"Copenhagen University Hospital-Copenhagen University Hospital" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Copenhagen University Hospital-Copenhagen University Hospital"' showing total 142 results

Start Over "Copenhagen University Hospital-Copenhagen University Hospital"

142 results on '"Copenhagen University Hospital-Copenhagen University Hospital"'

1. Evidence-based practice within nutrition

Author: Janus Christian Jakobsen, Martine Laville, Yves Boirie, Vittorio Bertele, Snezana Djurisic, Ana Rath, Christine Kubiak, Jacques Demotes-Mainard, Carlo La Vecchia, Cristina Ruano-Rodríguez, Christian Gluud, Annemie M. W. J. Schols, Silvio Garattini, Berenice Segrestin, Michael J Hiesmayr, Lluis Serra-Majem, Edmund Neugebauer, Maud Alligier, BMC, BMC, Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CIBER Fisiopatología de la Obesidad y Nutrición [Madrid, Spain] ( (CIBEROBN)), Instituto de Salud Carlos III [Madrid] (ISC), Nutrition Research Group [Las Palmas, Spain] (Research Institute of Biomedical and Health Sciences), University of Las Palmas de Gran Canaria [Spain] (ULPGC), Division of Cardiac, Thoracic, Vascular Anaesthesia and Intensive Care [Vienna, Austria], Vienna General Hospital Währinger Gürtel, Department of Respiratory Medicine [Maastricht, The Netherlands], University Medical Centre Maastricht-NUTRIM School of Nutrition and Translational Research in Metabolism [Maastricht, The Netherlands], Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano = University of Milan (UNIMI), Service de Nutrition Clinique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Plateforme d'information et de services pour les maladies rares et les médicaments orphelins (Orphanet), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Broussais-Institut National de la Santé et de la Recherche Médicale (INSERM), Brandenburg Medical School [Witten, Germany], Witten/Herdecke University, IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri' [Milan, Italy], European Clinical Research Infrastructures Network [Paris] (ECRIN), Ecrin, Copenhagen Trial Unit -CTU [Copenhagen, Denmark] (Centre for Clinical Intervention Research), Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital-Copenhagen University Hospital, Department of Cardiology [Holbaek, Denmark], Holbæk Hospital [Denmark], The ECRIN-IA grant from the EU FP7 (GA 284395) provided support for meetings and for the conduct of this review. The Mario Negri Institute housed the ECRIN-IA meeting in February 2013., French-Clinical Research Infrastructure Network [Lyon] (FCRIN INI-CRCT - Coordination Nationale Réseau FORCE), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Instituto de Salud Carlos III (ISC), Università degli studi di Milano [Milano], Service de nutrition clinique [CHU Gabriel Montpied, Clermont-Ferrand], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Broussais-Institut National de la Santé et de la Recherche Médicale (INSERM), Rigshospitalet [Copenhagen]-Copenhagen University Hospital, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Università degli Studi di Milano [Milano] (UNIMI), Copenhagen University Hospital-Rigshospitalet [Copenhagen], and Copenhagen University Hospital-Copenhagen University Hospital
Subjects: 0301 basic medicine, Research design, Databases, Factual, [SDV]Life Sciences [q-bio], méthodologie de recherche, Medicine (miscellaneous), Review, Evidence-based clinical practice, 0302 clinical medicine, approche nutritionnelle, Medicine, EPIDEMIOLOGY, Nutritional Physiological Phenomena, Pharmacology (medical), Registries, 030212 general & internal medicine, Randomized Controlled Trials as Topic, 2. Zero hunger, RISK, lcsh:R5-920, Randomised clinical trials, CANCER, 3. Good health, [SDV] Life Sciences [q-bio], MEDITERRANEAN DIET, Treatment Outcome, Research Design, Evidence-based medicine, Assessment, Specific barriers, Nutrition, ECRIN, European Clinical Infrastructure Network, Alimentation et Nutrition, SURVIVAL, Nutrition Therapy, HEALTH, lcsh:Medicine (General), COUNTRIES, Blinding, Evidence-based practice, Endpoint Determination, Médecine humaine et pathologie, Context (language use), Clinical nutrition, 03 medical and health sciences, ADHERENCE, FOOD, Humans, Food and Nutrition, étude clinique, Medical education, 030109 nutrition & dietetics, business.industry, Clinical study design, Diet, Clinical trial, Nutrition Assessment, PROSPECTIVE COHORT, Human health and pathology, business
Abstract: Background Evidence-based clinical research poses special barriers in the field of nutrition. The present review summarises the main barriers to research in the field of nutrition that are not common to all randomised clinical trials or trials on rare diseases and highlights opportunities for improvements. Methods Systematic academic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. Results Many nutrients occur in multiple forms that differ in biological activity, and several factors can alter their bioavailability which raises barriers to their assessment. These include specific difficulties with blinding procedures, with assessments of dietary intake, and with selecting appropriate outcomes as patient-centred outcomes may occur decennia into the future. The methodologies and regulations for drug trials are, however, applicable to nutrition trials. Conclusions Research on clinical nutrition should start by collecting clinical data systematically in databases and registries. Measurable patient-centred outcomes and appropriate study designs are needed. International cooperation and multistakeholder engagement are key for success. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2160-8) contains supplementary material, which is available to authorized users.
Published: 2017

2. Enterosignatures define common bacterial guilds in the human gut microbiome

Author: Frioux, Clémence, Ansorge, Rebecca, Özkurt, Ezgi, Ghassemi Nedjad, Chabname, Fritscher, Joachim, Quince, Christopher, Waszak, Sebastian, Hildebrand, Falk, from patterns to models in computational biodiversity and biotechnology (PLEIADE), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Quadram Institute, Biotechnology and Biological Sciences Research Council (BBSRC), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Earlham Institute [Norwich], Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, and European Project: erc-stg-948219,EPYC
Subjects: non-negative matrix factorization, metagenomics, human gut microbiome, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], dysbiosis, enterotypes, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], enterosignatures
Abstract: International audience; The human gut microbiome composition is generally in a stable dynamic equilibrium, but it can deteriorate into dysbiotic states detrimental to host health. To disentangle the inherent complexity and capture the ecological spectrum of microbiome variability, we used 5,230 gut metagenomes to characterize signatures of bacteria commonly co-occurring, termed enterosignatures (ESs). We find five generalizable ESs dominated by either Bacteroides, Firmicutes, Prevotella, Bifidobacterium, or Escherichia. This model confirms key ecological characteristics known from previous enterotype concepts, while enabling the detection of gradual shifts in community structures.Temporal analysis implies that the Bacteroides-associated ES is “core” in the resilience of westernized gut microbiomes, while combinations with other ESs often complement the functional spectrum. The model reliably detects atypical gut microbiomes correlated with adverse host health conditions and/or the presence of pathobionts. ESs provide an interpretable and generic model that enables an intuitive characterization of gut microbiome composition in health and disease.
Published: 2023

3. Researchers from Copenhagen University Hospital Provide Details of New Studies and Findings in the Area of Heart Attack (Cognitive Impairment and Psychopathology In Sudden Out-of-hospital Cardiac Arrest Survivors: Results From the Revival...).

Subjects: PATHOLOGICAL psychology, CARDIAC arrest, COGNITION disorders, UNIVERSITY hospitals, RESEARCH personnel, MYOCARDIAL infarction, SUDDEN death
Abstract: A recent report from Copenhagen University Hospital provides new data on cognitive impairment and psychopathology in out-of-hospital cardiac arrest (OHCA) survivors. The study found that during hospitalization, 65% of OHCA survivors experienced cognitive impairment, 25% reported symptoms of anxiety, 20% reported symptoms of depression, and 21% reported symptoms of traumatic distress. At the three-month follow-up, 53% still reported cognitive impairment, and the prevalence of symptoms of anxiety, depression, and traumatic distress decreased slightly. The study concluded that OHCA survivors often experience cognitive impairment and symptoms of psychopathology, which can have unfavorable mental health outcomes. [Extracted from the article]
Published: 2024

4. Genetic architecture of natural variation of cardiac performance from flies to humans

Author: Lionel Spinelli, Saswati Saha, Jaime A Castro Mondragon, Anaïs Kervadec, Michaela Lynott, Laurent Kremmer, Laurence Roder, Sallouha Krifa, Magali Torres, Christine Brun, Georg Vogler, Rolf Bodmer, Alexandre R Colas, Karen Ocorr, Laurent Perrin, Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, and Sanford Burnham Prebys Medical Discovery Institute
Subjects: General Immunology and Microbiology, General Neuroscience, Quantitative Trait Loci, Genetic Variation, Heart, General Medicine, General Biochemistry, Genetics and Molecular Biology, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Drosophila melanogaster, Phenotype, Animals, Humans, Gene Regulatory Networks, Genome-Wide Association Study
Abstract: Deciphering the genetic architecture of human cardiac disorders is of fundamental importance but their underlying complexity is a major hurdle. We investigated the natural variation of cardiac performance in the sequenced inbred lines of the Drosophila Genetic Reference Panel (DGRP). Genome-wide associations studies (GWAS) identified genetic networks associated with natural variation of cardiac traits which were used to gain insights as to the molecular and cellular processes affected. Non-coding variants that we identified were used to map potential regulatory non-coding regions, which in turn were employed to predict transcription factors (TFs) binding sites. Cognate TFs, many of which themselves bear polymorphisms associated with variations of cardiac performance, were also validated by heart-specific knockdown. Additionally, we showed that the natural variations associated with variability in cardiac performance affect a set of genes overlapping those associated with average traits but through different variants in the same genes. Furthermore, we showed that phenotypic variability was also associated with natural variation of gene regulatory networks. More importantly, we documented correlations between genes associated with cardiac phenotypes in both flies and humans, which supports a conserved genetic architecture regulating adult cardiac function from arthropods to mammals. Specifically, roles for PAX9 and EGR2 in the regulation of the cardiac rhythm were established in both models, illustrating that the characteristics of natural variations in cardiac function identified in Drosophila can accelerate discovery in humans.
Published: 2022

5. Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10

Author: Asma Chaoui, Peter Uldall, Nadege Bondurand, Elisabeth Sarrazin, Laurence Pierre-Louis, Goran Brandberg, Sylvie Manouvrier-Hanu, Veronique Pingault, Alain Verloes, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Biochimie et Génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de réanimation, de soins intensifs néonatals et de néonatologie, Maison de la Femme de la Mère et de l'Enfant [CHU de la Martinique] (MFME [Fort de France]), CHU de la Martinique [Fort de France]-CHU de la Martinique [Fort de France]-CHU Fort-de-France, Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence car i b é en des maladies rares neuromusculaires et neurologiques adultes et enfant (CERCA), Hôpital Pierre Zobda Quitman-CHU Fort-de-France, Pediatric and Adolescent Clinic [Falun], County Hospital, Pediatric and Adolescent Clinic [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital-The Juliane Marie Centre-University of Copenhagen = Københavns Universitet (UCPH), Laboratoire de Génétique Clinique, Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), This work was supported by the Institut de la Santé et de la Recherche Médicale (INSERM) , the Assistance Publique des Hôpitaux de Paris (AP - HP) , and the Agence Nationale de la Recherche (ANR - JCJC - 2010 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, University of Copenhagen = Københavns Universitet (KU)-Rigshospitalet [Copenhagen], and Copenhagen University Hospital-Copenhagen University Hospital-The Juliane Marie Centre
Subjects: Adult, Male, Adolescent, Hirschsprung disease, Genotype, Disease, Biology, Polymorphism, Single Nucleotide, Proto-Oncogene Mas, Article, 03 medical and health sciences, SOX10 protein, Proto, Genetics, medicine, Missense mutation, Humans, Family, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetic variability, Child, ret, Genetics (clinical), Pigmentation disorder, Waardenburg syndrome, 030304 developmental biology, 0303 health sciences, Pigmentation disorders, SOXE Transcription Factors, 030305 genetics & heredity, Infant, Newborn, Oncogene Protein, Infant, Middle Aged, medicine.disease, Phenotype, Pedigree, Child, Preschool, embryonic structures, Mutation, Sensorineural hearing loss, Female
Abstract: International audience; Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype-phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype-phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. © 2014 Wiley Periodicals, Inc.
Published: 2014

6. Establishment of CORONET, COVID-19 Risk in Oncology Evaluation Tool, to Identify Patients With Cancer at Low Versus High Risk of Severe Complications of COVID-19 Disease On Presentation to Hospital

Author: Lee, Rebecca J, Wysocki, Oskar, Zhou, Cong, Shotton, Rohan, Tivey, Ann, Lever, Louise, Woodcock, Joshua, Albiges, Laurence, Angelakas, Angelos, Arnold, Dirk, Aung, Theingi, Banfill, Kathryn, Baxter, Mark, Barlesi, Fabrice, Bayle, Arnaud, Besse, Benjamin, Bhogal, Talvinder, Boyce, Hayley, Britton, Fiona, Calles, Antonio, Castelo-Branco, Luis, Copson, Ellen, Croitoru, Adina E, Dani, Sourbha S, Dickens, Elena, Eastlake, Leonie, Fitzpatrick, Paul, Foulon, Stephanie, Frederiksen, Henrik, Frost, Hannah, Ganatra, Sarju, Gennatas, Spyridon, Glenthøj, Andreas, Gomes, Fabio, Graham, Donna M, Hague, Christina, Harrington, Kevin, Harrison, Michelle, Horsley, Laura, Hoskins, Richard, Huddar, Prerana, Hudson, Zoe, Jakobsen, Lasse H., Joharatnam-Hogan, Nalinie, Khan, Sam, Khan, Umair T, Khan, Khurum, Massard, Christophe, Maynard, Alec, McKenzie, Hayley, Michielin, Olivier, Mosenthal, Anne C, Obispo, Berta, Patel, Rushin, Pentheroudakis, George, Peters, Solange, Rieger-Christ, Kimberly, Robinson, Timothy, Rogado, Jacobo, Romano, Emanuela, Rowe, Michael, Sekacheva, Marina, Sheehan, Roseleen, Stevenson, Julie, Stockdale, Alexander, Thomas, Anne, Turtle, Lance, Viñal, David, Weaver, Jamie, Williams, Sophie, Wilson, Caroline, Palmieri, Carlo, Landers, Donal, Cooksley, Timothy, Dive, Caroline, Freitas, André, Armstrong, Anne C, Institut Gustave Roussy (IGR), Oncologie gynécologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Physikalisch-Technische Bundesanstalt [Braunschweig] (PTB), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cancer Research and Personalized Medicine - CARPEM [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Genetics, University of Southampton, 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, Hematology, Odense University Hospital, Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University of Manchester [Manchester], Lausanne University Hospital, Department of Medical Oncology, Ioannina University Hospital, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Liverpool, Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, University of Manchester, Universidade Estadual de Campinas = University of Campinas (UNICAMP), Cancer Research UK Department of Medical Oncology, and Christie Hospital NHS Foundation Trust
Subjects: Adult, Aged, 80 and over, Male, Adolescent, SARS-CoV-2, [SDV]Life Sciences [q-bio], COVID-19, General Medicine, Middle Aged, Hospitals, Oxygen, Young Adult, Neoplasms, Child, Preschool, COVID-19/complications, Humans, Female, Neoplasms/complications, Child, Aged
Abstract: PURPOSE Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET). METHODS Patients with active cancer (stage I-IV) and laboratory-confirmed COVID-19 disease presenting to hospitals worldwide were included. Discharge (within 24 hours), admission (≥ 24 hours inpatient), oxygen (O2) requirement, and death were combined in a 0-3 point severity scale. Association of features with outcomes were investigated using Lasso regression and Random Forest combined with Shapley Additive Explanations. The CORONET model was then examined in the entire cohort to build an online CORONET decision support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Finally, the CORONET model was validated on an external cohort. RESULTS The model development data set comprised 920 patients, with median age 70 (range 5-99) years, 56% males, 44% females, and 81% solid versus 19% hematologic cancers. In derivation, Random Forest demonstrated superior performance over Lasso with lower mean squared error (0.801 v 0.807) and was selected for development. During validation (n = 282 patients), the performance of CORONET varied depending on the country cohort. CORONET cutoffs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died (94% and 98% in validation, respectively). The specificity for mortality prediction was 92% and 83% in derivation and validation, respectively. Shapley Additive Explanations revealed that National Early Warning Score 2, C-reactive protein, and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation. CONCLUSION CORONET, a decision support tool validated in health care systems worldwide, can aid admission decisions and predict COVID-19 severity in patients with cancer.
Published: 2022

7. Incidence and risk factors of HIV-related non-Hodgkin's lymphoma in the era of combination antiretroviral therapy: a European multicohort study

