Author: "Bellvitge Biomedical Research Institute" - Searchworks@Jio Institute Digital Library Search Results

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3,163 results on '"Bellvitge Biomedical Research Institute"'

1. Role of Nutrition and Diet on Healthy Mental State

Author: Granero, Roser, Instituto Salud Carlos III. Ciber Fisiopatología Obesidad y Nutrición (CIBERobn), Bellvitge Biomedical Research Institute (IDIBELL). Neurosciences Programme, Granero, Roser, Instituto Salud Carlos III. Ciber Fisiopatología Obesidad y Nutrición (CIBERobn), and Bellvitge Biomedical Research Institute (IDIBELL). Neurosciences Programme
Published: 2022

2. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

Author: [ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, Rantala, Johanna, [ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, and Rantala, Johanna
Abstract: To access publisher's full text version of this article click on the hyperlink below, The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.

3. Antidepressant Efficacy of Psychotherapy and Citalopram in Patients With Breast Cancer and Major Depression (CAMAD)

Author: Institut Català d'Oncologia and Cinto Segalàs Cosi, MD, Psychiatrist at the Bellvitge University Hospital. Researcher at the Bellvitge Biomedical Research Institute (IDIBELL). Associate professor at the Clinical Sciences Department of the Barcelona University (UB).
Published: 2022

4. Structural disruption of BAF chromatin remodeller impairs neuroblastoma metastasis by reverting an invasiveness epigenomic program

Author: Carlos Jiménez, Roberta Antonelli, Mariona Nadal-Ribelles, Laura Devis-Jauregui, Pablo Latorre, Carme Solé, Marc Masanas, Adrià Molero-Valenzuela, Aroa Soriano, Josep Sánchez de Toledo, David Llobet-Navas, Josep Roma, Francesc Posas, Eulàlia de Nadal, Soledad Gallego, Lucas Moreno, Miguel F. Segura, Institut Català de la Salut, [Jiménez C, Antonelli R, Masanas M, Molero-Valenzuela A, Soriano A, Roma J, Segura MF] Grup de Recerca en Càncer i Malalties Hematològiques Infantils, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Nadal-Ribelles M, Latorre P, Solé C, Posas F, de Nadal E] Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Barcelona, Spain. Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra (UPF), Barcelona, Spain. [Devis-Jauregui L] Molecular Mechanisms and Experimental Therapy in Oncology Oncobell Program, Bellvitge Biomedical Research Institute, L’Hospitalet de Llobregat, Spain. [Sánchez de Toledo J] Grup de Recerca en Càncer i Malalties Hematològiques Infantils, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Catalan Institute of Oncology, L’Hospitalet de Llobregat, Spain. [Llobet-Navas D] Molecular Mechanisms and Experimental Therapy in Oncology Oncobell Program, Bellvitge Biomedical Research Institute, L’Hospitalet de Llobregat, Spain. Low Prevalence Tumors. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. [Gallego S, Moreno L] Grup de Recerca en Càncer i Malalties Hematològiques Infantils, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei d'Hematologia i Oncologia Pediàtriques, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Proteomics, Epigenomics, Genetic Phenomena::Genetic Structures::Chromosome Structures::Chromatin [PHENOMENA AND PROCESSES], Cancer Research, Chromosomal Proteins, Non-Histone, neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::tumores neuroectodérmicos primitivos::tumores neuroectodérmicos primitivos periféricos::neuroblastoma [ENFERMEDADES], Chromatin remodelling, Metastasis, Cromatina, Neuroblastoma, Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Neuroectodermal Tumors, Primitive::Neuroectodermal Tumors, Primitive, Peripheral::Neuroblastoma [DISEASES], disciplinas de las ciencias naturales::disciplinas de las ciencias biológicas::biología::biología computacional::genómica::epigenómica [DISCIPLINAS Y OCUPACIONES], Other subheadings::Other subheadings::/genetics [Other subheadings], Animals, Humans, Child, Càncer, Neuroblastoma - Aspectes genètics, Cancer, Mammals, Natural Science Disciplines::Biological Science Disciplines::Biology::Computational Biology::Genomics::Epigenomics [DISCIPLINES AND OCCUPATIONS], Otros calificadores::Otros calificadores::/genética [Otros calificadores], fenómenos genéticos::estructuras genéticas::estructuras cromosómicas::cromatina [FENÓMENOS Y PROCESOS], Chromatin Assembly and Disassembly, Epigenètica, Chromatin, SWI/SNF, Oncology, Molecular Medicine, Epigenetics
Abstract: Chromatin remodelling; Epigenetics; Metastasis Remodelación de cromatina; Epigenética; Metástasis Remodelació de cromatina; Epigenètica; Metàstasi Background Epigenetic programming during development is essential for determining cell lineages, and alterations in this programming contribute to the initiation of embryonal tumour development. In neuroblastoma, neural crest progenitors block their course of natural differentiation into sympathoadrenergic cells, leading to the development of aggressive and metastatic paediatric cancer. Research of the epigenetic regulators responsible for oncogenic epigenomic networks is crucial for developing new epigenetic-based therapies against these tumours. Mammalian switch/sucrose non-fermenting (mSWI/SNF) ATP-dependent chromatin remodelling complexes act genome-wide translating epigenetic signals into open chromatin states. The present study aimed to understand the contribution of mSWI/SNF to the oncogenic epigenomes of neuroblastoma and its potential as a therapeutic target. Methods Functional characterisation of the mSWI/SNF complexes was performed in neuroblastoma cells using proteomic approaches, loss-of-function experiments, transcriptome and chromatin accessibility analyses, and in vitro and in vivo assays. Results Neuroblastoma cells contain three main mSWI/SNF subtypes, but only BRG1-associated factor (BAF) complex disruption through silencing of its key structural subunits, ARID1A and ARID1B, impairs cell proliferation by promoting cell cycle blockade. Genome-wide chromatin remodelling and transcriptomic analyses revealed that BAF disruption results in the epigenetic repression of an extensive invasiveness-related expression program involving integrins, cadherins, and key mesenchymal regulators, thereby reducing adhesion to the extracellular matrix and the subsequent invasion in vitro and drastically inhibiting the initiation and growth of neuroblastoma metastasis in vivo. Conclusions We report a novel ATPase-independent role for the BAF complex in maintaining an epigenomic program that allows neuroblastoma invasiveness and metastasis, urging for the development of new BAF pharmacological structural disruptors for therapeutic exploitation in metastatic neuroblastoma. This work was funded by Instituto de Salud Carlos III (CP16/00006, PI17/00564 and PI20/00530 to MFS and MS17/00063 to DL-N); Asociación Española Contra el Cáncer (LABAE18009SEGU to MFS, LABAE19004LLOB to DL-N, PROYE18010POSA to FP); Generalitat de Catalunya (2017FI_B_00095 to CJ, 2017SGR799 to FP and EdN; institutional funding through CERCA Programme); La Caixa Foundation (LCF/BQ/PR20/11770001 to MN-R); Spanish Ministry of Economy and Competitiveness (PID2021-124723NB-C21 to FP and PID2021-124723NB-C22 to EdN); Spanish Ministry of Science, Innovation and Universities (institutional funding through Centres of Excellence Severo Ochoa Award); State Research Agency (institutional funding through Unidad de Excelencia María de Maeztu, CEX2018-000792-M); and the Catalan Institution for Research and Advanced Studies (Academia awards to EdN and FP). Funding was also received from NEN association; Joan Petit foundation; Asociación Pulseras Candela foundation; and the Rotary Clubs of Barcelona Eixample, Barcelona Diagonal, Santa Coloma de Gramanet, München-Blutenburg, Deutschland Gemeindienst, and others from Barcelona and its province.
Published: 2022

5. Half of the patients with subepithelial tumours present borderline or pathologic anxiety-distress and carcinophobia: multicentre cohort study

Author: Francesc Bas-Cutrina, Anna Casellas-Grau, Sebasti� Videla, Carme Loras, Xavi Andújar, Francisco Luis Gil, Maica Galán, Fernando Fernández-Aranda, Jo�o Carmezim, Joan B. Gornals, [Bas-Cutrina F] Endoscopy Unit. Department of Digestive Diseases. Hospital Universitari de Bellvitge. Barcelona, Spain. Bellvitge Biomedical Research Institute (IDIBELL). Barcelona, Spain. Department of Clinical Sciences. School of Medicine and Health Sciences. Universitat de Barcelona (UB). Barcelona, Spain. Digestive Diseases Unit. Hospital General de Granollers. Granollers, Spain. [Casellas-Grau A] Psycho-oncology Service. Institut Català d’Oncologia (ICO). L’Hospitalet de Llobregat, Barcelona. Spain. Department of Psychology. School of Education, Translation, Sports and Psychology. Universitat de Vic – Universitat Central de Catalunya (UVic-UCC). Vic, Barcelona. Spain. [Videla S] Bellvitge Biomedical Research Institute (IDIBELL). Barcelona, Spain. Department of Clinical Sciences. School of Medicine and Health Sciences. Universitat de Barcelona (UB). Barcelona, Spain. Clinical Research Support Unit. Hospital Universitari de Bellvitge. L´Hospitalet de Llobregat, Barcelona. Spain. [Loras C, Andújar X] Endoscopy Unit. Department of Digestive Diseases. Hospital Universitari Mútua de Terrassa. Terrassa, Barcelona. Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd). Instituto de Salud Carlos III. Madrid, Spain. [Gil FL] Psycho-oncology Service. Institut Català d’Oncologia (ICO). L’Hospitalet de Llobregat, Barcelona. Spain. Tecnocampus Mataró-Maresme Foundation. Universitat Pompeu Fabra (UPF). Barcelona, Spain. [Galán M] Department of Clinical Sciences. School of Medicine and Health Sciences. Universitat de Barcelona (UB). Barcelona, Spain. Department of Medical Oncology. Institut Català d’Oncologia (ICO). L’Hospitalet de Llobregat, Barcelona. Spain. [Fernández-Aranda F] Bellvitge Biomedical Research Institute (IDIBELL). Barcelona, Spain. Department of Clinical Sciences. School of Medicine and Health Sciences. Universitat de Barcelona (UB). Barcelona, Spain. Eating Disorders Unit. Department of Psychiatry. Hospital Universitari de Bellvitge. L´Hospitalet de Llobregat, Barcelona. Spain. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn). Instituto de Salud Carlos III. Madrid, Spain. [Carmezim J] Bellvitge Biomedical Research Institute (IDIBELL). Barcelona, Spain. , [Gornals JB] Endoscopy Unit. Department of Digestive Diseases. Hospital Universitari de Bellvitge. Barcelona, Spain. Bellvitge Biomedical Research Institute (IDIBELL). Barcelona, Spain. Department of Clinical Sciences. School of Medicine and Health Sciences. Universitat de Barcelona (UB). Barcelona, Spain. Faculty of Health Sciences. Universitat Oberta de Catalunya (UOC). Barcelona, Spain, and Hospital General de Granollers
Subjects: Mental Disorders::Anxiety Disorders [PSYCHIATRY AND PSYCHOLOGY], Ansietat, trastornos mentales::trastornos de ansiedad [PSIQUIATRÍA Y PSICOLOGÍA], Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms [DISEASES], neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales [ENFERMEDADES], Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics::Epidemiologic Studies::Cohort Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], técnicas de investigación::métodos epidemiológicos::características de los estudios epidemiológicos::estudios epidemiológicos::estudios de cohortes [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Gastroenterology, General Medicine, Avaluació, Aparell digestiu - Càncer
Abstract: Subepithelial tumors; Carcinophobia; Multicenter cohort study Tumores subepiteliales; Carcinofobia; Estudio de cohorte multicéntrico Tumors subepitelials; Carcinofòbia; Estudi de cohorts multicèntric Background and aims: Minor nonspecific gastrointestinal subepithelial lesions (usually defined by the term 'tumor') are usually associated with a malignant illness and cancer. The aim of this study was to assess anxiety-distress and carcinophobia in patients referred to specialized monographic outpatient clinics for evaluation and treatment of this type of lesion. Methods: Prospective, multicenter, cohort study. Specific self-reported questionnaires were used to report threatening life-experiences and to assess levels of distress (The Hospital Anxiety and Depression Scale) and cancer-related worries (The Cancer Worry Scale). Results: Forty participants were included and analyzed at baseline. Pathologic and borderline anxiety were detected in 13% (5/40, 95%CI: 4-27%) and 35% (14/40, 95%CI: 21-52%) of participants, respectively, whereas, cancer-related worries (moderate to very high) were observed in 48% (19/40, 95%CI: 32-64%) of participants. Pathologic global distress was identified in 25% (10/40, 95%CI: 13-42%) of subjects. Higher educational level (university studies), a lack of lifetime psychiatric comorbidity and a lack of family history of cancer were associated with less anxiety, global distress and carcinophobia. Conclusions: Almost half of the patients diagnosed with a minor nonspecific gastrointestinal subepithelial lesion presented anxiety-distress and/or carcinophobia. Specific associations with anxiety-distress reaction and fears were detected.
Published: 2022
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6. Impact of COVID-19 Lockdown in Eating Disorders: A Multicentre Collaborative International Study

Author: Isabel Baenas, Mikel Etxandi, Lucero Munguía, Roser Granero, Gemma Mestre-Bach, Isabel Sánchez, Emilio Ortega, Alba Andreu, Violeta L. Moize, Jose-Manuel Fernández-Real, Francisco J. Tinahones, Carlos Diéguez, Gema Frühbeck, Daniel Le Grange, Kate Tchanturia, Andreas Karwautz, Michael Zeiler, Hartmut Imgart, Annika Zanko, Angela Favaro, Laurence Claes, Ia Shekriladze, Eduardo Serrano-Troncoso, Raquel Cecilia-Costa, Teresa Rangil, Maria Eulalia Loran-Meler, José Soriano-Pacheco, Mar Carceller-Sindreu, Rosa Navarrete, Meritxell Lozano, Raquel Linares, Carlota Gudiol, Jordi Carratala, Maria T. Plana, Montserrat Graell, David González-Parra, José A. Gómez-del Barrio, Ana R. Sepúlveda, Jéssica Sánchez-González, Paulo P. P. Machado, Anders Håkansson, Ferenc Túry, Bea Pászthy, Daniel Stein, Hana Papezová, Jana Gricova, Brigita Bax, Mikhail F. Borisenkov, Sergey V. Popov, Denis G. Gubin, Ivan M. Petrov, Dilara Isakova, Svetlana V. Mustafina, Youl-Ri Kim, Michiko Nakazato, Nathalie Godart, Robert van Voren, Tetiana Ilnytska, Jue Chen, Katie Rowlands, Ulrich Voderholzer, Alessio M. Monteleone, Janet Treasure, Susana Jiménez-Murcia, Fernando Fernández-Aranda, Universidade do Minho, Institut Català de la Salut, [Baenas I, Munguía L, Sánchez I] Department of Psychiatry, Bellvitge University Hospital-IDIBELL, 08907 Barcelona, Spain. CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Barcelona, Spain. Psychoneurobiology of Eating and Addictive Behaviors Group, Neurosciences Programme, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain. [Etxandi M] Department of Psychiatry, Bellvitge University Hospital-IDIBELL, 08907 Barcelona, Spain. [Granero R] CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Barcelona, Spain. Psychoneurobiology of Eating and Addictive Behaviors Group, Neurosciences Programme, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain. Department of Psychobiology and Methodology, School of Psychology, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain. [Mestre-Bach G] Facultad de Ciencias de la Salud, Universidad Internacional de La Rioja, 26006 La Rioja, Spain. [Fernández-Real JM] CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Barcelona, Spain. Departament de Diabetis, Endocrinologia i Nutrició, Hospital Universitari de Girona Dr. Josep Trueta, Institut Català de la Salut (ICS), Girona, Spain. Institut d'Investigació Biomèdica de Girona (IDIBGi), Salt, Spain. Departament de Ciències Mèdiques, Universitat de Girona, Girona, Spain, Hospital Universitari de Girona Dr Josep Trueta, Baenas, I., Etxandi, M., Munguia, L., Granero, R., Mestre-Bac, G., Sanchez, I., Ortega, E., Andreu, A., Moize, V. L., Fernandez-Real, J. -M., Tinahones, F. J., Dieguez, C., Fruhbeck, G., Grange, D. L., Tchanturia, K., Karwautz, A., Zeiler, M., Imgart, H., Zanko, A., Favaro, A., Claes, L., Shekriladze, I., Serrano-Troncoso, E., Cecilia-Costa, R., Rangil, T., Loran-Meler, M. E., Soriano-Pacheco, J., Carceller-Sindreu, M., Navarrete, R., Lozano, M., Linares, R., Gudiol, C., Carratala, J., Plana, M. T., Graell, M., Gonzalez-Parra, D., Gomez-Del Barrio, J. A., Sepulveda, A. R., Sanchez-Gonzalez, J., Machado, P. P. P., Hakansson, A., Tury, F., Paszthy, B., Stein, D., Papezova, H., Gricova, J., Bax, B., Borisenkov, M. F., Popov, S. V., Gubin, D. G., Petrov, I. M., Isakova, D., Mustafina, S. V., Kim, Y. -R., Nakazato, M., Godart, N., Van Voren, R., Ilnytska, T., Chen, J., Rowlands, K., Voderholzer, U., Monteleone, A. M., Treasure, J., Jimenez-Murcia, S., Fernandez-Aranda, F., Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundação para a Ciência e a Tecnologia (Portugal), European Commission, Generalitat de Catalunya, Fundación Ciudadanía y Valores, Hospital Universitario de Bellvitge, 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, CB21/13/00009, INT19/00046, PI17/01167, PI20/132, Fundação para a Ciência e a Tecnologia, FCT: POCI-01-0145-FEDER-028145, Consejo Nacional de Ciencia y Tecnología, CONACYT, Ministerio de Economía y Competitividad, MINECO: PSI2015-68701-R, European Regional Development Fund, ERDF: 728018, Eat2beNICE/ H2020-SFS-2016-2, Departament de Salut, Generalitat de Catalunya: SLT006/17/00077, Acknowledgments: We thank CERCA Programme/Generalitat de Catalunya for institutional support. This manuscript and research was supported by grants from the Department of Health of the Generalitat de Catalunya by the call Pla estratègic de recerca i innovació en salut (PERIS, SLT006/17/00077), the Ministerio de Economía y Competitividad (PSI201568701R), Fondo de Inves-tigación Sanitario (FIS) (INT19/00046, PI17/01167, PI20/132), CIBERINFEC (CB21/13/00009) and co-funded by FEDER funds /European Regional Development Fund (ERDF), a way to build Europe (Eat2beNICE/ H2020-SFS-2016-2, Ref 728018, and PRIME/ H2020-SC1-BHC-2018-2020, Ref: 847879). CIBEROBN, CIBERSAM, CIBERINFEC and CIBERDEM are all initiatives of Instituto de Salud Carlos III (ISCIII). GMB is supported by a postdoctoral grant from FUNCIVA. PPM was supported, in part, by a Portuguese Foundation for Science and Technology grant (POCI-01-0145-FEDER-028145). IB was partially supported by a Post-Residency Grant from the Research Committee of the University Hospital of Bellvitge (HUB, Barcelona, Spain) 2020–2021. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., Funding: Fondo Investigación Sanitario-FIS, Grant/Award Numbers: FIS, INT19/00046, PI17/01167, Ministerio de Economía y Competitividad, Grant/Award Number: PSI2015-68701-R, Portuguese Foundation for Science and Technology grant, Grant/Award Number: POCI-01-0145-FEDER-028145, Consejo Nacional de Ciencia y Tecnología, and European Regional Development Fund.
Subjects: Male, Internationality, Mental Disorders::Feeding and Eating Disorders [PSYCHIATRY AND PSYCHOLOGY], Longitudinal Studie, COVID-19 (Malaltia), trastornos mentales::trastornos alimentarios y de la ingestión de alimentos [PSIQUIATRÍA Y PSICOLOGÍA], virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Pandèmia de COVID-19, 2020, TX341-641, Longitudinal Studies, Child, COVID-19 Isolation Eating Scale (CIES), COVID-19 lockdown, eating disorders, eating symptoms, psychological impact, Adolescent, Adult, Asia, COVID-19, Europe, Feeding and Eating Disorders, Female, Humans, Quarantine, SARS-CoV-2, Social Isolation, Young Adult, Nutrition and Dietetics, Eating disorder, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Environment and Public Health::Public Health::Public Health Practice::Communicable Disease Control::Infection Control::Quarantine [HEALTH CARE], OBESITY, Ciências Sociais::Psicologia, Confinament, características del estudio::estudio multicéntrico [CARACTERÍSTICAS DE PUBLICACIONES], Life Sciences & Biomedicine, MENTAL-HEALTH, Human, COVID-19 isolation eating scale (CIES), COVID-19 Pandemic, 2020, Article, Feeding and Eating Disorder, Trastorns de la conducta alimentària, Eating symptom, Science & Technology, Nutrition & Dietetics, Nutrition. Foods and food supply, ambiente y salud pública::salud pública::práctica de la salud pública::control de enfermedades transmisibles::control de infecciones::cuarentena [ATENCIÓN DE SALUD], Study Characteristics::Multicenter Study [PUBLICATION CHARACTERISTICS], Human medicine, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: Data Availability Statement: Individuals may inquire with Fernández-Aranda regarding availability of the data as there is ongoing studies using the data. To avoid overlapping research efforts, Fernández-Aranda will consider a request on a case-by-case basis., Background. The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. Aims. (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. Methods. The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). Results. Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. Conclusions. The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients., Fondo Investigacion Sanitario-FIS, Grant/Award Numbers: FIS, INT19/00046, PI17/01167; Ministerio de Economia y Competitividad, Grant/Award Number: PSI2015-68701-R; Portuguese Foundation for Science and Technology grant, Grant/Award Number: POCI-01-0145-FEDER-028145; Consejo Nacional de Ciencia y Tecnologia; Generalitat de Catalunya; European Regional Development Fund., We thank CERCA Programme/Generalitat de Catalunya for institutional support. This manuscript and research was supported by grants from the Department of Health of the Generalitat de Catalunya by the call Pla estratègic de recerca i innovació en salut (PERIS, SLT006/17/00077), the Ministerio de Economía y Competitividad (PSI201568701R), Fondo de Investigación Sanitario (FIS) (INT19/00046, PI17/01167, PI20/132), CIBERINFEC (CB21/13/00009) and co-funded by FEDER funds /European Regional Development Fund (ERDF), a way to build Europe (Eat2beNICE/ H2020-SFS-2016-2; Ref 728018; and PRIME/ H2020-SC1-BHC-2018-2020; Ref: 847879). CIBEROBN, CIBERSAM, CIBERINFEC and CIBERDEM are all initiatives of Instituto de Salud Carlos III (ISCIII). GMB is supported by a postdoctoral grant from FUNCIVA. PPM was supported, in part, by a Portuguese Foundation for Science and Technology grant (POCI-01-0145-FEDER-028145). IB was partially supported by a Post-Residency Grant from the Research Committee of the University Hospital of Bellvitge (HUB; Barcelona, Spain) 2020–2021. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Published: 2021
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7. Atrial Fibrillation in Heart Failure Is Associated with High Levels of Circulating microRNA-199a-5p and 22–5p and a Defective Regulation of Intracellular Calcium and Cell-to-Cell Communication

Author: Selma A. Serra, Julio Martí-Almor, Kathryn W. Aguilar-Agon, Josep Comín-Colet, Anna Garcia-Elias, Begoña Benito, Cristina Enjuanes, Laia Yañez-Bisbe, Svetlana Reilly, José M. Fernández-Fernández, Marta Tajes, Institut Català de la Salut, [Garcia-Elias A, Yañez-Bisbe L] Programa de Biologia Vascular i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Group of Biomedical Research in Heart Diseases, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. [Tajes M] Group of Biomedical Research in Heart Diseases, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. Research Group in Cardiovascular Disorders (BIOHEART), Bellvitge Biomedical Research Institute (IDIBELL), L′Hospitalet de Llobregat, Spain. [Enjuanes C] Research Group in Cardiovascular Disorders (BIOHEART), Bellvitge Biomedical Research Institute (IDIBELL), L′Hospitalet de Llobregat, Spain. Cardiology Department, Hospital de Bellvitge, L’Hospitalet de Llobregat, Spain. [Comín-Colet J] Research Group in Cardiovascular Disorders (BIOHEART), Bellvitge Biomedical Research Institute (IDIBELL), L′Hospitalet de Llobregat, Spain. Cardiology Department, Hospital de Bellvitge, L’Hospitalet de Llobregat, Spain. Department of Clinical Sciences, University of Barcelona School of Medicine, Barcelona, Spain. [Serra SA] Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain. [Benito B] Programa de Biologia Vascular i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Group of Biomedical Research in Heart Diseases, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Male, Cell Communication, Calcium in biology, Malalties del cor, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs::Circulating MicroRNA [CHEMICALS AND DRUGS], nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN::microARN circulante [COMPUESTOS QUÍMICOS Y DROGAS], Medicine, Sinus rhythm, Biology (General), Spectroscopy, Aged, 80 and over, NCX1, Ejection fraction, microRNA, Atrial fibrillation, General Medicine, Computer Science Applications, Diseases of the heart, Chemistry, Female, Intracellular, medicine.medical_specialty, Cardiovascular Diseases::Heart Diseases::Heart Failure [DISEASES], QH301-705.5, L-type calcium channels, enfermedades cardiovasculares::enfermedades cardíacas::arritmias cardíacas::fibrilación atrial [ENFERMEDADES], Heart failure, Article, Catalysis, Cell Line, Inorganic Chemistry, Internal medicine, Fibril·lació auricular, Humans, Calcium Signaling, Circulating MicroRNA, Insuficiència cardíaca - Complicacions, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Aged, Calcium metabolism, MicroARN, business.industry, Organic Chemistry, Connexin 40, enfermedades cardiovasculares::enfermedades cardíacas::insuficiencia cardíaca [ENFERMEDADES], medicine.disease, MicroRNAs, Endocrinology, RNA, HL-1 cells, Calcium regulation, Atrial remodeling, business, Cardiovascular Diseases::Heart Diseases::Arrhythmias, Cardiac::Atrial Fibrillation [DISEASES], Biomarkers, Other subheadings::Other subheadings::/complications [Other subheadings]
Abstract: HL-1 cells; L-type calcium channels; Calcium regulation Células HL-1; Canales de calcio tipo L; Regulación del calcio Cel·lules HL-1; Canals de calci tipus L; Regulació del calci MicroRNAs (miRNAs) participate in atrial remodeling and atrial fibrillation (AF) promotion. We determined the circulating miRNA profile in patients with AF and heart failure with reduced ejection fraction (HFrEF), and its potential role in promoting the arrhythmia. In plasma of 98 patients with HFrEF (49 with AF and 49 in sinus rhythm, SR), differential miRNA expression was determined by high-throughput microarray analysis followed by replication of selected candidates. Validated miRNAs were determined in human atrial samples, and potential arrhythmogenic mechanisms studied in HL-1 cells. Circulating miR-199a-5p and miR-22-5p were significantly increased in HFrEF patients with AF versus those with HFrEF in SR. Both miRNAs, but particularly miR-199a-5p, were increased in atrial samples of patients with AF. Overexpression of both miRNAs in HL-1 cells resulted in decreased protein levels of L-type Ca2+ channel, NCX and connexin-40, leading to lower basal intracellular Ca2+ levels, fewer inward currents, a moderate reduction in Ca2+ buffering post-caffeine exposure, and a deficient cell-to-cell communication. In conclusion, circulating miR-199a-5p and miR-22-5p are higher in HFrEF patients with AF, with similar findings in human atrial samples of AF patients. Cells exposed to both miRNAs exhibited altered Ca2+ handling and defective cell-to-cell communication, both findings being potential arrhythmogenic mechanisms. This work was funded by the following grants, awarded to B.B.: Sociedad Española de Cardiología, Sección de Arritmias y Electrofisiología 2012; Sociedad Española de Cardiología, Sección de Insuficiencia Cardíaca 2013; Fondo Investigación Sanitaria (FIS)—Instituto Carlos III 2013 (PI13/01830); and Societat Catalana de Cardiologia 2016. Awarded to K.W.A-A. and S.R.: British Heart Foundation (BHF) Intermediate Research Fellowship. Awarded to J.M.F.F.: grant from the Spanish Ministry of Science and Innovation (RTI2018-094809-B-I00). “María de Maeztu” Programme for Units of Excellence in R&D to the Departament de Ciències Experimentals i de la Salut (MDM-2014-0370) and FEDER (Fondo Europeo de Desarrollo Regional) also contributed to this work.
Published: 2021

