of California [San Francisco] (UCSF), University of California, University of Geneva [Switzerland], University of British Columbia (UBC), Cardiff University, Velindre Cancer Centre, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Leiden University Medical Center (LUMC), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Precision Medicine, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Orlhac, Fanny, University of Pennsylvania, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Université de Lausanne = University of Lausanne (UNIL), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Genève = University of Geneva (UNIGE), ACS - Heart failure & arrhythmias, CCA - Imaging and biomarkers, Amsterdam Neuroscience - Brain Imaging, and Radiology and nuclear medicine
Subjects: Lung Neoplasms, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, PREDICTION, quantitative image analysis, Image Processing, Medical and Health Sciences, Phantoms, reporting guidelines, 030218 nuclear medicine & medical imaging, Imaging, software quality assurance, 0302 clinical medicine, Computer-Assisted, Image Processing, Computer-Assisted, Tomography, Cancer, Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, Original Research, medicine.diagnostic_test, Phantoms, Imaging, Sarcoma, Reference Standards, Magnetic Resonance Imaging, CANCER, 3. Good health, X-Ray Computed, Nuclear Medicine & Medical Imaging, Phenotype, Positron emission tomography, Feature (computer vision), 030220 oncology & carcinogenesis, Calibration, Biomedical Imaging, Clinical Trials and Supportive Activities, Image processing, Bioengineering, Imaging phantom, Set (abstract data type), 03 medical and health sciences, Clinical Research, Fluorodeoxyglucose F18, TEXTURE ANALYSIS, medicine, Medical imaging, Humans, Radiology, Nuclear Medicine and imaging, standardization, Biomarkers, Positron-Emission Tomography, Radiopharmaceuticals, Reproducibility of Results, Tomography, X-Ray Computed, Software, Radiomics, business.industry, Pattern recognition, Data set, MODEL, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Good Health and Well Being, PET, Artificial intelligence, business
Abstract: International audience; Background Radiomic features may quantify characteristics present in medical imaging. However, the lack of standardized definitions and validated reference values have hampered clinical use. Purpose To standardize a set of 174 radiomic features. Materials and Methods Radiomic features were assessed in three phases. In phase I, 487 features were derived from the basic set of 174 features. Twenty-five research teams with unique radiomics software implementations computed feature values directly from a digital phantom, without any additional image processing. In phase II, 15 teams computed values for 1347 derived features using a CT image of a patient with lung cancer and predefined image processing configurations. In both phases, consensus among the teams on the validity of tentative reference values was measured through the frequency of the modal value and classified as follows: less than three matches, weak; three to five matches, moderate; six to nine matches, strong; 10 or more matches, very strong. In the final phase (phase III), a public data set of multimodality images (CT, fluorine 18 fluorodeoxyglucose PET, and T1-weighted MRI) from 51 patients with soft-tissue sarcoma was used to prospectively assess reproducibility of standardized features. Results Consensus on reference values was initially weak for 232 of 302 features (76.8%) at phase I and 703 of 1075 features (65.4%) at phase II. At the final iteration, weak consensus remained for only two of 487 features (0.4%) at phase I and 19 of 1347 features (1.4%) at phase II. Strong or better consensus was achieved for 463 of 487 features (95.1%) at phase I and 1220 of 1347 features (90.6%) at phase II. Overall, 169 of 174 features were standardized in the first two phases. In the final validation phase (phase III), most of the 169 standardized features could be excellently reproduced (166 with CT; 164 with PET; and 164 with MRI). Conclusion A set of 169 radiomics features was standardized, which enabled verification and calibration of different radiomics software. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kuhl and Truhn in this issue.
Published: 2020
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