Author: Bohlius, Julia, Schmidlin, Kurt, Costagliola, Dominique, Fã¤tkenheuer, Gerd, May, Margaret, Caro murillo, Ana Maria, Mocroft, Amanda, Bonnet, Fabrice, Clifford, Gary, Karafoulidou, Anastasia, Miro, Jose M., Lundgren, Jens, Chene, Genevieve, Egger, Matthias, Cohere, Coorth, CASTAGNA, ANTONELLA, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Infectious diseases, Other departments, Landsteiner Laboratory, Bohlius, Julia, Schmidlin, Kurt, Costagliola, Dominique, Fã¤tkenheuer, Gerd, May, Margaret, Caro murillo, Ana Maria, Mocroft, Amanda, Bonnet, Fabrice, Clifford, Gary, Karafoulidou, Anastasia, Miro, Jose M., Lundgren, Jen, Chene, Genevieve, Egger, Matthia, Cohere, Coorth, Castagna, Antonella, Institute of Social and Preventive Medicine (ISPM), University of Bern, Epidémiologie Clinique et Traitement de l'Infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine, University of Cologne, Department of Social Medicine, University of Bristol [Bristol], Centro Nacional de Epidemiología, Instituto de Salud Carlos III [Madrid] (ISC), Department of primary care and population sciences, University College of London [London] (UCL), Centre d'Information et de Soins de l'Immunodéficience Humaine (CISIH), CHU Bordeaux [Bordeaux], International Agency for Cancer Research (IACR), 2nd Blood Transfusion and Hemophilia Center, Laikon General Hospital, Infectious Diseases Service, Universitat de Barcelona (UB)-Hospital Clinic-IDIBAPS, Copenhagen HIV Programme, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital-University of Copenhagen = Københavns Universitet (KU), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Copenhagen University Hospital-Copenhagen University Hospital-University of Copenhagen = Københavns Universitet (UCPH), and Mouillet, Evelyne
Subjects: Male, HIV Infections, Rate ratio, 0302 clinical medicine, cohort studies, Risk Factors, immune system diseases, hemic and lymphatic diseases, HIV Infection, Pharmacology (medical), 030212 general & internal medicine, Prospective cohort study, Lymphoma, AIDS-Related, Brain Neoplasms, non-Hodgkin lymphoma, Incidence, Lymphoma, Non-Hodgkin, Medicine (all), Incidence (epidemiology), Hazard ratio, Non-Hodgkin's Lymphoma, virus diseases, viral load, 3. Good health, Europe, Infectious Diseases, 030220 oncology & carcinogenesis, multicohort study, Drug Therapy, Combination, Female, Viral load, Human, Adult, Cart, HIV patients, medicine.medical_specialty, Anti-HIV Agents, antiretroviral therapy, Article, AIDS-related lymphoma, Brain Neoplasm, 03 medical and health sciences, Internal medicine, mental disorders, medicine, Humans, Pharmacology, business.industry, Risk Factor, Kaposi sarcoma, Anti-HIV Agent, medicine.disease, Non-Hodgkin's lymphoma, nervous system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, HIV-1, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort Studie, business, immunodeficiency
Abstract: Background Incidence and risk factors of HIV-associated non-Hodgkin's lymphoma (NHL) are not well defined in the era of combination antiretroviral therapy (cART). Methods A total of 56,305 adult HIV type-1 (HIV-1)-infected patients who started cART in 1 of 22 prospective studies in Europe were included. Weibull random effects models were used to estimate hazard ratios (HRs) for developing systemic NHL and included CD4+ T-cell counts and viral load as time-updated variables. Results During the 212,042 person-years of follow-up, 521 patients were diagnosed with systemic NHL and 62 with primary brain lymphoma (PBL). The incidence rate of systemic NHL was 463 per 100,000 person-years not on cART and 205 per 100,000 person-years in treated patients for a rate ratio of 0.44 (95% confidence interval [CI] 0.37–0.53). The corresponding incidence rates of PBL were 57 and 24 per 100,000 person-years (rate ratio 0.43, 95% CI 0.25-0.73). Suppression of HIV-1 replication on cART (HR 0.60, 95% CI 0.44-0.81, comparing ≤500 with 10,000-99,999 copies/ml) and increases in CD4+ T-cell counts (HR 0.30, 0.22-0.42, comparing ≥350 with 100-199 cells/pl) were protective; a history of Kaposi's sarcoma (HR 1.70, 1.08-2.68, compared to no history of AIDS), transmission through sex between men (HR 1.57, 1.19-2.08, compared with heterosexual transmission) and older age (HR 3.71, 2.37-5.80, comparing ≥50 with 16-29 years) were risk factors for systemic NHL. Conclusions The incidence rates of both systemic NHL and PBL were substantially reduced in patients on cART. Timely initiation of therapy is key to the prevention of NHL in the era of cART.
Published: 2009

8. An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves

Author: Oskar, Wysocki, Cong, Zhou, Jacobo, Rogado, Prerana, Huddar, Rohan, Shotton, Ann, Tivey, Laurence, Albiges, Angelos, Angelakas, Dirk, Arnold, Theingi, Aung, Kathryn, Banfill, Mark, Baxter, Fabrice, Barlesi, Arnaud, Bayle, Benjamin, Besse, Talvinder, Bhogal, Hayley, Boyce, Fiona, Britton, Antonio, Calles, Luis, Castelo-Branco, Ellen, Copson, Adina, Croitoru, Sourbha S, Dani, Elena, Dickens, Leonie, Eastlake, Paul, Fitzpatrick, Stephanie, Foulon, Henrik, Frederiksen, Sarju, Ganatra, Spyridon, Gennatas, Andreas, Glenthøj, Fabio, Gomes, Donna M, Graham, Christina, Hague, Kevin, Harrington, Michelle, Harrison, Laura, Horsley, Richard, Hoskins, Zoe, Hudson, Lasse H, Jakobsen, Nalinie, Joharatnam-Hogan, Sam, Khan, Umair T, Khan, Khurum, Khan, Alexandra, Lewis, Christophe, Massard, Alec, Maynard, Hayley, McKenzie, Olivier, Michielin, Anne C, Mosenthal, Berta, Obispo, Carlo, Palmieri, Rushin, Patel, George, Pentheroudakis, Solange, Peters, Kimberly, Rieger-Christ, Timothy, Robinson, Emanuela, Romano, Michael, Rowe, Marina, Sekacheva, Roseleen, Sheehan, Alexander, Stockdale, Anne, Thomas, Lance, Turtle, David, Viñal, Jamie, Weaver, Sophie, Williams, Caroline, Wilson, Caroline, Dive, Donal, Landers, Timothy, Cooksley, André, Freitas, Anne C, Armstrong, Rebecca J, Lee, On Behalf Of The Esmo Co-Care, Institut Gustave Roussy (IGR), Oncologie gynécologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Physikalisch-Technische Bundesanstalt [Braunschweig] (PTB), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cancer Research and Personalized Medicine - CARPEM [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Genetics, University of Southampton, 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, Hematology, Odense University Hospital, Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University of Manchester [Manchester], Lausanne University Hospital, University of Liverpool, Department of Medical Oncology, Ioannina University Hospital, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, University of Manchester, Universidade Estadual de Campinas = University of Campinas (UNICAMP), Cancer Research UK Department of Medical Oncology, and Christie Hospital NHS Foundation Trust
Subjects: CORONET, Cancer Research, Oncology, Omicron, [SDV]Life Sciences [q-bio], cancer, COVID-19, outcomes, vaccination
Abstract: International audience; Simple Summary There have been huge improvements in both vaccination and the management of COVID-19 in patients with cancer. In addition, different variants may be associated with different presentations. Therefore, we examined whether indicators of the severity of COVID-19 in patients with cancer who present to hospital varied during different waves of the pandemic and we showed that these indicators remained predictive. We validated that the COVID-19 Risk in Oncology Evaluation Tool (CORONET), which predicts the severity of COVID-19 in cancer patients presenting to hospital, performed well in all waves. In addition, we examined patient outcomes and the factors that influence them and found that there was increased vaccination uptake and steroid use for patients requiring oxygen in later waves, which may be associated with improvements in outcome. Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.
Published: 2022

9. Parameter estimates for trends and patterns of excess mortality among persons on antiretroviral therapy in high-income European settings

Author: Juan Berenguer, Christoph Wyen, M. John Gill, Sophie Abgrall, Ard van Sighem, Matthias Cavassini, Sophie Grabar, Jordi Casabona, Margaret T May, Julia del Amo, Antonella d'Arminio Monforte, Robert Zangerle, John Stover, Niels Obel, Jonathan A C Sterne, Fabrice Bonnet, Adam Trickey, Medical Research Council (Reino Unido), Department for International Development (Reino Unido), NIH - National Institute on Alcohol Abuse and Alcoholism (NIAAA) (Estados Unidos), National Institute for Health Research (Reino Unido), Unión Europea, Agence Nationale de Recherches sur le sida et les hépatites virales (Francia), Institut National de la Santé et de la Recherche Médicale (Francia), Ministero della Salute (Italia), Ministerio de Sanidad y Consumo (España), Ministerio de Ciencia e Innovación (España), Red de Investigación Cooperativa en Investigación en Sida (España), Swiss National Science Foundation, University of Bristol [Bristol], Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), 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, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital General Universitario 'Gregorio Marañón' [Madrid], Instituto de Investigación Sanitaria Gregorio Marañón [Madrid, Spain] ( IiSGM), University Hospital of Cologne [Cologne], Centre d'Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), CIBER de Epidemiología y Salud Pública (CIBERESP), Università degli Studi di Milano = University of Milan (UNIMI), Ospedale San Paolo-Polo Universitario, ASST Santi Paolo e Carlo, Milan, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Université de Lausanne = University of Lausanne (UNIL), Instituto de Salud Carlos III [Madrid] (ISC), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University of Calgary, Department of Infectious Diseases [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Gestionnaire, Hal Sorbonne Université, Medical Research Council (United Kingdom), Department for International Development (United Kingdom), National Institute on Alcohol Abuse and Alcoholism (United States), National Institute for Health Research (United Kingdom), European Union, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), Institut National de la Santé et de la Recherche Médicale (France), and Red Española de Investigación en SIDA
Subjects: Adult, Male, 0301 basic medicine, Anti-HIV Agents, [SDV]Life Sciences [q-bio], Immunology, Population, HIV Infections, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Acquired immunodeficiency syndrome (AIDS), Risk Factors, death, cause-specific, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Mortality, education, United Nations Programme on HIV/AIDS, education.field_of_study, Models, Statistical, business.industry, Developed Countries, Mortality rate, duration, HIV, cohort, Middle Aged, medicine.disease, Confidence interval, 3. Good health, AIDS, [SDV] Life Sciences [q-bio], Europe, Anti-HIV Agents/therapeutic use, Europe/epidemiology, Female, HIV Infections/drug therapy, HIV Infections/mortality, Mortality/trends, Editorial, 030104 developmental biology, Infectious Diseases, Cohort, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, business, Developed country, Demography, Cohort study
Abstract: Supplemental Digital Content is available in the text, Introduction: HIV cohort data from high-income European countries were compared with the UNAIDS Spectrum modelling parameters for these same countries to validate mortality rates and excess mortality estimates for people living with HIV (PLHIV) on antiretroviral therapy (ART). Methods: Data from 2000 to 2015 were analysed from the Antiretroviral Therapy Cohort Collaboration (ART-CC) for Austria, Denmark, France, Italy, the Netherlands, Spain, and Switzerland. Flexible parametric models were used to compare all-cause mortality rates in the ART-CC and Spectrum. The percentage of AIDS-related deaths and excess mortality (both are the same within Spectrum) were compared, with excess mortality defined as that in excess of the general population mortality. Results: Analyses included 94 026 PLHIV with 585 784 person-years of follow-up, from which there were 5515 deaths. All-cause annual mortality rates in Spectrum for 2000–2003 were 0.0121, reducing to 0.0078 in 2012–2015, whilst the ART-CC's corresponding annual mortality rates were 0.0151 [95% confidence interval (95% CI): 0.0130–0.0171] reducing to 0.0049 (95% CI: 0.0039–0.0060). The percentage of AIDS-related deaths in Spectrum was 74.7% in 2000–2003, dropping to 43.6% in 2012–2015. In the ART-CC, AIDS-related mortality constitutes 45.3% (95% CI: 38.4–52.9%) of mortality in 2000–2003 and 26.7% (95% CI: 19–46%) between 2012 and 2015. Excess mortality in the ART-CC was broadly similar to the Spectrum estimates, dropping from 75.3% (95% CI: 60.3–95.2%) in 2000–2003 to 30.7% (95% CI: 25.5–63.7%) in 2012–2015. Conclusion: All-cause mortality assumptions for PLHIV on ART in high-income European settings should be adjusted in Spectrum to be higher in 2000–2003 and decline more quickly to levels currently captured for recent years.
Published: 2019

10. JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles

Author: Aziz Khan, Damir Baranasic, Benoit Ballester, Ieva Rauluseviciute, Fayrouz Hammal, Klaas Vandepoele, Paul Boddie, Anthony Mathelier, Daniel Schmelter, Rafael Riudavets-Puig, Wyeth W. Wasserman, Jérémy Lucas, François Parcy, Oriol Fornes, Boris Lenhard, Laura Turchi, Romain Blanc-Mathieu, Jaime A. Castro-Mondragon, Albin Sandelin, Nicolás Manosalva Pérez, Roza Berhanu Lemma, Tiffany Y. Leung, Alejandro Aguirre, Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Régulateurs du développement de la fleur (Flo_RE ), Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Stanford Cancer Institute - Stanford University School of Medicine, Department of Plant Biotechnology and Bioinformatics, Ghent University, VIBUGent Center for Plant Systems Biology, BC Children's Hospital Research Institute [Vancouver, BC, Canada] (BCCHR), University of British Columbia (UBC), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UCSC Genome Browser, University of California Santa Cruz, MRC London Institute of Medical Sciences (LMC), Institute of Clinical Sciences, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, University of Copenhagen, Department of Medical Genetics, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, NorwegianResearch Council [187615] and [288404], South-Eastern Norway Regional Health Authority (Helse Sør-Øst), Canadian Institutes of Health Research [PJT-162120], Natural Sciences andEngineeringResearch Council of Canada (NSERC) Discovery Grant [RGPIN-2017-06824], Norwegian Cancer Society [197884], NHGRI (National Human Genome Research Institute) [5U41HG002371-20], BOFgrant from Ghent University [BOF24Y2019001901], Novo Nordisk Foundation [NNF20OC0059951, NNF19OC0058262], Danish Cancer Foundation [R204A12359], Danish Independent Research Fund [611000207B, 7014-00120B], Carlsberg Foundation, ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), European Project: MSCA-ITN 2018,pHioniC, Universiteit Gent = Ghent University (UGENT), Imperial College London, University of Copenhagen = Københavns Universitet (UCPH), University of Oslo (UiO), Martin-Laffon, Jacqueline, CBH-EUR-GS - - CBH-EUR-GS2017 - ANR-17-EURE-0003 - EURE - VALID, Grenoble Alliance for Integrated Structural Cell Biology - - GRAL2010 - ANR-10-LABX-0049 - LABX - VALID, and pH and Ion Transport in Pancreatic Cancer - pHioniC - MSCA-ITN 2018 - INCOMING
Subjects: AcademicSubjects/SCI00010, Genome browser, Biology, computer.software_genre, MOUSE, Genome, Bioconductor, Mice, 03 medical and health sciences, 0302 clinical medicine, ENRICHMENT ANALYSIS, Databases, Genetic, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, Animals, Humans, Database Issue, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Taxonomic rank, MOTIF DATABASE, Transcription factor, TFBSSHAPE, 030304 developmental biology, TOOLS, 0303 health sciences, Binding Sites, Database, Computational Biology, Biology and Life Sciences, Genomics, Structural classification, Plants, GENE, DNA SHAPE-FEATURES, Vertebrates, computer, Software, 030217 neurology & neurosurgery, Protein Binding, Transcription Factors
Abstract: JASPAR (http://jaspar.genereg.net/) is an open-access database containing manually curated, non-redundant transcription factor (TF) binding profiles for TFs across six taxonomic groups. In this 9th release, we expanded the CORE collection with 341 new profiles (148 for plants, 101 for vertebrates, 85 for urochordates, and 7 for insects), which corresponds to a 19% expansion over the previous release. We added 298 new profiles to the Unvalidated collection when no orthogonal evidence was found in the literature. All the profiles were clustered to provide familial binding profiles for each taxonomic group. Moreover, we revised the structural classification of DNA binding domains to consider plant-specific TFs. This release introduces word clouds to represent the scientific knowledge associated with each TF. We updated the genome tracks of TFBSs predicted with JASPAR profiles in eight organisms; the human and mouse TFBS predictions can be visualized as native tracks in the UCSC Genome Browser. Finally, we provide a new tool to perform JASPAR TFBS enrichment analysis in user-provided genomic regions. All the data is accessible through the JASPAR website, its associated RESTful API, the R/Bioconductor data package, and a new Python package, pyJASPAR, that facilitates serverless access to the data.
Published: 2021