8. Neurohormonal activation induces intracellular iron deficiency and mitochondrial dysfunction in cardiac cells

Author: Alberto Garay, M. Tajes, Lidia Alcoberro, José González-Costello, J Comín-Colet, José Luis Ferreiro, Pedro Moliner, Silvia Gabriela Sosa, Carles Díez-López, Begoña Benito, Santiago Jiménez-Marrero, Cristina Enjuanes, Sergi Yun, L Yañez-Bisbe, Elena García-Romero, Institut Català de la Salut, [Tajes M, Ferreiro JL] Bio Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain. Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain. [Díez-López C] Bio Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain. Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain. Advanced Heart Failure and Heart Transplant Unit, Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain. Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain. [Enjuanes C, Moliner P, Garay A] Bio Heart Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain. Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain. Community Heart Failure Program, Cardiology Department, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain. [Yañez-Bisbe L] Programa de Biologia Vascular i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Benito B] Programa de Biologia Vascular i Metabolisme, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Anèmia ferropènica, medicine.medical_specialty, Amino Acids, Peptides, and Proteins::Proteins::Iron-Regulatory Proteins [CHEMICALS AND DRUGS], Cardiovascular Diseases::Heart Diseases::Heart Failure [DISEASES], QH301-705.5, Heart failure, Transferrin receptor, Insuficiència cardíaca, QD415-436, 030204 cardiovascular system & hematology, Hemic and Lymphatic Diseases::Hematologic Diseases::Anemia::Anemia, Hypochromic::Anemia, Iron-Deficiency [DISEASES], Biochemistry, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Hepcidin, Internal medicine, enfermedades hematológicas y linfáticas::enfermedades hematológicas::anemia::anemia hipocrómica::anemia ferropénica [ENFERMEDADES], medicine, Biology (General), Dèficit de ferro, biology, Research, Iron deficiency, Mitochondria function, MITOCHONDRIAL FERRITIN, Metabolism, enfermedades cardiovasculares::enfermedades cardíacas::insuficiencia cardíaca [ENFERMEDADES], Cardiac arrest, medicine.disease, Aturada cardíaca, Angiotensin II, Neurohormonal activation, aminoácidos, péptidos y proteínas::proteínas::proteínas reguladoras del hierro [COMPUESTOS QUÍMICOS Y DROGAS], Cardiac cell, 030104 developmental biology, Endocrinology, chemistry, biology.protein, Iron deficiency diseases, Adenosine triphosphate, TP248.13-248.65, Intracellular, Biotechnology
Abstract: Background Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, yet its role in the pathophysiology of HF is not well-defined. We sought to determine the consequences of HF neurohormonal activation in iron homeostasis and mitochondrial function in cardiac cells. Methods HF was induced in C57BL/6 mice by using isoproterenol osmotic pumps and embryonic rat heart-derived H9c2 cells were subsequently challenged with Angiotensin II and/or Norepinephrine. The expression of several genes and proteins related to intracellular iron metabolism were assessed by Real time-PCR and immunoblotting, respectively. The intracellular iron levels were also determined. Mitochondrial function was analyzed by studying the mitochondrial membrane potential, the accumulation of radical oxygen species (ROS) and the adenosine triphosphate (ATP) production. Results Hearts from isoproterenol-stimulated mice showed a decreased in both mRNA and protein levels of iron regulatory proteins, transferrin receptor 1, ferroportin 1 and hepcidin compared to control mice. Furthermore, mitoferrin 2 and mitochondrial ferritin were also downregulated in the hearts from HF mice. Similar data regarding these key iron regulatory molecules were found in the H9c2 cells challenged with neurohormonal stimuli. Accordingly, a depletion of intracellular iron levels was found in the stimulated cells compared to non-stimulated cells, as well as in the hearts from the isoproterenol-induced HF mice. Finally, neurohormonal activation impaired mitochondrial function as indicated by the accumulation of ROS, the impaired mitochondrial membrane potential and the decrease in the ATP levels in the cardiac cells. Conclusions HF characteristic neurohormonal activation induced changes in the regulation of key molecules involved in iron homeostasis, reduced intracellular iron levels and impaired mitochondrial function. The current results suggest that iron could be involved in the pathophysiology of HF.
Published: 2021
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9. Biallelic PI4KA variants cause a novel neurodevelopmental syndrome with hypomyelinating leukodystrophy

Author: Agatha Schlüter, Cyril Goizet, Miquel Raspall-Chaure, Almudena Chacón, Mehdi Benkirane, Lisa Pavinato, Agustí Rodríguez-Palmero, Isabelle Rouvet, Irene de la Calle, Francesco Saettini, Carlos Casasnovas, Michel Koenig, Vincent Michaud, Júlia Sala-Coromina, Melanie O’Leary, Emily O'Heir, Aurora Pujol, Alfons Macaya, Chiara Fossati, Precilla de Souza, Alfredo Brusco, David R. Adams, Heather C Mefford, Luis González Gutiérrez-Solana, Valentina Vélez-Santamaría, Maria Iascone, Estibaliz Barredo, Agathe Roubertie, Francesco Canonico, Anna Marcé-Grau, Giorgia Mandrile, Edgard Verdura, Heidi L. Rehm, Montserrat Ruiz, Laura Planas-Serra, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Català de la Salut, [Verdura E, Planas-Serra L] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Catalonia, Spain. Centre for Biomedical Research in Network on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029, Madrid, Spain. [Rodríguez-Palmero A] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Catalonia, Spain. Pediatric Neurology Unit, Department of Pediatrics, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Catalonia, Spain. [Vélez-Santamaria V] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Catalonia, Spain. Neuromuscular Unit, Neurology Department, Hospital Universitari de Bellvitge, Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain. [de la Calle I] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Catalonia, Spain. [Raspall-Chaure M] Grup de Recerca en Neurologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Neurologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Male, Mielina - Malalties - Aspectes genètics, [SDV]Life Sciences [q-bio], medicine.disease_cause, 0302 clinical medicine, Malalties hereditàries, PI4KA, hypomyelinating leukodystrophy, inborn errors of metabolism, phosphoinositol, spastic paraplegia, Child, Exome, 0303 health sciences, Mutation, Pediatria, medicine.diagnostic_test, AcademicSubjects/SCI01870, Otros calificadores::Otros calificadores::/genética [Otros calificadores], Malalties del sistema nerviós central, Metabolic disorder, Human brain, Phenotype, Pedigree, Blot, Phosphotransferases (Alcohol Group Acceptor), medicine.anatomical_structure, Child, Preschool, Female, enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades cerebrales metabólicas::enfermedades cerebrales metabólicas congénitas::enfermedades desmielinizantes hereditarias del sistema nervioso central [ENFERMEDADES], Genetic disorders, Central nervous system diseases, Adult, Adolescent, Health Occupations::Medicine::Pediatrics [DISCIPLINES AND OCCUPATIONS], Biology, Immunofluorescence, Minor Histocompatibility Antigens, 03 medical and health sciences, Other subheadings::Other subheadings::/genetics [Other subheadings], medicine, Humans, profesiones sanitarias::medicina::pediatría [DISCIPLINAS Y OCUPACIONES], Alleles, 030304 developmental biology, trastornos mentales::trastornos del desarrollo neurológico [PSIQUIATRÍA Y PSICOLOGÍA], Leukodystrophy, Infant, Newborn, Genetic Variation, Infant, Original Articles, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Brain Diseases, Metabolic::Brain Diseases, Metabolic, Inborn::Hereditary Central Nervous System Demyelinating Diseases [DISEASES], medicine.disease, Sistema nerviós - Malalties - Aspectes genètics, Hereditary Central Nervous System Demyelinating Diseases, Neurodevelopmental Disorders, Leukocytes, Mononuclear, Cancer research, AcademicSubjects/MED00310, Neurology (clinical), 030217 neurology & neurosurgery, Mental Disorders::Neurodevelopmental Disorders [PSYCHIATRY AND PSYCHOLOGY]
Abstract: Phosphoinositides are lipids that play a critical role in processes such as cellular signalling, ion channel activity and membrane trafficking. When mutated, several genes that encode proteins that participate in the metabolism of these lipids give rise to neurological or developmental phenotypes. PI4KA is a phosphoinositide kinase that is highly expressed in the brain and is essential for life. Here we used whole exome or genome sequencing to identify 10 unrelated patients harbouring biallelic variants in PI4KA that caused a spectrum of conditions ranging from severe global neurodevelopmental delay with hypomyelination and developmental brain abnormalities to pure spastic paraplegia. Some patients presented immunological deficits or genito-urinary abnormalities. Functional analyses by western blotting and immunofluorescence showed decreased PI4KA levels in the patients’ fibroblasts. Immunofluorescence and targeted lipidomics indicated that PI4KA activity was diminished in fibroblasts and peripheral blood mononuclear cells. In conclusion, we report a novel severe metabolic disorder caused by PI4KA malfunction, highlighting the importance of phosphoinositide signalling in human brain development and the myelin sheath., Verdura et al. report a novel rare brain metabolic disorder caused by recessive mutations in PI4KA, which encodes an enzyme with a pivotal role in phosphoinositide metabolism at the cell membrane. The description of this syndrome will simplify the identification of undiagnosed cases with similar clinical features.
Published: 2021
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10. Tumor-Associated Microbiome: Where Do We Stand?

Author: Nuria Mulet-Margalef, Paolo Nuciforo, Joan Mas, Marc Oliva, Victor Moreno, Laia Alemany, Stefania Napoli, Maria Ochoa-De-Olza, Eric J. Duell, Berta Laquente, Institut Català de la Salut, [Oliva M, Mulet-Margalef N, Laquente B] Medical Oncology Department, Catalan Institute of Oncology L’Hospitalet de Llobregat, Catalonia, Spain. ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Catalonia, Spain. [Ochoa-De-Olza M] Service of Immuno-Oncology, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland. Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland. [Napoli S, Nuciforo P] Molecular Oncology Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Mas J] ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Catalonia, Spain. Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), L’Hospitalet de Llobregat, Catalonia, Spain. Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Cytoplasm, fenómenos microbiológicos::microbiota::microbiota intestinal [FENÓMENOS Y PROCESOS], Carcinogenesis, Treatment outcome, gut microbiome, Review, Bioinformatics, medicine.disease_cause, lcsh:Chemistry, Mice, Càncer - Microbiologia, 0302 clinical medicine, Neoplasms, RNA, Ribosomal, 16S, Tumor Microenvironment, Carcinogènesi, lcsh:QH301-705.5, Spectroscopy, Microbiological Phenomena::Microbiota::Gastrointestinal Microbiome [PHENOMENA AND PROCESSES], Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment [PHENOMENA AND PROCESSES], Microbiota, Human microbiome, dysbiosis, General Medicine, Computer Science Applications, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, Disease Progression, carcinogenesis, Gene Expression Regulation, Viral, Antineoplastic Agents, Catalysis, Other subheadings::Other subheadings::/microbiology [Other subheadings], Inorganic Chemistry, neoplasias [ENFERMEDADES], 03 medical and health sciences, medicine, Animals, Humans, cancer, Intestins - Microbiologia, Microbiome, Physical and Theoretical Chemistry, Molecular Biology, Tumors, metagenomics, business.industry, Organic Chemistry, fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral [FENÓMENOS Y PROCESOS], Immunity, Computational Biology, Cancer, Gene Expression Regulation, Bacterial, medicine.disease, tumor microbiome, Gut microbiome, Gastrointestinal Microbiome, Neoplasms [DISEASES], 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Metagenomics, Metagenome, Otros calificadores::Otros calificadores::/microbiología [Otros calificadores], business, Dysbiosis
Abstract: Dysbiosis; Gut microbiome; Tumor Disbiosis; Microbioma intestinal; Tumor Disbiosi; Microbioma intestinal; Tumor The study of the human microbiome in oncology is a growing and rapidly evolving field. In the past few years, there has been an exponential increase in the number of studies investigating associations of microbiome and cancer, from oncogenesis and cancer progression to resistance or sensitivity to specific anticancer therapies. The gut microbiome is now known to play a significant role in antitumor immune responses and in predicting the efficacy of immune-checkpoint inhibitors in cancer patients. Beyond the gut, the tumor-associated microbiome-microbe communities located either in the tumor or within its body compartment-seems to interact with the local microenvironment and the tumor immune contexture, ultimately impacting cancer progression and treatment outcome. However, pre-clinical research focusing on causality and mechanistic pathways as well as proof-of-concept studies are still needed to fully understand the potential clinical utility of microbiome in cancer patients. Moreover, there is a need for the standardization of methodology and the implementation of quality control across microbiome studies to allow for a better interpretation and greater comparability of the results reported between them. This review summarizes the accumulating evidence in the field and discusses the current and upcoming challenges of microbiome studies.
Published: 2021

11. Characteristics and Outcomes of Staphylococcus aureus Bloodstream Infection Originating From the Urinary Tract: A Multicenter Cohort Study

Author: Ana Sanchez-Batanero, Cristian Tebé, José María Aguado, Rafael San-Juan, Luis Eduardo López-Cortés, Miquel Pujol, Jordi Carratalà, Sara Grillo, Antonio Lalueza, Guillermo Cuervo, Carmen Ardanuy, Dolors García-Somoza, Mariona Llaberia, Immaculada Grau, Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Red Española de Investigación en Patología Infecciosa, European Commission, [Grillo,S, Cuervo,G, Carratalà,J, Grau,I, Llaberia,M, Pujol,M] Department of Infectious Diseases, Bellvitge University Hospital, Barcelona, Spain. [Grillo,S, Ardanuy,C, García-Somoza,D, Pujol,M] Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. [Aguado,JM, Lalueza,A, Sanjuan,R] Unit of Infectious Diseases, 12 de Octubre University Hospital, Madrid, Spain. [Aguado,JM, Sanjuan,R] Research Institute Hospital 12 de Octubre (I+12), Madrid, Spain. [Lopez-Cortés,LE] Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/CSIC/Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain. [Sanchez-Batanero,A] Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/CSIC/Departamento de Medicina, Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain. [Ardanuy,C, García-Somoza,D] Department of Microbiology, Bellvitge University Hospital, Barcelona, Spain. [Grau,I, García-Somoza,D] CIBER of Respiratory Diseases, ISCIII, Madrid, Spain. [Grillo,S, Aguado,JM, Lopez-Cortés,LE, Sanjuan,R, and Ardanuy,C] Spanish Network for Research in Infectious Diseases (REIPI), Seville, Spain. [Ardanuy,C] Departmentos de Fundamentos Clínicos and Patología y Terapeútica Experimental, School of Medicine, of University of Barcelona (UB), Barcelona, Spain. [Aguado,JM] Complutense University of Madrid, Madrid, Spain. [Tebé,C] Biostatistics Unit, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Spain. [Tebé,C] Basic Clinical Practice Department, Rovira Virgili University, Reus, Spain. [Carratalà,J] University of Barcelona (UB), Barcelona, Spain.
Subjects: 0301 basic medicine, medicine.medical_specialty, Staphylococcus aureus, medicine.medical_treatment, Urinary system, 030106 microbiology, Check Tags::Male [Medical Subject Headings], Bacteremia, medicine.disease_cause, Urinary catheterization, Diseases::Bacterial Infections and Mycoses::Infection::Urinary Tract Infections [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 03 medical and health sciences, 0302 clinical medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Retrospective Studies [Medical Subject Headings], Aparell urinari, Internal medicine, Case fatality rate, Infecciones estafilocócicas, Medicine, Staphylococcal infections, 030212 general & internal medicine, Infecciones urinarias, Organisms::Bacteria::Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Rods::Staphylococcaceae::Staphylococcus::Staphylococcus aureus::Methicillin-Resistant Staphylococcus aureus [Medical Subject Headings], Anatomy::Urogenital System::Urinary Tract [Medical Subject Headings], Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Gram-Positive Bacterial Infections::Staphylococcal Infections [Medical Subject Headings], Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Urinary tract infection, business.industry, Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Bacteremia [Medical Subject Headings], Infeccions per estafilococs, Urinary devices, medicine.disease, Comorbidity, Methicillin-resistant Staphylococcus aureus, Urinary organs, Infectious Diseases, Oncology, Organisms::Bacteria::Gram-Positive Bacteria::Bacillales::Staphylococcaceae::Staphylococcus::Staphylococcus aureus [Medical Subject Headings], Bacteriemia, business, Cohort study
Abstract: [Background] Staphylococcus aureus bloodstream infection (SABSI) arising from a urinary tract source (UTS) is poorly understood., [Methods] We conducted a retrospective analysis in 3 major teaching hospitals in Spain of prospectively collected data of hospitalized patients with SABSI. SABSI-UTS was diagnosed in patients with urinary tract symptoms and/or signs, no evidence of an extra-urinary source of infection, and a urinary S. aureus count of ≥105 cfu/mL. Susceptibility of S. aureus strains and patient mortality were compared between SABSI from UTS (SABSI-UTS) and other sources (SABSI-other)., [Results] Of 4181 episodes of SABSI, we identified 132 (3.16%) cases of SABSI-UTS that occurred predominantly in patients who were male, had high Charlson comorbidity scores, were dependent for daily life activities, and who had undergone urinary catheterization and/or urinary manipulation before the infection. SABSI-UTS was more often caused by MRSA strains compared with SABSI-other (40.9% vs 17.5%; P < .001). Patients with SABSI-UTS caused by MRSA more often received inadequate empirical treatment compared with those caused by susceptible strains (59.7% vs 23.1%; P < .001). The 30-day case fatality rate was lower in patients with SABSI-UTS than in those with SABSI-other (14.4% vs 23.8%; P = .02). Factors independently associated with mortality were dependence for daily activities (aOR, 3.877; 95% CI, 1.08–13.8; P = .037) and persistent bacteremia (aOR, 7.88; 95% CI, 1.57–39.46; P = .012)., [Conclusions] SABSI-UTS occurs predominantly in patients with severe underlying conditions and in those who have undergone urinary tract manipulation. Moreover, it is frequently due to MRSA strains and causes significant mortality., This work was supported by Plan Nacional de I+D+i 2017–2021 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005, RD16/0016/0002, RD16/0016/0001) and was co-financed by the European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014–2020.
Published: 2020

12. Association between Polyphenol Intake and Gastric Cancer Risk by Anatomic and Histologic Subtypes: MCC-Spain

Author: Nuria Aragonés, Facundo Vitelli-Storelli, Inés Gómez-Acebo, Gemma Castaño-Vinyals, Eva Adarnaz, Marina Pollán, Raul Zamora-Ros, Juan Alguacil, Estefanía Toledo, Manolis Kogevinas, Antonio J. Molina, José Juan Jiménez-Moleón, Vicente Martín, Ana Molina-Barceló, María Rubín-García, Guillermo Fernández-Tardón, María Dolores Chirlaque, Beatriz Pérez-Gómez, Mireia Obón-Santacana, Instituto de Salud Carlos III, Fundación Marqués de Valdecilla, Ministerio de Economía y Competitividad (España), Red Temática de Investigación Cooperativa en Cáncer (España), Junta de Castilla y León (España), Regional Government of Andalusia (España), Generalitat Valenciana (España), Fundación La Caixa, Basque Government (España), Gobierno de la Región de Murcia (España), Unión Europea. Comisión Europea, Asociación Española Contra el Cáncer, Government of Catalonia (España), Fundación Caja de Ahorros de Asturias, University of Oviedo (España), Ministerio de Educación (España), University of Leon (España), Ministerio de Ciencia e Innovación (España), Junta de Castilla y León, Gobierno de Andalucía, Generalitat Valenciana, Recercaixa, Gobierno Vasco, Gobierno de Murcia, European Commission, Fundación Científica AECC, Generalitat de Catalunya, Universidad de Oviedo, Universidad de León, Universidad de Cantabria, [Rubín-García,M, Vitelli-Storelli,F, Molina,AJ, Martín,V] Group of Investigation in Interactions Gene-Environment and Health (GIIGAS), Institute of Biomedicine (IBIOMED), University of León, León, Spain. [Zamora-Ros,R] Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet del Llobregat, Barcelona, Spain. [Aragonés,N] Department of Health of Madrid, Epidemiology Section, Public Health Division, Madrid, Spain. [Aragonés,N, Adarnaz,E, Castaño-Vinyals,G, Gómez-Acebo,I, Fernández-Tardón,G, Jiménez-Moleón,JJ, Alguacil,J, Dolores Chirlaque,MD, Pérez-Gómez,B, Pollán,M, Kogevinas,M, Martín,V] Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Madrid, Spain. [Adarnaz,E, Toledo,E] Institute for Health Research (IdiSNA), Pamplona, Spain. [Castaño-Vinyals,G, Kogevinas,M] Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. [Castaño-Vinyals,G, Kogevinas,M] Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. [Castaño-Vinyals,G, Kogevinas,M] Department of Public Health, Universitat Pompeu Fabra (UPF), Campus del Mar, Barcelona, Spain. [Obón-Santacana,M] ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet De Llobregat, Barcelona, Spain. [Obón-Santacana,M] Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L’Hospitalet Del Llobregat, Barcelona, Spain. [Gómez-Acebo,I] Facultad de Medicina, Universidad de Cantabria, IDIVAL, Santander, Spain. [Molina-Barceló,A] Cancer and Public Health Area, FISABIO-Public Health, Valencia, Spain. [Fernández-Tardón,G] Health Research Institute of the Principality of Asturias (ISPA), Oncology Institute, University of Oviedo, Oviedo, Asturias. [Jiménez-Moleón,JJ] Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Hospitales Universitarios de Granada, Universidad de Granada, Granada, Spain. [Alguacil,J] Centro de Investigación en Recursos Naturales, Salud y Medio Ambiente (RENSMA), Universidad de Huelva, Campus Universitario de El Carmen, Huelva, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Campus de Ciencias de la Salud, El Palmar, Murcia, Spain. [Toledo,E] Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Institute of Health Carlos III, Madrid, Spain. [Toledo,E] Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain. [Pérez-Gómez,B, Pollán,M] Cancer and Environmental Epidemiology Unit, Department of Epidemiology and Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain. [Pérez-Gómez,B] Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro, IDIPHIM, Madrid, Spain., and The study was partially funded by the 'Accion Transversal del Cancer', approved by the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17CIII/00034), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)), by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 and 2014SGR850, by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. IDIBELL is a member of the CERCA Programme, Generalitat de Catalunya. R.Z.-R. was supported by the 'Miguel Servet' program (CP15/00100) from the Institute of Health Carlos III (Co-funded by the European Social Fund (ESF)-ESF investing in your future). M.R.-G., is supported by the Ministry of Education of Spain (FPU17/06488) and by University of León. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the 'Centro de Excelencia Severo Ochoa 2019–2023' Program (CEX2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program.
Subjects: 0301 basic medicine, Male, stilbenes, Logistic regression, Gastroenterology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, Eating, 0302 clinical medicine, Estilbenos, Risk Factors, Epidemiology, histologic, Odds Ratio, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], Prospective cohort study, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Nutrition and Dietetics, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Stomach, lignans, MCC-Spain, Middle Aged, anatomic, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models [Medical Subject Headings], Quartile, 030220 oncology & carcinogenesis, Dieta, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys::Diet Surveys [Medical Subject Headings], Female, epidemiology, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Benzyl Compounds::Lignans [Medical Subject Headings], lcsh:Nutrition. Foods and food supply, medicine.medical_specialty, Neoplasias gástricas, Polifenoles, Stomach cancer, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols::Polyphenols [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Anatomy::Digestive System::Gastrointestinal Tract::Upper Gastrointestinal Tract::Stomach [Medical Subject Headings], lcsh:TX341-641, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Diet Surveys, Article, 03 medical and health sciences, Stomach Neoplasms, Internal medicine, medicine, Epidemiología, Humans, Compuestos fenólicos, Epidemiologia, Nutrició, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutrition Processes::Eating [Medical Subject Headings], polyphenols, Nutrition, Aged, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Stomach Neoplasms [Medical Subject Headings], Càncer d'estómac, gastric cancer, Cancer, Lignanos, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, Phenolic acid, medicine.disease, Diet, 030104 developmental biology, Logistic Models, Check Tags::Female [Medical Subject Headings], chemistry, Polyphenol, Spain, Case-Control Studies, business, diet, phenolic acids, Food Science
Abstract: Several anticancer properties have been largely attributed to phenolics in in vivo and in vitro studies, but epidemiologic evidence is still scarce. Furthermore, some classes have not been studied in relation to gastric cancer (GC). The aim of this study was to assess the relationship between the intake of phenolic acids, stilbenes, and other phenolics and the risk of developing GC and its anatomical and histological subtypes. We used data from a multi-case-control study (MCC-Spain) obtained from di erent regions of Spain. We included 2700 controls and 329 GC cases. Odds ratios (ORs) were calculated using mixed e ects logistic regression considering quartiles of phenolic intake. Our results showed an inverse association between stilbene and lignan intake and GC risk (ORQ4 vs. Q1 = 0.47; 95% CI: 0.32–0.69 and ORQ4 vs. Q1 = 0.53; 95% CI: 0.36–0.77, respectively). We found no overall association between total phenolic acid and other polyphenol class intake and GC risk. However, hydroxybenzaldehydes (ORQ4 vs. Q1 = 0.41; 95% CI: 0.28–0.61), hydroxycoumarins (ORQ4 vs. Q1 = 0.49; 95% CI: 0.34–0.71), and tyrosols (ORQ4 vs. Q1 = 0.56; 95% CI: 0.39–0.80) were inversely associated with GC risk. No di erences were found in the analysis by anatomical or histological subtypes. In conclusion, a diet high in stilbenes, lignans, hydroxybenzaldehydes, hydroxycoumarins, and tyrosols was associated with a lower GC risk. Further prospective studies are needed to confirm our results., Instituto de Salud Carlos III, Instituto de Salud Carlos III European Union (EU) PI08/1770 PI08/0533 PI08/1359 PS09/00773-Cantabria PS09/01286-Leon PS09/01903-Valencia PS09/02078-Huelva PS09/01662-Granada PI11/01403 PI11/01889-FEDER PI11/00226 PI11/01810 PI11/02213 PI12/00488, Instituto de Salud Carlos III API 10/09, ICGC International Cancer Genome Consortium CLL (Spanish Ministerio de Economia y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)), ICGC International Cancer Genome Consortium CLL (Spanish Ministerio de Economia y Competitividad (MINECO) through Red Tematica de Investigacion del Cancer (RTICC) del ISCIII) RD12/0036/0036, Junta de Castilla y León LE22A10-2, Junta de Andalucía PI-0571-200 PI-0306-2011 salud201200057018tra, Conselleria de Sanitat of the Generalitat Valenciana AP_061/10, La Caixa Foundation 2010ACUP 00310, Regional Government of the Basque Country, Consejería de Sanidad de la Región de Murcia, European Commission European Commission Joint Research Centre FOOD-CT-2006-036224-HIWATE, Spanish Association Against Cancer (AECC) Scientific Foundation, Catalan Government Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 2014SGR850, Fundación Caja de Ahorros de Asturias, University of Oviedo, "Miguel Servet" program from the Institute of Health Carlos III (European Social Fund (ESF)-ESF investing in your future) CP15/00100, Ministry of Education of Spain FPU17/06488, University of Leon, Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019-2023" Program CEX2018-000806-S, Generalitat de Catalunya through the CERCA Program, The Instituto de Salud Carlos III-FEDER PI12/00265 PI12/01270 PI12/00715 PI12/00150 PI14/01219 PI14/0613 PI15/00069 PI15/00914 PI15/01032 PI17CIII/00034
Published: 2020