11. Bone phenotype of P2X4 receptor knockout mice: implication of a P2X7 receptor mutation?

Author: Maria Ellegaard, Niklas Rye Jørgensen, Ming Ding, Tanja Hegner, Lauriane Ulmann, Department of Clinical Biochemistry [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University of Southern Denmark (SDU), Odense University Hospital, Odense, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), LabEx Ion Channels Science and Therapeutics [France], and IT University of Copenhagen
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Bone metabolism, Transgene, [SDV]Life Sciences [q-bio], Biology, Brief Communication, Bone and Bones, Bone remodeling, Animals, Genetically Modified, P2X4 purinergic receptor, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Bone Density, Internal medicine, medicine, Animals, P2X7 purinergic receptor, Genetically modified animal, Receptor, Molecular Biology, Mice, Knockout, Wild type, X-Ray Microtomography, Cell Biology, Bone structure, Phenotype, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Mutation, Knockout mouse, Female, Bone Remodeling, Receptors, Purinergic P2X7, Signal transduction, Receptors, Purinergic P2X4, 030217 neurology & neurosurgery, Signal Transduction, Knockout mice
Abstract: International audience; Transgenic and knockout animal models are widely used to investigate the role of receptors, signaling pathways, and other peptides and proteins. Varying results are often published on the same model from different groups, and much effort has been put into understanding the underlying causes of these sometimes conflicting results. Recently, it has been shown that a P2X4R knockout model carries a so-called passenger mutation in the P2X7R gene, potentially affecting the interpretation of results from studies using this animal model. We therefore report this case to raise awareness about the potential pitfalls using genetically modified animal models, especially within P2 receptor research. Although purinergic signaling has been recognized as an important contributor to the regulation of bone remodeling, the process that maintains the bone quality during life, little is known about the role of the P2X4 receptor (P2X4R) in regulation of bone remodeling in health and disease. To address this, we analyzed the bone phenotype of P2rx4tm1Rass (C57BL/6J) knockout mice and corresponding wildtype using microCT and biomechanical testing. Overall, we found that the P2X4R knockout mice displayed improved bone microstructure and stronger bones in an age- and gender-dependent manner. While cortical BMD, trabecular BMD, and bone volume were higher in the 6-month-old females and 3-month-old males, this was not the case for the 3-month-old females and the 6-month-old males. Bone strength was only affected in the females. Moreover, we found that P2X4R KO mice carried the P2X7 receptor 451P wildtype allele, whereas the wildtype mice carried the 451L mutant allele. In conclusion, this study suggests that P2X4R could play a role in bone remodeling, but more importantly, it underlines the potential pitfalls when using knockout models and highlights the importance of interpreting results with great caution. Further studies are needed to verify any specific effects of P2X4R on bone metabolism.
Published: 2021

12. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism

Author: Philippe Gérard, Edek A. J. Williams, Jens F. Rehfeld, Ronaldo P. Ferraris, Sharon Barretto, Catherine Philippe, Chloé Melchior, Guillaume Gourcerol, Nicolas Lapaque, Pierre Larraufie, Christine Herberden, Hervé M. Blottière, Mahendra Mariadassou, Veronique Douard, J. Christopher Fritton, Daniel Vasiliauskas, Sandrine Ellero-Simatos, Fabienne Devime, Nathalie Dourmap, Lorraine Smith, Alexandra Grosfeld, Xufei Zhang, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Métabolisme et physiologie rénale (CRC - UMR_S 1138), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), Institut des Neurosciences de Paris-Saclay (Neuro-PSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Mathématiques et Informatique Appliquées du Génome à l'Environnement ( MaIAGE), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Department of Clinical Biochemistry [Rigshospitalet], Rigshospitalet [Copenhagen], Rutgers University [Newark], École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut des Neurosciences Paris-Saclay (NeuroPSI), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de la Recherche Agronomique (INRA), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Copenhagen University Hospital-Copenhagen University Hospital, Institut Benjamin Delessert, INRA, China Scholarship Council (CSC), PERIGNON, Alain, Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Hôpital Charles Nicolle [Rouen]
Subjects: 0301 basic medicine, KHK, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Fructose malabsorption, Enteroendocrine cell, Biochemistry, Mice, chemistry.chemical_compound, Cecum, 0302 clinical medicine, Cholecystokinin, Mice, Knockout, 2. Zero hunger, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, digestive, oral, and skin physiology, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, medicine.anatomical_structure, hormones, hormone substitutes, and hormone antagonists, Biotechnology, medicine.medical_specialty, Ileum, Fructose, digestive system, Cell Line, Fructokinases, 03 medical and health sciences, Internal medicine, Genetics, medicine, Animals, Humans, propionate, Molecular Biology, Research, CCK, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Metabolism, medicine.disease, Gastrointestinal Microbiome, 030104 developmental biology, Endocrinology, Gene Expression Regulation, chemistry, Peptide YY, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery
Abstract: International audience; Current fructose consumption levels often overwhelm the intestinal capacity to absorb fructose. We investigated the impact of fructose malabsorption on intestinal endocrine function and addressed the role of the microbiota in this process. To answer this question, a mouse model of moderate fructose malabsorption [ketohexokinase mutant (KHK)-/-] and wild-type (WT) littermate mice were used and received a 20%-fructose (KHK-F and WT-F) or 20%-glucose diet. Cholecystokinin (Cck) mRNA and protein expression in the ileum and cecum, as well as preproglucagon (Gcg) and neurotensin (Nts) mRNA expression in the cecum, increased in KHK-F mice. In KHK-F mice, triple-label immunohistochemistry showed major up-regulation of CCK in enteroendocrine cells (EECs) that were glucagon-like peptide-1 (GLP-1)+/Peptide YY (PYY-) in the ileum and colon and GLP-1-/PYY- in the cecum. The cecal microbiota composition was drastically modified in the KHK-F in association with an increase in glucose, propionate, succinate, and lactate concentrations. Antibiotic treatment abolished fructose malabsorption-dependent induction of cecal Cck mRNA expression and, in mouse GLUTag and human NCI-H716 cells, Cck mRNA expression levels increased in response to propionate, both suggesting a microbiota-dependent process. Fructose reaching the lower intestine can modify the composition and metabolism of the microbiota, thereby stimulating the production of CCK from the EECs possibly in response to propionate.-Zhang, X., Grosfeld, A., Williams, E., Vasiliauskas, D., Barretto, S., Smith, L., Mariadassou, M., Philippe, C., Devime, F., Melchior, C., Gourcerol, G., Dourmap, N., Lapaque, N., Larraufie, P., Blottière, H. M., Herberden, C., Gerard, P., Rehfeld, J. F., Ferraris, R. P., Fritton, J. C., Ellero-Simatos, S., Douard, V. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism.
Published: 2019

13. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Author: Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Víšek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerová, Barbora, Córdoba-Mascuñano, Raúl, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Čerňan, Martin, Jakšić, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valković, Toni, Poulsen, Christian Bjørn, Machado, Marina, Glenthøj, Andreas, Stoma, Igor, Ráčil, Zdeněk, Piukovics, Klára, Navrátil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, García-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Vélez, Irati, Fernández, Noemí, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antić, Darko, Al-Khabori, Murtadha, García-Sanz, Ramón, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Čolović, Natasa, Schönlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Méndez, Gustavo-Adolfo, Petzer, Verena, Novák, Jan, Besson, Caroline, Duléry, Rémy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Žák, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiří, López-García, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Aleš, Herbrecht, Raoul, Núñez-Martín-Buitrago, Lucía, Mancini, Valentina, Shwaylia, Hawraa, Sciumè, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinić, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbényi, Zita, Çolak, Gökçe Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramón-Sánchez, Cristina, Cornely, Oliver A., Finizio, Olimpia, Fazzi, Rita, Sapienza, Giuseppe, Chauchet, Adrien, Van Praet, Jens, Prattes, Juergen, Dargenio, Michelina, Rossi, Cédric, Shirinova, Ayten, Malak, Sandra, Tafuri, Agostino, Ommen, Hans-Beier, Bologna, Serge, Khedr, Reham Abdelaziz, Choquet, Sylvain, Joly, Bertrand, Ceesay, M. Mansour, Philippe, Laure, Kho, Chi Shan, Desole, Maximilian, Tsirigotis, Panagiotis, Otašević, Vladimir, Borducchi, Davimar M. M., Antoniadou, Anastasia, Gaziev, Javid, Almaslamani, Muna A., García-Poutón, Nicole, Paterno, Giovangiacinto, Torres-López, Andrea, Tarantini, Giuseppe, Mellinghoff, Sibylle, Gräfe, Stefanie, Börschel, Niklas, Passweg, Jakob, Merelli, Maria, Barać, Aleksandra, Wolf, Dominik, Shaikh, Mohammad Usman, Thiéblemont, Catherine, Bernard, Sophie, Funke, Vaneuza Araújo Moreira, Daguindau, Etienne, Khostelidi, Sofya, Nucci, Fabio Moore, Martín-González, Juan-Alberto, Landau, Marianne, Soussain, Carole, Laureana, Cécile, Lacombe, Karine, Kohn, Milena, Aliyeva, Gunay, Piedimonte, Monica, Fouquet, Guillemette, Rêgo, Mayara, Hoell-Neugebauer, Baerbel, Cartron, Guillaume, Pinto, Fernando, Alburquerque, Ana Munhoz, Passos, Juliana, Yilmaz, Asu Fergun, Redondo-Izal, Ana-Margarita, Altuntaş, Fevzi, Heath, Christopher, Kolditz, Martin, Schalk, Enrico, Guolo, Fabio, Karthaus, Meinolf, Della Pepa, Roberta, Vinh, Donald, Noël, Nicolas, Deau Fischer, Bénédicte, Drenou, Bernard, Mitra, Maria Enza, Meletiadis, Joseph, Bilgin, Yavuz M., Jindra, Pavel, Espigado, Ildefonso, Drgoňa, Ľuboš, Serris, Alexandra, Di Blasi, Roberta, Ali, Natasha, EPICOVIDEHA working group, [missing], Pagano, Livio, Salmanton-Garcia, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Visek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerova, Barbora, Cordoba-Mascunano, Raul, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Cernan, Martin, Jaksic, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valkovic, Toni, Poulsen, Christian Bjorn, Machado, Marina, Glenthoj, Andreas, Stoma, Igor, Racil, Zdenek, Piukovics, Klara, Navratil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, Garcia-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Velez, Irati, Fernandez, Noemi, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antic, Darko, Al-Khabori, Murtadha, Garcia-Sanz, Ramon, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Colovic, Natasa, Schonlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Mendez, Gustavo-Adolfo, Petzer, Verena, Novak, Jan, Besson, Caroline, Dulery, Remy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Zak, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiri, Lopez-Garcia, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Ales, Herbrecht, Raoul, Nunez-Martin-Buitrago, Lucia, Mancini, Valentina, Shwaylia, Hawraa, Sciume, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinic, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbenyi, Zita, Colak, Gokce Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramon-Sanchez, Cristina, Cornely, Oliver A., Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Stem Cell Aging Leukemia and Lymphoma (SALL), Salvy-Córdoba, Nathalie, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, IFO - Istituto Nazionale Tumori Regina Elena [Roma] (IRE), Città della Salute e della Scienza University-Hospital, IRCCS Istituto Nazionale dei Tumori [Milano], University of California [San Diego] (UC San Diego), University of California (UC), Medical University of Graz, Odessa National I.I.Mechnikov University, Faculty of Medicine [Cologne], University Hospital of Cologne [Cologne]-University of Cologne, King's College Hospital (KCH), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Faculty of Medicine in Hradec Kralove [Republique Tchèque], Charles University [Prague] (CU), Ankara University School of Medicine [Turkey], Azienda Ospedaliera Universitaria Integrata of Verona, Masaryk University [Brno] (MUNI), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Ospedale SS Antonio e Biagio e Cesare Arrigo, Churchill Hospital Oxford Centre for Haematology, IRCCS San Raffaele Scientific Institute [Milan, Italie], ASST Spedali Civili of Brescia, Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Instituto Português de Oncologia de Lisboa Francisco Gentil, Ospedale San Luigi Gonzaga, University Medical Center Groningen [Groningen] (UMCG), Institut de Cancérologie de Strasbourg Europe (ICANS), Palacky University Olomouc, Zagreb School of Medicine [Zagreb, Croatia] (Dubrava University Hospital), University of Zagreb, Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hamad Medical Corporation [Doha, Qatar], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Rijeka, Croatian Cooperative Group for Hematological Diseases (CROHEM), Zealand University Hospital [Roskilde, Denmark], Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Homieĺ State Medical University (GSMU), Institute of Hematology and Blood Transfusion [Prague, Czech Republic], University of Szeged [Szeged], University Hospital Ostrava, Mansoura University [Egypt], Marmara University [Kadıköy - İstanbul], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Karolinska University Hospital [Stockholm], Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Hospital de São João [Porto], Faculdade de Medicina da Universidade do Porto (FMUP), Clinic Barcelona Hospital Universitari, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy, Pavlov First Saint Petersburg State Medical University [St. Petersburg], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Complejo Hospitalario de Navarra, Hospital Universitario Marqués de Valdecilla [Santander], La Paz University Hospital, Azienda Usl Toscana centro [Firenze], AZ Klina, Clinical Center of Serbia (KCS), University of Belgrade [Belgrade], Sultan Qaboos University Hospital, Partenaires INRAE, Hospital Universitario de Salamanca, Servicio de Haematologia, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), University of Wrocław [Poland] (UWr), San Bortolo Hospital, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospital Universitario 12 de Octubre [Madrid], Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Universidad Rey Juan Carlos [Madrid] (URJC), University of Basel (Unibas), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University Hospital Kralovské Vinohrady, Centre Hospitalier de Versailles André Mignot (CHV), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universidade Federal do Estado do Rio de Janeiro (UNIRIO), San Gerardo Hospital of Monza, Oxford NIHR Biomedical Research Centre, IRCCS Ospedale San Raffaele [Milan, Italy], Assi Sette Llaghi Varese, Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), University Hospital Olomouc [Czech Republic], ASST Grande Ospedale Metropolitano Niguarda, University Hospital Centre Zagreb, Instituto Nacional do Câncer, Copenhagen University Hospital, Republican Scientific and Practical Center (RSPC) for organ and Tissue Transplantation, Minsk, Republican Scientific and Practical Center (RSPC) for Organ and Transplantation, German Centre for Infection Research (DZIF), Gilead Sciences, Pagano, Livio [0000-0001-8287-928X], Salmanton-García, Jon [0000-0002-6766-8297], Marchesi, Francesco [0000-0001-6353-2272], Busca, Alessandro [0000-0001-5361-5613], Corradini, Paolo [0000-0002-9186-1353], Hoenigl, Martin [0000-0002-1653-2824], Klimko, Nikolay [0000-0001-6095-7531], Koehler, Philipp [0000-0002-7386-7495], Pagliuca, Antonio [0000-0003-2519-0333], Passamonti, Francesco [0000-0001-8068-5289], Verga, Luisa [0000-0003-1142-8435], Víšek, Benjamin [0000-0001-8268-452X], Ilhan, Osman [0000-0003-1665-372X], Weinbergerová, Barbora [0000-0001-6460-2471], Córdoba, Raúl [0000-0002-7654-8836], Marchetti, Monia [0000-0001-7615-0572], Farina, Francesca [0000-0002-5124-6970], Cattaneo, Chiara [0000-0003-0031-3237], Cabirta, Alba [0000-0001-7198-8894], Gomes-Silva, Maria [0000-0002-6993-2450], Itri, Federico [0000-0002-3532-5281], Doesum, Jaap van [0000-0003-0214-3219], Ledoux, Marie-Pierre [0000-0002-3261-3616], Čerňan, Martin [0000-0003-2345-1229], Jakšić, Ozren [0000-0003-4026-285X], Magliano, Gabriel [0000-0002-9129-1530], Omrani, Ali S. [0000-0001-5309-6358], Fracchiolla, Nicola S. [0000-0002-8982-8079], Kulasekararaj, Austin G. [0000-0003-3180-3570], Valković, Toni [0000-0001-6083-8815], Poulsen, Christian Bjørn [0000-0001-9785-1378], Machado, Marina [0000-0002-8370-2248], Glenthøj, Andrea [0000-0003-2082-0738], Stoma, Igor [0000-0003-0483-7329], Ráčil, Zdeněk [0000-0003-3511-4596], Piukovics, Klára [0000-0003-4480-3131], Emarah, Ziad [0000-0003-0622-2598], Sili, Uluhan [0000-0002-9939-9298], Maertens, Johan [0000-0003-4257-5980], Bergantim, Rui [0000-0002-7811-9509], García-Vidal, Carolina [0000-0002-8915-0683], Prezioso, Lucia [0000-0003-1660-4960], Principe, Maria Ilaria del [0000-0002-3958-0669], Popova, Marina [0000-0001-8536-5495], Jonge, Nick de [0000-0002-9901-0887], Ormazabal-Vélez, Irati [0000-0003-1141-5546], Falces-Romero, Iker [0000-0001-5888-7706], Cuccaro, Annarosa [0000-0002-0237-1839], Meers, Stef [0000-0003-1754-2175], Buquicchio, Caterina [0000-0002-3683-5953], Antić, Darko [0000-0002-2608-1342], Al-Khabori, Murtadha [0000-0002-2937-8838], García-Sanz, Ramón [0000-0003-4120-2787], Biernat, Monika [0000-0003-3161-3398], Tisi, Maria Chiara [0000-0001-8231-6700], Sal, Ertan [0000-0003-2761-2675], Rahimli, Laman [0000-0003-2266-445X], Schönlein, Martin [0000-0002-1010-0975], Calbacho, María [0000-0001-8106-4863], Tascini, Carlo [0000-0001-9625-6024], Miranda-Castillo, Carolina [0000-0001-8763-9576], Khanna, Nina [0000-0002-2642-419X], Méndez, Gustavo-Adolfo [0000-0003-0514-7004], Petzer, Verena [0000-0002-9205-1440], Besson, Caroline [0000-0003-4364-7173], Duléry, Rémy [0000-0002-5024-1713], Lamure, Sylvain [0000-0001-5980-305X], Nucci, Marcio [0000-0003-4867-0014], Zambrotta, Giovanni [0000-0002-8612-2994], Žák, Pavel [0000-0003-4465-5343], Cengiz Seval, Guldane [0000-0001-9433-2054], Bonuomo, Valentina [0000-0001-6491-8337], Mayer, Jiří [0000-0003-0567-9887], López-García, Alberto [0000-0002-5354-5261], Sacchi, Maria Vittoria [0000-0001-8133-3357], Booth, Stephen [0000-0003-2687-0234], Ciceri, Fabio [0000-0003-0873-0123], Nunes-Rodrigues, Raquel [0000-0002-8347-4281], Ammatuna, Emanuele [0000-0001-8247-4901], Obr, Aleš [0000-0002-6758-3074], Herbrecht, Raoul [0000-0002-9381-4876], Shwaylia, Hawraa [0000-0002-4098-6092], Sciumè, Mariarita [0000-0001-7958-4966], Essame, Jenna [0000-0003-0926-5577], Batinić, Josip [0000-0001-5595-9911], Gonzaga, Yung [0000-0003-1416-2118], Regalado-Artamendi, Isabel [0000-0002-9673-9015], Karlsson, Linda Katharina [0000-0003-3317-7550], Shapetska, Maryia [0000-0002-1223-9161], El-Ashwah, Shaimaa [0000-0003-2210-1534], Çolak, Gökçe Melis [0000-0002-7662-7454], Dragonetti, Giulia [0000-0003-1775-6333], Rinaldi, Amelia [0000-0002-8211-5076], Ramón, Cristina de [0000-0002-8167-6410], Cornely, Oliver A. [0000-0001-9599-3137], Institut Català de la Salut, [Pagano L] Hematology, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy. Università Cattolica del Sacro Cuore, Rome, Italy. [Salmanton-García J] Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Excellence Center for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. Cologne Excellence Cluster On Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. [Marchesi F] Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Busca A] Stem Cell Transplant Center, AOU Citta’ Della Salute E Della Scienza, Turin, Italy. [Corradini P] University of Milan and Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. [Hoenigl M] Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA, USA. Clinical and Translational Fungal Working Group, University of California San Diego, La Jolla, CA, USA. Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria. [Cabirta A, Izuzquiza M] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Hematology, Salmanton-García, Jon, Klimko, Nikolay, Víšek, Benjamin, Weinbergerová, Barbora, Córdoba, Raúl, Doesum, Jaap van, Čerňan, Martin, Jakšić, Ozren, Magliano, Gabriel, Kulasekararaj, Austin G., Valković, Toni, Poulsen, Christian Bjørn, Glenthøj, Andrea, Ráčil, Zdeněk, Piukovics, Klára, García-Vidal, Carolina, Principe, Maria Ilaria del, Jonge, Nick de, Ormazabal-Vélez, Irati, Antić, Darko, García-Sanz, Ramón, Biernat, Monika, Schönlein, Martin, Calbacho, María, Méndez, Gustavo-Adolfo, Duléry, Rémy, Žák, Pavel, Cengiz Seval, Guldane, Mayer, Jiří, López-García, Alberto, Obr, Aleš, Sciumè, Mariarita, Batinić, Josip, Çolak, Gökçe Melis, Ramón, Cristina de, and Universidad de Sevilla. Departamento de Medicina
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Cancer Research, MESH: Registries, Epidemiology, MESH: Hospitalization, Hematological malignancies, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], MESH: Aged, 80 and over, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Malalties - Factors de risc, Risk of mortality, Medicine and Health Sciences, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 80 and over, Medicine, MESH: COVID-19, Registries, Sang - Malalties - Complicacions, RC254-282, Cause of death, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, MESH: Aged, Aged, 80 and over, Hematology, MESH: Middle Aged, Mortality rate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, CANCER, Europe, Hospitalization, Intensive Care Units, Oncology, MESH: Young Adult, Hematologic Neoplasms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19, EHA, Pandemic, Aged, Humans, SARS-CoV-2, Young Adult, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.CAN] Life Sciences [q-bio]/Cancer, Intensive care, Internal medicine, Diseases of the blood and blood-forming organs, MESH: SARS-CoV-2, neoplasias::neoplasias por localización::neoplasias hematológicas [ENFERMEDADES], Molecular Biology, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, pandemic, hematological malignancies, epidemiology, MESH: Humans, Science & Technology, business.industry, Myelodysplastic syndromes, Research, MESH: Adult, Neoplasms::Neoplasms by Site::Hematologic Neoplasms [DISEASES], medicine.disease, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15, MESH: Male, Settore MED/15 - MALATTIE DEL SANGUE, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19 (Malaltia) - Diagnòstic, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], MESH: Europe, RC633-647.5, business, MESH: Female, Other subheadings::Other subheadings::/complications [Other subheadings], MESH: Hematologic Neoplasms
Abstract: Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value, EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).
Published: 2021

14. Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Author: Leurs, CE, Twaalfhoven, HAM, Lissenberg-Witte, BI, van Pesch, V, Dujmovic, I, Drulovic, J, Castellazzi, M, Bellini, T, Pugliatti, M, Kuhle, J, Villar, LM, Alvarez-Cermeño, JC, Alvarez-Lafuente, R, Hegen, H, Deisenhammer, F, Walchhofer, LM, Thouvenot, E, Comabella, M, Montalban, X, Vécsei, L, Rajda, C, Galimberti, D, Scarpini, E, Altintas, A, Rejdak, K, Frederiksen, JL, Pihl-Jensen, G, Jensen, PEH, Khalil, M, Voortman, MM, Fazekas, F, Saiz, Albert, La Puma, D, Vercammen, M, Vanopdenbosch, L, Uitdehaag, BMJ, Killestein, J, Bridel, C, Teunissen, Charlotte E, Universitat Autònoma de Barcelona, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Basic (bio-) Medical Sciences, Ayşe, Altıntaş, Leurs, C.E., Twaalfhoven, H.A.M., Lissenberg-Witte, B.I., van Pesch, V., Dujmovic, I., Drulovic, J., Castellazzi, M., Bellini, T., Pugliatti, M., Kuhle, J., Villar, L.M., Alvarez-Cermeño, J.C., Alvarez-Lafuente, R., Hegen, H., Deisenhammer, F., Walchhofer, L.M., Thouvenot, E., Comabella, M., Montalban, X., Vécsei, L., Rajda, C., Galimberti, D., Scarpini, E., Rejdak, K., Frederiksen, J.L., Pihl-Jensen, G., Jensen, P.E.H., Khalil, M., Voortman, M.M., Fazekas, F., Saiz, A., La Puma, D., Vercammen, M., Vanopdenbosch, L., Uitdehaag, B.M.J., Killestein, J., Bridel, C., Teunissen, C., School of Medicine, Department of Neurology, Neurology, Laboratory Medicine, Epidemiology and Data Science, APH - Methodology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Department of Anatomy and Neurosciences [Amsterdam, The Netherlands] (Amsterdam Neuroscience), Section Clinical Neuroanatomy [Amsterdam, The Netherlands], VU University Medical Center [Amsterdam]-VU University Medical Center [Amsterdam], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Cliniques Universitaires Saint-Luc [Bruxelles], Clinical Centre of Serbia, Università degli Studi di Ferrara (UniFE), University Hospital Basel [Basel], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Red Española de Esclerosis Múltiple (REEM), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Department of Neurology, Medical University of Innsbruck, Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre d'Esclerosi Múltiple de Catalunya (CemCat), Vall d'Hebron University Hospital [Barcelona], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Szeged [Szeged], Centro Dino Ferrari [Milano], Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Koç University, Medical University of Lublin, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Danish Multiple Sclerosis Research Centre, Copenhagen University Hospital-Copenhagen University Hospital, Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Department of Neurology, AZ Sint Jan Brugge Oostende, Neuroscience Amsterdam, VU University Medical Centre, 1081HV 1117, Amsterdam, Amsterdam Neuroscience [Pays-Bas], and Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam]
Subjects: KFLC (kappa free light chain), Adult, Male, Multiple Sclerosis, Clinical Neurology, Esclerosi múltiple, CSF, CSF (cerebrospinal fluid), Immunoglobulin light chain, Sensitivity and Specificity, NO, Multiple sclerosis, Immunoglobulin kappa-Chains, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Immunoglobulin lambda-Chains, Humans, Medicine, Diagnostic biomarker, biomarkers, KFLC, OCB, 030304 developmental biology, 0303 health sciences, business.industry, Biochemical markers, Oligoclonal Bands, Reproducibility of Results, Middle Aged, OCB (oligoclonal IgG band), Free Light Chain, Biomarkers, Neurology, Multicenter study, Marcadors bioquímics, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), business, Original Research Papers, 030217 neurology & neurosurgery, Kappa
Abstract: Objective: to validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: we performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: the cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS., NA
Published: 2020

15. Identification of key tissue-specific, biological processes by integrating enhancer information in maize gene regulatory networks

Author: Anthony Venon, Julien Rozière, Johann Joets, Olivier Turc, Stéphanie Pateyron, Marieke L. Kuijjer, Maike Stam, Clémentine Vitte, Maud Fagny, Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Leiden University Medical Center (LUMC), Swammerdam Institute for Life Sciences (SILS), University of Amsterdam [Amsterdam] (UvA), Écophysiologie des Plantes sous Stress environnementaux (LEPSE), Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-10-BTBR-0001,AMAIZING,Développer de nouvelles variétés de maïs pour une agriculture durable: une approche intégrée de la génomique à la sélection(2010), ANR-17-EURE-0007,SPS-GSR,Ecole Universitaire de Recherche de Sciences des Plantes de Paris-Saclay(2017), Investment for the Future ANR-10-BTBR-01-01 Amaizing program, Amaizing, Plant Development & (Epi)Genetics (SILS, FNWI), Universiteit Leiden, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0106 biological sciences, Systems biology, Gene regulatory network, Computational biology, Biology, Zea mays, 01 natural sciences, 03 medical and health sciences, mite, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, Genetics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, TIR transposon, Enhancer, gene regulatory networks, Transcription factor, Gene, Original Research, 030304 developmental biology, Epigenomics, 2. Zero hunger, 0303 health sciences, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], husk, Maize, DNA binding site, transcription factor binding sites, enhancers, transposable elements, 010606 plant biology & botany
Abstract: Enhancers are important regulators of gene expression during numerous crucial processes including tissue differentiation across development. In plants, their recent molecular characterization revealed their capacity to activate the expression of several target genes through the binding of transcription factors. Nevertheless, identifying these target genes at a genome-wide level remains a challenge, in particular in species with large genomes, where enhancers and target genes can be hundreds of kilobases away. Therefore, the contribution of enhancers to regulatory network is still poorly understood in plants. In this study, we investigate the enhancer-driven regulatory network of two maize tissues at different stages: leaves at seedling stage and husks (bracts) at flowering. Using a systems biology approach, we integrate genomic, epigenomic and transcriptomic data to model the regulatory relationship between transcription factors and their potential target genes. We identify regulatory modules specific to husk and V2-IST, and show that they are involved in distinct functions related to the biology of each tissue. We evidence enhancers exhibiting binding sites for two distinct transcription factor families (DOF and AP2/ERF) that drive the tissue-specificity of gene expression in seedling immature leaf and husk. Analysis of the corresponding enhancer sequences reveals that two different transposable element families (TIR transposon Mutator and MITE Pif/Harbinger) have shaped the regulatory network in each tissue, and that MITEs have provided new transcription factor binding sites that are involved in husk tissue-specificity.SignificanceEnhancers play a major role in regulating tissue-specific gene expression in higher eukaryotes, including angiosperms. While molecular characterization of enhancers has improved over the past years, identifying their target genes at the genome-wide scale remains challenging. Here, we integrate genomic, epigenomic and transcriptomic data to decipher the tissue-specific gene regulatory network controlled by enhancers at two different stages of maize leaf development. Using a systems biology approach, we identify transcription factor families regulating gene tissue-specific expression in husk and seedling leaves, and characterize the enhancers likely to be involved. We show that a large part of maize enhancers is derived from transposable elements, which can provide novel transcription factor binding sites crucial to the regulation of tissue-specific biological functions.
Published: 2020

16. Systematic review finds that appraisal tools for medical research studies address conflicts of interest superficially

Author: Kristine Rasmussen, Lesley A. Stewart, Asbjørn Hróbjartsson, Lasse Østengaard, Andreas Lundh, Isabelle Boutron, Centre for Evidence-Based Medicine Odense (CEBMO), Odense University Hospital (OUH), Open Patient data Exploratory Network (OPEN), Department of Clinical Research, University of Southern Denmark (SDU), Department of Infectious Diseases, Hvidovre Hospital, Cochrane Nordic, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University Library of Southern Denmark, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre for Reviews and Dissemination, and University of York [York, UK]
Subjects: Biomedical Research, Conflict of Interest, Epidemiology, business.industry, Industry funding, Critical appraisal tools, Medical journals, Public relations, Medical research, 03 medical and health sciences, 0302 clinical medicine, Political science, Systematic review, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030212 general & internal medicine, Conflicts of interest, Journal policies, business, Editorial Policies, 030217 neurology & neurosurgery
Abstract: ObjectivesThe objective of this study was to identify and summarize 1) appraisal tools and other guides which address conflicts of interest in medical research studies; and 2) top journals with policies on managing conflicts of interest in journal papers.Study Design and SettingWe searched bibliographic databases, other sources, and websites of 30 top medical journals. Two authors selected documents and extracted data.ResultsWe included 27 appraisal tools. None were designed specifically for addressing conflicts of interest and they included only 1-2 short items on conflicts of interest. We also included eight other types of guides. Of 27 appraisal tools, 23 addressed study funding, and 19 authors’ conflicts of interest. Nine tools addressed availability of conflicts of interest information, 13 reported conflicts of interest, and five influence from conflicts of interest. Twelve of 30 top journals had conflicts of interest managing policies (beyond disclosure). One journal restricted nonresearch papers (e.g., editorials) to authors without financial conflicts of interest and ten only restricted under certain circumstances.ConclusionAppraisal tools that address conflicts of interest typically do so superficially and rarely address how conflicts of interest may influence studies. Less than half of top medical journals have explicit policies on managing conflicts of interest. ObjectivesThe objective of this study was to identify and summarize 1) appraisal tools and other guides which address conflicts of interest in medical research studies; and 2) top journals with policies on managing conflicts of interest in journal papers.Study Design and SettingWe searched bibliographic databases, other sources, and websites of 30 top medical journals. Two authors selected documents and extracted data.ResultsWe included 27 appraisal tools. None were designed specifically for addressing conflicts of interest and they included only 1-2 short items on conflicts of interest. We also included eight other types of guides. Of 27 appraisal tools, 23 addressed study funding, and 19 authors’ conflicts of interest. Nine tools addressed availability of conflicts of interest information, 13 reported conflicts of interest, and five influence from conflicts of interest. Twelve of 30 top journals had conflicts of interest managing policies (beyond disclosure). One journal restricted nonresearch papers (e.g., editorials) to authors without financial conflicts of interest and ten only restricted under certain circumstances.ConclusionAppraisal tools that address conflicts of interest typically do so superficially and rarely address how conflicts of interest may influence studies. Less than half of top medical journals have explicit policies on managing conflicts of interest.
Published: 2020