13. An epigenetic switch controls an alternative NR2F2 isoform 2 that unleashes a metastatic program in melanoma

Author: Davalos, Verónica, Lovell, Claudia, von Itter, Richard, Dolgalev, Igor, Agrawal, Praveen, Baptiste, Gillian, Kahler, David, Sokolova, Elena, Moran, Sebastian, Piqué, Laia, Vega-Saenz de Miera, Eleazar, Fontanals-Cirera, Barbara, Karz, Alcida, Tsirigos, Aristotelis, Yun, Chi, Darvishian, Farbod, Etchevers, Heather, Osman, Iman, Esteller, Manel, Schober, Markus, Hernando, Eva, Department of Pathology, New York University Grossman School of Medicine, NY 10016, USA, Applied Bioinformatics Laboratories, New York University Grossman School of Medicine, NY 10016, USA, Bellvitge Biomedical Research Institute, Partenaires INRAE, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain, New York University School of Medicine (NYU Grossman School of Medicine), National Tsing Hua University [Hsinchu] (NTHU), City University of Hong Kong [Hong Kong] (CUHK), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Marseille Maladies Rares (MarMaRa), Aix Marseille Université (AMU), Interdisciplinary Melanoma Cooperative Group, Perlmutter Cancer Center, New York University School of Medicine, NY 10016, USA (NYUSM), Institució Catalana de Recerca i Estudis Avançats (ICREA), Josep Carreras Leukaemia Research Institute (IJC), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Universitat de Barcelona (UB), New York University [New York] (NYU), NYU System (NYU), and We thank the NYU Experimental Pathology Core, the NYU Genome Technology Center, the NYUCenter for Biospecimen Research and Development, and the Small Animal Imaging core, all partially supported by the Laura and Isaac Perlmutter Cancer Center Support Grant (CCSG) NIH/NCI P30CA016087 (NIH/NCI), and National Institute of Health S10 Grants NIH/ORIP S10OD01058 and S10OD018338. We thank the High Throughput Biology Core partially funded by P30CA16087 and NYSTEM Contract C026719. V.D. was supported by the People Program (Marie Curie Actions) of the European Union's Seventh Framework Program (FP7-PEOPLE30 2013-IOF) under REA grant agreement n° PIOF-GA-2013-623443. This work was funded by NCI/NIH R01CA202027, R01CA274100, P01CA206980 and NYU Melanoma SPOREP50CA225450 (PI: I.O).
Subjects: [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Metastatic melanoma develops once transformed melanocytic cells begin to de-differentiate into migratory and invasive melanoma cells with neural crest cell (NCC)-like and epithelial-tomesenchymal transition (EMT)-like features. However, it is still unclear how transformed melanocytes assume a metastatic melanoma cell state. Here, we define DNA methylation changes that accompany metastatic progression in melanoma patients and discover Nuclear Receptor Subfamily 2 Group F, Member 2 – isoform 2 (NR2F2-Iso2) as an epigenetically regulated metastasis driver. NR2F2-Iso2 is transcribed from an alternative transcriptional start site (TSS) and it is truncated at the N-terminal end which encodes the NR2F2 DNA-bindingdomain. We find that NR2F2-Iso2 expression is turned off by DNA methylation when NCCs differentiate into melanocytes. Conversely, this process is reversed during metastatic melanoma progression, when NR2F2-Iso2 becomes increasingly hypomethylated and re-expressed. Our functional and molecular studies suggest that NR2F2-Iso2 drives metastatic melanomaprogression by modulating the activity of full-length NR2F2 (Isoform 1) over EMT- and NCC-associated target genes. Our findings indicate that DNA methylation changes play a crucial role during metastatic melanoma progression, and their control of NR2F2 activity allows transformed melanocytes to acquire NCC-like and EMT-like features. This epigenetically regulated transcriptional plasticity facilitates cell state transitions and metastatic spread.
Published: 2023
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14. Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis

Author: Broséus, Julien, Hergalant, Sébastien, Vogt, Julia, Tausch, Eugen, Kreuz, Markus, Dartigeas, Caroline, Schneider, Christof, Mottok, Anja, Roos-Weil, Damien, Quinquenel, Anne, Moulin, Charline, Ott, German, Blanchet, Odile, Tomowiak, Cécile, Lazarian, Grégory, Rouyer, Pierre, Tournilhac, Olivier, Bernhart, Stephan H., Chteinberg, Emil, Gauchotte, Guillaume, Lomazzi, Sandra, Chapiro, Elise, Nguyen-Khac, Florence, Chery, Céline, Davi, Frédéric, Hunault, Mathilde, Houlgatte, Rémi, Rosenwald, Andreas, Delmer, Alain, Meyre, David, Béné, Marie-Christine, Thieblemont, Catherine, Lichter, Peter, Guéant, Jean-Louis, Guièze, Romain, Martin-Subero, José Ignacio, Ammerpohl, Ole, Cymbalista, Florence, Feugier, Pierre, Siebert, Reiner, Stilgenbauer, Stephan, Publica, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Universität Ulm - Ulm University [Ulm, Allemagne], Universitätsklinikum Ulm - University Hospital of Ulm, Fraunhofer Institute for Cell Therapy and Immunology (Fraunhofer IZI), Fraunhofer (Fraunhofer-Gesellschaft), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Service d'Hématologie [CHRU Nancy], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Robert-Bosch-Krankenhaus, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Interdisciplinary Centre for Bioinformatics [Leipzig] (IZBI), Universität Leipzig [Leipzig], Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre de Ressources Biologiques - [Nancy] (CRB Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy], Service d'hématologie [Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institute of pathology [Würzburg], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), 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), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), and Hergalant, Sébastien
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Epigenomics, Chronic lymphocytic leukaemia, Lymphoma, B-Cell, B-Zell-Lymphom, biostatistics, General Physics and Astronomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, General Biochemistry, Genetics and Molecular Biology, integrative genomics, DDC 570 / Life sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:570, ddc:610, Transcriptomics, Epigenetik, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Multidisciplinary, B-cell lymphoma, Gene Expression Profiling, Computational Biology, classifiers, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, bioinformatics, General Chemistry, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computational biology and bioinformatics, DLBCL, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Chronic lymphocytic leukemia, Epigenetics, Richter syndrome, DDC 610 / Medicine & health, CLL
Abstract: Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). We characterize 58 primary human RS samples by genome-wide DNA methylation and whole-transcriptome profiling. Our comprehensive approach determines RS DNA methylation profile and unravels a CLL epigenetic imprint, allowing CLL-RS clonal relationship assessment without the need of the initial CLL tumor DNA. DNA methylation- and transcriptomic-based classifiers were developed, and testing on landmark DLBCL datasets identifies a poor-prognosis, activated B-cell-like DLBCL subset in 111/1772 samples. The classification robustly identifies phenotypes very similar to RS with a specific genomic profile, accounting for 4.3-8.3% of de novo DLBCLs. In this work, RS multi-omics characterization determines oncogenic mechanisms, establishes a surrogate marker for CLL-RS clonal relationship, and provides a clinically relevant classifier for a subset of primary “RS-type DLBCL” with unfavorable prognosis., publishedVersion
Published: 2023
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15. Loss of seryl-tRNA synthetase ( SARS1 ) causes complex spastic paraplegia and cellular senescence

Author: Edgard Verdura, Bruno Senger, Miquel Raspall-Chaure, Agatha Schlüter, Nathalie Launay, Montserrat Ruiz, Carlos Casasnovas, Agustí Rodriguez-Palmero, Alfons Macaya, Hubert Dominique Becker, Aurora Pujol, Génétique et Physiopathologie des Maladies Cérébro-Vasculaires (U1161 / UMR_S 1161), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universitat Autònoma de Barcelona (UAB), Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), CIBER de Enfermedades Raras (CIBERER), Pediatrics Department, Hospital Universitari Germans Trias I Pujol, Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Neurometabolic Diseases Laboratory [Barcelona, Spain], Centre for Biomedical Research on Rare Diseases [Barcelona, Spain] (CIBERER), Hospital Sant Joan de Déu [Barcelona], Institució Catalana de Recerca i Estudis Avançats (ICREA), Institut Català de la Salut, [Verdura E, Schlüter A, Launay N, Ruiz M] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908, Barcelona, Catalonia, Spain. Centre for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain. [Senger B] Université de Strasbourg 1, Strasbourg, France. [Raspall-Chaure M] Grup de Recerca en Neurologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Macaya A] Grup de Recerca en Neurologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Neurologia Pediàtrica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: nervous system diseases, Paraplegia - Aspectes genètics, Sequence analysis, RNA, pediatrics, sequence analysis, Otros calificadores::Otros calificadores::/genética [Otros calificadores], neurology, [SDV]Life Sciences [q-bio], Cell Physiological Phenomena::Cellular Senescence [PHENOMENA AND PROCESSES], genetic research, Nervous system diseases, Pediatrics, Nervous System Diseases::Neurologic Manifestations::Paralysis::Paraplegia [DISEASES], enfermedades del sistema nervioso::manifestaciones neurológicas::parálisis::paraplejía [ENFERMEDADES], Neurology, Other subheadings::Other subheadings::/genetics [Other subheadings], Genetics, RNA, fenómenos fisiológicos celulares::senescencia celular [FENÓMENOS Y PROCESOS], Cèl·lules - Envelliment, Genetic research, Genetics (clinical)
Abstract: Genetic research; Nervous system diseases; Pediatrics Investigación genética; Enfermedades del sistema nervioso; Pediatría Recerca genètica; Malalties del sistema nerviós; Pediatria Background Aminoacyl-tRNA synthetases (ARS) are key enzymes catalysing the first reactions in protein synthesis, with increasingly recognised pleiotropic roles in tumourgenesis, angiogenesis, immune response and lifespan. Germline mutations in several ARS genes have been associated with both recessive and dominant neurological diseases. Recently, patients affected with microcephaly, intellectual disability and ataxia harbouring biallelic variants in the seryl-tRNA synthetase encoded by seryl-tRNA synthetase 1 (SARS1) were reported. Methods We used exome sequencing to identify the causal variant in a patient affected by complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly. Complementation and serylation assays using patient’s fibroblasts and an Saccharomyces cerevisiae model were performed to examine this variant’s pathogenicity. Results A de novo splice site deletion in SARS1 was identified in our patient, resulting in a 5-amino acid in-frame insertion near its active site. Complementation assays in S. cerevisiae and serylation assays in both yeast strains and patient fibroblasts proved a loss-of-function, dominant negative effect. Fibroblasts showed an abnormal cell shape, arrested division and increased beta-galactosidase staining along with a senescence-associated secretory phenotype (raised interleukin-6, p21, p16 and p53 levels). Conclusion We refine the phenotypic spectrum and modes of inheritance of a newly described, ultrarare neurodevelopmental disorder, while unveiling the role of SARS1 as a regulator of cell growth, division and senescence. This study was supported by grants from the Undiagnosed Rare Disease programme URD-Cat (SLT002/16/00174) from the Generalitat de Catalunya, the Center for Biomedical Research on Rare Diseases (CIBERER) (ACCI19-759), the ASL-HSP France and the Hesperia Foundation to AP. This study was also funded by the Instituto de Salud Carlos III and ‘Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, una manera de hacer Europa’ (FIS PI20/00758) to CC and ‘La Marató de TV3’ Foundation (202006-30) to CC and AP. This study was also funded by Instituto de Salud Carlos III (Sara Borrell programme, CD19/00221) to EV, the Spanish Ministerio de Economia, Industria y Competividad (Juan de la Cierva programme FJCI-2016-28811) to EV, and the Center for Biomedical Research on Rare Diseases (CIBERER) to MR and NL. This study was supported by the French National Programme Investissement d’Avenir administered by the ‘Agence National de la Recherche’ (ANR), ‘MitoCross’ Laboratory of Excellence (Labex), funded as ANR-10-IDEX-0002-02, the University of Strasbourg and CNRS (to HB, BS). The CERCA Programme/Generalitat de Catalunya provided institutional support. AP is member of the Undiagnosed Disease Network International (UDNI).
Published: 2022
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16. Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score

Author: Amanda J. Cross, Kristin Benjaminsen Borch, Anne Kirstine Eriksen, Elio Riboli, José María Huerta, H. Bas Bueno-de-Mesquita, Giovanna Masala, Núria Sala, Anne Tjønneland, Anika Hüsing, Rudolf Kaaks, Sara Grioni, Anne M. May, Fanny Artaud, Antonia Trichopoulou, Pilar Amiano, Eleni Peppa, Marc J. Gunter, Timothy J. Key, Aurelio Barricarte Gurrea, Jonna Berntsson, Anna Karakatsani, Mazda Jenab, Elisabete Weiderpass, Isabel Drake, Christina C. Dahm, Torkjel M. Sandanger, Bethany Van Guelpen, Robin Reichmann, María José Sánchez, Guri Skeie, Konstantinos K. Tsilidis, Gianluca Severi, Carlotta Sacerdote, Sjoerd G. Elias, José Ramón Quirós, Marie-Christine Boutron-Ruault, Salvatore Panico, Krasimira Aleksandrova, Rosario Tumino, Sophia Harlid, Elom K. Aglago, [Aleksandrova,K, Reichmann,R] Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Aleksandrova,K, Reichmann,R] Institute of Nutritional Science, University of Potsdam, Potsdam, Germany. [Aleksandrova,K] Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany. [Kaaks,R, Hüsing,A] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Jenab,M, Weiderpass,E, Aglago,EK, Gunter,MJ] International Agency for Research on Cancer, World Health Organization, Lyon, France. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Cross,AJ, Tsilidis,KK, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Dahm,CC] Department of Public Health, Aarhus University, Aarhus, Denmark. [Eriksen,AK, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Artaud,F, Boutron-Ruault,MC, Severi,G] CESP, Faculté de Medicine, Université Paris-Saclay, Villejuif, France. [Artaud,F, Severi,G] Institut Gustave Roussy, Villejuif, France. [Severi,G] Dipartimento di Statistica, Informatica e Applicazioni 'G. Parenti' (DISIA), University of Florence, Florence, Italy. [Trichopoulou,A, Karakatsani,A, Peppa,E] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Panico,S] EPIC Centre of Naples, Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Naples, Italy. [Masala,G] 1Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Grioni,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy. [Tumino,R] Cancer Registry and Histopathology Department, Provincial Health Authority (ASP), Ragusa, Italy. [Elias,SG, May,AM] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. [Borch,KB, Sandanger,TM, Skeie,G] Department of Community Medicine, Health Faculty, UiT-the Arctic university of Norway, Tromsø, Norway. [Sánchez,MJ] Escuela Andaluza de Salud Pública (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Sánchez,MJ, Huerta,JM, Gurrea,AB, Amiano,P] Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Sánchez,MJ] Universidad de Granada, Granada, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Sala,N] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Translational Research Laboratory, Catalan Institute of Oncology (ICO), Barcelona, Spain. [Sala,N] Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. [Gurrea,AB] Navarra Public Health Institute, Pamplona, Spain. [Gurrea,AB] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Amiano,P] Ministry of Health of the Basque Government, Public Health Division of Gipuzkoa, Biodonostia Health Research Institute, Donostia-San Sebastian, Spain. [Berntsson,J] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Drake,I] Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. [van Guelpen,B, Harlid,S] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Key,T] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., This work was supported by the German Research Foundation (DFG) (grant AL 1784/3-1), which funded the research position of Dr. Aleksandrova for organizing study conduct and analysis. 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, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) and Federal Ministry of Education and Research (BMBF) (Germany), 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), Health Research Fund (FIS), Instituto de salud Carlos III PI13/00061 to Granada, PI13/ 01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and Catalonia (Catalan Institute of Oncology – ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (C864/A14136 to EPIC-Norfolk and C8221/A19170 to EPICOxford), Medical Research Council (MR/N003284/1 and MC-UU_12015/1 to EPIC-Norfolk and MR/M012190/1 to EPIC-Oxford) (United Kingdom). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Open Access funding enabled and organized by Projekt DEAL.
Subjects: Male, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk::Risk Assessment [Medical Subject Headings], lcsh:Medicine, Cancer prevention, Cohort Studies, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Calibration [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Neoplasias colorrectales, Medicine, 030212 general & internal medicine, Prospective Studies, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], 10. No inequality, Prospective cohort study, 11 Medical and Health Sciences, Framingham Risk Score, Risk screening, Lifestyle behaviour, Risk prediction, Colorectal cancer, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030220 oncology & carcinogenesis, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], Female, Risk assessment, Colorectal Neoplasms, Research Article, Cohort study, Estils de vida, Waist, Lifestyles, Nutritional Status, Check Tags::Male [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Estil de vida, Risk Assessment, Riesgo, Estilo de vida, 03 medical and health sciences, Càncer colorectal, General & Internal Medicine, Humans, Life Style, business.industry, lcsh:R, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk [Medical Subject Headings], Technology and Food and Beverages::Food and Beverages::Food::Vegetables [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], Nomogram, Lifestyle, Diet, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Check Tags::Female [Medical Subject Headings], Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], business, Prevención de Enfermedades, Demography
Abstract: Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level., German Research Foundation (DFG) AL 1784/3-1, European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) (Germany), Federal Ministry of Education & Research (BMBF), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro (AIRC), Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Instituto de Salud Carlos III PI13/00061 PI13/01162, Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) 6236, Regional Government of Navarra (Spain), Regional Government of Catalonia (Catalan Institute of Oncology -ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK C864/A14136 C8221/A19170, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/N003284/1 MC-UU_12015/1 MR/M012190/1, Projekt DEAL
Published: 2021
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17. Overcoming Paradoxical Kinase Priming by a Novel MNK1 Inhibitor

Author: Elisabeth Bou-Petit, Stefan Hümmer, Helena Alarcon, Konstantin Slobodnyuk, Marta Cano-Galietero, Pedro Fuentes, Pedro J. Guijarro, María José Muñoz, Leticia Suarez-Cabrera, Anna Santamaria, Roger Estrada-Tejedor, José I. Borrell, Santiago Ramón y Cajal, Institut Català de la Salut, [Bou-Petit E, Alarcon H] Grup de Química Farmacèutica, IQS School of Engineering, Universitat Ramon Llull, Barcelona, Spain. [Hümmer S, Slobodnyuk K, Cano-Galietero M, Muñoz MJ, Ramón Y Cajal S] Grup de Recerca de Patologia Molecular Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain. [Fuentes P] Grup de Recerca de Patologia Molecular Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Madrid, Spain. Laboratory of Cancer Metabolism, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. [Guijarro PJ] Grup de Recerca de Patologia Molecular Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Suarez-Cabrera L, Santamaria A] Laboratori de Cicle Cel·lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Models, Molecular, Càncer - Tractament, técnicas de investigación::modelos teóricos::modelos moleculares [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Intracellular Signaling Peptides and Proteins, Medicaments antineoplàstics - Ús terapèutic, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS], Protein Serine-Threonine Kinases, Molècules - Models, Neoplasms [DISEASES], neoplasias [ENFERMEDADES], Adenosine Triphosphate, Investigative Techniques::Models, Theoretical::Models, Molecular [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Drug Discovery, Molecular Medicine, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS], Signal Transduction
Abstract: Inhibidor de MNK1; Oncología Inhibidor de MNK1; Oncologia MNK1 inhibitor; Oncology Targeting the kinases MNK1 and MNK2 has emerged as a valuable strategy in oncology. However, most of the advanced inhibitors are acting in an adenosine triphosphate (ATP)-competitive mode, precluding the evaluation of different binding modes in preclinical settings. Using rational design, we identified and validated the 4,6-diaryl-pyrazolo[3,4-b]pyridin-3-amine scaffold as the core for MNK inhibitors. Signaling pathway analysis confirmed a direct effect of the hit compound EB1 on MNKs, and in line with the reported function of these kinases, EB1 only affects the growth of tumor but not normal cells. Molecular modeling revealed the binding of EB1 to the inactive conformation of MNK1 and the interaction with the specific DFD motif. This novel mode of action appears to be superior to the ATP-competitive inhibitors, which render the protein in a pseudo-active state. Overcoming this paradoxical activation of MNKs by EB1 represents therefore a promising starting point for the development of a novel generation of MNK inhibitors. This work was supported by the Instituto de Salud Carlos III (PI17/02247), (PI20/01687), and CIBERONC (CB16/12/00363). S.R.y.C. acknowledges support from the Generalitat de Catalunya (2017-9015-385045). E. Bou-Petit thanks the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (2017 FI_B2 00139) and the European Social Funds for her predoctoral fellowship.
Published: 2022

18. Tobacco products in the European Union Common Entry Gate (EU-CEG): A tool for monitoring the EU tobacco products directive

Author: Dolors Carnicer-Pont, Olena Tigova, Anne Havermans, Eline Remue, Matus Ferech, Katharina Vejdovszky, Renata Solimini, Silvano Gallus, Emilia Nunes, Carl Lange, Cristina Gomez-Chacon, Francisco Ruiz-Dominguez, Panagiotis Behrakis, Constantine Vardavas, Esteve Fernandez, [Carnicer-Pont,D, Tigova,O, Fernandez,E] Cancer Prevention and Control Programme, Cancer Epidemiology and Prevention Department, Catalan Institute of Oncology, Barcelona, Spain. [Carnicer-Pont,D, Fernandez,E] Tobacco Control Research Group, Epidemiology and Public Health Programme, Bellvitge Biomedical Research Institute, Barcelona, Spain. [Carnicer-Pont,D, Fernandez,E] School of Medicine and Clinical Sciences, University of Barcelona, Barcelona, Spain. [Carnicer-Pont,D, Fernandez,E] Centre for Biomedical Research Network, CIBERES, Madrid, Spain. [Havermans,A] Centre for Health Protection, National Institute for Public Health and the Environment, RIVM, Bilthoven, The Netherlands. [Remue,E] Federal Public Service Health, Food Chain Safety and Environment, Brussels, Belgium. [Ferech,M] Tobacco Control Team, DG SANTE B2, Crossborder Healthcare and Tobacco Control, Brussels, Belgium. [Vejdovszky,K] Austrian Agency for Health and Food Safety, Vienna, Austria. [Solimini,R] National Centre on Addiction and Doping, Istituto Superiore di Sanità, Rome, Italy. [Gallus,S] Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milan, Italy. [Nunes,E] Department of Health, Ministry of Health, Lisbon, Portugal. [Lange,CC] The Danish Safety Technology Authority, Copenhagen, Denmark. [Gomez-Chacon,C] Tobacco Prevention and Control Unit, Deputy Direction of Promotion, Prevention and Quality, General Direction of Public Health, Ministry of Health, Madrid, Spain. [Ruiz-Dominguez,F] General Directorate of Public Health and Pharmaceutical Management, Regional Ministry of Health and Families of Andalusia, Sevilla, Spain. [Behrakis.P, and Vardavas,CI] George D. Behrakis Research Lab, Hellenic Cancer Society, Athens, Greece.
Subjects: Health Care::Health Services Administration::Patient Care Management::Delivery of Health Care::Health Care Reform [Medical Subject Headings], Health (social science), Ingredients, Epidemiology, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], EU-CEG, Països de la Unió Europea, ingredients, Legislación como asunto, Health Professions (miscellaneous), Tobacco Products Directive, Tabac, Tobacco, Fumar, Geographical Locations::Geographic Locations::Historical Geographic Locations::European Union [Medical Subject Headings], Tobacco products directive, Priority additives, Technology and Food and Beverages::Technology, Industry, and Agriculture::Manufactured Materials::Tobacco Products::Tobacco, Smokeless [Medical Subject Headings], Productos de tabaco, European Union countries, Public Health, Environmental and Occupational Health, Monitoreo, Health Care::Health Services Administration::Organization and Administration::Public Health Administration [Medical Subject Headings], Diseases::Chemically-Induced Disorders::Substance-Related Disorders::Tobacco Use Disorder [Medical Subject Headings], CAS number, priority additives, Tabaco, Health Care::Health Care Economics and Organizations::Social Control, Formal::Legislation as Topic [Medical Subject Headings], Cigarette characterizing flavor, Technology and Food and Beverages::Technology, Industry, and Agriculture::Manufactured Materials::Tobacco Products [Medical Subject Headings], Información, cigarette characterizing flavor
Abstract: Introduction: Under the European Union (EU) Tobacco Products Directive (2014/40/EU) (TPD), manufacturers and importers of tobacco products are required to report information to the European Commission (EC) and Member States (MS) on products intended to be placed on the market. We describe the distribution of notifications to the EU Common Entry Gate (EU-CEG) and identify key fields for improvement on reporting cigarettes or roll-your-own (RYO) tobacco. Methods: A cross-sectional analysis of secondary data reported in the EU-CEG was conducted for tobacco products notified within EU-CEG between June 2016 and October 2019 for 12 EU MS. Analysis of compliance to specific regulations for priority additives that refer to cigarettes and RYO was conducted for 10 EU countries. Results: Overall, 39170 tobacco products were notified. This included 16762 (42.8%) notifications of cigars, followed by cigarettes 11242 (28.7 %), waterpipes 3291 (8.4%), cigarillos (n=1783), pipe (n=1715), RYO (n=1635), chewing tobacco (n=1021), novel tobacco products (n=839), herbal products for smoking (n=535), other (n=258), nasal (n=74) and oral tobacco (n=15). In cigarettes and RYO tobacco products, the proportion of ingredients notified in all countries that contained an unknown Chemical Abstract Services (CAS) number was 3.8% and 2.1%, respectively. The proportion of underreporting flagging of priority additives ranged from 15.9% in Malta to 41.3% in Lithuania, the mean proportion of underreporting of the variable ‘priority additive’ for the 10 countries together was 24.7%. Conclusions: In the EU-CEG data base, for the period of analysis, a significant number of product notifications took place while large variations in the number of types of tobacco products notified across EU countries was noted. The timely monitoring of these data is needed so that products non-compliant within the EU-CEG system are assessed. This study is derived from the Joint Action on Tobacco Control funded by the European Union's Health Program (2014-2020) under the grant agreement - 761297. The Tobacco Control Research Group at ICO-IDIBELL (DCP, OT, EF) is partly supported by the Ministry of Universities and Research, Government of Catalonia (2017SGR319). DCP, OT and EF also thank CERCA Programme Generalitat de Catalunya for the institutional support to IDIBELL. Yes
Published: 2022

19. The role of neurotrophin genes involved in the vulnerability to gambling disorder

Author: Neus Solé-Morata, Isabel Baenas, Mikel Etxandi, Roser Granero, Sonia V. Forcales, Manel Gené, Carme Barrot, Mónica Gómez-Peña, José M. Menchón, Nicolás Ramoz, Philip Gorwood, Fernando Fernández-Aranda, Susana Jiménez-Murcia, Martinez Rico, Clara, Bellvitge University Hospital [Barcelona, Spain], Bellvitge Biomedical Research Institute [Barcelona, Spain] ((IDIBELL)), L’Hospitalet de Llobregat [Barcelona, Spain], Instituto de Salud Carlos III [Madrid] (ISC), Universitat Autònoma de Barcelona (UAB), University of Barcelona, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Multidisciplinary, Addiction, Proteins, Joc compulsiu, [SDV.GEN] Life Sciences [q-bio]/Genetics, Predictive markers, Polymorphism, Single Nucleotide, Gene Frequency, Haplotypes, Gambling, Genetics, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Nerve Growth Factors, Compulsive gambling, Proteïnes, Genètica
Abstract: Altres ajuts: Delegación del Gobierno para el Plan Nacional sobre Drogas (2021I031 and 2019I47), EU Grant Eat2beNice (H2020-SFS-2016-2; Ref728018), PRIME (H2020-SC1-BHC-2018-2020, ref.847879) and COST Action (CA19115). Evidence about the involvement of genetic factors in the development of gambling disorder (GD) has been assessed. Among studies assessing heritability and biological vulnerability for GD, neurotrophin (NTF) genes have emerged as promising targets, since a growing literature showed a possible link between NTF and addiction-related disorders. Thus, we aimed to explore the role of NTF genes and GD with the hypothesis that some NTF gene polymorphisms could constitute biological risk factors. The sample included 166 patients with GD and 191 healthy controls. 36 single nucleotide polymorphisms (SNPs) from NTFs (NGF, NGFR, NTRK1, BDNF, NTRK2, NTF3, NTRK3, NTF4, CNTF and CNTFR) were selected and genotyped. Linkage disequilibrium (LD) and haplotype constructions were analyzed, in relationship with the presence of GD. Finally, regulatory elements overlapping the identified SNPs variants associated with GD were searched. The between groups comparisons of allele frequencies indicated that 6 SNPs were potentially associated with GD. Single and multiple-marker analyses showed a strong association between both NTF3 and NTRK2 genes, and GD. The present study supports the involvement of the NTF family in the aetiopathogenesis of GD. An altered cross-regulation of different NTF members signalling pathways might be considered as a biological vulnerability factor for GD.
Published: 2022
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20. Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples

Author: Mireia Olivan, Marta Garcia, Leticia Suárez, Marc Guiu, Laura Gros, Olga Méndez, Marina Rigau, Jaume Reventós, Miguel F. Segura, Inés de Torres, Jacques Planas, Xavier de la Cruz, Roger R. Gomis, Juan Morote, Ruth Rodríguez-Barrueco, Anna Santamaria, Institut Català de la Salut, [Olivan M] Translational Oncology Laboratory, Anatomy Unit, Department of Pathology and Experimental Therapy, School of Medicine, Universitat de Barcelona (UB), 08907 L’Hospitalet de Llobregat, Spain. Molecular Mechanisms and Experimental Therapy in Oncology-Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L’Hospitalet de Llobregat, Spain. Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Garcia M] Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Developmental Tumor Biology Laboratory, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain. [Suárez L, Gros L, Méndez O, Santamaria A] Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Guiu M] Cancer Science Programme, Institute for Research in Biomedicine (IRB-Barcelona), 08028 Barcelona, Spain. [Segura MF] Grup de Recerca Translacional en Càncer en la Infància i l’Adolescència, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [de Torres I] Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Planas J, Morote J] Laboratori de Cicle Cel•lular i Càncer, Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei d’Urologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [de la Cruz X] Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain. Grup de Recerca en Bioinformàtica Clínica i Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, MicroARN, miRNA-135b, prostate cancer, bone metastasis, miRNAs, Prostate cancer, Càncer de pròstata, Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [DISEASES], Biochemical markers, Neoplasms::Neoplastic Processes::Neoplasm Metastasis [DISEASES], Neoplasms. Tumors. Oncology. Including cancer and carcinogens, urologic and male genital diseases, Article, Metastasis, neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata [ENFERMEDADES], Oncology, Metàstasi, neoplasias::procesos neoplásicos::metástasis neoplásica [ENFERMEDADES], Marcadors bioquímics, Pròstata - Càncer - Prognosi, Diagnosis::Prognosis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], diagnóstico::pronóstico [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], RC254-282
Abstract: Simple Summary Prostate cancer (PCa) is the most prevalent cancer in males worldwide, and it was the fifth leading cause of cancer mortality in this group in 2020. Near 70% of advanced-stage PCa patients will undergo bone metastasis, suffering pathological complications that severely affect patients’ quality of life and probably progress in most cases to lethal PCa. Our main objective was to unveil novel molecules associated with choosing the bone as a metastatic niche. For this purpose, we generated and characterized a cell line with increased tropism to bone. Its molecular analysis has led us to identify factors with a potential role in bone metastasis that could also be used as biomarkers of disease progression. These data help us to understand the mechanisms that increase bone metastasis penetrance of PCa cells and could provide new therapeutic tools in the future for patients with worse prognoses. Abstract About 70% of advanced-stage prostate cancer (PCa) patients will experience bone metastasis, which severely affects patients’ quality of life and progresses to lethal PCa in most cases. Hence, understanding the molecular heterogeneity of PCa cell populations and the signaling pathways associated with bone tropism is crucial. For this purpose, we generated an animal model with high penetrance to metastasize to bone using an intracardiac percutaneous injection of PC3 cells to identify PCa metastasis-promoting factors. Using genomic high-throughput analysis we identified a miRNA signature involved in bone metastasis that also presents potential as a biomarker of PCa progression in human samples. In particular, the downregulation of miR-135b favored the incidence of bone metastases by significantly increasing PCa cells’ migratory capacity. Moreover, the PLAG1, JAKMIP2, PDGFA, and VTI1b target genes were identified as potential mediators of miR-135b’s role in the dissemination to bone. In this study, we provide a genomic signature involved in PCa bone growth, contributing to a better understanding of the mechanisms responsible for this process. In the future, our results could ultimately translate into promising new therapeutic targets for the treatment of lethal PCa.
Published: 2021

21. Mixed-method research protocol: Development and evaluation of a nursing intervention in patients discharged from the intensive care unit

Author: Ana Isabel Núñez Delgado, Cecilia Cuzco, Pilar Delgado-Hito, M. Antonia Martínez Momblan, Raquel Marín Pérez, Dolors Estrada Reventós, Gemma Martinez Estalella, Marta Romero García, Pedro Castro Rebollo, Institut Català de la Salut, [Cuzco C] Hospital Clinic, Barcelona, Spain. Faculty of Medicine and Health Sciences, School of Nursing, Department of Fundamental and Medical-Surgical Nursing, Universitat de Barcelona, Barcelona, Spain. Biomedical Research Institute August Pi Sunyer (IDIBAPS), Hospital Clinic Barcelona, Barcelona, Spain. [Castro Rebollo P] Hospital Clinic, Barcelona, Spain. Biomedical Research Institute August Pi Sunyer (IDIBAPS), Hospital Clinic Barcelona, Barcelona, Spain. School of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain. [Marín Pérez R] Hospital Bellvitge, L'Hospitalet de Llobregat, Spain. [Núñez Delgado AI] Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Romero García M] Faculty of Medicine and Health Sciences, School of Nursing, Department of Fundamental and Medical-Surgical Nursing, Universitat de Barcelona, Barcelona, Spain. Nursing Research Group (GRIN), Bellvitge Biomedical Research Institute (IDIBELL), l’Hospitalet de Llobregat, Spain. [Martínez Momblan MA] Faculty of Medicine and Health Sciences, School of Nursing, Department of Fundamental and Medical-Surgical Nursing, Universitat de Barcelona, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: mixed‐method design, RT1-120, nursing intervention, Nursing, Anxiety, Hospital Anxiety and Depression Scale, law.invention, Nonprobability sampling, Hospitals, University, Study Protocol, post‐intensive care syndrome, law, Intervention (counseling), medicine, Humans, Multicenter Studies as Topic, Behavior and Behavior Mechanisms::Emotions::Anxiety [PSYCHIATRY AND PSYCHOLOGY], Unitats de cures intensives, General Nursing, business.industry, Multimethodology, ICU discharge, conducta y mecanismos de la conducta::emociones::ansiedad [PSIQUIATRÍA Y PSICOLOGÍA], diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Simple random sample, Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Intensive care unit, Post-intensive care syndrome, Patient Discharge, Intensive Care Units, Ansietat, Health Care Facilities, Manpower, and Services::Health Facilities::Hospital Units::Intensive Care Units [HEALTH CARE], instalaciones, servicios y personal de asistencia sanitaria::centros sanitarios::unidades hospitalarias::unidades de cuidados intensivos [ATENCIÓN DE SALUD], Research Design, Avaluació de resultats (Assistència sanitària), medicine.symptom, business
Abstract: Alta de la UCI; Diseño de un método mixto; Intervención de enfermería Alta de la UCI; Disseny d'un mètode mixt; Intervenció d'infermeria ICU discharge; Mixed-method design; Nursing intervention Aim (a) To understand patients’ lived experience at intensive care unit (ICU) discharge and (b) to evaluate the impact of a nursing empowerment intervention (NEI) on patients’ anxiety and depression levels at ICU discharge. Design A mixed-methods approach will be applied. Methods In the qualitative phase, the hermeneutic phenomenological method will be used. Participants will be patients from three university hospitals who will be selected by purposive sampling. Data will be gathered through in-depth interviews and analysed using content analysis. The qualitative data obtained will be employed to develop the nursing intervention. Subsequently, a multicenter, parallel-group, experimental pre-test/post-test design with a control group will be used to measure the effectiveness of the nursing empowerment intervention in the quantitative phase by means of the Hospital Anxiety and Depression Scale (HADS). Simple random probabilistic sampling will include 172 patients in this phase.
Published: 2021

22. PICO Questions and DELPHI Methodology for the Management of Venous Thromboembolism Associated with COVID-19

Author: Riera-Mestre, Antoni, Jara-Palomares, Luis, Lecumberri, Ramón, Trujillo-Santos, Javier, Grau, Enric, Blanco-Molina, Angeles, Carbonell, Ana Piera, Jiménez, Sonia, Vargas, Manuel Frías, Fuset, Mari, Bellmunt-Montoya, Sergi, Monreal, Manuel, Jiménez, David, Project, on behalf of the COVILAX, Institut Català de la Salut, [Riera-Mestre A] Internal Medicine Department, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. Faculty of Medicine and Health Sciences, Universitat de Barcelona, Barcelona, Spain. [Jara-Palomares L] Medical-Surgical Unit for Respiratory Diseases, Virgen del Rocío University Hospital, Sevilla, Spain. Center for Biomedical Research in Respiratory Diseases Network (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. [Lecumberri R] Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain. Center for Biomedical Research Network on Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. [Trujillo-Santos J] Internal Medicine Department, Hospital General Universitario Santa Lucía, Cartagena, Spain. Faculty of Health Sciences, Universidad Católica San Antonio de Murcia (UCAM), Murcia, Spain. [Grau E] Hematology Department, Lluis Alcanyis de Xativa Hospital, Valencia, Spain. [Blanco-Molina A] Internal Medicine Unit, Hospital Universitario Reina Sofía, Córdoba, Spain. [Bellmunt-Montoya S] Servei de Angiologia, Cirurgia Vascular i Endovascular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Cirurgia, Universitat Autònoma de Barcelona, Bellaterra, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: pulmonary embolism, Delphi Technique, Coronaviruses, Deep vein, Delphi method, coronavirus, law.invention, law, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Medicine, Trombosi, enfermedades cardiovasculares::enfermedades vasculares::embolia y trombosis::tromboembolia::tromboembolia venosa [ENFERMEDADES], anticoagulation, COVID-19 (Malaltia) - Complicacions, Embòlia pulmonar, Cardiovascular Diseases::Vascular Diseases::Embolism and Thrombosis::Thromboembolism::Venous Thromboembolism [DISEASES], Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Venous Thromboembolism, Medicina clínica - Presa de decisions, Intensive care unit, Thrombosis, QR1-502, Pulmonary embolism, Ciencias de la información::análisis de sistemas::técnica Delfos [CIENCIA DE LA INFORMACIÓN], Infectious Diseases, medicine.anatomical_structure, Information Science::Systems Analysis::Delphi Technique [INFORMATION SCIENCE], medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.drug_class, Low molecular weight heparin, Microbiology, Article, deep vein thrombosis, Virology, Humans, Intensive care medicine, Tromboembolisme, Duration of Therapy, business.industry, fungi, Anticoagulants, COVID-19, Heparin, Low-Molecular-Weight, medicine.disease, Coronavirus, Embolism, business, venous thromboembolic disease
Abstract: Patients with coronavirus disease 2019 (COVID-19) have a higher risk of venous thromboembolic disease (VTE) than patients with other infectious or inflammatory diseases, both as macrothrombosis (pulmonar embolism and deep vein thrombosis) or microthrombosis. However, the use of anticoagulation in this scenario remains controversial. This is a project that used DELPHI methodology to answer PICO questions related to anticoagulation in patients with COVID-19. The objective was to reach a consensus among multidisciplinary VTE experts providing answers to those PICO questions. Seven PICO questions regarding patients with COVID-19 responded with a broad consensus: 1. It is recommended to avoid pharmacological thromboprophylaxis in most COVID-19 patients not requiring hospital admission, 2. In most hospitalized patients for COVID-19 who are receiving oral anticoagulants before admission, it is recommended to replace them by low molecular weight heparin (LMWH) at therapeutic doses, 3. Thromboprophylaxis with LMWH at standard doses is suggested for COVID-19 patients admitted to a conventional hospital ward, 4. Standard-doses thromboprophylaxis with LMWH is recommended for COVID-19 patients requiring admission to Intensive Care Unit, 5. It is recommended not to determine D-Dimer levels routinely in COVID-19 hospitalized patients to select those in whom VTE should be suspected, or as a part of the diagnostic algorithm to rule out or confirm a VTE event, 6. It is recommended to discontinue pharmacological thromboprophylaxis at discharge in most patients hospitalized for COVID-19, 7. It is recommended to withdraw anticoagulant treatment after 3 months in most patients with a VTE event associated with COVID-19. The combination of PICO questions and DELPHI methodology provides a consensus on different recommendations for anticoagulation management in patients with COVID-19.
Published: 2021
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23. Evidence Update on the Relationship between Diet and the Most Common Cancers from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study: A Systematic Review

Author: Ubago-Guisado, Esther, Rodríguez-Barranco, Miguel, Ching-López, Ana, Petrova, Dafina, Molina-Montes, Esther, Amiano, Pilar, Barricarte-Gurrea, Aurelio, Chirlaque, María-Dolores, Agudo, Antonio, Sánchez, María-José, [Ubago-Guisado,E, Rodríguez-Barranco,M, Ching-López,A, Petrova,D, Sánchez,MJ] Cancer Registry of Granada, Escuela Andaluza de Salud Pública, Granada, Spain. [Ubago-Guisado,E, Molina-Montes,E, Amiano,P, Barricarte-Gurrea,A, Chirlaque,MD, Sánchez,MJ] Epidemiology and Control of Chronic Diseases, CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Ubago-Guisado,E, Sánchez,MJ] Cancer Epidemiology Group, Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Petrova,D] Department of Experimental Psychology, Mind, Brain and Behavior Research Center (CIMCYC), University of Granada, Granada, Spain. [Molina-Montes,E] Department of Nutrition and Food Science, Campus of Cartuja, University of Granada, Granada, Spain. [Molina-Montes,E] Institute of Nutrition and Food Technology (INYTA) ‘José Mataix’, Biomedical Research Centre, University of Granada, Granada, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain. [Barricarte-Gurrea,A] Navarra Public Health Institute, Pamplona, Spain. [Barricarte-Gurrea,A] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology, L’Hospitalet de Llobregat, Spain. [Agudo,A] Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute—IDIBELL, L’Hospitalet de Llobregat, Spain. [Sánchez,MJ] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain., and E.U.-G. is supported by the Programa Operativo Fondo Social Europeo (FSE) de Andalucía (2014–2020) and Junta de Andalucía (reference DOC_01618).
Subjects: Metaanalisis, Frutas, Meat, Neoplasias de la próstata, Neoplasias pulmonares, Etanol, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms [Medical Subject Headings], Carne, Fruits, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Ingestión de alimentos, Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings], Breast cancer, Neoplasias colorrectales, Vegetables, Prospective Studies, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Prostate cancer, Revisión sistemática, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Diseases::Neoplasms [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena [Medical Subject Headings], Colorectal cancer, Fish, Verduras, Neoplasias de la mama, Intake, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], Lung cancer, Alcohol
Abstract: The European Prospective Investigation into Cancer and Nutrition (EPIC) is a multicentre prospective study conducted in 23 centres in 10 European countries. Here we review the findings from EPIC on the relationship between diet-related exposures and incidence or mortality from the four most frequent cancers in the European population: colorectal, breast, lung, and prostate cancer. We conducted a systematic review following PRISMA guidelines and identified 110 high-quality studies based on the EPIC cohort. Fruit and vegetable consumption had a protective effect against colorectal, breast, and lung cancer, whereas only fruit had a protective effect against prostate cancer. A higher consumption of fish and lower consumption of red and processed meat were related with a lower risk of colorectal cancer; and higher consumption of fatty fish with lower risk of breast cancer. Calcium and yogurt intake were found to protect against colorectal and prostate cancer. Alcohol consumption increased the risk for colorectal and breast cancer. Finally, adherence to the Mediterranean diet emerged as a protective factor for colorectal and breast cancer. The EPIC study results are in agreement with the latest evidence from leading authorities on cancer prevention and help to inform public prevention policies and strategies. Yes
Published: 2021

24. Transplantation of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in a Swine Model of Geographic Atrophy

Author: Angel Raya, Eduardo Fernández, Elisabeth Izquierdo, B. Aran, Eduardo Rodríguez-Bocanegra, E Trias, Marc Biarnés, Anna Veiga, Lucia L. Ferraro, Gema Martínez-Navarrete, Jordi Monés, Bernd Kuebler, Anna Duarri, Ricardo P. Casaroli-Marano, Eli Aguilera-Xiol, Míriam Garcia, Institut Català de la Salut, [Duarri A] Program for Clinical Translation of Regenerative Medicine in Catalonia–P-CMR[C], Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, 08908 Barcelona, Spain. National Stem Cell Bank-Barcelona Node, Biomolecular and Bioinformatics Resources Platform PRB2, ISCIII, IDIBELL, Hospitalet de Llobregat, 08908 Barcelona, Spain. Grup de Recerca en Oftalmologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Rodríguez-Bocanegra E, Biarnés M, García M, Ferraro LL] Barcelona Macula Foundation: Research for Vision, 08022 Barcelona, Spain. Institut de la Màcula, Centro Médico Teknon, 08022 Barcelona, Spain. [Martínez-Navarrete G] Networking Research Center of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain. Institute of Bioengineering, Universidad Miguel Hernández, 03202 Alicante, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: pig, Pathology, retina, Swine, Retinal Pigment Epithelium, Retina - Malalties - Trasplantació, Stem cells, células::células madre::células madre adultas::células madre pluripotentes inducidas [ANATOMÍA], Biology (General), Induced pluripotent stem cell, Spectroscopy, Transplantation of organs, iPSC, Animal models in research, General Medicine, Sense Organs::Eye::Pigment Epithelium of Eye::Retinal Pigment Epithelium [ANATOMY], Computer Science Applications, Chemistry, medicine.anatomical_structure, Interaction with host, Age-related macular degeneration (AMD), Regenerative medicine, Heterografts, Geographic atrophy, RPE, Stem cell, medicine.medical_specialty, QH301-705.5, Induced Pluripotent Stem Cells, Degeneració macular - Cirurgia, Cells::Stem Cells::Adult Stem Cells::Induced Pluripotent Stem Cells [ANATOMY], regenerative medicine, Biology, Cèl·lules mare adultes, Article, Catalysis, Retina, Inorganic Chemistry, Otros calificadores::Otros calificadores::Otros calificadores::/trasplante [Otros calificadores], Atrophy, Eye Diseases::Retinal Diseases::Retinal Degeneration::Macular Degeneration::Geographic Atrophy [DISEASES], Ipsc, stem cells, geographic atrophy, medicine, Animals, Humans, oftalmopatías::enfermedades de la retina::degeneración retiniana::degeneración macular::atrofia geográfica [ENFERMEDADES], Animal model, advanced cell therapy, Physical and Theoretical Chemistry, Advanced cell therapy, Molecular Biology, QD1-999, Other subheadings::Other subheadings::Other subheadings::/transplantation [Other subheadings], Pig, age-related macular degeneration (AMD), Retinal pigment epithelium, animal model, Organic Chemistry, medicine.disease, Antigens, Differentiation, Epithelium, eye diseases, Trasplantament d'òrgans, Transplantation, Disease Models, Animal, Gene Expression Regulation, sense organs, Models animals en la investigació, órganos de los sentidos::ojo::epitelio pigmentado ocular::epitelio pigmentado de la retina [ANATOMÍA]
Abstract: Modelo animal; Medicina regenerativa; Retina Model animal; Medicina regenerativa; Retina Animal model; Regenerative medicine; Retina Background: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). Methods: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO3 into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. Results: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. Conclusions: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA. This work was supported by Spanish Ministry of Science and Innovation (MICINN, RTI2018-095377-B-100), Instituto de Salud Carlos III ISCIII/FEDER (PRB2 PT13/0001/0041; TerCel RD16/0011/0024 and Oftared-RETICS RD16/0008), ERA-NET EuroNanoMed III/ISCIII (AC19/00080), the Catalan Government, AGAUR (2017-SGR-899), CERCA Programme/Generalitat de Catalunya, and by Fundació Carmen i Mª José Godó (Fundació CMJ Godó 2017).
Published: 2021
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25. Impact of the Epigenetically Regulated Hoxa-5 Gene in Neural Differentiation from Human Adipose-Derived Stem Cells

Author: Miguel López, Gloria Perazzoli, Consolación Melguizo, Fernando Setien, Raúl Ortiz, Rosa Hernández, María Berdasco, Manel Esteller, Cristina Jiménez-Luna, Jose Prados, [Hernández,R, Jiménez-Luna,C, Ortiz,R, Perazzoli,G, Prados,J, Melguizo,C] Center of Biomedical Research (CIBM), Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, Spain, Melguizo,C] Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, Granada, Spain. [Ortiz,R, Melguizo,C] Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain. [Setién,F, López,M, Esteller,M, Berdasco,M] Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, L’Hospitalet de Llobregat, Barcelona, Spain, [Setién,F, Esteller,M] Cancer Epigenetics Group, Cancer and Leukemia Epigenetics and Biology Program (PEBCL), Josep Carreras Leukemia Research Institute (IJC), Barcelona, Spain. [López,M, Berdasco,M] Epigenetic Therapies Group, Experimental and Clinical Hematology Program (PHEC), Josep Carreras Leukemia Research Institute, Barcelona, Spain, and Fundació La Marató TV3 (111430/31) and by the financial support from the CTS-107 Group from Junta de Andalucía.
Subjects: Epigenetic changes, QH301-705.5, Adipose tissue, Células madre mesenquimatosas, CRISPR/ dCas9, Hoxa-5, Biology, General Biochemistry, Genetics and Molecular Biology, Article, Cell therapy, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Malalties del sistema nerviós, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Essential [Medical Subject Headings], Neurosphere, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intercellular Signaling Peptides and Proteins::Nerve Growth Factors::Neuregulins [Medical Subject Headings], Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Base Sequence::Repetitive Sequences, Nucleic Acid::Tandem Repeat Sequences::Inverted Repeat Sequences::Clustered Regularly Interspaced Short Palindromic Repeats [Medical Subject Headings], Epigenetics, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Cell- and Tissue-Based Therapy [Medical Subject Headings], Biology (General), Gene, neuronal differentiation, mesenchymal stem cells, General Immunology and Microbiology, Fibroblast growth factor receptor 1, Mesenchymal stem cell, epigenetic changes, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], Nervous system Diseases, Adipose tissues, Mesenchymal Stem Cells, Epigenètica, Cell biology, Teixit adipós, Neuronal differentiation, Essential gene, Proteína 9 asociada a CRISPR, Diseases::Nervous System Diseases [Medical Subject Headings], Nervous system--Diseases, CRISPR/dCas9, General Agricultural and Biological Sciences, Epigénesis genética, Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological [Medical Subject Headings]
Abstract: Human adipose-derived mesenchymal stem cells (hASCs) may be used in some nervous system pathologies, although obtaining an adequate degree of neuronal differentiation is an important barrier to their applicability. This requires a deep understanding of the expression and epigenetic changes of the most important genes involved in their differentiation. We used hASCs from human lipoaspirates to induce neuronal-like cells through three protocols (Neu1, 2, and 3), determined the degree of neuronal differentiation using specific biomarkers in culture cells and neurospheres, and analyzed epigenetic changes of genes involved in this differentiation. Furthermore, we selected the Hoxa-5 gene to determine its potential to improve neuronal differentiation. Our results showed that an excellent hASC neuronal differentiation process using Neu1 which efficiently modulated NES, CHAT, SNAP25, or SCN9A neuronal marker expression. In addition, epigenetic studies showed relevant changes in Hoxa-5, GRM4, FGFR1, RTEL1, METRN, and PAX9 genes. Functional studies of the Hoxa-5 gene using CRISPR/dCas9 and lentiviral systems showed that its overexpression induced hASCs neuronal differentiation that was accelerated with the exposure to Neu1. These results suggest that Hoxa-5 is an essential gene in hASCs neuronal differentiation and therefore, a potential candidate for the development of cell therapy strategies in neurological disorders., Fundació La Marató TV3 (111430/31), CTS-107 Group from Junta de Andalucía
Published: 2021
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26. Bisphenol-A exposure and risk of breast and prostate cancer in the Spanish European Prospective Investigation into Cancer and Nutrition study

Author: Sandra Colorado, María José Sánchez, Ana Jimenez, Antonio Agudo, Pilar Amiano, Elena Salamanca-Fernández, Marcela Guevara, Nicolás Olea, Fernando Vela, Josu Delfrade, Juan P. Arrebola, Miguel Rodríguez-Barranco, Maria Dolores Chirlaque, [Salamanca-Fernández,E, Rodríguez-Barranco,M, Sánchez,MJ] Andalusian School of Public Health (EASP), Campus Universitario de Cartuja, Granada, Spain. [Salamanca-Fernández,E, Arrebola,JP, Vela,F, Olea,N, Sánchez,MJ] Instituto de Investigación Biosanitaria ibs. GRANADA, Granada, Spain. [Rodríguez-Barranco,M, Amiano,P, Delfrade,J, Chirlaque,MD, Colorado,S, Guevara,M, Sánchez,MJ] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Amiano,P, Jimenez,A] Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain. [Delfrade,J, Guevara,M] Navarra Public Health Institute, Pamplona, Spain. [Delfrade,J, Guevara,M] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Chirlaque,MD, Colorado,S] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque,MD] Department of Health and Sciences, University of Murcia, Murcia, Spain. [Colorado,S] Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia. [Arrebola,JP, Sánchez,MJ] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. [Olea,N] Department of Radiology, University of Granada, Granada, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, Nutrition and Cancer Group, Bellvitge Biomedical Research Institute - IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain., and This work was supported by the Ministry of economy and competitiveness and the National Institute of Health: Instituto de Salud Carlos III (ISCIII). Exps: PI14/00067, PI14/01716, PI14/01880, PI14/00556. BA15/00093. FFIS-CC 2016–06 AECC 'Junta provincial de Murcia'. FEDER and AECC 2015. Dr. J.P. Arrebola is under contract within Ramon y Cajal program (RYC-2016-20155, Ministerio de Economía, Industria y Competitividad, Spain). The EPIC-Spain cohort was supported by the Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain).
Subjects: Oncology, Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants [Medical Subject Headings], Male, Neoplasias de la próstata, Health, Toxicology and Mutagenesis, Endocrine Disruptors, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Prostate cancer, Breast cancer, Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Acrylates::Methacrylates::Bisphenol A-Glycidyl Methacrylate [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, Factors de risc en les malalties, Hazard ratio, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Health Care::Environment and Public Health::Public Health::Environmental Pollution::Environmental Exposure [Medical Subject Headings], Environmental pollutants, Diseases::Male Urogenital Diseases::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings], Bisphenol a, Endocrine disruptor, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], Neoplasias de la mama, Population study, Female, Public aspects of medicine, RA1-1270, Disruptores endocrinos, Adult, Risk, medicine.medical_specialty, endocrine system, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Risk factors in diseases, Population, Estudios de cohortes, Case-cohort, Check Tags::Male [Medical Subject Headings], Breast Neoplasms, Càncer de mama, Phenols, Bisfenol A glicidil metacrilato, Internal medicine, Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], medicine, Humans, Benzhydryl Compounds, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Càncer de pròstata, Proportional hazards model, business.industry, urogenital system, Research, Public Health, Environmental and Occupational Health, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Endocrine Disruptors [Medical Subject Headings], Prostatic Neoplasms, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Benzhydryl Compounds [Medical Subject Headings], Environmental Exposure, medicine.disease, Industrial medicine. Industrial hygiene, RC963-969, Check Tags::Female [Medical Subject Headings], Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Sensitivity and Specificity::Limit of Detection [Medical Subject Headings], business, Contaminantes ambientales
Abstract: This work was supported by the Ministry of economy and competitiveness and the National Institute of Health: Instituto de Salud Carlos III (ISCIII). Exps: PI14/00067, PI14/01716, PI14/01880, PI14/00556. BA15/00093. FFIS-CC 2016-06 AECC "Junta provincial de Murcia". FEDER and AECC 2015. Dr. J.P. Arrebola is under contract within Ramon y Cajal program (RYC-2016-20155, Ministerio de Economia, Industria y Competitividad, Spain). The EPIC-Spain cohort was supported by the Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology -ICO (Spain)., Background Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). Methods We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios. Results Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 (p = 0.022), 37% increase for tertile 2 (p = 0.034) and 31% increase for tertile 3 (p = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk. Conclusions We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk., Ministry of economy and competitiveness, National Institute of Health: Instituto de Salud Carlos III (ISCIII), AECC "Junta provincial de Murcia" PI14/00067- PI14/01716- PI14/01880- PI14/00556- BA15/00093- FFIS-CC 2016-06, Spanish Government RYC-2016-20155, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Catalan Institute of Oncology -ICO (Spain)
Published: 2021

27. SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade

Author: Romero, Octavio A., Vilarrubi, Andrea, Alburquerque-Béjar, Juan Jos, Gómez Moruno, Antonio, Andrades, Álvaro, Trastulli, Deborah, Pros, Eva, Setien, Fernando, Verdura, Sara, Farre, Lourdes, Martín-Tejera, Juan F., Llabata, Paula, Oaknin, Ana, Saigi, María, Piulats, Josep M., Matias-Guiu, Xavier, Medina, Pedro P., Vidal, August, Villanueva, Alberto, Sanchez-Cespedes, Montse, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Romero OA, Vilarrubi A, Alburquerque-Bejar JJ] Cancer Genetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Spain. [Gomez A] Grup de Recerca en Reumatologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Andrades A] Department of Biochemistry and Molecular Biology I. Faculty of Sciences, University of Granada, Granada, Spain. GENYO. Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Granada, Spain. [Trastulli D] Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute-IDIBELL Barcelona, Barcelona, Spain. [Oaknin A] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Jumonji Domain-Containing Histone Demethylases, Cancer therapy, General Physics and Astronomy, Gene Expression, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Histones, Transactivation, Mice, 0302 clinical medicine, Neoplasms, Càncer, Cancer, Histone Demethylases, Multidisciplinary, Chemistry, Càncer - Tractament, Histone deacetylase inhibitor, Nuclear Proteins, 3. Good health, 030220 oncology & carcinogenesis, SMARCA4, Epigenetics, Antioncogenes, Transcriptional Activation, Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasm [PHENOMENA AND PROCESSES], medicine.drug_class, Cell Survival, Science, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Antineoplastic Agents, General Biochemistry, Genetics and Molecular Biology, Article, neoplasias [ENFERMEDADES], 03 medical and health sciences, Cell Line, Tumor, medicine, Animals, Humans, Viability assay, Lung cancer, Resistència als medicaments, Tumors, fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos [FENÓMENOS Y PROCESOS], Oncogene, DNA Helicases, General Chemistry, Benzazepines, medicine.disease, Epigenètica, Antioncogens, Neoplasms [DISEASES], Histone Deacetylase Inhibitors, 030104 developmental biology, Pyrimidines, Drug Resistance, Neoplasm, Cancer research, Transcription Factors
Abstract: The authors thank Isabel Bartolessis (Cancer Genetics Group) at IJC for technical assistance. This work was supported by the Spanish Ministry of Economy and CompetitivityMINECO (grant number SAF-2017-82186R, to M.S.-C., and grant PI19/01320 to A. Villanueva) and from the Fundacion Cientifica of the Asociacion Espanola Contra el Cancer (AECC) (grant number GCB14142170MONT) to M.S.-C. A. Villanueva is also funded by the Department of Health of the Generalitat de Catalunya (2014SGR364). O.A. R. received a Juan de la Cierva postdoctoral contract (grant No. IJCI-2016-28201, until November 2019) and an AECC research contract (INVES19045ROME from December 2019). A. Vilarrubi, P.L. and A.A. are supported by pre-doctoral contracts from the Spanish MINECO (FPI-fellowship: PRE2018-084624, BES-2015-072204 and FPU17/00067). M.S. was supported by a Rio Hortega contract from the Instituto de Salud Carlos III (CM17/00180). L.F. received a European Union Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Actions grant agreement, number 799850., Despite the genetic inactivation of SMARCA4, a core component of the SWI/SNF-complex commonly found in cancer, there are no therapies that effectively target SMARCA4-deficient tumours. Here, we show that, unlike the cells with activated MYC oncogene, cells with SMARCA4 inactivation are refractory to the histone deacetylase inhibitor, SAHA, leading to the aberrant accumulation of H3K27me3. SMARCA4-mutant cells also show an impaired transactivation and significantly reduced levels of the histone demethylases KDM6A/UTX and KDM6B/JMJD3, and a strong dependency on these histone demethylases, so that its inhibition compromises cell viability. Administering the KDM6 inhibitor GSK-J4 to mice orthotopically implanted with SMARCA4-mutant lung cancer cells or primary small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), had strong anti-tumour effects. In this work we highlight the vulnerability of KDM6 inhibitors as a characteristic that could be exploited for treating SMARCA4-mutant cancer patients., Spanish Ministry of Economy and Competitivity-MINECO SAF-2017-82186R PI19/01320, Fundacion Cientifica of the Asociacion Espanola Contra el Cancer (AECC) GCB14142170MONT, Department of Health of the Generalitat de Catalunya 2014SGR364, Juan de la Cierva postdoctoral contract IJCI-2016-28201, AECC research contract INVES19045ROME, Spanish MINECO PRE2018-084624 BES-2015-072204 FPU17/00067, Instituto de Salud Carlos III European Commission CM17/00180, European Union Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Actions grant agreement 799850
Published: 2021

28. Stratifying the humoral risk of candidates to a solid organ transplantation: a proposal of the ENGAGE working group

Author: Olivier Thaunat, Nicos Kessaris, Lionel Couzi, Oriol Bestard, Marta Crespo, Bellvitge University Hospital [Barcelona, Spain], Bellvitge Biomedical Research Institute IDIBELL [Barcelona, Spain], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], IMIM-Hospital del Mar, Generalitat de Catalunya, Hospital del Mar Medical Research Institute [Barcelona, Spain] (IMIM), Universitat Pompeu Fabra [Barcelona] (UPF), Guy's Hospital [London], King‘s College London, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS 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), and Admin, Oskar
Subjects: Graft Rejection, [SDV.IMM] Life Sciences [q-bio]/Immunology, Humoral alloimmune response, Human leukocyte antigen, 030230 surgery, Binary division, Serology, 03 medical and health sciences, 0302 clinical medicine, Presensitization, HLA Antigens, Isoantibodies, Humans, Medicine, Transplantation, biology, business.industry, Graft Survival, Circulating antibodies, Organ Transplantation, Kidney Transplantation, Antibody-mediated rejection, Antibody mediated rejection, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Antibody, Solid organ transplantation, business
Abstract: International audience; Detection of circulating antibodies directed against human leukocyte antigen (HLA) molecules, which corresponds to the current definition of ‘sensitized patient’, has been shown to have a severe impact on both access to transplantation and, if the anti-HLA antibodies are specific to the selected donor, survival of the graft. However, not all donor-specific antibodies (DSA) are equally harmful to the graft and progress in the understanding of humoral memory has led to the conclusion that absence of DSA at transplantation does not rule out the possibility that the patient has a preformed cellular humoral memory against the graft (thereby defining a category of DSA-negative sensitized recipients). Technological progress has led to the generation of new assays that offer unprecedented precision in exploring the different layers (serological and cellular) of alloimmune humoral memory. Based on this recent knowledge, the EuropeaN Guidelines for the mAnagement of Graft rEcipients (ENGAGE) working group to propose an updated definition of sensitization in candidates for solid organ transplantation – one that moves away from the current binary division towards a definition based on homogenous strata with similar humoral risk.
Published: 2021
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29. Activation-induced deaminase is critical for the establishment of DNA methylation patterns prior to the germinal center reaction

Author: Dieter Weichenhan, Tianlu Li, Felipe Prosper, Sven Kracker, Pere Soler-Palacín, Lennart Hammarström, Andrea Martín-Nalda, Javier Rodríguez-Ubreva, Anne Durandy, Mónica Martínez-Gallo, Romina Dieli-Crimi, Anna G. Ferreté-Bonastre, Pavlo Lutsik, Ángel F. Álvarez-Prado, Laura Ciudad, Bodo Grimbacher, Jacques G. Rivière, Carsten Speckmann, Christoph Plass, Esteban Ballestar, Christian Klemann, Amaya Vilas-Zornoza, Hassan Abolhassani, Francesc Català-Moll, Roger Colobran, Institut Català de la Salut, [Català-Moll F, Ferreté-Bonastre AG, Li T, Ciudad L] Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), 08916 Badalona, Barcelona, Spain. Chromatin and Disease Group, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L’Hospitalet de Llobregat, Barcelona, Spain. [Weichenhan D, Lutsik P] Division of Cancer Epigenomics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. [Martínez-Gallo M, Dieli-Crimi R] Divisió d’Immunologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Immunologia Diagnòstica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Rivière JG, Martín-Nalda A, Soler-Palacín P] Unitat de Patologia Infecciosa i Immunodeficiències de Pediatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Grup de Recerca d’Infecció en els Pacients Pediàtrics Immunodeprimits, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Spain. [Colobran R] Divisió d’Immunologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Immunologia Diagnòstica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Spain. Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: AcademicSubjects/SCI00010, Bisulfite sequencing, ADN, Autoimmunity, Cèl·lules B - Immunologia, Hyper-IgM Immunodeficiency Syndrome, 0302 clinical medicine, AID, Activation-induced (cytidine) deaminase, Otros calificadores::Otros calificadores::/inmunología [Otros calificadores], 0303 health sciences, B-Lymphocytes, ADN - Metilació, medicine.anatomical_structure, células::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos B [ANATOMÍA], DNA methylation, Metilació, Rearrangements, Sequencing reveals, Cèl·lules B, Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA::Whole Genome Sequencing [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Naive B cell, Somatic hypermutation, Receptors, Antigen, B-Cell, Biology, Methylation, Cells::Antibody-Producing Cells::B-Lymphocytes [ANATOMY], 03 medical and health sciences, técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN::secuenciación del genoma completo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Other subheadings::Other subheadings::/immunology [Other subheadings], B-Cell receptor, Cytidine Deaminase, Genetics, medicine, Immune Tolerance, Humans, B cell, Seqüència de nucleòtids, 030304 developmental biology, B cells, Genetic Phenomena::DNA Methylation [PHENOMENA AND PROCESSES], Whole Genome Sequencing, Hypermutation, Gene regulation, Chromatin and Epigenetics, Germinal center, fenómenos genéticos::metilación del ADN [FENÓMENOS Y PROCESOS], DNA, DNA Methylation, Germinal Center, Molecular biology, Induced cytidine deaminase, Demethylation, Super-enhancers, DNA demethylation, biology.protein, Transcription factor, Class-switch recombination, Transcriptome, Immunologic Memory, 030217 neurology & neurosurgery
Abstract: Limfòcits b; Metilació de l'ADN; Genoma Linfocitos b; Metilación de ADN; Genoma B-lymphocytes; DNA methylation; Genome Activation-induced deaminase (AID) initiates antibody diversification in germinal center B cells by deaminating cytosines, leading to somatic hypermutation and class-switch recombination. Loss-of-function mutations in AID lead to hyper-IgM syndrome type 2 (HIGM2), a rare human primary antibody deficiency. AID-mediated deamination has been proposed as leading to active demethylation of 5-methycytosines in the DNA, although evidence both supports and casts doubt on such a role. In this study, using whole-genome bisulfite sequencing of HIGM2 B cells, we investigated direct AID involvement in active DNA demethylation. HIGM2 naïve and memory B cells both display widespread DNA methylation alterations, of which ∼25% are attributable to active DNA demethylation. For genes that undergo active demethylation that is impaired in HIGM2 individuals, our analysis indicates that AID is not directly involved. We demonstrate that the widespread alterations in the DNA methylation and expression profiles of HIGM2 naïve B cells result from premature overstimulation of the B-cell receptor prior to the germinal center reaction. Our data support a role for AID in B cell central tolerance in preventing the expansion of autoreactive cell clones, affecting the correct establishment of DNA methylation patterns. Spanish Ministry of Science, Innovation and Universities [SAF2017-88086-R to E.B.]; cofunded by FEDER funds/European Regional Development Fund (ERDF)—a way to build Europe. E.B is supported by Instituto de Salud Carlos III (ISCIII), Ref. AC18/00057, associated with i-PAD project (ERARE European Union program); P.L. and C.P. are supported by the German Cancer Aid project CO-CLL [70113869]; B.G. is funded by the Deutsche Forschungsgemeinschaft [GR1617/14-1/iPAD, SFB1160/2_B5, RESIST–EXC 2155–Project ID 390874280, CIBSS–EXC-2189–Project ID 390939984]; BMBF [GAIN 01GM1910A]. Funding for open access charge: Spanish Ministry of Science, Innovation and Universities [SAF2017-88086-R].
Published: 2021

30. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author: Isabel Almeida, Divi Cornec, Torsten Witte, Tania F. Rowley, Tianlu Li, Elena Carnero-Montoro, Mariana Brandão, Antonio Garcia-Gomez, Nancy Azevedo, Esmeralda Neves, Ana Lisa Taylor Tavares, Ana Campar, Jacques-Olivier Pers, Nicolas Hunzelmann, Ellen De Langhe, Ernst R. Dow, Magdolna Deák, Jorge Kageyama, Francisco Javier Garrancho, Gerard Espinosa, Carlo Chizzolini, Laleh Khodadadi, Falk Hiepe, Maria Angeles Aguirre-Zamorano, Marta E. Alarcón-Riquelme, Rosario Lopez-Pedrera, Anne Buttgereit, Ricard Cervera, Javier Rodríguez-Ubreva, Fernanda Genre, Jerome Wojcik, Begoña Ubilla Garcia, Héctor Navarro-Linares, Maria Orietta Borghi, N.T. Baerlecken, Katja Kniesch, Yolanda Jiménez Gómez, Zuzanna Makowska, Martin Kerick, Elena Trombetta, Pierre-Emmanuel Jouve, Lorenzo Beretta, Ricardo Blanco Alonso, Bénédicte Rouvière, Isabel Díaz Quintero, Michael Zauner, Ralf Lesche, Daniel Toro-Domínguez, Manuel Rodriguez Maresca, Attila Balog, Pier Luigi Meroni, Qingyu Cheng, Georg Stummvoll, Johan Frostegård, Javier Martín, Márta Bocskai, Joerg Mueller, Tommaso Schioppo, Chris Chamberlain, Sonja Dulic, László Kovács, Raquel López Mejías, Velia Gerl, Francesc Català-Moll, Robert J. Benschop, Sara Remuzgo, Carolina Artusi, María Teruel, Eduardo Collantes-Estevez, Miguel A. González-Gay, Silvia Thiel, Bernard Lauwerys, Maria Gerosa, Yves Renaudineau, Pedro Carmona-Sáez, Raquel Faria, Rocío Aguilar-Quesada, Sepideh Babaei, Nuria Barbarroja, Maria Hernandez-Fuentes, María Concepción Fernández Roldán, Sambasiva P. Rao, Aurélie De Groof, Montserrat Alvarez, Anne-Lise Maudoux, Sikander Hayat, Guillermo Barturen, Maria Juarez, Damiana Álvarez-Errico, Alfonso Corrales Martínez, Julie Ducreux, Lucas Le Lann, Norberto Ortego, Jacqueline Marovac, Sandrine Jousse-Joulin, Enrique Raya, Laurence Laigle, Concepción Marañón, Esteban Ballestar, Manuel Martínez-Bueno, Barbara Vigone, Rik Lories, Doreen Belz, Gabriella Kádár, Gaia Montanelli, Fátima Farinha, Divya Thiagaran, M.C. Castro-Villegas, Christophe Jamin, Alain Saraux, Carlos Vasconcelos, Emanuele de Rinaldis, Donatienne Wynar, Enrique de Ramón, Antonio López-Berrio, Tania Anjos, Alejandro Escudero-Contreras, Ian White, Valérie Devauchelle-Pensec, Ignasi Rodríguez-Pintó, Nieves Varela, Quentin Simon, Michaela Lehner, Inmaculada Jiménez Moleón, Aleksandra Maria Dufour, Rafaela Ortega-Castro, Marialbert Acosta-Herrera, Mcdonald Fiona Mcdougall, Yiannis Ioannou, Jonathan Cremer, António Marinho, Jordi Martorell-Marugán, Centre for Genomics and Oncological Research (GENYO) Pfizer, University of Granada, Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), University of Barcelona, Centro de Genomica e Investigacion Oncologica (GENYO), Department of Bioinformatics, Center for Genomics and Oncological Research (GENYO), Granada, Spain, Institute of Parasitology and Biomedicine (IPB - GRANADA), Spanish National Research Council (CSIC), LabEX IGO Immunothérapie Grand Ouest, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), UCB Pharma, Slough SL1 3WE, United Kingdom, Centre for Genomics and Oncological Reearch (GENYO), Andalusian Public Health System Biobank, Granada, Spain, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Universidade do Porto, Servico de Immunologica EX-CICAP, Servico de Imunologica EX-CICAP, Unidade de Imunologia Clínica, Centro Hospitalar do Porto, Portugal, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Scleroderma Unit, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Bellvitge Biomedical Research Institute IDIBELL [Barcelona, Spain], Karolinska Institutet [Stockholm], Universidad de Cantabria [Santander], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Klinikum Leverkusen Teaching Hospital of the University of Cologne, Hannover Medical School [Hannover] (MHH), Medical University of Vienna, Vienna, Austria, Medical University of Vienna, General Hospital of Vienna, Hospital Reina Sofía, Hospital Regional Universitario de Málaga [Spain], Hospital Universitario San Cecilio, Hospital Universitario Virgen de las Nieves, Università degli Studi di Milano [Milano] (UNIMI), Université Catholique de Louvain = Catholic University of Louvain (UCL), AltraBio [Lyon], Geneva University Hospital (HUG), University of Szeged [Szeged], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Sanofi [Cambridge, MA, USA], Sanofi Genzyme, Eli Lilly, Indianapolis, USA, UCB Celltech [Slough, UK], Institut de Recherches Internationales Servier [Suresnes] (IRIS), Quartzbio, Geneva, Instituto de Parasitología y Biomedicina 'López-Neyra', Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico [Milan, Italy], Bellvitge Institute for Biomedical Research, Bayer HealthCare, Berlin, Centre for Genomics and Oncological Research Pfizer [Granada, Spain], University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], Michel, Geneviève, Universidad de Granada = University of Granada (UGR), Nantes Université (Nantes Univ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Universidade do Porto = University of Porto, University of Cologne, Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Università degli Studi di Milano = University of Milan (UNIMI), Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, and UCL - (SLuc) Service de rhumatologie
Subjects: 0301 basic medicine, Adult, Epigenomics, Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cross-sectional study, Immunology, Arthritis, Bioinformatics, Scleroderma, Autoimmune Diseases, Transcriptome, Arthritis, Rheumatoid, 03 medical and health sciences, Epigenome, 0302 clinical medicine, Rheumatology, medicine, Immunology and Allergy, Cluster Analysis, Humans, Lupus Erythematosus, Systemic, Undifferentiated Connective Tissue Diseases, Aged, Mixed Connective Tissue Disease, 030203 arthritis & rheumatology, Inflammation, Science & Technology, Lupus erythematosus, Scleroderma, Systemic, business.industry, Gene Expression Profiling, Case-control study, Middle Aged, medicine.disease, Antiphospholipid Syndrome, 3. Good health, Clinical trial, Gene expression profiling, 030104 developmental biology, Cross-Sectional Studies, Sjogren's Syndrome, Case-Control Studies, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Interferons, business, Life Sciences & Biomedicine
Abstract: OBJECTIVE: Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. METHODS: Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. RESULTS: Four clusters were identified and validated. Three were pathologic, representing "inflammatory," "lymphoid," and "interferon" patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. CONCLUSION: Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases. ispartof: ARTHRITIS & RHEUMATOLOGY vol:73 issue:6 pages:1073-1085 ispartof: location:United States status: published
Published: 2021
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31. Malignant Arrhythmogenic Role Associated with RBM20: A Comprehensive Interpretation Focused on a Personalized Approach

Author: Jordà, Paloma, Toro, Rocío, Diez, Carles, Salazar-Mendiguchía, Joel, Fernandez-Falgueras, Anna, Perez-Serra, Alexandra, Coll, Monica, Puigmulé, Marta, Arbelo, Elena, García-Álvarez, Ana, Sarquella-Brugada, Georgia, Cesar, Sergi, Tiron, Coloma, Iglesias, Anna, Brugada, Josep, Brugada, Ramon, Campuzano, Oscar, [Jordà,P, Arbelo,E, García-Álvarez,A, Brugada,J] Cardiology Department, Hospital Clinic, University of Barcelona-IDIBAPS, Barcelona, Spain. [Toro,R] Medicine Department, School of Medicine, University of Cadiz, Cadiz, Spain. [Toro,R] Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cadiz, Spain. [Diez,C, Salazar-Mendiguchía,J] Cardiovascular Diseases Research Group Bellvitge Biomedical Research Institute (IDIBELL) Hospitalet de Llobregat, Barcelona, Spain. [Diez,C] Advanced Heart Failure and Heart Transplant Unit Department of Cardiology Bellvitge University Hospital Hospitalet de Llobregat, Barcelona, Spain. [Fernandez-Falgueras,A, Perez-Serra,A, Coll,M, Puigmulé,M, Iglesias,A, Brugada,R, Campuzano,O] Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain. [Perez-Serra,A, Brugada,J, Campuzano,O] Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. [Sarquella-Brugada,G, Cesar,S, Campuzano,O] Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Cardiology Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain. [Sarquella-Brugada,G, Campuzano,O] Medical Science Department, School of Medicine, University of Girona, Girona, Spain. [Tiron,C, Brugada,R] Cardiology Service, Hospital Josep Trueta, University of Girona, Girona, Spain., and This work was supported by Obra Social 'La Caixa Foundation' (LCF/PR/GN16/50290001 and LCF/PR/GN19/50320002), Fondo Investigacion Sanitaria (FIS PI16/01203 and FIS, PI17/01690) from Instituto Salud Carlos III (ISCIII), and 'Fundacio Privada Daniel Bravo Andreu'. CIBERCV is an initiative of the ISCIII, Spanish Ministry of Economy and Competitiveness.
Subjects: RBM20, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Anatomy::Musculoskeletal System::Muscles [Medical Subject Headings], Dilated cardiomyopathy, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nucleoproteins::RNA-Binding Proteins [Medical Subject Headings], Supresión genética, Genética, Arritmias cardíacas, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Sudden cardiac death, Cardiomiopatía dilatada, Diseases::Cardiovascular Diseases::Heart Diseases::Arrhythmias, Cardiac [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::RNA Processing, Post-Transcriptional::RNA Splicing [Medical Subject Headings], Muerte súbita cardíaca, Diseases::Cardiovascular Diseases::Heart Diseases::Cardiomyopathies [Medical Subject Headings], Genetics, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::RNA Processing, Post-Transcriptional::RNA Splicing::Alternative Splicing [Medical Subject Headings], Arrhythmia
Abstract: The RBM20 gene encodes the muscle-specific splicing factor RNA-binding motif 20, a regulator of heart-specific alternative splicing. Nearly 40 potentially deleterious variants in RBM20 have been reported in the last ten years, being found to be associated with highly arrhythmogenic events in familial dilated cardiomyopathy. Frequently, malignant arrhythmias can be a primary manifestation of disease. The early recognition of arrhythmic genotypes is crucial in avoiding lethal episodes, as it may have an impact on the adoption of personalized preventive measures. Our study performs a comprehensive update of data concerning rare variants in RBM20 that are associated with malignant arrhythmogenic phenotypes with a focus on personalized medicine. Yes
Published: 2021

32. EV-associated miRNAs from pleural lavage as potential diagnostic biomarkers in lung cancer

Author: [Roman-Canal B] Department of Pathology and Molecular Genetics/Oncologic, University of Lleida, Lleida, Spain. Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain. CIBERONC, Madrid, Spain. Department of Pathology, University Hospital of Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Spain. [Moiola CP] Department of Pathology and Molecular Genetics/Oncologic, University of Lleida, Lleida, Spain. Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain. CIBERONC, Madrid, Spain. Recerca biomèdica en ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Gatius S, Ruiz-Miró M] Department of Pathology and Molecular Genetics/Oncologic, University of Lleida, Lleida, Spain. Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain. CIBERONC, Madrid, Spain. [Bonnin S] Centre for Genomic Regulation (CRG), The Barcelona Institute or Science and Technology, Barcelona, Spain. [González E] Exosomes Laboratory and Metabolomics Platform. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain. CIBEREHD, Madrid, Spain. [Gil-Moreno A] Recerca biomèdica en ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Servei d’Oncologia en Ginecologia, Vall Hebron Hospital Universitari, Barcelona, Spain. CIBERONC, Madrid, Spain. [Colas E] Recerca biomèdica en ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. CIBERONC, Madrid, Spain and Hospital Universitari Vall d'Hebron
Subjects: MicroARN, Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Antisense::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::MicroRNAs [CHEMICALS AND DRUGS], Enfermedades Respiratorias::Enfermedades Pulmonares::Enfermedades Respiratorias::Neoplasias Pulmonares [ENFERMEDADES], Marcadors tumorals, Pulmons - Càncer - Diagnòstic, Other subheadings::/diagnosis [Other subheadings], Otros calificadores::/diagnóstico [Otros calificadores], factores biológicos::biomarcadores::marcadores tumorales [COMPUESTOS QUÍMICOS Y DROGAS], Biological Factors::Biomarkers::Biomarkers, Tumor [CHEMICALS AND DRUGS], Respiratory Tract Diseases::Lung Diseases::Respiratory Tract Diseases::Lung Neoplasms [DISEASES], Ácidos Nucleicos, Nucleótidos y Nucleósidos::Elementos sin Sentido (Genética)::ARN sin Sentido::MicroARNs [COMPUESTOS QUÍMICOS Y DROGAS]
Published: 2021

33. Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Author: Teruel, María, Barturen, Guillermo, Martínez Bueno, Manuel, Castellini Pérez, Olivia, Barroso Gil, Miguel, Povedano, Elena, Kerick, Martin, Català Moll, Francesc, Makowska, Zuzanna, Buttgereit, Anne, Beretta, Lorenzo, Chizzolini, Carlo, Zuber, Aleksandra, Wynar, Donatienne, Kovács, Laszló, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Rodriguez Maresca, Manuel, López Berrio, Antonio, Aguilar Quesada, Rocío, Navarro Linares, Héctor, Alvarez, Montserrat, Álvarez Errico, Damiana, Azevedo, Nancy, Barbarroja, Nuria, Cheng, Qingyu, Cremer, Jonathan, Groof, Aurélie de, Langhe, Ellen de, Ducreux, Julie, Dufour, Aleksandra, Hernández Fuentes, María, Khodadadi, Laleh, Kniesch, Katja, Li, Tianlu, López Pedrera, Chary, Marañón, Concepción, Muchmore, Brian, Neves, Esmeralda, Rouvière, Bénédicte, Simon, Quentin, Trombetta, Elena, Varela, Nieves, Witte, Torsten, Pers, Jacques-olivier, Ballestar, Esteban, Martin, Javier, Carnero Montoro, Elena, Alarcón Riquelme, Marta, Precisesads Clinical Consortium, Precisesads Flow Cytometry Study Group, Vigone, Barbara, Pers, Jacques Olivier, Saraux, Alain, Devauchelle-Pensec, Valérie, Cornec, Divi, Jousse-Joulin, Sandrine, Lauwerys, Bernard, Maudoux, Anne-lise, Vasconcelos, Carlos, Tavares, Ana, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Ángel, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Cervera, Ricard, Rodríguez Pintó, Ignasi, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega Castro, Rafaela, Aguirre Zamorano, Mª Angeles, Escudero Contreras, Alejandro, Castro Villegas, Mª Carmen, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Jiménez Moleón, Inmaculada, Ramon, Enrique de, Díaz Quintero, Isabel, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, PRECISESADS Clinical Consortium, PRECISESADS Flow Cytometry Study Group, [Teruel,M, Barturen,G, Martínez-Bueno,M, Castellini-Pérez,O, Barroso-Gil,M, Povedano,E, Marañón,C, Carnero-Montoro,E, Alarcón-Riquelme,ME] GENYO, Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain. [Kerick,M, Martin,J] IPBLN-CSIC, Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científcas, Granada, Spain. [Català-Moll,F, Ballestar,E] Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), Badalona, Barcelona, Spain. [Català-Moll,F, Ballestar,E] IDIBELL, Bellvitge Biomedical Research Institute L’Hospitalet de Llobregat, Barcelona, Spain. [Makowska,Z, Buttgereit,A] Pharmaceuticals Division, Bayer Pharma Aktiengesellschaft, Berlin, Germany. [Pers,JO] Université de Brest, INSERM, Labex IGO, CHU de Brest, Brest, France.[Alarcón-Riquelme,ME] Institute for Environmental Medicine, Karolinska Institutet, Solna, Sweden., and Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement nº 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies’ in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucía (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuró for design support.
Subjects: Epigenomics, Male, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation [Medical Subject Headings], Autoimmune diseases, Gene Expression, Quantitative trait, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Interferons [Medical Subject Headings], 0302 clinical medicine, Rheumatic diseases, HLA Antigens, Genetics, Regulation of gene expression, 0303 health sciences, education.field_of_study, Multidisciplinary, Malalties autoimmunitàries, Molecular medicine, Epigenetic, Autoanticuerpos, Genomics, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::Epigenomics [Medical Subject Headings], 3. Good health, Sjogren's Syndrome, DNA methylation, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::DNA Methylation [Medical Subject Headings], Medicine, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens [Medical Subject Headings], Epigenetics, Female, Phenomena and Processes::Genetic Phenomena::Genetic Variation [Medical Subject Headings], Extracellular matrix organization, Science, Population, Check Tags::Male [Medical Subject Headings], Human leukocyte antigen, Biology, Variación genética, Article, 03 medical and health sciences, Rheumatology, Enfermedades autoinmunes, Diseases::Immune System Diseases::Autoimmune Diseases [Medical Subject Headings], Immunogenetics, Diseases::Immune System Diseases::Autoimmune Diseases::Arthritis, Rheumatoid::Sjogren's Syndrome [Medical Subject Headings], Humans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies [Medical Subject Headings], education, Gene, 030304 developmental biology, Autoantibodies, 030203 arthritis & rheumatology, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], Genetic Variation, DNA Methylation, Epigenètica, Check Tags::Female [Medical Subject Headings], Gene Expression Regulation, Epigenómica, Síndrome de Sjögren, Interferons, Expresión génica
Abstract: Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies' in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucia (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuro for design support., Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population., Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Program (FP7/2007-2013) 115,565, EFPIA companies, Junta de Andalucia PI/0017/2016, Innovative Medicines Initiative 2 Joint Undertaking 806975 European Union's Horizon 2020 research and innovation programme, EFPIA, Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness FJCI_2014_20652
Published: 2021

34. Impact of the COVID-19 pandemic on tuberculosis management in Spain

Author: M. A. Jimenez-Fuentes, R. Zules, J.V. San Martin, Iris García, I. Sanjoaquin, J. F. Garcia Rodriguez, N. Jove, V. Pomar, Teresa Tórtola, J. Cacho, María Luisa Aznar, Nuria Saborit, F. Sanchez Martinez, Juan Espinosa-Pereiro, Adrián Sánchez-Montalvá, Lisbeth Goncalves De Freitas, M.L. De Souza-Galvao, J. Llenas-Garcia, A. Vitoria, S. Perez-Recio, Eugenia Gallardo, Israel Molina, Institut Català de la Salut, [Aznar ML, Sánchez-Montalvá A] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. PROSICS Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Mycobacteria Infection Study Group (GEIM, Spanish acronym) from Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC, Spanish acronym), Spain. [Espinosa-Pereiro J, Saborit N, Molina I] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. PROSICS Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Jové N, Sánchez Martinez F] Unitat Clínica de Tuberculosis, Hospital del Mar, Barcelona, Spain. [Pérez-Recio S] Tuberculosis Unit, Service of Infectious Diseases, Bellvitge University Hospital-Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, L’Hospitalet de Llobregat, Spain. [Jiménez-Fuentes MÁ, De Souza-Galvao ML] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Tórtola T] Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Zules R] Servei de Medicina Preventiva i Epidemiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Pediatrics, medicine.medical_treatment, España, Infectious and parasitic diseases, RC109-216, 0302 clinical medicine, Pandemic, Other subheadings::/diagnosis [Other subheadings], virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 030212 general & internal medicine, Child, Transmission (medicine), Household contact screening, Tuberculosi - Diagnòstic - Espanya, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], General Medicine, Geographic Locations::Europe::Spain [GEOGRAPHICALS], Infectious Diseases, Impact, Pandèmia de COVID-19, 2020- - Espanya, Tuberculosis management, Microbiology (medical), medicine.medical_specialty, Tuberculosis, Coronavirus disease 2019 (COVID-19), Tuberculosi, Infecciones por coronavirus, 030106 microbiology, Otros calificadores::/diagnóstico [Otros calificadores], Article, 03 medical and health sciences, Tuberculosis diagnosis, Epidemia, medicine, Humans, Transmission, Bacterial Infections and Mycoses::Bacterial Infections::Gram-Positive Bacterial Infections::Actinomycetales Infections::Mycobacterium Infections::Tuberculosis [DISEASES], Pandemics, Retrospective Studies, localizaciones geográficas::Europa (continente)::España [DENOMINACIONES GEOGRÁFICAS], business.industry, SARS-CoV-2, COVID-19, Retrospective cohort study, medicine.disease, infecciones bacterianas y micosis::infecciones bacterianas::infecciones por bacterias grampositivas::infecciones por Actinomycetales::micobacteriosis::tuberculosis [ENFERMEDADES], Spain, Contact Tracing, business, Contact tracing
Abstract: Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impacte; Tuberculosi Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impacto; Tuberculosis Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Impact; Tuberculosis Background The impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown. Methods Participating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected. Results A total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 ( P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 ( P = 0.001). Conclusions The COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures. This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. MLA was supported by a postdoctoral grant “Rio Hortega” and ASM was supported by a postdoctoral grant “Juan Rodés” (JE18/00022) from the Instituto de Salud Carlos III through the Spanish Ministry of economy and competitiveness.
Published: 2021

35. Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis

Author: Colomé, Nuria, Abián, Joaquín, Aloria, Kerman, Arizmendi, Jesús M., Barceló-Batllori, Silvia, Braga-Lagache, Sophie, Burlet-Schiltz, Odile, Carrascal, Montserrat, Casal, J. Ignacio, Chicano-Gálvez, Eduardo, Chiva, Cristina, Clemente, Luis Felipe, Elortza, Felix, Estanyol, Josep M., Fernández-Irigoyen, Joaquín, Fernandez-Puente, Patricia, Fidalgo, María José, Froment, Carine, Fuentes, Manuel, Fuentes-Almagro, Carlos, Gay, Marina, Hainard, Alexandre, Heller, Manfred, Hernández, María Luisa, Ibarrola, Nieves, Iloro, Ibon, Kieselbach, Thomas, Lario, Antonio, Locard-Paulet, Marie, Marina, Anabel, Martín, Luna, Morato-López, Esperanza, Muñoz, Javier, Navajas, Rosana, Odena, Maria Antonia, Odriozola, Leticia, Oliveira, Eliandre, Paradela, Alberto, Pasquarello, Carla, Ríos, Vivian de los, Ruiz-Romero, Cristina, Sabidó, Eduard, Sánchez del Pino, Manuel M., Sancho, Jaime, Santamaría, Enrique, Schaeffer-Reiss, Christine, Schneider, Justine, De la Torre, Carolina, Valero, M. Luz, Vilaseca, Marta, Wu, Shuai, Wu, Linfeng, Ximénez de Embún, Pilar, Canals, Francesc, Corrales, Fernando J., ProteoRed-ISCIII, EuPA, Instituto de Salud Carlos III, Abián, Joaquín [0000-0003-2823-5429], Aloria, Kerman [0000-0001-7268-7700], Arizmendi, Jesús M. [0000-0002-1412-4042], Barceló-Batllori, Silvia [0000-0002-5352-9747], Burlet-Schiltz, Odile [0000-0002-3606-2356], Carrascal, Montserrat [0000-0002-0205-2176], Casal, J. Ignacio [0000-0003-1085-2840], Chicano-Gálvez, Eduardo [0000-0002-9481-9628], Chiva, Cristina [0000-0001-8150-6203], Elortza, Felix [0000-0001-8839-5438], Estanyol, Josep M. [0000-0001-8621-0057], Fernández-Irigoyen, Joaquín [0000-0001-5072-4099], Fernandez-Puente, Patricia [0000-0001-9968-1034], Froment, Carine [0000-0003-3688-5560], Fuentes-Almagro, Carlos [0000-0001-9940-9065], Gay, Marina [0000-0002-8827-7092], Heller, Manfred [0000-0002-6364-7325], Ibarrola, Nieves [0000-0002-9259-5739], Iloro, Ibon [0000-0002-9537-1714], Kieselbach, Thomas [0000-0001-5577-2938], Lario, Antonio [0000-0002-7457-2402], Locard-Paulet, Marie [0000-0003-2879-9224], Morato-López, Esperanza [0000-0003-4768-895X], Muñoz, Javier [0000-0003-3288-3496], Navajas, Rosana [0000-0002-4481-0553], Odena, Maria Antonia [0000-0002-4530-7829], Oliveira, Eliandre [0000-0003-4771-5719], Paradela, Alberto [0000-0001-6837-7056], Ríos, Vivian de los [0000-0001-5582-6879], Ruiz-Romero, Cristina [0000-0001-7649-9803], Sabidó, Eduard 0000-0001-6506-7714], Sánchez del Pino, Manuel M. [0000-0001-9696-7600], Sancho, Jaime [0000-0003-3852-7951], Santamaría, Enrique [0000-0001-8046-8102], Schaeffer-Reiss, Christine [0000-0003-0672-1979], Valero, M. Luz [0000-0002-2082-4600], Vilaseca, Marta [0000-0002-1666-1300], Canals, Francesc [0000-0002-0650-1135], Institut Català de la Salut, [Colomé N, Martín L, Canals F] ProteoRed-ISCIII, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Abian J] ProteoRed-ISCIII, Instituto de Investigaciones Biomédicas de Barcelona, IIBB-CSIC/IDIBAPS, Barcelona, Spain. [Aloria K] ProteoRed-ISCIII, Proteomics Core Facility-SGIKER, University of the Basque Country (UPV/EHU), Leioa, Spain. [Arizmendi JM] Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Spain. [Barceló-Batllori S] ProteoRed-ISCIII, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. [Braga-Lagache S] Department for BioMedical Research (DBMR), Proteomics and Mass Spectrometry Core Facility, University of Bern, Bern, Switzerland, Vall d'Hebron Barcelona Hospital Campus, Abián, Joaquín, Aloria, Kerman, Arizmendi, Jesús M., Barceló-Batllori, Silvia, Burlet-Schiltz, Odile, Carrascal, Montserrat, Casal, J. Ignacio, Chicano-Gálvez, Eduardo, Chiva, Cristina, Elortza, Felix, Estanyol, Josep M., Fernández-Irigoyen, Joaquín, Fernandez-Puente, Patricia, Froment, Carine, Fuentes-Almagro, Carlos, Gay, Marina, Heller, Manfred, Ibarrola, Nieves, Iloro, Ibon, Kieselbach, Thomas, Lario, Antonio, Locard-Paulet, Marie, Morato-López, Esperanza, Muñoz, Javier, Navajas, Rosana, Odena, Maria Antonia, Oliveira, Eliandre, Paradela, Alberto, Ríos, Vivian de los, Ruiz-Romero, Cristina, Sánchez del Pino, Manuel M., Sancho, Jaime, Santamaría, Enrique, Schaeffer-Reiss, Christine, Valero, M. Luz, Vilaseca, Marta, Canals, Francesc, Universidad Pública de Navarra. Departamento de Ciencias de la Salud, and Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila
Subjects: Proteomics, enrichment, Standardization, Proteome, Computer science, Cellbiologi, Mass-spectrometry, Biophysics, 610 Medicine & health, Computational biology, Bioinformatik och systembiologi, Proteòmica, Chemical Phenomena::Biochemical Phenomena::Phosphorylation [PHENOMENA AND PROCESSES], Biochemistry, Experiment, Fosforilació, Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Proteomics [DISCIPLINES AND OCCUPATIONS], Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Reproducibility of Results [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Inter-laboratory, Phosphorylation, quality control, Epidemiologia, Bioinformatics and Systems Biology, Fosfoproteïnes, fenómenos químicos::fenómenos bioquímicos::fosforilación [FENÓMENOS Y PROCESOS], disciplinas de las ciencias naturales::disciplinas de las ciencias biológicas::bioquímica::proteómica [DISCIPLINAS Y OCUPACIONES], Phosphoproteomics, Biochemistry and Molecular Biology, Reproducibility of Results, Cell Biology, Reference Standards, técnicas de investigación::métodos epidemiológicos::diseño de la investigación epidemiológica::reproducibilidad de los resultados [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Normalització, Phosphoproteins, Reference sample, Phosphoproteome, Laboratory experiment, Laboratories, Biokemi och molekylärbiologi
Abstract: 6 p.-2 fig.-2 tab., Global analysis of protein phosphorylation by mass spectrometry proteomic techniques has emerged in the last decades as a powerful tool in biological and biomedical research. However, there are several factors that make the global study of the phosphoproteome more challenging than measuring non-modified proteins. The low stoichiometry of the phosphorylated species and the need to retrieve residue specific information require particular attention on sample preparation, data acquisition and processing to ensure reproducibility, qualitative and quantitative robustness and ample phosphoproteome coverage in phosphoproteomic workflows. Aiming to investigate the effect of different variables in the performance of proteome wide phosphoprotein analysis protocols, ProteoRed-ISCIII and EuPA launched the Proteomics Multicentric Experiment 11 (PME11). A reference sample consisting of a yeast protein extract spiked in with different amounts of a phosphomix standard (Sigma/Merck) was distributed to 31 laboratories around the globe. Thirty-six datasets from 23 laboratories were analyzed. Our results indicate the suitability of the PME11 reference sample to benchmark and optimize phosphoproteomics strategies, weighing the influence of different factors, as well as to rank intra and inter laboratory performance., ProteoRed, PRB3 is supported by grant PT17/0019/0001, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF.
Published: 2021
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36. Social mobility and healthy behaviours from a gender perspective in the Spanish multicase-control study (MCC-Spain)

Author: Leire Gil-Majuelo, Tania Fernández-Villa, Nuria Aragonés, Pilar Amiano, Esther Gracia-Lavedan, Juan Alguacil, Inmaculada Salcedo-Bellido, A. Delgado-parrilla, Cristina O'Callaghan-Gordo, Virginia Lope, Maria Dolores Chirlaque, Marta Maria Rodriguez-Suarez, Rafael Marcos-Gragera, Marcela Guevara, Dolores Salas, Rosana Peiró-Pérez, Inés Gómez-Acebo, Gemma Castaño-Vinyals, Marina Pollán, Trinidad Dierssen-Sotos, M. Pinto-carbó, Manolis Kogevinas, Antonio J. Molina, Conchi Moreno-Iribas, Mercedes Vanaclocha-Espi, Beatriz Pérez-Gómez, Mireia Obón-Santacana, Ana Molina-Barceló, Universidad de Cantabria, Universitat Oberta de Catalunya (UOC), Universidad de Granada, Universidad de Huelva, Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBEResp), Instituto de Salud Carlos III, European Regional Development Fund, Fundación Marqués de Valdecilla, International Cancer Genome Consortium, Ministerio de Economía y Competitividad (España), Red Temática de Investigación Cooperativa en Cáncer (España), Junta de Castilla y León (España), Regional Government of Andalusia (España), Generalitat Valenciana (España), Fundación La Caixa, Basque Government (España), Gobierno de Murcia, Unión Europea. Comisión Europea, Asociación Española Contra el Cáncer, Government of Catalonia (España), Fundación Caja de Ahorros de Asturias, University of Oviedo (España), [Pinto-Carbo,M, Molina-Barcelo,A, Vanaclocha-Espi,M, Salas,D] Cancer and Public Health Area, Foundation for the Promotion of the Research in Healthcare and Biomedicine (FISABIO-Salud Pública), Valencia, Valencian Community, Spain. [Peiró-Pérez,R] Inequalities Area, Foundation for the Promotion of the Research in Healthcare and Biomedicine (FISABIO-Salud Pública), Valencia, Valencian Community, Spain. [Peiró-Pérez,R, Salas,D] General Directorate of Public Health, Valencia, Valencian Community, Spain. [Peiró-Pérez,R, Alguacil,J, Castaño-Vinyals,G, O’Callaghan-Gordo,C, Gràcia-Lavedan,E, Pérez-Gómez,B, Lope,V, Aragonés,N, Amiano,P, Dierssen-Soto,T, Gómez-Acebo,I, Guevara,M, Obón-Santacana,M, Salcedo-Bellido,I, Marcos-Gragera,R, Chirlaque,MD, Kogevinas,M, Pollán,M, Salas,D] Consortium for Biomedical Research in Epidemiology and Public Health (CIBEResp), Madrid, Spain. [Alguacil,J, Delgado-Parrilla,A] Centre for Health and Environmental Research, Huelva University, Huelva, Andalucia, Spain. [Castaño-Vinyals,G, Kogevinas,M] Barcelona Institute for Global Health (ISGlobal), Barcelona, Catalonia, Spain. [Castaño-Vinyals,G, O’Callaghan-Gordo,G, Kogevinas,M] Universitat Pompeu Fabra, Plaça de la Mercè, Barcelona, Catalonia, Spain. [Castaño-Vinyals,G, Kogevinas,M] Hospital del Mar Medical Research Institute, Barcelona, Catalonia, Spain. [O’Callaghan-Gordo,C] Faculty of Health Science,Universitat Oberta de Catalunya, Barcelona, Catalonia, Spain. [Pérez-Gómez,B, Pollán,M] Department of Epidemiology of Chronic Diseases, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain. [Aragonés,N] Epidemiology Section, Public Health Division, Department of Health of Madrid, Madrid, Spain. [Molina,AJ, Fernández-Villa,T] The Research Group in Gene—Environment and Health Interactions, Institute of Biomedicine (IBIOMED), University of León, León, Castilla y León, Spain. [Gil-Majuelo,L, Amiano,P] Ministry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, San Sebastián, Gipuzkoa, Spain. [Gil-Majuelo,L, Amiano,P] Biodonostia Health Research Institute, Group of Epidemiology of Chronic and Communicable Diseases, San Sebastián, Gipuzkoa, Spain. [Dierssen-Sotos,T, Gómez-Acebo,I] Cantabria University, Santander, Cantabria, Spain. [Guevara,M, Moreno-Iribas,C] Navarra Public Health Institute, Pamplona, Navarra, Spain. [Guevara,M, Moreno-Iribas,C] Navarra Institute for Health Research (IdiSNA), Pamplona, Navarra, Spain. [Obón-Santacana,M] Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Barcelona, Catalonia, Spain. [Obón-Santacana,M] ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain. [Rodríguez-Suárez,MM] Preventive Medicine and Public Health Area, Oviedo University, Oviedo, Asturias, Spain. [Rodríguez-Suárez,MM] Central University Hospital of Asturias, Public Health Service of the Principe de Asturias, Oviedo, Asturias, Spain. [Salcedo-Bellido,I] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Andalucia, Spain. [Salcedo-Bellido,I] Departamento de Medicina Preventiva y Salud Publica, Universidad de Granada, Granada, Andalucia, Spain. [Marcos-Gragera,R] Epidemiology Unit and Girona Cancer Registry, Oncology Coordination Plan, Department of Health, Autonomous Government of Catalonia, Catalan Institute of Oncology, Girona, Catalonia, Spain. [Marcos-Gragera,R] Descriptive Epidemiology, Genetics and Cancer Prevention Group [Girona Biomedical Research Institute], Girona, Catalonia, Spain. [Chirlaque,D] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, El Palmar, Murcia, Spain., and This research was supported by the 'Acción Transversal del Cancer', approved by the Spanish Council of Ministers on 11th October 2007, by the Instituto de Salud Carlos III-FEDER [grant number:PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/ 01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI11/01810, PI14/01219, PI11/02213, PIE16/00049, PI17/01179, PI17-00092], by the Fundación Marqués de Valdecilla [grant number: API 10/09], by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)), by the Red Temática de Investigación del Cáncer (RTICC) del ISCIII [grant number: RD12/0036/0036], by the Junta de Castilla y León [grant number: LE22A10-2], by the Consejería de Salud of the Junta de Andalucía [grant number: PI-0571-2009, PI-0306-2011, salud201200057018tra], by the Conselleria de Sanitat of the Generalitat Valenciana [grant number: AP_061/10], by the Recercaixa [grant number: 2010ACUP00310], by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission [grant number: FOOD-CT-2006-036224-HIWATE], by the Spanish Association Against Cancer (AECC) Scientific Foundation [grant number: GCTRA18022MORE], by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) [grant number: 2014SGR647, 2014SGR850 and 2017SGR723], by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo.
Subjects: Male, Behavioral and social aspects of health, Health Behavior, España, Social Sciences, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Tobacco Use::Smoking [Medical Subject Headings], Gender perspective, healthy behaviours, Hàbits sanitaris, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Movilidad social, Sociology, Social mobility, Medicine and Health Sciences, Socioeconomic aspects of health, Public and Occupational Health, European commission, Alcohol consumption, Salut, 030212 general & internal medicine, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Sociology::Social Class [Medical Subject Headings], Perspectiva de género, Aged, 80 and over, Multidisciplinary, Estudios de casos y controles, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Sex Factors [Medical Subject Headings], multicase-control study, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Health Behavior [Medical Subject Headings], Middle Aged, Sexual and gender issues, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Sociology::Social Class::Social Mobility [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models [Medical Subject Headings], Health, language, Medicine, Female, 0305 other medical science, Persons::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings], Research Article, Adult, Science, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys::Diet Surveys [Medical Subject Headings], Healthy lifestyle, Clase social, Check Tags::Male [Medical Subject Headings], Genre studies, Education, socioeconomic status, 03 medical and health sciences, Young Adult, Sex Factors, Political science, Cancer genome, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Sociology::Socioeconomic Factors [Medical Subject Headings], Humans, social mobility, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Health behavior, Exercise, Educational Attainment, Nutrition, Aged, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], 030505 public health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys [Medical Subject Headings], Physical activity, Biology and Life Sciences, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Health Surveys, language.human_language, Diet, Health Care, Check Tags::Female [Medical Subject Headings], Social Class, Socioeconomic Factors, Estudis de gènere, Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise [Medical Subject Headings], Spain, Case-Control Studies, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Catalan, Gender studies, Estilo de vida saludable, Humanities
Abstract: This research was supported by the “Acción Transversal del Cancer”, approved by the Spanish Council of Ministers on 11th October 2007, by the Instituto de Salud Carlos III-FEDER [grant number:PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/ 01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI11/01810, PI14/01219, PI11/02213, PIE16/00049, PI17/01179, PI17-00092], by the Fundación Marqués de Valdecilla [grant number: API 10/09], by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)), by the Red Temática de Investigación del Cáncer (RTICC) del ISCIII [grant number: RD12/0036/0036], by the Junta de Castilla y León [grant number: LE22A10-2], by the Consejería de Salud of the Junta de Andalucía [grant number: PI-0571-2009, PI-0306-2011, salud201200057018tra], by the Conselleria de Sanitat of the Generalitat Valenciana [grant number: AP_061/10], by the Recercaixa [grant number: 2010ACUP00310], by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission [grant number: FOOD-CT-2006-036224-HIWATE], by the Spanish Association Against Cancer (AECC) Scientific Foundation [grant number: GCTRA18022MORE], by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) [grant number: 2014SGR647, 2014SGR850 and 2017SGR723], by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., There is evidence for the influence of socioeconomic status (SES) on healthy behaviours but the effect of social mobility (SM) is not yet well known. This study aims to analyse the influence of origin and destination SES (O-SES and D-SES) and SM on healthy behaviours and co-occurrence, from an integrated gender and age perspective. Data were obtained from the controls of MCC-Spain between 2008–2013 (3,606 participants). Healthy behaviours considered: healthy diet, moderate alcohol consumption, non-smoking and physical activity. SM was categorized as stable high, upward, stable medium, downward or stable low. Binary and multinomial logistic regression models were adjusted. Those aged, “Acción Transversal del Cancer” by the Spanish Council of Ministers, Instituto de Salud Carlos III-FEDER [grant number:PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/ 01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI11/01810, PI14/01219, PI11/02213, PIE16/00049, PI17/01179, PI17-00092, Fundación Marqués de Valdecilla [grant number: API 10/09], ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)), Red Temática de Investigación del Cáncer (RTICC) del ISCIII [grant number: RD12/0036/0036], Junta de Castilla y León [grant number: LE22A10-2], Consejería de Salud of the Junta de Andalucía [grant number: PI-0571-2009, PI-0306-2011, salud201200057018tra], Conselleria de Sanitat of the Generalitat Valenciana [grant number: AP_061/10], Recercaixa [grant number: 2010ACUP00310], Regional Government of the Basque Country, Consejería de Sanidad de la Región de Murcia, European Commission [grant number: FOOD-CT-2006-036224-HIWATE], Spanish Association Against Cancer (AECC) Scientific Foundation [grant number: GCTRA18022MORE, Catalan Government-Agency for Management of University and Research Grants (AGAUR) [grant number: 2014SGR647, 2014SGR850 and 2017SGR723], Fundación Caja de Ahorros de Asturias, University of Oviedo
Published: 2021

37. Epigenome-wide association study of COVID-19 severity with respiratory failure

Author: Maria J. Arranz, David Dalmau, Sergiu Albu, Jesús Troya, Aurora Pujol, Valentina Vélez-Santamaría, Roger Colobran, Francesc Vidal, Anna M. Planas, Jair Tenorio, Laia Llucià-Carol, Carles Arribas, Juan Valencia-Ramos, Sergio Aguilera-Albesa, Damiana Álvarez-Errico, Agustí Rodríguez-Palmero, Andrea Martín-Nalda, Jordi Pérez-Tur, Israel Fernandez-Cadenas, Paula Villares, Manuel Castro de Moura, Carlos Casasnovas, Pere Soler-Palacín, Anna Rull, Juan Pablo Horcajada, Laia Reverté, Beatriz Dietl, Judit Villar-García, Manel Esteller, Montserrat Ruiz, Veronica Davalos, Laura Planas-Serra, Josep Carreras Leukemia Foundation, Fundació Privada Cellex, Generalitat de Catalunya, Institut Català de la Salut, [Castro de Moura M, Davalos V, Alvarez-Errico D, Arribas C] Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Catalonia, Spain. [Planas-Serra L, Ruiz M] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain. [Colobran R] Servei d’Immunologia, Servei de Genètica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Martin-Nalda A, Soler-Palacin P] Unitat de Patologia Infecciosa i Immunodeficiències de Pediatria, Vall d'Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, enfermedades respiratorias::trastornos respiratorios::insuficiencia respiratoria [ENFERMEDADES], Male, Medicine (General), Genome-wide association study, Disease, medicine.disease_cause, COVID-19 (Malaltia), Severity of Illness Index, Cohort Studies, Epigenome, 0302 clinical medicine, Insuficiència respiratòria - Aspectes genètics, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Medicine, Coronavirus, DNA methylation, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], General Medicine, Methylation, Middle Aged, Respiratory Tract Diseases::Respiration Disorders::Respiratory Insufficiency [DISEASES], CpG site, 030220 oncology & carcinogenesis, Female, Epigenetics, Respiratory Insufficiency, Respiratory insufficiency, Research Paper, Adult, Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Genome-Wide Association Study [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Other subheadings::Other subheadings::Other subheadings::/virology [Other subheadings], General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Young Adult, R5-920, Humans, Otros calificadores::Otros calificadores::Otros calificadores::/virología [Otros calificadores], business.industry, SARS-CoV-2, Reproducibility of Results, COVID-19, Epigenètica, Genòmica, 030104 developmental biology, Insuficiència respiratòria, Spain, Immunology, técnicas de investigación::métodos epidemiológicos::diseño de la investigación epidemiológica::estudio de asociación genómica completa [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], CpG Islands, Interferons, business, Genome-Wide Association Study
Abstract: Background: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities. Methods: Peripheral blood samples were obtained from 407 confirmed COVID-19 patients 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support. The set of cases was divided into discovery (n = 207) and validation (n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients. Findings: The DNA methylation status of 44 CpG sites was associated with the clinical severity of COVID-19. Of these loci, 23 (52.3%) were located in 20 annotated coding genes. These genes, such as the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C) candidates, were mainly involved in the response of interferon to viral infection. We used the EWAS-identified sites to establish a DNA methylation signature (EPICOVID) that is associated with the severity of the disease. Interpretation: We identified DNA methylation sites as epigenetic susceptibility loci for respiratory failure in COVID-19 patients. These candidate biomarkers, combined with other clinical, cellular and genetic factors, could be useful in the clinical stratification and management of patients infected with the SARS-CoV-2., The Unstoppable campaign of the Josep Carreras Leukaemia Foundation, the Cellex Foundation and the CERCA Programme/Generalitat de Catalunya.
Published: 2021

38. Neuronal Differentiation-Related Epigenetic Regulator ZRF1 Has Independent Prognostic Value in Neuroblastoma but Is Functionally Dispensable In Vitro