17. JASPAR 2020: update of the open-access database of transcription factor binding profiles

Author: Albin Sandelin, Solenne Correard, Xi Zhang, Aziz Khan, Boris Lenhard, Oriol Fornes, Ge Tan, Robin van der Lee, François Parcy, Phillip A. Richmond, Anthony Mathelier, Benoit Ballester, Bhavi P. Modi, Wyeth W. Wasserman, Jaime A. Castro-Mondragon, Walter Santana-Garcia, Jeanne Chèneby, Marius Gheorghe, Damir Baranasic, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute and Department of Medical Genetics, University of British Columbia (UBC), Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Computational Regulatory Genomics, Imperial College London, Institute of Clinical Sciences, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Functional Genomics Center Zurich, University of Zürich [Zürich] (UZH)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulateurs du développement de la fleur (Flo_RE), Physiologie cellulaire et végétale (LPCV), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Biotech Research and Innovation Centre (BRIC), University of Copenhagen = Københavns Universitet (KU), Sars International Center for Marine Molecular Biology, Oslo University Hospital Radiumhospitalet, NorwegianResearch Council [187615] [288404], Helse Sør-Øst, University of Oslo through the Centre for Molecular Medicine Norway, The Norwegian Cancer Society [197884], Canadian Institutes of Health [BOP-149430 and PJT-162120], Genome Canada and Genome British Columbia [255ONT and 275SIL], Michael Smith Foundation for Health Research [17746], Natural Sciences and Engineering Research Council of Canada Discovery Grant [RGPIN-2017-06824], CREATE programs, Weston Brain Institute [20R74681], BC Children’s Hospital Foundation and Research Institute, Netherlands Organization for Scientific Research [Rubicon fellow-ship, 452172015], Genome British Columbia [SIP007], Grants from the Lundbeck Foundation, the DanishCancer Foundation, the Danish Innovation Fund and the Danish Council forIndependent Research, ANR-16-CE92-0023,FLOPINET,Floral Pioneer Factors, ANR-10- LABX-49-01,Labex GRAL,Labex GRAL, Copenhagen University Hospital-Copenhagen University Hospital, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universität Zürich [Zürich] = University of Zurich (UZH)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Régulateurs du développement de la fleur (Flo_RE ), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), ANR-16-CE92-0023,FLOPINET,Floral Pioneer Factors(2016), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), Institut de biologie de l'ENS Paris (IBENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), University of Copenhagen = Københavns Universitet (UCPH), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Biology, Web Browser, computer.software_genre, Bioconductor, 03 medical and health sciences, User-Computer Interface, 0302 clinical medicine, Databases, Genetic, Genetics, Animals, Database Issue, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Taxonomic rank, 030304 developmental biology, 0303 health sciences, Web browser, Binding Sites, Database, Computational Biology, Genomics, Multiple species, 3. Good health, 030220 oncology & carcinogenesis, computer, Software, Protein Binding, Transcription Factors
Abstract: JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release. JASPAR 2020 comes with a novel collection of unvalidated TF-binding profiles for which our curators did not find orthogonal supporting evidence in the literature. This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles. Moreover, we created a Q&A forum to ease the communication between the user community and JASPAR curators. Finally, we updated the genomic tracks, inference tool, and TF-binding profile similarity clusters. All the data is available through the JASPAR website, its associated RESTful API, and through the JASPAR2020 R/Bioconductor package.
Published: 2020

18. Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers

Author: Mavaddat, N., Antoniou, A.C., Mooij, T.M., Hooning, M.J., Heemskerk-Gerritsen, B.A., Nogues, C., Laborde, L., Breysse, E., Stoppa-Lyonnet, D., Gauthier-Villars, M., Buecher, B., Caron, O., Fourme-Mouret, E., Fricker, J.P., Lasset, C., Bonadona, V., Berthet, P., Faivre, L., Luporsi, E., Mari, V., Gladieff, L., Gesta, P., Sobol, H., Eisinger, F., Longy, M., Dugast, C., Colas, C., Coupier, I., Pujol, P., Corsini, C., Lortholary, A., Vennin, P., Adenis, C., Nguyen, T.D., Delnatte, C., Tinat, J., Tennevet, I., Limacher, J.M., Maugard, C., Bignon, Y.J., Demange, L., Penet, C., Dreyfus, H., Cohen-Haguenauer, O., Venat-Bouvet, L., Leroux, D., Zattara-Cannoni, H., Fert-Ferrer, S., Bera, O., Ellis, S., Barrowdale, D., Frost, D., Evans, D.G., Izatt, L., Adlard, J., Eeles, R., Brewer, C., Tischkowitz, M., Henderson, A., Cook, J., Eccles, D., Hogervorst, F.B.L., Collee, J.M., Asperen, C.J. van, Mensenkamp, A.R., Ausems, M.G.E.M., Meijers-Heijboer, H.E.J., Engelen, K. van, Blok, M.J., Oosterwijk, J.C., Verloop, J., Broek, E. van den, Mourits, M.J.E., Koppert, L.B., Hopper, J.L., John, E.M., Chung, W.K., Andrulis, I.L., Daly, M.B., Buys, S.S., Benitez, J., Caldes, T., Jakubowska, A., Simard, J., Singer, C.F., Tan, Y., Olah, E., Navratilova, M., Foretova, L., Gerdes, A.M., Roos-Blom, M.J., Leeuwen, F.E. van, Arver, B., Olsson, H., Schmutzler, R.K., Engel, C., Kast, K., Phillips, K.A., Terry, M.B., Milne, R.L., Goldgar, D.E., Rookus, M.A., Andrieu, N., Easton, D.F., GENEPSO, EMBRACE, HEBON, kConFab Investigators, IBCCS, kConFab, BCFR, University of Cambridge [UK] (CAM), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Erasmus MC Cancer Institute, Rotterdam, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Curie [Paris], Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Catherine-de-Sienne [Nantes] (CCS), Manchester University NHS Foundation Trust (MFT), Guy's & St Thomas' NHS Foundation Trust, Chapel Allerton Hospital, University of Leeds, Royal Marsden NHS Foundation Trust, Royal Devon & Exeter Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Sheffield Children's NHS Foundation Trust, Wessex clinical genetics service, Vrije Universiteit Amsterdam [Amsterdam] (VU), University Medical Center Groningen [Groningen] (UMCG), Department of Medical Genetics, University Medical Center [Utrecht], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, Department of Epidemiology, Cancer Prevention Institute of California, Columbia University [New York], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Division of Population Science, Fox Chase Cancer Center, Department of Internal Medicine, Huntsman Cancer Institute, Departemento Genetica Humana, Centro Nacional Investigaciones Oncologicas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Department of Genetics and Pathology, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Medizinische Universität Wien = Medical University of Vienna, National Institute of Oncology, Masaryk Memorial Cancer Institute (MMCI), Masaryk University [Brno] (MUNI), Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, The Netherlands Cancer Institute [Amsterdam, The Netherlands], Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Oncology, Lund University Hospital, Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, Dept of Haematology and Medical Oncology, Peter MacCallum Cancer Center, Department of Epidemiology [Columbia University], Columbia University [New York]-Columbia Mailman School of Public Health, Cancer Epidemiology Centre, Cancer Council Victoria, International Agency for Cancer Research (IACR), Netherlands Cancer Institute, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Andrieu, Nadine, Human genetics, Epidemiology and Data Science, Mavaddat, Nasim [0000-0003-0307-055X], Eeles, Ros [0000-0002-3698-6241], Engel, Christoph [0000-0002-7247-282X], Apollo - University of Cambridge Repository, Pomeranian Medical University-International Hereditary Cancer Centre, Masaryk Memorial Cancer Institute (RECAMO), Columbia Mailman School of Public Health-Columbia University [New York], Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Antoniou, Antonis [0000-0001-9223-3116], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Medical Oncology, Surgery, Cancer Research UK (Reino Unido), NIH - National Cancer Institute (NCI) (Estados Unidos), United States Department of Health and Human Services, Ministerio de Economía y Competitividad (España), Unión Europea. Comisión Europea. European Research Council (ERC), Norwegian EEA Financial Mechanism, Hungarian Scientific Research Fund (Hungría), Ministry of Education, Youth and Sports (República Checa), MH CZ -DRO (MMCI), National Health and Medical Research Council (Australia), Australian National Breast Cancer Foundation, Cancer Australia, ERA-NET TRANSAN JTC 2012 Cancer, Transcan grant, Biotechnology and Biological Sciences Research Council (Reino Unido), Pink Ribbons Project, Netherlands Organisation of Scientific Research, Dutch Cancer Society (Holanda), Instituto de Salud Carlos III, Deutsche Krebshilfe, National Institute for Health Research (Reino Unido), Unión Europea. Comisión Europea. 7 Programa Marco, Ministry of Economic Development, Innovation and Export Trade-grant, Canadian Institutes of Health Research, Cancer Research UK, NIH National Cancer Institute (NCI), United States Department of Health & Human Services National Institutes of Health (NIH) - USA, Ministerio de Economia y Competividad (MINECO), European Research Council (ERC), Hungarian Research Grants, MEYS -NPS I, National Health and Medical Research Council of Australia, BBMRI grant, Pink Ribbon grants, Netherlands Organisation of Scientific Research grant, KWF Kankerbestrijding, Instituto de Salud Carlos III - ISCIII, National Institute for Health Research (NIHR), European Union Seventh Framework Program (2007-2013), Canadian Institutes of Health Research (CIHR), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), United States of Department of Health & Human Services, European Research Council, APH - Quality of Care, APH - Methodology, Graduate School, ARD - Amsterdam Reproduction and Development, RS: GROW - R4 - Reproductive and Perinatal Medicine, and MUMC+: DA KG Lab Centraal Lab (9)
Subjects: endocrine system diseases, SURGERY, [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, Cohort Studies, 0302 clinical medicine, BRCA2 Mutation, Breast cancer, Surgical oncology, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, Salpingo-oophorectomy/methods, 0303 health sciences, Natural menopause, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Obstetrics, BRCA1 Protein, Breast Neoplasms/epidemiology, Incidence (epidemiology), Incidence, WOMEN, ASSOCIATION, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, OVARIAN, BRCA2 Protein/genetics, 3. Good health, Menopause, Risk-reducing salpingo-oophorectomy, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SURVIVAL, Female, Research Article, Cohort study, Adult, medicine.medical_specialty, Salpingo-oophorectomy, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, lcsh:RC254-282, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, METAANALYSIS, 030304 developmental biology, BRCA2 Protein, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, CONSORTIUM, risk-reducing salpingo-oophorectomy, International Agencies, medicine.disease, BRCA1, BRCA2, KCONFAB, REDUCTION, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, LINK, Mutation, BRCA1 Protein/genetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Risk Reduction Behavior
Abstract: The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO. The BCFR was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the BCFR. CNIO was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare Diseases (CIBERER). CNIO was also partially supported by FISPI16/00440. INHERIT was supported by the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program-grant #CRN-87521-and the Ministry of Economic Development, Innovation and Export Trade-grant #PSR-SIIRI-701. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (GPH-129344), the Ministere de l'Economie, de la Science et de l' Innovation du Quebec through Genome Quebec, and The Quebec Breast Cancer Foundation. Jacques Simard is a Chairholder of the Canada Research Chair in Oncogenetics. EMBRACE is supported by the Cancer Research UK grants C1287/A23382 and C1287/A16563. D. Gareth Evans is supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by the Cancer Research UK grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Antonis C. Antoniou is funded by Cancer Research UK grants C12292/A20861 and C12292/A11174. MT is funded by the European Union Seventh Framework Program (2007-2013)/European Research Council (310018). The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 110837, Rita K. Schmutzler). The national French cohort, GENEPSO, had been supported by a grant from the Fondation de France and the Ligue Nationale Contre le Cancer and is being supported by a grant from INCa as part of the European program ERA-NET on Translational Cancer Research (TRANSCAN-JTC2012, no. 2014-008). HCSC was supported by CIBERONC 161200301 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46, and the Transcan grant JTC 2012 Cancer 12-054. The IHCC was supported by Grant PBZ_ KBN_122/P05/2004 and ERA-NET TRANSAN JTC 2012 Cancer 12-054 (ERA-NET-TRANSCAN/07/2014). This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195); the Australian National Breast Cancer Foundation (IF 17); the National Health and Medical Research Council (454508, 288704, 145684); the National Institute of Health U.S.A. (1RO1CA159868); the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; and the Cancer Foundation of Western Australia. KAP is an Australian National Breast Cancer Foundation fellow. MODSQUAD-Czech Republic, Brno, was supported by MH CZ -DRO (MMCI, 00209805) and by MEYS -NPS I -LO1413 to LF and MN. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, NKFI OTKA K-112228, and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced Grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society. The funders had no role in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. Sí
Published: 2020

19. Trials on oxygen supplementation in sepsis: better late than never

Author: Audrey De Jong, Anders Perner, Manu Shankar-Hari, Department of Intensive Care [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Copenhagen University Hospital, 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), Guy's and St Thomas' NHS Foundation Trust, London, SE17EH, UK., School of Immunology and Microbial Sciences, Kings College, London, SE1 9RT, UK, and MORNET, Dominique
Subjects: Oxygen inhalation therapy, medicine.medical_specialty, Oxygen supplementation, business.industry, Pain medicine, [SDV]Life Sciences [q-bio], MEDLINE, 030208 emergency & critical care medicine, Critical Care and Intensive Care Medicine, medicine.disease, Sepsis, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Anesthesiology, Respiration, medicine, 030212 general & internal medicine, Intensive care medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

20. Integration and Enterprise Architecture Challenges in E-Government: A European Perspective.

Author: Weerakkody, Vishanth, Janssen, Marijn, and Hjort-Madsen, Kristian
Published: 2007
Full Text: View/download PDF

21. Uptake of Tenofovir-Based Antiretroviral Therapy among HIV–HBV-Coinfected Patients in the EuroSIDA Study

Author: Jens D Lundgren, Anna Lisa Ridolfo, Jelena Smidt, Elena Kuzovatova, Stéphane De Wit, Roxana Radoi, Santiago Moreno, Djordje Jevtovic, Vesnadarjan Haziosmanovic, Helen Sambatakou, Lars Peters, Jose Zapirain, Amanda Mocroft, Chloe Orkin, Daniel Grint, Anna Grzeszczuk, Jürgen K. Rockstroh, Igor Karpov, Alexandra Calmy, Karine Lacombe, Magnus Gottfredsson, Department of Infectious Diseases [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University College of London [London] (UCL), London School of Hygiene and Tropical Medicine (LSHTM), Instituto Ramon y Cajal de Investigacion Sanitaria [Madrid, Spain] (IRYCIS), Universidad de Alcalá - University of Alcalá (UAH), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Hippokration General Hospital, University of Athens Medical School [Athens], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Pierre, Universitätsklinikum Bonn (UKB), Belarus State Medical University, University of Bialystok, Clinical Center University of Sarajevo, UNIVERSITY OF SARAJEVO - UNIVERZITET U SARAJEVU, Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], Victor Babeş University of Medicine and Pharmacy (UMFT), National Research Lobachevsky State University of Nizhny Novgorod (UNN), Royal London Hospital, Ospedale L. Sacco, IT University of Copenhagen (ITU), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, 0301 basic medicine, HBsAg, [SDV]Life Sciences [q-bio], HIV Infections, Polyethylene Glycols, immune system diseases, Antiretroviral Therapy, Highly Active, Adefovir, Medicine, Pharmacology (medical), Prospective Studies, Coinfection, virus diseases, Entecavir, Middle Aged, Hepatitis B, Recombinant Proteins, Europe, [SDV] Life Sciences [q-bio], Infectious Diseases, Anti-Retroviral Agents, Lamivudine, Practice Guidelines as Topic, Female, medicine.drug, Adult, Cart, Hepatitis B virus, medicine.medical_specialty, Guanine, 030106 microbiology, Organophosphonates, Lower risk, 03 medical and health sciences, Hepatitis B, Chronic, Internal medicine, Drug Resistance, Viral, Humans, Tenofovir, Adverse effect, Pharmacology, Hepatitis B Surface Antigens, business.industry, Adenine, HIV, Interferon-alpha, medicine.disease, Drug Utilization, CD4 Lymphocyte Count, Discontinuation, DNA, Viral, business
Abstract: Background According to guidelines all HIV–HBV-coinfected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV–HBV patients in the EuroSIDA study. Methods All hepatitis B surface antigen (HBsAg)+ patients followed up after 1 March 2002 were included. Changes in the proportion taking tenofovir-based cART over time were described. Poisson regression was used to investigate the relationship between tenofovir use and clinical events. Results 953 HIV–HBV patients were included. Median age was 41 years and patients were predominantly male (85%), White (82%) and ART-experienced (88%). 697 and 256 were from Western and Eastern Europe, respectively. 55 started cART during follow-up, the proportion starting with CD4+ T-cell count 3 decreased from 85% to 52% in the periods 2002–2006 to 2007–2015. Tenofovir use, among those taking cART, increased from 4% in 2002 to 73% in 2015. Compared to West, tenofovir use was lower in East in 2005 (7% versus 42%), and remained lower in 2015 (63% versus 76%). Among 602 patients taking tenofovir-based cART during follow-up, 155 (26%) discontinued tenofovir. 27 of all discontinuations were due to adverse effects. Only 14 started entecavir and/or adefovir after tenofovir discontinuation, whereas 10 started pegylated interferon. Tenofovir use was not significantly associated with lower risk of liver-related clinical events ( n=51), adjusted incidence rate ratio (IRR) 0.64 (95% CI 0.35, 1.18) for comparing patients on tenofovir with those off tenofovir. Conclusions Although use of tenofovir-based cART among HIV–HBV patients has increased across Europe, a substantial proportion are still starting cART late and are receiving suboptimal HBV therapy.
Published: 2017