Author: G. Guillén, Roberta Antonelli, David Llobet-Navas, Josep Roma, Aroa Soriano, Lucas Moreno, Jessica Camacho, Raquel Hladun, Carlos Jiménez, Laura Devis-Jauregui, Luz Jubierre, Miguel F. Segura, Josep Sánchez de Toledo, Marc Masanas, Soledad Gallego, Ainara Magdaleno, Institut Català de la Salut, [Jiménez C, Antonelli R, Masanas M, Soriano A, Magdaleno A, Jubierre L, Roma J, Segura MF] Recerca Translacional en Càncer en la Infància i l’Adolescència, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Devis-Jauregui L] Molecular Mechanisms and Experimental Therapy in Oncology-Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. [Camacho J] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Guillén G] Recerca Translacional en Càncer en la Infància i l’Adolescència, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Cirurgia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Hladun R, Moreno L, Gallego S] Recerca Translacional en Càncer en la Infància i l’Adolescència, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei d’Oncologia i Hematologia Pediàtriques, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Sánchez de Toledo J] Recerca Translacional en Càncer en la Infància i l’Adolescència, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Catalan Institute of Oncology (ICO), L’Hospitalet de Llobregat, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Carcinògens, Cancer Research, fenómenos genéticos::regulación de la expresión génica::epigénesis genética [FENÓMENOS Y PROCESOS], neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::tumores neuroectodérmicos primitivos::tumores neuroectodérmicos primitivos periféricos::neuroblastoma [ENFERMEDADES], Cellular differentiation, Regulator, Otros calificadores::/diagnóstico [Otros calificadores], Biology, Neuroblastoma - Prognosi, Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Neuroectodermal Tumors, Primitive::Neuroectodermal Tumors, Primitive, Peripheral::Neuroblastoma [DISEASES], neuroblastoma, Neuroblastoma, medicine, Other subheadings::/diagnosis [Other subheadings], Epigenetics, Progenitor cell, Gene, neuronal differentiation, RC254-282, epigenetics, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Epigenètica, Pediatric cancer, pediatric cancer, Oncology, Tumor progression, Genetic Phenomena::Gene Expression Regulation::Epigenesis, Genetic [PHENOMENA AND PROCESSES], Cancer research, Carcinogens, ZRF1
Abstract: Epigenética; Diferenciación neuronal; Cáncer pediátrico Epigenètica; Diferenciació neuronal; Càncer pediàtric Epigenetics; Neuronal differentiation; Pediatric cancer Neuroblastoma is a pediatric tumor of the peripheral nervous system that accounts for up to ~15% of all cancer-related deaths in children. Recently, it has become evident that epigenetic deregulation is a relevant event in pediatric tumors such as high-risk neuroblastomas, and a determinant for processes, such as cell differentiation blockade and sustained proliferation, which promote tumor progression and resistance to current therapies. Thus, a better understanding of epigenetic factors implicated in the aggressive behavior of neuroblastoma cells is crucial for the development of better treatments. In this study, we characterized the role of ZRF1, an epigenetic activator recruited to genes involved in the maintenance of the identity of neural progenitors. We combined analysis of patient sample expression datasets with loss- and gain-of-function studies on neuroblastoma cell lines. Functional analyses revealed that ZRF1 is functionally dispensable for those cellular functions related to cell differentiation, proliferation, migration, and invasion, and does not affect the cellular response to chemotherapeutic agents. However, we found that high levels of ZRF1 mRNA expression are associated to shorter overall survival of neuroblastoma patients, even when those patients with the most common molecular alterations used as prognostic factors are removed from the analyses, thereby suggesting that ZRF1 expression could be used as an independent prognostic factor in neuroblastoma. This work was funded by Instituto de Salud Carlos III (Grant no. CP16/00006, PI17/00564 and PI20/00530 to M.F Segura and MS17/00063 to D. Llobet-Navas); Asociación Española Contra el Cáncer (LABAE18009SEGU, LABAE19004LLOB); Generalitat de Catalunya AGAUR/European Social Fund (Grant no. 2017FI_B_00095 to C Jiménez); Asociación NEN; Joan Petit foundation; Asociación Pulseras Candela foundation; the #delhospitalalacatedral initiative led by Xavi Vallés; and the Rotary Clubs of Barcelona Eixample, Barcelona Diagonal, Santa Coloma de Gramanet, München-Blutenburg, Deutschland Gemeindienst, and others from Barcelona and its province.
Published: 2021

39. Predicting Clinical Outcome with Phenotypic Clusters in COVID-19 Pneumonia: An Analysis of 12,066 Hospitalized Patients from the Spanish Registry SEMI-COVID-19

Author: Maria Jose Esteban Giner, Maria Candelaria Martin Gonzalez, Begoña Cortés Rodríguez, Pedro Jesus Esteve Atienzar, Susana Plaza Canteli, Anabel Martin-Urda Diez-Canseco, Marta Leon Tellez, José Nicolás Alcalá Pedrajas, Manuel Rubio-Rivas, José Manuel Ramos-Rincón, José María Mora-Luján, Almudena Lopez Sampalo, Eva Garcia Sardon, Jose Loureiro-Amigo, Ricardo Gómez-Huelgas, Xavier Corbella, Jose Luis Serrano Carrillo de Albornoz, Jose Angel Martin Oterino, Ruth Gonzalez Ferrer, Pablo Telleria Gomez, Luis Felipe Diez Garcia, Antia Perez Pineiro, Carmen Yera Bergua, Leyre Jorquer Vidal, Ignacio Pérez Catalán, [Rubio-Rivas,M, Corbella,X, and Mora-Luján,JM] Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, University of Barcelona, Barcelona, Spain. [Corbella,X] Hestia Chair in Integrated Health and Social Care, School of Medicine, Universitat Internacional de Catalunya, Barcelona, Spain. [Loureiro-Amigo,J] Internal Medicine Department, Moisès Broggi Hospital, Sant Joan Despí, Barcelona, Spain. [López Sampalo,A] Internal Medicine Department, Regional University Hospital of Málaga, Málaga, Spain. [Yera Bergua,C] Internal Medicine Department, Virgen de la Salud Hospital, Toledo, Spain. [Esteve Atiénzar,PJ] Internal Medicine Department, San Juan de Alicante University Hospital, San Juan de Alicante, Alicante, Spain. [Díez García,LF] Internal Medicine Department, Torrecárdenas Hospital, Almería, Spain. [Gonzalez Ferrer,R] Internal Medicine Department, Tajo Hospital, Aranjuez, Madrid, Spain. [Plaza Canteli,S] Internal Medicine Department, Severo Ochoa University Hospital, Leganés, Madrid, Spain. [Pérez Piñeiro,A] Internal Medicine Department, Valle del Nalón Hospital, Riaño, Langreo, Asturias, Spain. [Cortés Rodríguez,B] Internal Medicine Department, Alto Guadalquivir Hospital, Andújar, Jaén, Spain. [Jorquer Vidal,L] Internal Medicine Department, Francesc de Borja Hospital, Gandia, Valencia, Spain. [Pérez Catalán,I] Internal Medicine Department, Castellón General University Hospital, Castellón de la Plana, Spain. [León Téllez,M] Internal Medicine Department, Santa Bárbara Hospital, Soria, Spain. [Martín Oterino,JA] Internal Medicine Department, Salamanca University Hospital Complex, Salamanca, Spain. [Martín González,MC] Internal Medicine Department, Canarias University Hospital, Santa Cruz de Tenerife, Spain. [Serrano Carrillo de Albornoz,JL] Internal Medicine Department, Poniente Hospital, Almería, Spain. [García Sardon,E] Internal Medicine Department, San Pedro de Alcántara Hospital, Cáceres, Spain. [Alcalá Pedrajas,JN] Internal Medicine Department, Pozoblanco Hospital, Pozoblanco, Córdoba, Spain. [Martin-Urda Diez-Canseco,A] Internal Medicine Department, Palamós Hospital, Palamós, Girona, Spain. [Esteban Giner,MJ] Internal Medicine Department, Virgen de los Lirios Hospital, Alcoy, Alicante, Spain. [Tellería Gómez,P] Internal Medicine Department, Valladolid Clinical University Hospital, Valladolid, Spain. [Ramos-Rincón,JM] Department of Clinical Medicine, Miguel Hernandez University of Elche, Alicante, Spain. [Gómez-Huelgas,R] Internal Medicine Department, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Malaga, Spain.
Subjects: Abdominal pain, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Phenomena and Processes::Circulatory and Respiratory Physiological Phenomena::Respiratory Physiological Phenomena::Respiratory Physiological Processes::Respiration::Respiratory Rate [Medical Subject Headings], lcsh:Medicine, Diseases::Virus Diseases::Pneumonia, Viral [Medical Subject Headings], Pneumònia, 030204 cardiovascular system & hematology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Diseases::Respiratory Tract Diseases::Respiration Disorders::Respiratory Insufficiency [Medical Subject Headings], Sore throat, 030212 general & internal medicine, COVID-19 (malaltia), Pronóstico, General Medicine, Prognosis, Fenotip, Persons::Persons::Patients [Medical Subject Headings], Diarrhea, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Hospitalization [Medical Subject Headings], Phenotype, Hypertension, Vomiting, Hipertensió, medicine.symptom, Fenotipo, medicine.medical_specialty, Pronòstic mèdic, phenotype, Anosmia, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Cluster Analysis [Medical Subject Headings], Article, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Neumonía, Hipertensión, medicine, Diseases::Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Obstructive::Pulmonary Disease, Chronic Obstructive [Medical Subject Headings], Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, lcsh:R, COVID-19, Pneumonia, Ageusia, medicine.disease, Análisis por conglomerados, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Cluster Analysis [Medical Subject Headings], prognosis, business, cluster analysis
Abstract: (1) Background: Different clinical presentations in COVID-19 are described to date, from mild to severe cases. This study aims to identify different clinical phenotypes in COVID-19 pneumonia using cluster analysis and to assess the prognostic impact among identified clusters in such patients. (2) Methods: Cluster analysis including 11 phenotypic variables was performed in a large cohort of 12,066 COVID-19 patients, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish Society of Internal Medicine (SEMI)-COVID-19 Registry. (3) Results: Of the total of 12,066 patients included in the study, most were males (7052, 58.5%) and Caucasian (10,635, 89.5%), with a mean age at diagnosis of 67 years (standard deviation (SD) 16). The main pre-admission comorbidities were arterial hypertension (6030, 50%), hyperlipidemia (4741, 39.4%) and diabetes mellitus (2309, 19.2%). The average number of days from COVID-19 symptom onset to hospital admission was 6.7 (SD 7). The triad of fever, cough, and dyspnea was present almost uniformly in all 4 clinical phenotypes identified by clustering. Cluster C1 (8737 patients, 72.4%) was the largest, and comprised patients with the triad alone. Cluster C2 (1196 patients, 9.9%) also presented with ageusia and anosmia, cluster C3 (880 patients, 7.3%) also had arthromyalgia, headache, and sore throat, and cluster C4 (1253 patients, 10.4%) also manifested with diarrhea, vomiting, and abdominal pain. Compared to each other, cluster C1 presented the highest in-hospital mortality (24.1% vs. 4.3% vs. 14.7% vs. 18.6%, p &lt, 0.001). The multivariate study identified age, gender (male), body mass index (BMI), arterial hypertension, chronic obstructive pulmonary disease (COPD), ischemic cardiopathy, chronic heart failure, chronic hepatopathy, Charlson&rsquo, s index, heart rate and respiratory rate upon admission &gt, 20 bpm, lower PaO2/FiO2 at admission, higher levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH), and the phenotypic cluster as independent factors for in-hospital death. (4) Conclusions: The present study identified 4 phenotypic clusters in patients with COVID-19 pneumonia, which predicted the in-hospital prognosis of clinical outcomes.
Published: 2020

40. Impact of non-adherence to radiotherapy on 1-year survival in cancer patients in Catalonia, Spain

Author: M. Molla, Josep A. Espinàs, A. Eraso, Meritxell Arenas, Agustin Pedro, J.M. Solé, Moises Mira, M. Macia, Josep M. Borràs, Rebeca Font, Victòria Tuset, M. Algara, Nuria Farré, J. Solà, R. Verges, Institut Català de la Salut, [Borras JM] Department of Clinical Sciences, University of Barcelona and Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. [Font R, Solà J] Cancer Strategy, Department of Health, Barcelona, Spain. [Macia M] Radiation Oncology Department, Institut Català d’Oncologia, Hospital Duran i Reynals, L’Hospitalet de Llobregat, Spain. [Tuset V] Radiation Oncology Department, Institut Català d’Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain. [Arenas M] Radiation Oncology Department, Hospital Universitari Sant Joan de Reus, Reus, Spain. Faculty of Medicine, University of Rovira i Virgili, Reus, Spain. [Verges R] Servei d’Oncologia Radioteràpica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Male, medicine.medical_specialty, Catalonia, Survival, medicine.medical_treatment, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Radioteràpia, Otros calificadores::Otros calificadores::/radioterapia [Otros calificadores], Breast Neoplasms, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, External beam radiotherapy, Càncer, Supervivència, Mama - Càncer - Radioteràpia - Espanya, Cancer, Proportional Hazards Models, Retrospective Studies, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], localizaciones geográficas::Europa (continente)::España [DENOMINACIONES GEOGRÁFICAS], Radiotherapy, Proportional hazards model, business.industry, Other subheadings::Other subheadings::/radiotherapy [Other subheadings], Hazard ratio, Prostate, External radiotherapy, Catalunya, Retrospective cohort study, Hematology, Middle Aged, medicine.disease, Comorbidity, Radiation therapy, Geographic Locations::Europe::Spain [GEOGRAPHICALS], Oncology, Spain, Adherence, Dose, 030220 oncology & carcinogenesis, Female, business
Abstract: Dosi; Radioteràpia externa; Supervivència Dosis; Radioterapia externa; Supervivencia Dose; External radiotherapy; Survival Background This study aims to assess the effects of non-adherence to external beam radiation therapy in cancer patients receiving treatment with a curative. Methods This retrospective cohort study collected health records data for all cancer patients treated with external beam radiotherapy with curative intent in 2016 in Catalonia, Spain. Adherence was defined as having received at least 90% of the total dose prescribed. A logistic regression model was used to assess factors related to non-adherence, and its association with one-year survival was evaluated using Cox regression. Results The final sample included 8721 patients (mean age 63.6 years): breast cancer was the most common tumour site (38.1%), followed by prostate and colon/rectum. Treatment interruptions prolonged the total duration of therapy in 70.7% of the patients, and 1.0% were non-adherent. Non-adherence was associated with advanced age, female gender, and some localization of primary tumour (head and neck, urinary bladder, and haematological cancers). The risk of death in non-adherent patients was higher than in adherent patients (hazard ratio [HR] 1.63, 95% confidence interval 0.97–2.74), after adjusting for the potential confounding effect of age, gender, tumour site and comorbidity. Conclusion Non-adherence to radiotherapy, as measured by the received dose, is very low in our setting, and it may have an impact on one-year survival. We thank CERCA Programme/Generalitat de Catalunya for institutional support (AGAUR 2017SGR735). This study has been funded by the project PI15/00945, (Co-funded by European Regional Development Fund. ERDF, a way to build Europe).
Published: 2020

41. Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage

Author: Manuel Francisco Blanco, Daniela Celeste Profico, Elena González-Muñoz, Beatriz Fernández-Muñoz, Miguel Ángel Montiel, Cristina Rosell-Valle, María Muñoz-Escalona, Rosario Sanchez-Pernaute, María Martín-López, Julia Alba-Amador, Rafael Campos-Cuerva, Javier Márquez-Rivas, Daniela Ferrari, Alessandra Giorgetti, Luis Lopez‐Navas, Fernandez-Munoz, B, Rosell-Valle, C, Ferrari, D, Alba-Amador, J, Montiel, M, Campos-Cuerva, R, Lopez-Navas, L, Munoz-Escalona, M, Martin-Lopez, M, Profico, D, Blanco, M, Giorgetti, A, Gonzalez-Munoz, E, Marquez-Rivas, J, Sanchez-Pernaute, R, Junta de Andalucía, Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, [Fernández-Muñoz,B, Rosell-Valle,C, Alba-Amador,J, Montiel,MÁ, Campos-Cuerva,R, Muñoz-Escalona,M, Martín-López,M, Blanco,MF] Unidad de Producción y Reprogramación Celular (UPRC), Red Andaluza para el diseño y traslación de Terapias Avanzadas, Sevilla, Spain. [Fernández-Muñoz,B, Márquez-Rivas,J] Grupo de Neurociencia aplicada, Instituto de Biomedicina de Sevilla, Sevilla, Spain. [Ferrari,D] Department of Biotechnology and Biosciences, University Milan-Bicocca, Milan, Italy. [Campos-Cuerva,R] Centro de Transfusiones, Tejidos y Células de Sevilla (CTTS), Sevilla, Spain. [Lopez-Navas,L, Sanchez-Pernaute,R] Departamento de Preclínica, Red Andaluza de Diseño y Traslación de Terapias Avanzadas, Sevilla, Spain. [Profico,DC] Fondazione IRCCS Casa Sollievo della Sofferenza, Production Unit of Advanced Therapies (UPTA), San Giovanni Rotondo, Italy. [Giorgetti,A] Regenerative Medicine Program, Bellvitge Biomedical Research Institute (IDIBELL), Program for Translation of Regenerative Medicine in Catalonia (P-CMRC), Barcelona, Spain. [González-Muñoz,E] Department of Cell Biology, Genetics and Physiology, University of Málaga, Málaga, Spain. [González-Muñoz,E] Department of Regenerative Nanomedicine, Andalusian Center for Nanomedicine and Biotechnology-BIONAND, Málaga, Spain. [González-Muñoz,E] Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Carlos III Health Institute (ISCIII), Spain. [Márquez-Rivas,J] Neurosurgery Department, Hospital Virgen del Rocío, Sevilla, Spain., and This work was supported by research funds from the Andalusian Consejería de Salud to the Red Andaluza de Diseño y Traslación de Terapias Avanzadas with contribution from the COST Action CA16122 for STSM and networking. AG is supported by Ramon y Cajal Program (RyC-2013-13221), MINECO(SAF2016-80205-R) and CERCA Pro gram/Generalitat de Catalunya.
Subjects: 0301 basic medicine, Male, Neurobiologia del desenvolupament, Pathology, Premature infant, Infants prematurs, neural stem cell, 0302 clinical medicine, Cerebrospinal fluid, Neural Stem Cells, Tissue‐specific Progenitor and Stem Cells, Organisms::Eukaryota::Animals [Medical Subject Headings], AC133 Antigen, Developmental neurobiology, Hemorragia cerebral intraventricular, Anatomy::Cells::Stem Cells::Neural Stem Cells [Medical Subject Headings], lcsh:R5-920, lcsh:Cytology, Premature infants, Líquido cefalorraquídeo, Neurogenesis, Gene Expression Regulation, Developmental, General Medicine, Human brain, Recién nacido prematuro, Neural stem cell, premature infant, Anatomy::Fluids and Secretions::Body Fluids::Extracellular Fluid::Cerebrospinal Fluid [Medical Subject Headings], Persons::Persons::Age Groups::Infant::Infant, Newborn::Infant, Premature [Medical Subject Headings], Intraventricular hemorrhage, medicine.anatomical_structure, Centro germinal, Female, lcsh:Medicine (General), Infant, Premature, medicine.medical_specialty, neurogenesi, Mice, Nude, Check Tags::Male [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Developmental [Medical Subject Headings], intraventricular hemorrhage, cerebrospinal fluid, 03 medical and health sciences, medicine, Animals, lcsh:QH573-671, Cerebral Hemorrhage, Células madre nerviosas, business.industry, Germinal zone, germinal zone, Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Hemorrhages::Cerebral Hemorrhage [Medical Subject Headings], BIO/13 - BIOLOGIA APPLICATA, Líquid cefalorraquidi, Endoscopy, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, Nude [Medical Subject Headings], Cell Biology, medicine.disease, Transplantation, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Cell culture, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Surgical::Endoscopy [Medical Subject Headings], Forebrain, business, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology., Germinal zone neural stem cells (Gz‐NSC) are isolated from the hemorrhagic cerebrospinal fluid of preterm infants with severe intraventricular hemorrhage. These cells express ventral and posterior forebrain markers, can be differentiated and do not cause tumors. Gz‐NSC represent a valuable tool for the development of new cell therapies and the study of human Gz biology.
Published: 2020

42. Postnatal development of the astrocyte perivascular MLC1/GlialCAM complex defines a temporal window for the gliovascular unit maturation

Author: Vidal, Xabier, Gilbert, Alice, Vidal, Xabier Elorza, Estévez, Raúl, Cohen-Salmon, Martine, Boulay, Anne-Cécile, Bellvitge Biomedical Research Institute [Barcelona, Spain] ((IDIBELL)), L’Hospitalet de Llobregat [Barcelona, Spain], Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), 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 Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biochemistry and Molecular Biology, and University of Barcelona
Subjects: Male, Histology, [SDV]Life Sciences [q-bio], Central nervous system, Vascular compartment, Nerve Tissue Proteins, In Vitro Techniques, Blood–brain barrier, 050105 experimental psychology, Mice, 03 medical and health sciences, 0302 clinical medicine, Lectins, medicine, Animals, 0501 psychology and cognitive sciences, ATP Binding Cassette Transporter, Subfamily B, Member 1, Claudin-5, ComputingMilieux_MISCELLANEOUS, Aquaporin 4, Chemistry, General Neuroscience, Cell Adhesion Molecules, Neuron-Glia, 05 social sciences, Age Factors, Brain, Gene Expression Regulation, Developmental, Membrane Proteins, Transmembrane protein, Cell biology, Experimental strategy, medicine.anatomical_structure, Animals, Newborn, Blood-Brain Barrier, Astrocytes, Multiprotein Complexes, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Anatomy, 030217 neurology & neurosurgery, Astrocyte, Blood vessel
Abstract: Astrocytes, the most abundant glial cells of the central nervous system are morphologically complex. They display numerous processes interacting with synapses and blood vessels. At the vascular interface, astrocyte endfeet-terminated processes almost entirely cover the blood vessel surface and participate to the gliovascular unit where important vascular properties of the brain are set such as the blood-brain barrier (BBB) integrity. How specific morphological and functional interactions between astrocytes and the vascular compartment develop has not been fully investigated. Here, we elaborated an original experimental strategy to study the postnatal development of astrocyte perivascular endfeet. Using purified gliovascular units, we focused on the postnatal expression of MLC1 and GlialCAM, two transmembrane proteins forming a complex enriched at the junction between mature astrocyte perivascular endfeet. We showed that MLC1 and GlialCAM were enriched and assembled into mature complexes in astrocyte perivascular endfeet between postnatal days 10 and 15, after the formation of astrocyte perivascular Aquaporin 4 water channels. These events correlated with the increased expression of Claudin-5 and P-gP, two endothelial-specific BBB components. These results illustrate for the first time that astrocyte perivascular endfeet differentiation is a complex and progressive process which correlates with BBB maturation. Moreover, our results suggest that maturation of the astrocyte endfeet MLC1/GlialCAM complex between postnatal days 10 and 15 might be a key event in the gliovascular unit maturation.
Published: 2019
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43. Public Perceptions of the Role of Lifestyle Factors in Cancer Development: Results from the Spanish Onco-Barometer 2020

Author: José Juan Jiménez Moleón, Dafina Petrova, Josep M. Borràs, Eloísa Bayo Lozano, Marina Pollán, María José Sánchez, David Vicente, Instituto de Salud Carlos III, Asociación Española Contra el Cáncer, Ministerio de Ciencia (España), Agencia Estatal de Investigación (España), [Petrova,D, Pollán,M, Jiménez Moleón,JJ, Sánchez,MJ] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Petrova,D, Sánchez,MJ] Escuela Andaluza de Salud Pública (EASP), Granada, Spain. [Petrova,D, Sánchez,MJ] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Borrás,JM] Department of Clinical Sciences, University of Barcelona, Barcelona, Spain. [Borrás,JM] Bellvitge Biomedical Research Institute, Hospitalet, Spain. [Borrás,JM] NHS Cancer Strategy, Ministry of Health, Madrid, Spain. [Pollán,M] National Center for Epidemiology, Health Institute Carlos III, Madrid, Spain. [Bayo Lozano,E, Vicente,D] University Hospital Virgen Macarena, Seville, Spain. [Jiménez Moleón,JJ, Sánchez,MJ] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain, and The Onco-barometer survey was funded by the Cancer Observatory of the Spanish Associa tion against Cancer (Asociación Española contra el Cáncer, www.aecc.es, accessed on 3 October 2021). This work was also supported by the Cancer Epidemiological Surveillance Subprogram (VICA) of the CIBERESP, Health Institute Carlos III, Madrid, Spain. Dafina Petrova was supported by a Sara Borrell fellowship from the Health Institute Carlos III (Expde: CD19/00203) and a Juan de la Cierva Fellowship from the Ministry of Science and the National Research Agency (MCIN/AEI, JC2019- 039691-I, http://dx.doi.org/10.13039/501100011033, accessed on 3 October 2021).
Subjects: Male, Health, Toxicology and Mutagenesis, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Tobacco Use::Smoking [Medical Subject Headings], Alcohol drinking, Percepción, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Public knowledge, Cancer prevention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], perceptions, population-based survey, Neoplasms, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Sociology::Social Control, Informal::Public Opinion [Medical Subject Headings], risk factors, Perceptions, awareness, media_common, education.field_of_study, cancer prevention, Smoking, Organisms::Eukaryota::Plants::Viridiplantae::Streptophyta::Embryophyta::Angiosperms::Solanaceae::Tobacco [Medical Subject Headings], Population-based survey, public knowledge, Diseases::Neoplasms [Medical Subject Headings], Awareness, Consumo de bebidas alcohólicas, Neoplasias, Lifestyle factors, Medicine, Cancer development, Concienciación, Factores de riesgo, medicine.medical_specialty, Alcohol Drinking, media_common.quotation_subject, Population, Check Tags::Male [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Tobacco Use [Medical Subject Headings], Article, Estilo de vida, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Motivation::Goals [Medical Subject Headings], Perception, Environmental health, Tobacco, medicine, Humans, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Sociology::Socioeconomic Factors [Medical Subject Headings], education, Life Style, lifestyle habits, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Consumption (economics), Lifestyle habits, Anthropology, Education, Sociology and Social Phenomena::Social Sciences::Demography [Medical Subject Headings], business.industry, Public health, Public Health, Environmental and Occupational Health, Cancer, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], medicine.disease, Tabaco, Risk factors, Public Opinion, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], business
Abstract: The European Code against Cancer recommends not to smoke, to avoid alcohol consumption, to eat a healthy diet, and maintain a healthy weight to prevent cancer. To what extent is the public aware of the influence of these lifestyle factors on cancer development? The goal of the current study was to describe the perceived influence of four lifestyle factors (tobacco, alcohol, diet, and weight) on cancer development in the general population and identify factors related to low perceptions of influence. We analyzed data from the 2020 Onco-barometer (n = 4769), a representative population-based survey conducted in Spain. With the exception of smoking, lifestyle factors were among those with the least perceived influence, more so among the demographic groups at higher risk from cancer including men and older individuals (65+ years). Individuals from lower socio-economic groups were more likely to report not knowing what influence lifestyle factors have on cancer. Lower perceived influence was also consistently related to perceiving very low risk from cancer. Overall, although there is variation in perceptions regarding the different lifestyle factors, low perceived influence clusters among those at higher risk for cancer. These results signal the need for public health campaigns and messages informing the public about the preventive potential of lifestyle factors beyond avoiding tobacco consumption., Cancer Observatory of the Spanish Association against Cancer, Cancer Epidemiological Surveillance Subprogram (VICA) of the CIBERESP, Health Institute Carlos III, Madrid, Spain, Health Institute Carlos III (Expde: CD19/00203), Juan de la Cierva Fellowship from the Ministry of Science and the National Research Agency (MCIN/AEI, JC2019- 039691-I, http://dx.doi.org/10.13039/501100011033, 3 October 2021).
Published: 2021
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44. Neurocognitive signatures of phonemic sequencing in expert backward speakers