22. Survey of diagnostic and treatment practices for multiple sclerosis in Europe

Author: G. Comi, Patrick Vermersch, Carlo Pozzilli, B. Tackenberg, P. S. Soerensen, Gilles Edan, H.-P. Hartung, M. Delvecchio, Ludwig Kappos, Oscar Fernández, G. Gionvannoni, Sten Fredrikson, Eva Havrdova, SDA Bocconi Scuola di Direzione Aziendale, Service de Neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Department of Clinical Neurosciences, Neurology Division, Karolinska Institutet, Queen Mary's School of Medicine and Dentistry, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Department of Neurological Sciences, University of Roma 'La Sapienza', Danish Multiple Sclerosis Research Centre, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Neurology, Philipps Universität Marburg, Hospital Regional Universitario Carlos Haya, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), departmet of Neurology, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Department of neurology, Charles University [Prague] (CU), Department of Neurology [Suisse], University Hospital Basel [Basel], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Philipps Universität Marburg = Philipps University of Marburg, CHU Lille, Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, European Charcot Foundation, Barillot, Christian, Fernã¡ndez, O., Delvecchio, M., Edan, G., Fredrikson, S., Gionvannoni, G., Hartung, H. . P., Havrdova, E., Kappos, L., Pozzilli, C., Soerensen, P. S., Tackenberg, B., Vermersch, P., Comi, Giancarlo, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Université de Lille, Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CentraleSupélec-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)
Subjects: Male, MESH: Multiple Sclerosis, Relapsing-Remitting, Delphi Technique, Modified delphi, Disease, MESH: Health Care Surveys, Relapsing-Remitting, Spinal Puncture, MESH: Delphi Technique, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Surveys and Questionnaires, relapsingâ remitting, 030212 general & internal medicine, clinically isolated syndrome, radiologically isolated syndrome, relapsingâremitting, Adult, Disease Progression, Europe, Female, Humans, Magnetic Resonance Imaging, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Neurologists, Health Care Surveys, Neurology, Neurology (clinical), Clinically isolated syndrome, 3. Good health, Clinical Practice, MESH: Disease Progression, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.medical_specialty, Steering committee, MESH: Spinal Puncture, relapsing−remitting, Disease activity, 03 medical and health sciences, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Mild form, MESH: Neurologists, MESH: Surveys and Questionnaires, MESH: Humans, business.industry, Multiple sclerosis, MESH: Adult, MESH: Multiple Sclerosis, medicine.disease, MESH: Male, Family medicine, Physical therapy, MESH: Europe, business, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; Background and purpose - Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice. Methods - A steering committee of MS neurologists used a modified Delphi process to develop case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case-based questions were developed for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and RRMS with breakthrough disease. Results - Multiple sclerosis neurologists from 11 European countries responded to survey 1 (n = 233) and survey 2 (n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first-line injectables and oral treatments for mild RRMS, and moved to second-line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented. Conclusions - Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe.
Published: 2017

23. High-Density Lipoproteins Exert Pro-inflammatory Effects on Macrophages via Passive Cholesterol Depletion and PKC-NF-kappa B/STAT1-IRF1 Signaling

Author: Casper G. Schalkwijk, Leonie F. A. Huitema, Lhousseine Touqui, Marion J.J. Gijbels, Kerry-Anne Rye, Shahla Abdollahi-Roodsaz, Marjo M. P. C. Donners, Emiel P. C. van der Vorst, Kosta Theodorou, Ine M. J. Wolfs, Debby P.Y. Koonen, Christina A. Bursill, Menno P.J. de Winther, Marten A. Hoeksema, Michael Leitges, Pieter Goossens, Jogchum Plat, Marijke J.E. Kuijpers, Sander W. Tas, Toby Lawrence, Taghi Aliyev, Erik A.L. Biessen, Yongzheng Wu, Chih Chieh Wang, Miranda Van Eck, Kimberly R. McDaniels, Biologie cellulaire de l'Infection microbienne - Cellular Biology of Microbial Infection, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Metabolism and Vascular Medicine, Academic Hospital Maastricht, Department of rheumatology, Radboud University [Nijmegen], Biotechnology center of Oslo, Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Human Biology, Division of Biopharmaceutics, Universiteit Leiden, Heart Research Institute, Institut Pasteur [Paris] (IP), Mucoviscidose et bronchopathies chroniques : biopathologie et phénotypes cliniques (EA 2511), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Biologie cellulaire de l'Infection microbienne, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Radboud university [Nijmegen], Universiteit Leiden [Leiden], Institut Pasteur [Paris], CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Promovendi CD, Pathologie, RS: CARIM - R3.06 - The vulnerable plaque: makers and markers, Ondersteunend personeel CD, Biochemie, Moleculaire Genetica, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, Interne Geneeskunde, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: NUTRIM - HB/BW section B, RS: NUTRIM - R1 - Metabolic Syndrome, Center for Liver, Digestive and Metabolic Diseases (CLDM), Cardiovascular Centre (CVC), Graduate School, Medical Biochemistry, AII - Inflammatory diseases, ACS - Amsterdam Cardiovascular Sciences, Clinical Immunology and Rheumatology, AII - Amsterdam institute for Infection and Immunity, and ACS - Atherosclerosis & ischemic syndromes
Subjects: 0301 basic medicine, Physiology, NF-KAPPA-B, 030204 cardiovascular system & hematology, Mice, chemistry.chemical_compound, 0302 clinical medicine, Macrophage, Receptor, Respiratory Tract Infections, Lipid raft, Cells, Cultured, Protein Kinase C, Toll-Like Receptors, NF-kappa B, 3. Good health, Cell biology, RECEPTORS, Cholesterol, STAT1 Transcription Factor, [SDV.IMM]Life Sciences [q-bio]/Immunology, lipids (amino acids, peptides, and proteins), medicine.symptom, Lipoproteins, HDL, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Signal Transduction, EXPRESSION, medicine.medical_specialty, Inflammation, Biology, SUPPRESS, Models, Biological, 03 medical and health sciences, Membrane Microdomains, Immune system, In vivo, Internal medicine, medicine, Animals, Humans, Molecular Biology, Innate immune system, Base Sequence, Macrophages, Biological Transport, NF-κB, Cell Biology, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, chemistry, ATHEROSCLEROSIS, CELLS, Interferon Regulatory Factor-1, HDLS
Abstract: Item does not contain fulltext Membrane cholesterol modulates a variety of cell signaling pathways and functions. While cholesterol depletion by high-density lipoproteins (HDLs) has potent anti-inflammatory effects in various cell types, its effects on inflammatory responses in macrophages remain elusive. Here we show overt pro-inflammatory effects of HDL-mediated passive cholesterol depletion and lipid raft disruption in murine and human primary macrophages in vitro. These pro-inflammatory effects were confirmed in vivo in peritoneal macrophages from apoA-I transgenic mice, which have elevated HDL levels. In line with these findings, the innate immune responses required for clearance of P. aeruginosa bacterial infection in lung were compromised in mice with low HDL levels. Expression analysis, ChIP-PCR, and combinatorial pharmacological and genetic intervention studies unveiled that both native and reconstituted HDL enhance Toll-like-receptor-induced signaling by activating a PKC-NF-kappaB/STAT1-IRF1 axis, leading to increased inflammatory cytokine expression. HDL's pro-inflammatory activity supports proper functioning of macrophage immune responses.
Published: 2017

24. Effect of Selepressin vs Placebo on Ventilator- and Vasopressor-Free Days in Patients With Septic Shock

Author: Laterre, Pierre-François, Berry, Scott, Blemings, Allan, Carlsen, Jan, Francois, Bruno, Graves, Todd, Jacobsen, Karsten, Lewis, Roger, Opal, Steven, Perner, Anders, Pickkers, Peter, Russell, James, Windeløv, Nis, Yealy, Donald, Asfar, Pierre, Bestle, Morten, Muller, Grégoire, Bruel, Cédric, Brule, Noëlle, Decruyenaere, Johan, Dive, Alain-Michel, Dugernier, Thierry, Krell, Kenneth, Lefrant, Jean-Yves, Mégarbane, Bruno, Mercier, Emmanuelle, Mira, Jean-Paul, Quenot, Jean-Pierre, Rasmussen, Bodil Steen, Thorsen-Meyer, Hans-Christian, Vander Laenen, Margot, Vang, Marianne Lauridsen, Vignon, Philippe, Vinatier, Isabelle, Wichmann, Sine, Wittebole, Xavier, Kjolbye, Anne Louise, Angus, Derek, Cliniques universitaires St Luc [Bruxelles], Université Catholique de Louvain = Catholic University of Louvain (UCL), Ferring Pharmaceuticals A/S, Centre d'Investigation Clinique de Limoges (CIC1435), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Limoges, Los Angeles Biomedical Research Institute (LA BioMed), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Warren Alpert Medical School of Brown University, Department of Intensive Care [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Radboud University Medical Center [Nijmegen], University of British Columbia (UBC), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional d'Orléans (CHRO), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Ghent University Hospital, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Lariboisière-Fernand-Widal [APHP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Cochin [AP-HP], Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Ziekenhuis Oost-Limburg (ZOL), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, University of Pittsburgh (PITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Importance: Norepinephrine, the first-line vasopressor for septic shock, is not always effective and has important catecholaminergic adverse effects. Selepressin, a selective vasopressin V1a receptor agonist, is a noncatecholaminergic vasopressor that may mitigate sepsis-induced vasodilatation, vascular leakage, and edema, with fewer adverse effects.Objective: To test whether selepressin improves outcome in septic shock.Design, setting, and participants: An adaptive phase 2b/3 randomized clinical trial comprising 2 parts that included adult patients (n = 868) with septic shock requiring more than 5 μg/min of norepinephrine. Part 1 used a Bayesian algorithm to adjust randomization probabilities to alternative selepressin dosing regimens and to trigger transition to part 2, which would compare the best-performing regimen with placebo. The trial was conducted between July 2015 and August 2017 in 63 hospitals in Belgium, Denmark, France, the Netherlands, and the United States, and follow-up was completed by May 2018.Interventions: Random assignment to 1 of 3 dosing regimens of selepressin (starting infusion rates of 1.7, 2.5, and 3.5 ng/kg/min; n = 585) or to placebo (n = 283), all administered as continuous infusions titrated according to hemodynamic parameters.Main outcomes and measures: Primary end point was ventilator- and vasopressor-free days within 30 days (deaths assigned zero days) of commencing study drug. Key secondary end points were 90-day mortality, kidney replacement therapy-free days, and ICU-free days.Results: Among 868 randomized patients, 828 received study drug (mean age, 66.3 years; 341 [41.2%] women) and comprised the primary analysis cohort, of whom 562 received 1 of 3 selepressin regimens, 266 received placebo, and 817 (98.7%) completed the trial. The trial was stopped for futility at the end of part 1. Median study drug duration was 37.8 hours (IQR, 17.8-72.4). There were no significant differences in the primary end point (ventilator- and vasopressor-free days: 15.0 vs 14.5 in the selepressin and placebo groups; difference, 0.6 [95% CI, -1.3 to 2.4]; P = .30) or key secondary end points (90-day mortality, 40.6% vs 39.4%; difference, 1.1% [95% CI, -6.5% to 8.8%]; P = .77; kidney replacement therapy-free days: 18.5 vs 18.2; difference, 0.3 [95% CI, -2.1 to 2.6]; P = .85; ICU-free days: 12.6 vs 12.2; difference, 0.5 [95% CI, -1.2 to 2.2]; P = .41). Adverse event rates included cardiac arrhythmias (27.9% vs 25.2% of patients), cardiac ischemia (6.6% vs 5.6%), mesenteric ischemia (3.2% vs 2.6%), and peripheral ischemia (2.3% vs 2.3%).Conclusions and relevance: Among patients with septic shock receiving norepinephrine, administration of selepressin, compared with placebo, did not result in improvement in vasopressor- and ventilator-free days within 30 days. Further research would be needed to evaluate the potential role of selepressin for other patient-centered outcomes in septic shock.Trial registration: ClinicalTrials.gov Identifier: NCT02508649.
Published: 2019

25. A proposal for standardized magnetic resonance imaging (MRI) descriptors of abnormally invasive placenta (AIP) – from the International Society for AIP

Author: Morel, O, Collins, SL, Uzan-Augui, J, Masselli, G, Duan, J, Chabot-Lecoanet, A-C, Braun, T, Langhoff-Roos, J, Soyer, P, Chantraine, F, (IS-AIP), International Society for Abnormally Invasive Placenta, BIRKER, Juliette, Service d'Obstétrique et de Gynécologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), 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), University of Oxford, Service de Radiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Freie Universität Berlin, Humboldt University Of Berlin, Department of Obstetrics [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Université de Liège, Centre Hospitalier Universitaire de Liège (CHU-Liège), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Humboldt-Universität zu Berlin, and 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)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Placenta Diseases, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030218 nuclear medicine & medical imaging, Terminology, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, 0302 clinical medicine, Blood loss, Pregnancy, Terminology as Topic, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Radiology, Nuclear Medicine and imaging, Medical physics, ComputingMilieux_MISCELLANEOUS, 030219 obstetrics & reproductive medicine, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, General Medicine, Magnetic Resonance Imaging, 3. Good health, Standardized terminology, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Abnormally invasive placenta (AIP) is used to describe a placenta that does not separate naturally after delivery and cannot be extirpated without causing abnormally high blood loss. Recently, the use of a standardized terminology for descriptors of AIP signs seen on ultrasound has been prosed but to date no such unified descriptors have been developed for magnetic resonance imaging (MRI). The purpose of this paper is to propose a unified terminology based on a consensus opinion from the members of the International Society for AIP (IS-AIP) that include obstetricians, gynecologists, radiologists, pathologists, anesthesiologists and basic science researchers. We assume that using these standardized MRI descriptors for AIP will be useful for clinical use, education, teaching and future research projects, thus assumably improving care of patients with this condition. In addition, using a uniform terminology for AIP should become the first step of a standardized MRI report.
Published: 2019

26. SUPERNOVA: will its energy trigger the formation of a new therapeutic star?

Author: Anders Perner, Audrey De Jong, Thomas Bein, Systèmes de Référence Temps Espace (SYRTE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), University Hospital Regensburg, 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), Department of Intensive Care [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Center for Kræft og Organsygdomme, and MORNET, Dominique
Subjects: Extracorporeal Circulation, business.industry, Pain medicine, [SDV]Life Sciences [q-bio], Extracorporeal circulation, MEDLINE, Astronomy, 030208 emergency & critical care medicine, Star (graph theory), Carbon Dioxide, Critical Care and Intensive Care Medicine, [SDV] Life Sciences [q-bio], 03 medical and health sciences, Supernova, 0302 clinical medicine, Renal Dialysis, Medicine, 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

27. Surgical consensus guidelines on sentinel node biopsy (SNB) in patients with oral cancer

Author: Willem M.C. Klop, Remco de Bree, Bernhard Frerich, JF Tvedskov, Isabel Sassoon, Renaud Garrel, Jeremy McMahon, Naoyuki Kohno, Clare Schilling, M.G. Vigili, Richard Shaw, Georges Lawson, Sando J Stoeckli, Mark McGurk, David Cognetti, J. Alvarez, Stephen Y. Lai, Anders Christensen, Cyrus Kerawala, Christian von Buchwald, Anil K. D'Cruz, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/CARS - Computer Assisted Robotic Surgery, UCL - (MGD) Service d'oto-rhino-laryngologie, University of Freiburg [Freiburg], Kantonsspital St Gallen [Switzerland], University Medical Center [Utrecht], The University of Texas M.D. Anderson Cancer Center [Houston], Hospital Universitario Cruces = Cruces University Hospital, Copenhagen University Hospital, Department of Otorhinolaryngology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Jefferson (Philadelphia University + Thomas Jefferson University), Service d'ORL, Hôpital Gui de Chauliac (CHRU de Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Kyorin University School of Medicine [Tokyo, Japan], Kyorin University [Tokyo, Japan], The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, NHS Foundation Trust [London], The Royal Marsden, Université Catholique de Louvain = Catholic University of Louvain (UCL), Southern General Hospital, Glasgow, King‘s College London, and University of Liverpool
Subjects: occult metastasis, medicine.medical_specialty, media_common.quotation_subject, education, MEDLINE, Oral squamous cell cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, sentinel node biopsy, oral squamous cell cancer, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, Voting, Journal Article, medicine, Medical physics, elective neck dissection, Operative technique, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030223 otorhinolaryngology, media_common, Sentinel node biopsy, Mouth neoplasm, business.industry, Occult metastasis, Head and neck cancer, Cancer, Sentinel node, medicine.disease, operative technique, 3. Good health, Otorhinolaryngology, Elective neck dissection, 030220 oncology & carcinogenesis, business
Abstract: International audience; Background : The eighth international symposium for sentinel node biopsy (SNB) in head and neck cancer was held in 2018. This consensus conference aimed to deliver current multidisciplinary guidelines. This document focuses on the surgical aspects of SNB for oral cancer.Method : Invited expert faculty selected topics requiring guidelines. Topics were reviewed and evidence evaluated where available. Data were presented at the consensus meeting, with live debate from panels comprising expert, nonexpert, and patient representatives followed by voting to assess the level of support for proposed recommendations. Evidence review, debate, and voting results were all considered in constructing these guidelines. Results/conclusion : A range of topics were considered, from patient selection to surgical technique and follow-up schedule. Consensus was not achieved in all areas, highlighting potential issues that would benefit from prospective studies. Nevertheless these guidelines represent an up-to-date pragmatic recommendation based on current evidence and expert opinion.
Published: 2019