Author: Diana López-Barroso, María José Torres-Prioris, Lucas Sedeño, Sol Fittipaldi, Agustín Ibáñez, Marcelo L. Berthier, Adolfo M. García, Estela Camara, [Torres-Prioris,MJ, López-Barroso,D, Berthier,ML] Cognitive Neurology and Aphasia Unit, Centro de Investigaciones Médico‑Sanitarias, Instituto de Investigación Biomédica de Málaga (IBIMA), University of Malaga, Malaga, Spain. [Torres-Prioris,MJ, López-Barroso,D] Area of Psychobiology, Faculty of Psychology and Speech Therapy, University of Malaga, Malaga, Spain. [Càmara,E] Cognition and Brain Plasticity Unit, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain. [Fittipaldi,S, Ibáñez,A, García,AM] Universidad de San Andrés, Victoria, Buenos Aires, Argentina. [Fittipaldi,S, Sedeño,L, García,AM] National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina. [Ibáñez,A] Universidad Autónoma del Caribe, Barranquilla, Colombia. [Ibáñez,A] Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibáñez, Santiago, Chile. [Ibáñez,A, García,AM] Global Brain Health Institute, University of California, San Francisco, United States. [García,AM] Faculty of Education, National University of Cuyo (UNCuyo), Mendoza, Argentina. [García,AM] Departamento de Lingüística Y Literatura, Facultad de Humanidades, Universidad de Santiago de Chile, Santiago, Chile., This work was supported by CONICET, FONCYT-PICT [2017-1818, 2017-1820], CONICYT/FONDECYT Regular [grant number 1170010], FONDAP [grant number 15150012], Programa Interdisciplinario de Investigación Experimental en Comunicación y Cognición (PIIECC), Facultad de Humanidades, USACH, GBHI ALZ UK-20-639295, and and the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), funded by the National Institutes of Aging of the National Institutes of Health under award number R01AG057234, an Alzheimer’s Association grant (SG-20-725707-ReDLat), the Rainwater Foundation, and the Global Brain Health Institute. MJTP has been funded by the Spanish Ministry of Education, Culture and Sport under the FPU program (FPU14/04021) and by a postdoctoral fellowship from the University of Malaga. DLB has been supported by the Juan de la Cierva postdoctoral programme (IJCI-2017-34164) and by I+D+i Project, Andalucia and European Union Funds (FEDER) (UMA18-FEDERJA-221).
Subjects: Male, Imagen por resonancia magnética, lcsh:Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Magnetic Resonance Imaging [Medical Subject Headings], computer.software_genre, Parla, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Voxel, PHONEMIC SEQUENCING, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Nervous System Physiological Phenomena::Nervous System Physiological Processes::Speech [Medical Subject Headings], Gray Matter, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Neuroimaging::Functional Neuroimaging [Medical Subject Headings], lcsh:Science, Neurolinguistics, purl.org/becyt/ford/5.1 [https], Language, Multidisciplinary, purl.org/becyt/ford/5 [https], BACKWARD SPEECH, 05 social sciences, Imagen de difusión tensora, Habla, Brain, Middle Aged, Magnetic Resonance Imaging, Memoria a corto plazo, Diffusion Tensor Imaging, Memory, Short-Term, medicine.anatomical_structure, VOXEL-BASED MORPHOMETRY, Encéfalo, Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Memory::Memory, Short-Term [Medical Subject Headings], Identity (object-oriented programming), Psychology, Memory, short-term, Cognitive psychology, Adult, Anatomy::Nervous System::Nerve Net [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Grey matter, Neural circuits, Article, 050105 experimental psychology, 03 medical and health sciences, Magnetic resonance imaging, Neuroimaging, RESTING-STATE FUNCTIONAL CONNECTIVITY, Functional neuroimaging, medicine, Humans, Speech, 0501 psychology and cognitive sciences, Gray matter, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Neuroimaging::Diffusion Tensor Imaging [Medical Subject Headings], purl.org/becyt/ford/6 [https], Working memory, Functional Neuroimaging, lcsh:R, Neurolingüística, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], purl.org/becyt/ford/6.2 [https], Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings], Sustancia gris, lcsh:Q, Nerve Net, DIFFUSION TENSOR IMAGING, Neuroimagen funcional, computer, Neurocognitive, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: Despite its prolific growth, neurolinguistic research on phonemic sequencing has largely neglected the study of individuals with highly developed skills in this domain. To bridge this gap, we report multidimensional signatures of two experts in backward speech, that is, the capacity to produce utterances by reversing the order of phonemes while retaining their identity. Our approach included behavioral assessments of backward and forward speech alongside neuroimaging measures of voxel-based morphometry, diffusion tensor imaging, and resting-state functional connectivity. Relative to controls, both backward speakers exhibited behavioral advantages for reversing words and sentences of varying complexity, irrespective of working memory skills. These patterns were accompanied by increased grey matter volume, higher mean diffusivity, and enhanced functional connectivity along dorsal and ventral stream regions mediating phonological and other linguistic operations, with complementary support of areas subserving associative-visual and domain-general processes. Still, the specific loci of these neural patterns differed between both subjects, suggesting individual variability in the correlates of expert backward speech. Taken together, our results offer new vistas on the domain of phonemic sequencing, while illuminating neuroplastic patterns underlying extraordinary language abilities. Fil: Torres Prioris, María José. Universidad de Málaga; España Fil: López Barroso, Diana. Universidad de Málaga; España Fil: Càmara, Estela. Universidad de Málaga; España Fil: Fittipaldi, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina Fil: Sedeño, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina Fil: Ibañez, Agustin Mariano. Universidad de San Andrés; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Autónoma del Caribe; Colombia. University of California; Estados Unidos. Universidad Adolfo Ibañez; Chile Fil: Berthier, Marcelo L.. Universidad de Málaga; España Fil: García, Adolfo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo; Argentina. Universidad de San Andrés; Argentina. University of California; Estados Unidos. Universidad de Santiago de Chile; Chile
Published: 2020

45. Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and risk of in situ breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Christina C. Dahm, Marc J. Gunter, Carlotta Sacerdote, Carmen Santiuste, Sabine Rohrmann, Merete Ellingjord-Dale, Cecilie Kyrø, Anika Hüsing, Renée T. Fortner, Eva Ardanaz, Antonia Trichopoulou, María Dolores López, Claudia Agnoli, Elisabete Weiderpass, Virginia Menéndez, Rudolf Kaaks, Signe Borgquist, Marina Kvaskoff, Patrick Arveux, Anne Tjønneland, Carlo La Vecchia, Helene Tilma Vistisen, Marije F. Bakker, Antonio Agudo, María José Sánchez, Agnès Fournier, Laure Dossus, Kay-Tee Khaw, Timothy J. Key, Guri Skeie, Eleni Peppa, Rosario Tumino, Elio Riboli, Salma Butt, Carla H. van Gils, Nena Karavasiloglou, Kostantinos K. Tsilidis, Tilman Kühn, Giovanna Masala, Inge Huybrechts, Matthias B. Schulze, Domenico Palli, Anna Karakatsani, Jenny Chang-Claude, Salvatore Panico, Apollo - University of Cambridge Repository, [Karavasiloglou,N, Rohrmann,S] Division of Chronic Disease Epidemiology, Institute for Epidemiology, Biostatistics and Prevention, University of Zurich, Zurich, Switzerland. [Karavasiloglou,N, Rohrmann,S] Cancer Registry Zurich and Zug, University Hospital Zurich, Zurich, Switzerland. [Karavasiloglou,N, Hüsing,A, Turzanski Fortner,R, Chang-Claude,J, Kaaks,R, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Masala,G, Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [van Gils,CH, Bakker,MF] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. [Huybrechts,I, Weiderpass,E, Dossus,L] International Agency for Research on Cancer, Lyon, France. [Weiderpas,E, Skeie,G] Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Arveux,P, Fournier,A, Kvaskoff,M] CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Arveux,P, Kvaskoff,M] Gustave Roussy, Villejuif, France. [Arveux,P] Breast and Gynaecologic Cancer Registry of Côte d’Or, Georges-François Leclerc Cancer Centre, UNICANCER, Dijon, France. [Tjønneland,A] Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [Tjønneland,A, Kyrø,C] Danish Cancer Society Research Center, Copenhagen, Denmark. [Dahm,CC, Vistisen,HT] Department of Public Health, Aarhus University, Aarhus, Denmark. [Sánchez,MJ] Andalusian School of Public Health (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain. [Sánchez,MJ, Chirlaque López,MD, Santiuste,C, Ardanaz,E] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Sánchez,MJ] Universidad de Granada, Granada, Spain. [Chirlaque López,MD, Santiuste,C] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque López,MD] Department of Health and Social Sciences, Murcia University, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Menéndez,V] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, Nutrition and Cancer Group, Bellvitge Biomedical Research Institute - IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Trichopoulou,A, Karakatsani,A, La Vecchia,C, Peppa,E] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, 'ATTIKON' University Hospital, National and Kapodistrian University of Athens, Haidari, Greece. [La Vecchia,C] Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Panico,S] Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Department, Azienda Sanitaria Provinciale (ASP), Ragusa, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy. [Butt,ST] Department of Clinical Sciences, Lund University, Malmö, Sweden. [Butt,ST] Department of Surgery, Skåne University Hospital, Malmö, Sweden. [Borgquist,S] Department of Oncology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark. [Borgquist,S] Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden. [Skeie,G] Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK. [Schulze,M] Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany. [Key,T] Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Khaw,KT] Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Tsilidis,KK, Ellingjord-Dale,M, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., The coordination of the European Prospective Investigation into Cancer and Nutrition (EPIC) is supported financially by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the 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 (France), German Cancer Aid, German Cancer Research Center (German Cancer Research Center), Federal Ministry of Education and Research (Federal Ministry of Education and Research), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany), 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 (Ministry of Health, Welfare and Sport), Netherlands Cancer Registry (Netherlands Cancer Registry), LK Research Funds, Dutch Prevention Funds, Dutch Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands), Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO, 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), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK)., Tjønneland, Anne [0000-0003-4385-2097], Dahm, Christina C [0000-0003-0481-2893], Tumino, Rosario [0000-0003-2666-414X], and Borgquist, Signe [0000-0001-7938-8893]
Subjects: 0301 basic medicine, Male, Breastfeeding, lcsh:Medicine, Breast carcinoma in situ, GUIDELINES, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Breast cancer, Risk Factors, Medicine, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, Medicine(all), Geographical Locations::Geographic Locations::Americas::North America::United States [Medical Subject Headings], Hazard ratio, Academies and Institutes, Cohort, General Medicine, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Lifestyle Score, Europe, POSTMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, Female, CONCORDANCE, Life Sciences & Biomedicine, PROJECT, In situ breast cancer, Cohort study, Research Article, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Estudios de cohortes, RECREATIONAL PHYSICAL-ACTIVITY, Check Tags::Male [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Data Collection::Nutrition Assessment [Medical Subject Headings], Breast Neoplasms, Estilo de vida, Càncer de mama, 03 medical and health sciences, Medicine, General & Internal, Medicina preventiva, DIETARY, General & Internal Medicine, Journal Article, Humans, VDP::Medisinske Fag: 700, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Carcinoma de mama in situ, Preventive medicine, 030109 nutrition & dietetics, Cancer prevention, Science & Technology, business.industry, Prevention, lcsh:R, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], medicine.disease, Lifestyle, United States, VDP::Medical disciplines: 700, Nutrition Assessment, Health Care::Health Care Economics and Organizations::Organizations::Academies and Institutes [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer research, Life style, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], business
Abstract: Background Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort. Methods Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93–1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73–0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94–1.05). Conclusions While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies.
Published: 2019
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46. A Novel Saliva-Based miRNA Signature for Colorectal Cancer Diagnosis

Author: Óscar Rapado-González, Roberto Díaz-Peña, Leticia Suárez-Cabrera, Maria Mercedes Suarez-Cunqueiro, Antonio Gil-Moreno, Rafael López-López, Anna Santamaria, Ana Álvarez-Castro, Alicia Abalo, Blanca Majem, Laura Muinelo-Romay, Institut Català de la Salut, [Rapado-González Ó] Department of Surgery and Medical-Surgical Specialties, Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain. Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain. [Majem B] Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Cell Death Regulation Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain. [Álvarez-Castro A] Medical Digestive Service, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain. [Díaz-Peña R] Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain. Faculty of Health Sciences, Universidad Autónoma de Chile, Talca 3460000, Chile. [Abalo A] Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain. [Suárez-Cabrera L, Santamaría A] Grup de Recerca Biomèdica en Urologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Gil-Moreno A] Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain. Unitat de Ginecologia Oncològica i Patologia del Tracte Genital Inferior, Servei de Ginecologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, and Universidade de Santiago de Compostela. Departamento de Cirurxía e Especialidades Médico-Cirúrxicas
Subjects: Epigenomics, Oncology, Saliva, Circulating biomarkers, Colorectal cancer, lcsh:Medicine, 0302 clinical medicine, Carcinoembryonic antigen, Còlon - Càncer, Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs::Circulating MicroRNA [CHEMICALS AND DRUGS], nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN::microARN circulante [COMPUESTOS QUÍMICOS Y DROGAS], Other subheadings::/diagnosis [Other subheadings], 0303 health sciences, microRNA, biology, Biochemical markers, circulating biomarkers, MicroRNA, General Medicine, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], 030220 oncology & carcinogenesis, Marcadors bioquímics, Recte - Càncer, medicine.medical_specialty, Otros calificadores::/diagnóstico [Otros calificadores], colorectal cancer, Malignancy, Article, 03 medical and health sciences, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], Càncer colorectal, Internal medicine, medicine, Liquid biopsy, 030304 developmental biology, saliva, MicroARN, liquid biopsy, Receiver operating characteristic, business.industry, lcsh:R, Cancer, medicine.disease, digestive system diseases, epigenomics, biology.protein, business
Abstract: Salivary microRNAs (miRNAs) are of high interest as diagnostic biomarkers for non-oral cancer. However, little is known about their value for colorectal cancer (CRC) detection. Our study aims to characterize salivary miRNAs in order to identify non-invasive markers for CRC diagnosis. The screening of 754 miRNAs was performed in saliva samples from 14 CRC and 10 healthy controls. The differential expressed miRNAs were validated by RT-qPCR in 51 CRC, 19 adenomas and 37 healthy controls. Receiver operating characteristic (ROC) curves and logistic regression models were performed to analyze the clinical value of these miRNAs. Twenty-two salivary miRNAs were significantly deregulated in CRC patients vs. healthy individuals (P &lt, 0.05) in the discovery phase. From those, five upregulated miRNAs (miR-186-5p, miR-29a-3p, miR-29c-3p, miR-766-3p, and miR-491-5p) were confirmed to be significantly higher in the CRC vs. healthy group (P &lt, 0.05). This five-miRNA signature showed diagnostic value (72% sensitivity, 66.67% specificity, AUC = 0.754) to detect CRC, which was even higher in combination with carcinoembryonic antigen (CEA) levels. Overall, after the first global characterization of salivary miRNAs in CRC, a five-miRNA panel was identified as a promising tool to diagnose this malignancy, representing a novel approach to detect cancer-associated epigenetic alterations using a non-invasive strategy.
Published: 2019

47. Generation of cattle knockout for galactose‐α1,3‐galactose and N‐glycolylneuraminic acid antigens

Author: Perota, Andrea, Lagutina, Irina, Duchi, Roberto, Zanfrini, Elisa, Lazzari, Giovanna, Judor, Jean Paul, Conchon, Sophie, Bach, Jean Marie, Bottio, Tomaso, Gerosa, Gino, Costa Farré, Cristina, Galiñanes, Manuel, Roussel, Jean Christian, Padler-Karavani, Vered, Cozzi, Emanuele, Soulillou, Jean Paul, Galli, Cesare, Universitat Autònoma de Barcelona, Avantea Laboratory of Reproductive Technologies [Cremona, Italy], Fondazione Avantea [Cremona, Italy], Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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)-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), Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Department of Cardiac, Thoracic and Vascular Sciences and Public Health [Padova, Italy] (Cardiac Surgery Unit), Padova University School of Medicine [Padova, Italy] -Consorzio per la Ricerca Sanitaria - CORIS [Padova, Italy], Infectious Diseases and Transplantation Division [Barcelona, Spain], L’Hospitalet de Llobregat [Barcelona, Spain]-Bellvitge Biomedical Research Institute IDIBELL [Barcelona, Spain], Department of Cardiac Surgery & Reparative Therapy of the Heart [Barcelona, Spain], Vall d’Hebron Institute of Research [Barcelona, Spain]-Hospital Universitari Vall d'Hebron [Barcelona, Spain], Département de chirurgie thoracique et cardiovasculaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Cell Research and Immunology, Tel Aviv University [Tel Aviv], Transplantation Immunology Unit [Padua, Italy] (Department of Transfusion Medicine), University of Padua–Ospedale Giustinianeo [Padua, Italy], Le Bihan, Sylvie, Defining the role of xeno-directed and autoimmune events in patients receiving animal-derived bioprosthetic heart valves - TRANSLINK - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 603049 - VALID, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Università degli Studi di Padova = University of Padua (Unipd)-Consorzio per la Ricerca Sanitaria - CORIS [Padova, Italy], Vall d'Hebron University Hospital [Barcelona]-Vall d’Hebron Research Institute (VHIR), Tel Aviv University (TAU), Università degli Studi di Padova = University of Padua (Unipd), and European Project: 603049,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,TRANSLINK(2013)
Subjects: Male, 0301 basic medicine, knockout, Neu5Gc, 030230 surgery, Epitope, Mixed Function Oxygenases, law.invention, Animals, Genetically Modified, Gene Knockout Techniques, chemistry.chemical_compound, 0302 clinical medicine, Carn de boví, N-Glycolylneuraminic acid, law, xenotransplantation, Polymerase chain reaction, 2. Zero hunger, Sanger sequencing, Heart valves, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Immunogenicity, Galactosyltransferases, Vàlvules cardíaques, Heart Valve Prosthesis, symbols, bioprosthetic Heart Valve (BHV), Somatic cell nuclear transfer, Xenotransplantation, Female, Original Article, Beef, cattle, CMAH, GGTA1, αGal, Food Hypersensitivity, Knockout, Transplantation, Heterologous, Immunology, Biology, 03 medical and health sciences, symbols.namesake, Antigens, Heterophile, Cytidine Monophosphate, Animals, Humans, Gene, Bioprosthesis, Galactosyltransferase, Transplantation, Galactose, Original Articles, Fibroblasts, Bioprosthetic Heart Valve (BHV), Molecular biology, 030104 developmental biology, chemistry, Cattle, Neuraminic Acids, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Two well-characterized carbohydrate epitopes are absent in humans but present in other mammals. These are galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc) which are introduced by the activities of two enzymes including α(1,3) galactosyltransferase (encoded by the GGTA1 gene) and CMP-Neu5Gc hydroxylase (encoded by the CMAH gene) that are inactive in humans but present in cattle. Hence, bovine-derived products are antigenic in humans who receive bioprosthetic heart valves (BHVs) or those that suffer from red meat syndrome. Using programmable nucleases, we disrupted (knockout, KO) GGTA1 and CMAH genes encoding for the enzymes that catalyse the synthesis of αGal and Neu5Gc, respectively, in both male and female bovine fibroblasts. The KO in clonally selected fibroblasts was detected by polymerase chain reaction (PCR) and confirmed by Sanger sequencing. Selected fibroblasts colonies were used for somatic cell nuclear transfer (SCNT) to produce cloned embryos that were implanted in surrogate recipient heifers. Fifty-three embryos were implanted in 33 recipients heifers; 3 pregnancies were carried to term and delivered 3 live calves. Primary cell cultures were established from the 3 calves and following molecular analyses confirmed the genetic deletions. FACS analysis showed the double-KO phenotype for both antigens confirming the mutated genotypes. Availability of such cattle double-KO model lacking both αGal and Neu5Gc offers a unique opportunity to study the functionality of BHV manufactured with tissues of potentially lower immunogenicity, as well as a possible new clinical approaches to help patients with red meat allergy syndrome due to the presence of these xenoantigens in the diet.
Published: 2019
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48. Music Training Positively Influences the Preattentive Perception of Voice Onset Time in Children with Dyslexia: A Longitudinal Study

Author: Mireille Besson, Jean-Luc Velay, Clément François, Aline Frey, Julie Chobert, Michel Habib, Cognitions Humaine et ARTificielle (CHART), Université Paris 8 Vincennes-Saint-Denis (UP8)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Cognition and Brain Plasticity Group [Barcelona, Spain], L'Hospitalet de Llobregat-Bellvitge Biomedical Research Institute IDIBELL [Barcelona, Spain], Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Département de Neurologie Pédiatrique, CHU Timone, Cuban Neuroscience Center, ANR-07-NEUR-0024,MUSAPDYS,Influence de l¿apprentissage de la musique sur le traitement des aspects temporels du langage et sur la remédiation de la dyslexie(2007), ANR-16-CONV-0002,ILCB,ILCB: Institute of Language Communication and the Brain(2016), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), École pratique des hautes études (EPHE)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANR-07-NEUR-0024,MUSAPDYS,Influence de l'apprentissage de la musique sur le traitement des aspects temporels du langage et sur la remédiation de la dyslexie(2007), and Université Paris 8 Vincennes-Saint-Denis (UP8)-École Pratique des Hautes Études (EPHE)
Subjects: medicine.medical_specialty, media_common.quotation_subject, education, Mismatch negativity, Audiology, Development, Biological theories of dyslexia, behavioral disciplines and activities, 050105 experimental psychology, Article, lcsh:RC321-571, Dyslexia, 03 medical and health sciences, 0302 clinical medicine, Perception, Vowel, Music training, Mismatch Negativity (MMN), medicine, 0501 psychology and cognitive sciences, EEG, syllables, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Children, ComputingMilieux_MISCELLANEOUS, media_common, 4. Education, General Neuroscience, Music -- Instruction and study, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, Voice-onset time, Dislèxia, longitudinal study, Training effect, children with dyslexia, Music education, [SCCO.LING]Cognitive science/Linguistics, medicine.disease, humanities, Duration (music), [SCCO.PSYC]Cognitive science/Psychology, Ensenyament de la música, School-aged children, Psychology, Infants, 030217 neurology & neurosurgery
Abstract: Previous results showed a positive influence of music training on linguistic abilities at both attentive and preattentive levels. Here, we investigate whether six months of active music training is more efficient than painting training to improve the preattentive processing of phonological parameters based on durations that are often impaired in children with developmental dyslexia (DD). Results were also compared to a control group of Typically Developing (TD) children matched on reading age. We used a Test&ndash, Training&ndash, Retest procedure and analysed the Mismatch Negativity (MMN) and the N1 and N250 components of the Event-Related Potentials to syllables that differed in Voice Onset Time (VOT), vowel duration, and vowel frequency. Results were clear-cut in showing a normalization of the preattentive processing of VOT in children with DD after music training but not after painting training. They also revealed increased N250 amplitude to duration deviant stimuli in children with DD after music but not painting training, and no training effect on the preattentive processing of frequency. These findings are discussed in view of recent theories of dyslexia pointing to deficits in processing the temporal structure of speech. They clearly encourage the use of active music training for the rehabilitation of children with language impairments.
Published: 2019
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49. Right structural and functional reorganization in four-year-old children with perinatal arterial ischemic stroke predict language production

Author: Pablo Ripollés, Laura Bosch, Alfredo García-Alix, Laura Ferreri, Robert J. Zatorre, Antoni Rodríguez-Fornells, Joanna Sierpowska, Clément François, Jordi Muchart, Carme Fons, Mónica Rebollo, Jorgina Solé, Cognition and Brain Plasticity Group [Barcelona, Spain], L'Hospitalet de Llobregat-Bellvitge Biomedical Research Institute IDIBELL [Barcelona, Spain], Department of Cognition, Development and Educational Psychology [Barcelona, Spain], University of Barcelona, Sección de Errores Congénitos del Metabolismo (IBC). Servicio de Bioquímica y Genética Molecular, McGill University = Université McGill [Montréal, Canada], Cognition and Brain Plasticity Unit, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), and BIAL foundation Department of Health of the Generalitat de Catalunya 'Acció instrumental d’incorporació de científics i tecnòlegs' Grant SLT002/16/00390
Subjects: Male, Neurobiologia del desenvolupament, Isquèmia cerebral, Neuropsychological Tests, Functional Laterality, Brain Ischemia, Language in Interaction, 0302 clinical medicine, Cognitive development, Medicine, Developmental neurobiology, Stroke, Children, Brain Mapping, 0303 health sciences, Neuronal Plasticity, hyperconnectivity, General Neuroscience, fMRI, Brain, 3.1, General Medicine, New Research, Cerebral ischemia, diffusion tensor imaging, Magnetic Resonance Imaging, perinatal arterial ischemic stroke, Language development, Child, Preschool, [SCCO.PSYC]Cognitive science/Psychology, Female, Infants, Lateralization of brain function, 03 medical and health sciences, Neuroimaging, Humans, Speech, 030304 developmental biology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Neuro- en revalidatiepsychologie, Resting state fMRI, Language production, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, interhemispheric plasticity, Neuropsychology and rehabilitation psychology, [SCCO.LING]Cognitive science/Linguistics, medicine.disease, Disorders of the Nervous System, business, Neuroscience, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, language production, Diffusion MRI
Abstract: Contains fulltext : 207577.pdf (Publisher’s version ) (Open Access) Brain imaging methods have contributed to shed light on the mechanisms of recovery after early brain insult. The assumption that the unaffected right hemisphere can take over language functions after left perinatal stroke is still under debate. Here, we report how patterns of brain structural and functional reorganization were associated with language outcomes in a group of four-year-old children with left perinatal arterial ischemic stroke (PAIS). Specifically, we gathered specific fine-grained developmental measures of receptive and productive aspects of language as well as standardized measures of cognitive development. We also collected structural neuroimaging data as well as functional activations during a passive listening story-telling fMRI task and a resting state session (rs-fMRI). Children with a left perinatal stroke showed larger lateralization indices of both structural and functional connectivity of the dorsal language pathway towards the right hemisphere that, in turn, were associated with better language outcomes. Importantly, the pattern of structural asymmetry was significantly more right-lateralized in children with a left perinatal brain insult than in a group of matched healthy controls. These results strongly suggest that early lesions of the left dorsal pathway and the associated perisylvian regions can induce the interhemispheric transfer of language functions to right homolog regions. This study provides combined evidence of structural and functional brain reorganization of language networks after early stroke with strong implications for neurobiological models of language development. 18 p.
Published: 2019
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50. EV-associated miRNAs from pleural lavage as potential diagnostic biomarkers in lung cancer

Author: Sonia Gatius, Berta Roman-Canal, Juan M. Falcón-Pérez, Eva Colas, Xavier Matias-Guiu, Sarah Bonnin, Julia Ponomarenko, José Luis Recuero, Antonio Gil-Moreno, Amaia Ojanguren, José M. Porcel, Maria Ruiz-Miró, Esperanza Gonzalez, Cristian Pablo Moiola, [Roman-Canal B] Department of Pathology and Molecular Genetics/Oncologic, University of Lleida, Lleida, Spain. Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain. CIBERONC, Madrid, Spain. Department of Pathology, University Hospital of Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Spain. [Moiola CP] Department of Pathology and Molecular Genetics/Oncologic, University of Lleida, Lleida, Spain. Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain. CIBERONC, Madrid, Spain. Recerca biomèdica en ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Gatius S, Ruiz-Miró M] Department of Pathology and Molecular Genetics/Oncologic, University of Lleida, Lleida, Spain. Pathology Group, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain. CIBERONC, Madrid, Spain. [Bonnin S] Centre for Genomic Regulation (CRG), The Barcelona Institute or Science and Technology, Barcelona, Spain. [González E] Exosomes Laboratory and Metabolomics Platform. CIC bioGUNE, Bizkaia Technology Park, Derio, Spain. CIBEREHD, Madrid, Spain. [Gil-Moreno A] Recerca biomèdica en ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Servei d’Oncologia en Ginecologia, Vall Hebron Hospital Universitari, Barcelona, Spain. CIBERONC, Madrid, Spain. [Colas E] Recerca biomèdica en ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. CIBERONC, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Oncology, Male, Differential expression analysis, Lung Neoplasms, lcsh:Medicine, factores biológicos::biomarcadores::marcadores tumorales [COMPUESTOS QUÍMICOS Y DROGAS], Other subheadings::/diagnosis [Other subheadings], Pulmons -- Càncer, lcsh:Science, Aged, 80 and over, Multidisciplinary, Middle Aged, Marcadors bioquímics, Pleura, Female, Lung cancer, medicine.medical_specialty, Otros calificadores::/diagnóstico [Otros calificadores], Extracellular vesicles, Article, Extracellular Vesicles, Internal medicine, microRNA, medicine, TaqMan, Pulmons - Càncer - Diagnòstic, Biomarkers, Tumor, Diagnostic biomarker, Humans, RNA, Messenger, Biological Factors::Biomarkers::Biomarkers, Tumor [CHEMICALS AND DRUGS], Therapeutic Irrigation, Respiratory Tract Diseases::Lung Diseases::Respiratory Tract Diseases::Lung Neoplasms [DISEASES], Aged, MicroARN, business.industry, lcsh:R, Marcadors tumorals, Cancer, Diagnostic markers, medicine.disease, enfermedades respiratorias::enfermedades pulmonares::enfermedades respiratorias::neoplasias pulmonares [ENFERMEDADES], Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Antisense::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::MicroRNAs [CHEMICALS AND DRUGS], MicroRNAs, Gene Ontology, Potential biomarkers, lcsh:Q, nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN [COMPUESTOS QUÍMICOS Y DROGAS], business
Abstract: Lung cancer is the leading cause of cancer-related deaths among men and women in the world, accounting for the 25% of cancer mortality. Early diagnosis is an unmet clinical issue. In this work, we focused to develop a novel approach to identify highly sensitive and specifc biomarkers by investigating the use of extracellular vesicles (EVs) isolated from the pleural lavage, a proximal fuid in lung cancer patients, as a source of potential biomarkers. We isolated EVs by ultracentrifuge method from 25 control pleural fuids and 21 pleural lavages from lung cancer patients. Analysis of the expression of EVassociated miRNAs was performed using Taqman OpenArray technology through which we could detect 288 out of the 754 miRNAs that were contained in the OpenArray. The diferential expression analysis yielded a list of 14 miRNAs that were signifcantly dysregulated (adj. p-value
Published: 2019

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