28. Analgesic use — prevalence, biomonitoring and endocrine and reproductive effects

Author: Tania Serrano, Bernard Jégou, David Møbjerg Kristensen, Laurianne Lesné, Pierre Gaudriault, Sverine Mazaud-Guittot, Katharina M. Main, Department of Growth and Reproduction [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Danish Council for Independent Research (Medical Sciences), Fondation pour la Recherche Medicale, Inserm (Institut national de la sante et de la recherche medicale), Rennes 1 University, EHESP-School of Public Health, ANSM (Agence Nationale de la Securite du Medicament) [AAP-2012-037, HAP-2014-073], Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Meconium, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, nonsteroidal antiinflammatory drugs, postmenopausal women, Ibuprofen, Endocrine Disruptors, Pharmacology, 0302 clinical medicine, Endocrinology, Pregnancy, persistent pulmonary-hypertension, education.field_of_study, Aspirin, 030219 obstetrics & reproductive medicine, Anti-Inflammatory Agents, Non-Steroidal, Commerce, Pregnancy Outcome, Environmental exposure, Analgesics, Non-Narcotic, 3. Good health, Prenatal Exposure Delayed Effects, acetylsalicylic-acid, Female, Over-the-counter, Drug Monitoring, Salicylic Acid, medicine.drug, low-dose aspirin, Analgesic, Population, Pain, intrauterine exposure, Congenital Abnormalities, 03 medical and health sciences, Environmental health, medicine, Humans, Pain Management, Endocrine system, Tooth, Deciduous, education, over-the-counter, Acetaminophen, prenatal paracetamol exposure, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Milk, Human, blood-plasma levels, business.industry, Environmental Exposure, medicine.disease, Molar, 030104 developmental biology, Urogenital Abnormalities, business, n-acetyl-4-aminophenol paracetamol
Abstract: International audience; Paracetamol and NSAIDs, in particular acetylsalicylic acid (aspirin) and ibuprofen, are among the most used and environmentally released pharmaceutical drugs. The differences in international trends in the sale and consumption of mild analgesics reflect differences in marketing, governmental policies, habits, accessibility, disease patterns and the age distribution of each population. Biomonitoring indicates ubiquitous and high human exposure to paracetamol and to salicylic acid, which is the main metabolite of acetylsalicylic acid. Furthermore, evidence suggests that analgesics can have endocrine disruptive properties capable of altering animal and human reproductive function from fetal life to adulthood in both sexes. Medical and public awareness about these health concerns should be increased, particularly among pregnant women.
Published: 2016

29. Unsupervised High-Dimensional Analysis Aligns Dendritic Cells across Tissues and Species

Author: Bjarne Bogen, Mahesh Choolani, Dedrick Kok Hong Chan, Tony Lim Kiat Hon, Charles-Antoine Dutertre, Jerry Kok Yen Chan, Florent Ginhoux, Anis Larbi, Sandrine Henri, Svetoslav Chakarov, Citra Nurfarah Zaini Mattar, Evan W. Newell, Naomi McGovern, Sofie Van Gassen, Jinmiao Chen, Simon Tavernier, Tam John Kit Chung, Michael Poidinger, Sergio Erdal Irac, Dorine Sichien, Hervé Luche, Ivy Low, Hermi Sumatoh, Sofie De Prijck, Gillian Low, Ker-Kan Tan, Bart N. Lambrecht, Even Fossum, Martin Guilliams, Yvan Saeys, Bernard Malissen, Charlotte L. Scott, Pulmonary Medicine, McGovern, Naomi [0000-0001-5200-2698], Apollo - University of Cambridge Repository, Department of Biomedical Molecular Biology [Ghent], Universiteit Gent = Ghent University (UGENT), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unit of Immunoregulation and Mucosal Immunology [Ghent, Belgium], VIB Inflammation Research Center [Ghent, Belgium], Program in Emerging Infectious Disease, Duke-NUS Medical School [Singapore], Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Department of Information Technology [Gent], Data Mining and Modeling for Biomedicine [Ghent, Belgium], Department of Internal Medicine [Ghent, Belgium], Experimental Fetal Medicine Group [Singapore], National University of Singapore (NUS)-Yong Loo Lin School of Medicine [Singapore], Department of Surgery [Singapore], Department of Pathology [Singapour], National University of Singapore (NUS), K.G. Jebsen Centre for Influenza Vaccine Research [Oslo, Norway], University of Oslo (UiO)-Oslo University Hospital [Oslo], Center for Immune Regulation [Oslo] (CIR), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Reproductive Medicine [Singapore], KK Women's and Children's Hospital [Singapore], Cancer and Stem Cell Biology Program [Singapore], Centre d'Immunophénomique (CIPHE), Department of Pulmonary Medicine [Rotterdam, The Netherlands], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Universiteit Gent = Ghent University [Belgium] (UGENT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Universiteit Gent, and HENRI, Sandrine
Subjects: EXPRESSION, 0301 basic medicine, Resource, STEADY-STATE, HOMEOSTASIS, BLOOD, [SDV.IMM] Life Sciences [q-bio]/Immunology, BONE-MARROW, Cellular differentiation, Immunology, Inflammation, Computational biology, Biology, Macaque, Flow cytometry, 03 medical and health sciences, Mice, 0302 clinical medicine, biology.animal, medicine, Immunology and Allergy, Macrophage, Animals, Humans, Mass cytometry, MACROPHAGES, SIGNALING CONTROLS, LYMPH-NODES, medicine.diagnostic_test, Biology and Life Sciences, hemic and immune systems, Cell Differentiation, Dendritic Cells, Flow Cytometry, CLONOGENIC PROGENITOR, Mice, Inbred C57BL, Protein Transport, 030104 developmental biology, Infectious Diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Macaca, medicine.symptom, Conventional Dendritic Cell, Function (biology), RESPONSES, 030215 immunology
Abstract: Summary Dendritic cells (DCs) are professional antigen-presenting cells that hold great therapeutic potential. Multiple DC subsets have been described, and it remains challenging to align them across tissues and species to analyze their function in the absence of macrophage contamination. Here, we provide and validate a universal toolbox for the automated identification of DCs through unsupervised analysis of conventional flow cytometry and mass cytometry data obtained from multiple mouse, macaque, and human tissues. The use of a minimal set of lineage-imprinted markers was sufficient to subdivide DCs into conventional type 1 (cDC1s), conventional type 2 (cDC2s), and plasmacytoid DCs (pDCs) across tissues and species. This way, a large number of additional markers can still be used to further characterize the heterogeneity of DCs across tissues and during inflammation. This framework represents the way forward to a universal, high-throughput, and standardized analysis of DC populations from mutant mice and human patients., Graphical Abstract Image 1, Highlights • A conserved gating strategy aligns dendritic cells (DCs) in mouse and human tissues • Unsupervised computational analysis of flow cytometry data outperforms manual analysis • Mass cytometry reveals heterogeneity of DC subsets across mouse and human tissues • DC activation upon inflammation tracked by automated analysis of mass cytometry, Using unsupervised analysis of flow cytometry and mass cytometry data obtained from multiple mouse, macaque, and human tissues, Guilliams et al. provide a universal toolbox for the automated identification of dendritic cells. This framework represents the way forward to high-throughput and standardized analysis of dendritic cells from mutant mice and patients.
Published: 2016

30. Fate of manuscripts rejected by Intensive Care Medicine from 2013 to 2016: a follow-up analysis

Author: Ellen Deutsch, Elie Azoulay, Elisa Sala, Jean-François Timsit, Martin Lavillonnière, Anders Perner, Giuseppe Citerio, Samir Jaber, University of Milano-Bicocca [Italy], Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Department of Intensive Care [Rigshospitalet], Rigshospitalet [Copenhagen], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de réanimation médicale, Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Citerio, G, Deutsch, E, Sala, E, Lavillonnière, M, Perner, A, Jaber, S, Timsit, J, Azoulay, E, Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Copenhagen University Hospital-Copenhagen University Hospital, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Publishing, medicine.medical_specialty, Manuscripts as Topic, Critical Care, business.industry, Journal, reviewing process, Pain medicine, [SDV]Life Sciences [q-bio], 030208 emergency & critical care medicine, Critical Care and Intensive Care Medicine, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Family medicine, Anesthesiology, Medicine, Humans, 030212 general & internal medicine, Periodicals as Topic, business, ComputingMilieux_MISCELLANEOUS, Forecasting
Abstract: International audience
Published: 2018

31. Human Enhancers Harboring Specific Sequence Composition, Activity, and Genome Organization Are Linked to the Immune Response

Author: Anthony Mathelier, Wyeth W. Wasserman, Charles-Henri Lecellier, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Department of Medical Genetics, Faculty of Medicine-Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], and Copenhagen University Hospital-Copenhagen University Hospital
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Genomics, Computational biology, Investigations, Biology, immune response, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Transcription (biology), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Humans, Nucleosome, Gene Regulatory Networks, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Enhancer, Transcription factor, 030304 developmental biology, Genomic organization, Base Composition, Immunity, Cellular, 0303 health sciences, Base Sequence, Genome, Human, sequence-level instructions, Chromatin, Cap analysis gene expression, Enhancer Elements, Genetic, 030104 developmental biology, chemistry, Human genome, enhancer, transcription, 030217 neurology & neurosurgery, DNA
Abstract: The FANTOM5 consortium recently characterized 65,423 human enhancers from 1829 cell and tissue samples using the Cap Analysis of Gene Expression technology. We showed that the guanine and cytosine content at enhancer regions distinguishes two classes of enhancers harboring distinct DNA structural properties at flanking regions. A functional analysis of their predicted gene targets highlighted one class of enhancers as significantly enriched for associations with immune response genes. Moreover, these enhancers were specifically enriched for regulatory motifs recognized by transcription factors involved in immune response. We observed that enhancers enriched for links to immune response genes were more cell-type specific, preferentially activated upon bacterial infection, and with specific response activity. Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically associating domains and chromatin loops. Our results suggest that specific nucleotide compositions encode for classes of enhancers that are functionally distinct and specifically organized in the human genome.
Published: 2018

32. Godina 2017. u kardiologiji: aorta i periferna cirkulacija

Author: Henrik Sillesen, Marco De Carlo, Maarit Venermo, Victor Aboyans, Sigrid Kufaas Brækkan, Lucia Mazzolai, Verisuonikirurgian yksikkö, Clinicum, Department of Surgery, HUS Abdominal Center, Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Department of Vascular Surgery, Rigshospitalet [Copenhagen], and Copenhagen University Hospital-Copenhagen University Hospital
Subjects: Carotid Artery Diseases, medicine.medical_specialty, PULMONARY-EMBOLISM, education, DEEP VENOUS THROMBOSIS, Aortic Diseases, Catheter directed thrombolysis, 030204 cardiovascular system & hematology, VEIN-THROMBOSIS, CATHETER-DIRECTED THROMBOLYSIS, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, CARDIOVASCULAR-DISEASE EVENTS, Internal medicine, medicine, CRITICAL LIMB ISCHEMIA, Humans, ARTERY-DISEASE, 030212 general & internal medicine, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, Croatian, Gynecology, Peripheral Vascular Diseases, business.industry, Venous Thromboembolism, Critical limb ischemia, RANDOMIZED CONTROLLED-TRIAL, medicine.disease, language.human_language, Pulmonary embolism, Vein thrombosis, Lower Extremity, PROSPECTIVE COHORT, 3121 General medicine, internal medicine and other clinical medicine, language, Cardiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, Cardiology and Cardiovascular Medicine, business, FOLLOW-UP
Abstract: International audience
Published: 2018

33. Loss of Function of the Nuclear Receptor NR2F2, Encoding COUP-TF2, Causes Testis Development and Cardiac Defects in 46,XX Children

Author: Caroline Eozenou, David Rodriguez-Buritica, Zita Halász, Jean-Pierre Siffroi, Joelle Bignon-Topalovic, Anne Jorgensen, Sophie Lambert, Rajpert-De Meyts E, János Sólyom, Anu Bashamboo, Ken McElreavey, Paye-Jaouen A, Rita Bertalan, Attila Tar, Capucine Hyon, John C. Achermann, Peter Nagy, Laetitia Martinerie, Génétique du développement humain, Institut Pasteur [Paris], Department of Growth and Reproduction [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pál Heim Children's Hospital = Heim Pál Gyermekkórház [Budapest], First Department of Pathology and Experimental Cancer Research, Semmelweis University [Budapest], Chirurgie viscérale et urologie pédiatriques [AP-HP Robert Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Endocrinologie et Diabétologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, McGovern Medical School [Houston, Texas], The University of Texas Health Science Center at Houston (UTHealth), Copenhagen University Hospital, Institute of Child Health [London], University College of London [London] (UCL), A.B. is funded in part by the program Actions Concertees Interpasteuriennes (ACIP) and a research grant from the European Society of Pediatric Endocrinology. A.B. and K.McE. are funded by a research grant from the EuroDSD in the European Community’s Seventh Framework Programme FP7/2007-2013 under grant agreement no. 201444 as well as grant no. 295097 as part of the EU call FP7-INCO-2011-6. J.C.A. is a Wellcome Trust Senior Research Fellow in Clinical Science (grant 098513/Z/12/Z, 209328/Z/17/Z) with research support from Great Ormond Street Hospital Children's Charity (grant V2518) and the NIHR GOSH BRC (IS-BRC-1215-20012)., This work is supported by the COST Action DSDnet BM1303., This work was funded by the Agence Nationale de la Recherche (Laboratoire d’Excellence Revive, Investissement d’Avenir, ANR-10-LABX-73)., The authors wish to thank Dr. Etienne Patin for comments on the manuscript., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), European Project: 201444,EC:FP7:HEALTH,FP7-HEALTH-2007-A,EURODSD(2008), European Project: 295097,EC:FP7:INCO,FP7-INCO-2011-6,GM_NCD_IN_CO(2011), Génétique du Développement humain - Human developmental genetics, and Institut Pasteur [Paris] (IP)
Subjects: Forkhead Box Protein L2, Male, 0301 basic medicine, new syndrome, 46, XX Disorders of Sex Development, [SDV]Life Sciences [q-bio], MESH: 46, XX Disorders of Sex Development / genetics, sex determination, MESH: Amino Acid Sequence, MESH: Loss of Function Mutation / genetics, MESH: Base Sequence, Bioinformatics, medicine.disease_cause, COUP Transcription Factor II, 0302 clinical medicine, Loss of Function Mutation, MESH: Ovary / growth & development, MESH: Child, Testis, MESH: Testis / growth & development, nuclear receptor, Child, Frameshift Mutation, Exome, Genetics (clinical), MESH: Heterozygote, 0303 health sciences, education.field_of_study, Mutation, MESH: Testis / abnormalities, MESH: COUP Transcription Factor II / genetics, Cell biology, Phenotype, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, medicine.symptom, Heterozygote, medicine.drug_class, Population, Ovary, Biology, MESH: COUP Transcription Factor II / chemistry, MESH: Phenotype, Frameshift mutation, [SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction, 03 medical and health sciences, MESH: Forkhead Box Protein L2 / metabolism, Report, Genetics, medicine, Humans, Amino Acid Sequence, education, testicular DSD, Loss function, 030304 developmental biology, MESH: Humans, Base Sequence, Virilization, MESH: Frameshift Mutation / genetics, Androgen, MESH: Ovary / metabolism, NR2F2, MESH: Male, 030104 developmental biology, Nuclear receptor, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, COUP-TF2, Cardiac defects, MESH: Female
Abstract: International audience; Emerging evidence from murine studies suggests that mammalian sex determination is the outcome of an imbalance between mutually antagonistic male and female regulatory networks that canalize development down one pathway while actively repressing the other. However, in contrast to testis formation, the gene regulatory pathways governing mammalian ovary development have remained elusive. We performed exome or Sanger sequencing on 79 46,XX SRY-negative individuals with either unexplained virilization or with testicular/ovotesticular disorders/differences of sex development (TDSD/OTDSD). We identified heterozygous frameshift mutations in NR2F2, encoding COUP-TF2, in three children. One carried a c.103_109delGGCGCCC (p.Gly35Argfs∗75) mutation, while two others carried a c.97_103delCCGCCCG (p.Pro33Alafs∗77) mutation. In two of three children the mutation was de novo. All three children presented with congenital heart disease (CHD), one child with congenital diaphragmatic hernia (CDH), and two children with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). The three children had androgen production, virilization of external genitalia, and biochemical or histological evidence of testicular tissue. We demonstrate a highly significant association between the NR2F2 loss-of-function mutations and this syndromic form of DSD (p = 2.44 × 10-8). We show that COUP-TF2 is highly abundant in a FOXL2-negative stromal cell population of the fetal human ovary. In contrast to the mouse, these data establish COUP-TF2 as a human "pro-ovary" and "anti-testis" sex-determining factor in female gonads. Furthermore, the data presented here provide additional evidence of the emerging importance of nuclear receptors in establishing human ovarian identity and indicate that nuclear receptors may have divergent functions in mouse and human biology.
Published: 2018

34. Molecular assays for antimalarial drug resistance surveillance:A target product profile

Author: Xavier C. Ding, Eric Legrand, Naomi W. Lucchi, Hans-Peter Beck, Sidsel Nag, Sanjeev Krishna, Sarah K. Volkman, Christian Nsanzabana, Harald Noedl, Cally Roper, Edwin Kamau, Frédéric Ariey, Philip J. Rosenthal, Steve M. Taylor, Iveth J. González, Olivo Miotto, Henk D. F. H. Schallig, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Foundation for Innovative New Diagnostics (FIND), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de parasitologie-mycologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Medical Parasitology and Infection Biology [Basel, Suisse] (MPI), Swiss Tropical and Public Health Institute [Basel], University of Basel (Unibas), Walter Reed Army Institute of Research, United States Army Medical Research Directorate [Kenya] (USAMRD-K), Institute for Infection and Immunity [Londres, UK], St George's, University of London, Génétique du paludisme et résistance - Malaria Genetics and Resistance, Institut Pasteur [Paris] (IP), Division of Parasitic Diseases and Malaria [Atlanta, GA, États-Unis] (DPDM), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention-Centers for Disease Control and Prevention, Mahidol Oxford Tropical Medicine Research Unit, University of Oxford-Mahidol University [Bangkok], The Wellcome Trust Sanger Institute [Cambridge], Big Data Institute, University of Oxford, Centre for Medical Parasitology [Copenhagen], Department of Immunology and Microbiology [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Department of Infectious Disease [Copenhague, Danemark], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Institute of Specific Prophylaxis and Tropical Medicine = Institut für Spezifische Prophylaxe und Tropenmedizin [Vienne, Autriche], Medizinische Universität Wien = Medical University of Vienna, London School of Hygiene and Tropical Medicine (LSHTM), Department of Medicine [San Francisco], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Experimental parasitology [Amsterdam, Pays-Bas], Department of Medical Microbiology [Academic Medical Center], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Duke University Medical Center, Department of Immunology and Infectious Diseases (IID), Harvard T.H. Chan School of Public Health, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Simmons University [Boston, USA], This study was funded by the by the Department of Foreign Affairs and Trade of the Australian Government. The URL of the funder’s website is https://dfat.gov.au/. Grant number is AUSCORE-02, and the funding was received by the Foundation for Innovative New Diagnostics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Legrand, Eric, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Pasteur [Paris], University of Oxford [Oxford]-Mahidol University [Bangkok], University of Oxford [Oxford], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), University of California [San Francisco] (UCSF), and University of California-University of California
Subjects: 0301 basic medicine, Research Facilities, Molecular biology, DNA hybridization, Electrophoretic techniques, Drug Resistance, DNA electrophoresis, lcsh:Medicine, Drug resistance, Biochemistry, MESH: Biological Assay / economics, 0302 clinical medicine, Medicine and Health Sciences, Artemisinin, lcsh:Science, DNA extraction, MESH: Biological Assay / methods, Multidisciplinary, Drugs, 3. Good health, Nucleic acids, Costs and Cost Analysis, MESH: Drug Resistance, Biological Assay, Research Laboratories, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, medicine.drug, Research Article, Combination therapy, MESH: Antimalarials / pharmacology, 030231 tropical medicine, 030106 microbiology, Early detection, Computational biology, Microbiology, MESH: Costs and Cost Analysis, 03 medical and health sciences, Antimalarials, Antibiotic resistance, Extraction techniques, Microbial Control, parasitic diseases, medicine, Genetics, Parasitic Diseases, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Temporal information, Pharmacology, Molecular probe techniques, business.industry, Product profile, lcsh:R, Biology and Life Sciences, DNA, medicine.disease, Tropical Diseases, Probe hybridization, Malaria, Research and analysis methods, Molecular biology techniques, lcsh:Q, Antimicrobial Resistance, business, Government Laboratories
Abstract: International audience; Antimalarial drug resistance is a major constraint for malaria control and elimination efforts. Artemisinin-based combination therapy is now the mainstay for malaria treatment. However, delayed parasite clearance following treatment with artemisinin derivatives has now spread in the Greater Mekong Sub region and may emerge or spread to other malaria endemic regions. This spread is of great concern for malaria control programmes, as no alternatives to artemisinin-based combination therapies are expected to be available in the near future. There is a need to strengthen surveillance systems for early detection and response to the antimalarial drug resistance threat. Current surveillance is mainly done through therapeutic efficacy studies; however these studies are complex and both time- and resource-intensive. For multiple common antimalarials, parasite drug resistance has been correlated with specific genetic mutations, and the molecular markers associated with antimalarial drug resistance offer a simple and powerful tool to monitor the emergence and spread of resistant parasites. Different techniques to analyse molecular markers associated with antimalarial drug resistance are available, each with advantages and disadvantages. However, procedures are not adequately harmonized to facilitate comparisons between sites. Here we describe the target product profiles for tests to analyse molecular markers associated with antimalarial drug resistance, discuss how use of current techniques can be standardised, and identify the requirements for an ideal product that would allow malaria endemic countries to provide useful spatial and temporal information on the spread of resistance.
Published: 2018

35. De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation

Author: Olivier Vanakker, Maria Kirchhoff, Christian Gilissen, Jenny Morton, Ineke van der Burgt, Kelly Radtke, Tugce Aktas, Sarah Vergult, Diana Johnson, Tobias Rumpf, Tony Roscioli, André Reis, Alan Fryer, Salima El Chehadeh, Christel Thauvin-Robinet, Ange Line Bruel, Rolph Pfundt, Sander Pajusalu, David Francis, Asifa Akhtar, Iben Bache, Tiong Yang Tan, Vera M. Kalscheuer, Meredith Wilson, Björn Menten, Giuseppe Semplicio, Julien Thevenon, Richard Fisher, Yannis Duffourd, Gerhard Mittler, Witold G. Szymanski, M. Felicia Basilicata, Victoria McKay, Kristin Lindstrom, Han G. Brunner, Katrin Õunap, Jaya Ganesh, Claudia Isabelle Keller Valsecchi, Megan T. Cho, Laurence Faivre, MUMC+: DA Klinische Genetica (5), Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), West Midlands Regional Genetics Laboratory and Clinical Genetics Unit, Birmingham Women's Hospital, Copenhagen University Hospitals, Radboud University Medical Center [Nijmegen], Center for Medical Genetics [Ghent], Ghent University Hospital, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], GeneDx [Gaithersburg, MD, USA], Murdoch Children's Research Institute (MCRI), Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Department of Clinical Genetics (Sheffield Children’s NHS Foundation Trust), Sheffield Children's NHS Foundation Trust, Liverpool Women's NHS Foundation Trust, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Male, 0301 basic medicine, CHROMATIN, INTELLECTUAL DISABILITY, Chromosomal Proteins, Non-Histone, CHROMOSOME, Cohort Studies, Histones, Mice, Genes, X-Linked, MSL complex, Child, Cells, Cultured, Histone Acetyltransferases, Epigenomics, Acetylation, Genetic Diseases, X-Linked, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Syndrome, Chromatin, Cell biology, DNA-Binding Proteins, DROSOPHILA, Histone, ACETYLTRANSFERASE, Child, Preschool, Female, Adolescent, Mice, Transgenic, Biology, Article, Histone H4, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Genetics, Animals, Humans, CELL-CYCLE, Epigenetics, DEACETYLASE, MOF, MSL3, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], DOSAGE COMPENSATION COMPLEX, Infant, Dosage compensation complex, PROTEIN INTERACTIONS, HEK293 Cells, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neurodevelopmental Disorders, Case-Control Studies, Mutation, biology.protein, Histone deacetylase, Protein Processing, Post-Translational, Transcription Factors, Ultra-rare developmental disorders
Abstract: International audience; The etiological spectrum of ultra-rare developmental disorders remains to be fully defined. Chromatin regulatory mechanisms maintain cellular identity and function, where misregulation may lead to developmental defects. Here, we report pathogenic variations in MSL3, which encodes a member of the chromatin-associated male-specific lethal (MSL) complex responsible for bulk histone H4 lysine 16 acetylation (H4K16ac) in flies and mammals. These variants cause an X-linked syndrome affecting both sexes. Clinical features of the syndrome include global developmental delay, progressive gait disturbance, and recognizable facial dysmorphism. MSL3 mutations affect MSL complex assembly and activity, accompanied by a pronounced loss of H4K16ac levels in vivo. Patient-derived cells display global transcriptome alterations of pathways involved in morphogenesis and cell migration. Finally, we use histone deacetylase inhibitors to rebalance acetylation levels, alleviating some of the molecular and cellular phenotypes of patient cells. Taken together, we characterize a syndrome that allowed us to decipher the developmental importance of MSL3 in humans.
Published: 2018

36. Screening for heart transplantation and left ventricular assist system: results from the ScrEEning for advanced Heart Failure treatment (SEE-HF) study

Author: Lund, Lars H., Trochu, Jean-Noel, Meyns, Bart, Caliskan, Kadir, shaw, steven, Schmitto, Jan D., Schibilsky, David, Damme, Laura, Heatley, Jerry, Gustafsson, Finn, Cardiology, Karolinska Inst, Dept Med Biochem & Biophys, Solna, Sweden, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), 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)-Centre National de la Recherche Scientifique (CNRS), Department of Cardiology, B2142, Rigshospitalet [Copenhagen], and Copenhagen University Hospital-Copenhagen University Hospital
Subjects: Left ventricular assist system, Mechanical circulatory support, [SDV]Life Sciences [q-bio], Screening, Heart failure, Heart transplantation
Abstract: International audience; BACKGROUND: Heart transplantation (HTx) and implantable left ventricular assist systems (LVAS) improve outcomes in advanced heart failure but may be underutilized. We hypothesized that screening can identify appropriate candidates. METHODS AND RESULTS: The ScrEEning for advanced Heart Failure treatment (SEE-HF) study was a multicentre prospective study screening patients with existing cardiac resynchronization therapy (CRT) and/or implantable cardioverter-defibrillator (ICD) for ejection fraction ≤40% and New York Heart Association (NYHA) class III-IV, and subsequently for guideline-based HTx and LVAS indication. Of 1722 (mean age 64 ± 14 years, 26% women) patients screened at eight centres in seven European countries, 121 (7.0%) were eligible and 99 (5.7%; mean age 61 ± 10 years, 19% women) patients were enrolled for detailed assessment. Twenty-six of the 99 enrolled patients (26%) were eligible for either HTx or LVAD (18 eligible for HTx; 7 eligible for LVAD; and 1 eligible for both). Eleven patients were listed for HTx and three received an LVAS. Eligible patients were 61 ± 8 years and 19% women, whereas those actually receiving intervention were 56 ± 8 years and 8% women. CONCLUSIONS: Among patients with CRT and/or ICD, a minority have NYHA class III-IV heart failure and ejection fraction ≤40%. Among these, however, more than one-quarter have an unrecognized need for HTx or LVAS. When patients are offered intervention based on screening, many decline. Discrepancies exist between clinical and patient equipoise. Clinical Trial Registration ClinicalTrials.gov Unique Identifier: NCT00894387.
Published: 2018

37. JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework

Author: Oriol Fornes, Anthony Mathelier, Benoit Ballester, Jeanne Chèneby, Marius Gheorghe, Arnaud Stigliani, Ge Tan, François Parcy, Aziz Khan, David J. Arenillas, Robin van der Lee, Wyeth W. Wasserman, Klaas Vandepoele, Jaime A. Castro-Mondragon, Damir Baranasic, Albin Sandelin, Shubhada Rajabhau Kulkarni, Boris Lenhard, Adrien Bessy, Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Department of Medical Genetics, Faculty of Medicine-Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), Physiologie cellulaire et végétale (LPCV), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Plant Systems Biology, VIB, and Department of Plant Biotechnology and Bioinformatics, Ghent University [Belgium] (UGENT), Computational Regulatory Genomics, Imperial College London, Institute of Clinical Sciences, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Bioinformatics Centre, Department of Biology [Copenhagen], Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Sars International Centre for Marine Molecular Biology, University of Bergen (UIB), Oslo University Hospital Radiumhospitalet, Genome Canada and Canadian Institutes of Health Research (On-Target Grants) [255ONT and BOP-149430], Natural Sciences and Engineering Research Council of Canada (Discovery Grant) [RGPIN-2017–06824], Independent Research Fund Denmark, Innovation Fund Denmark, Elixir Denmark, Wellcome Trust [106954], Biotechnology and Biological Sciences Research Council [BB/N023358/1], Medical Research Council UK [MC UP 1102/1], Weston Brain Institute: [20R74681], Research Foundation Flanders Grant [G001015N], Lundbeck Foundation, ANR-10- LABX-49-01,Labex GRAL,Labex GRAL, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute and Department of Medical Genetics, University of British Columbia (UBC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Copenhagen University Hospital-Copenhagen University Hospital, Radboud University Medical Center [Nijmegen], Universiteit Gent = Ghent University [Belgium] (UGENT), Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute-University of British Columbia (UBC), Biotech Research and Innovation Centre (BRIC), University of Copenhagen = Københavns Universitet (KU), Center for Plant Systems Biology (PSB Center), Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), VIB Department of Plant Systems Biology, University of Bergen (UiB), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Universiteit Gent = Ghent University (UGENT), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), University of Copenhagen = Københavns Universitet (UCPH), Biotechnology and Biological Sciences Research Council (BBSRC), and Wellcome Trust
Subjects: 0301 basic medicine, REPRESENTATION, Nematodes, [SDV]Life Sciences [q-bio], 05 Environmental Sciences, SPECIFICITIES, DIVERSITY, Genome browser, computer.software_genre, Genome, Bioconductor, User-Computer Interface, 0302 clinical medicine, Databases, Genetic, Database Issue, Taxonomic rank, base de données, 0303 health sciences, Database, Web application framework, BIOINFORMATICS, Genomics, Plants, ARABIDOPSIS, Multiple species, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], GENOME, Insects, 030220 oncology & carcinogenesis, Vertebrates, Erratum, Life Sciences & Biomedicine, Protein Binding, EXPRESSION, Biochemistry & Molecular Biology, libre accès, Biology, 03 medical and health sciences, Open Access, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], JASPAR, Journal Article, Genetics, Animals, Humans, Position-Specific Scoring Matrices, 030304 developmental biology, Internet, Science & Technology, Binding Sites, LANDSCAPE, Fungi, Biology and Life Sciences, 06 Biological Sciences, Binding, SITE PREDICTIONS, 030104 developmental biology, DISCOVERY, profil, 08 Information and Computing Sciences, actualisation, Transcription factor, computer, facteur de transcription, Developmental Biology, Transcription Factors
Abstract: International audience; JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) and TF flexible models (TFFMs) for TFs across multiple species in six tax-onomic groups. In the 2018 release of JASPAR, the CORE collection has been expanded with 322 new PFMs (60 for vertebrates and 262 for plants) and 33 PFMs were updated (24 for vertebrates, 8 for plants and 1 for insects). These new profiles represent a 30% expansion compared to the 2016 release. In addition , we have introduced 316 TFFMs (95 for vertebrates , 218 for plants and 3 for insects). This release incorporates clusters of similar PFMs in each taxon and each TF class per taxon. The JASPAR 2018 CORE vertebrate collection of PFMs was used to predict TF-binding sites in the human genome. The predictions are made available to the scientific community through a UCSC Genome Browser track data hub. Finally , this update comes with a new web framework with an interactive and responsive user-interface, along with new features. All the underlying data can be retrieved programmatically using a RESTful API and through the JASPAR 2018 R/Bioconductor package .
Published: 2017

38. O12.4. EFFECTS OF THE GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST EXENATIDE ON BONE STATUS IN OBESE, NON-DIABETIC, ANTIPSYCHOTIC-TREATED SCHIZOPHRENIA SPECTRUM PATIENTS.

Author: Eriksson, Robert, Broberg, Brian V, Ishoy, Pelle Lau, Bak, Nikolaj, Andersen, Ulrik B, Jørgensen, Niklas R, Knop, Filip K, and Ebdrup, Bjorn
Subjects: OBESITY risk factors, OBESITY treatment, DRUG therapy for schizophrenia, CONFERENCES & conventions, TREATMENT effectiveness, GLUCAGON-like peptide-1 agonists, EXENATIDE, ANTIPSYCHOTIC agents, SECONDARY analysis
Abstract: Background Low bone mineral density (BMD) may constitute an underestimated comorbidity in schizophrenia patients undergoing long-term antipsychotic treatment. Glucagon-like peptide 1 (GLP-1) receptor agonists are antidiabetic drugs, which may also affect bone turnover. The current study comprises planned secondary analyses of the 'TAO study': Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist. The TAO study was an investigator-initiated, double-blind, randomized, placebo-controlled trial, investigating the effects of three months treatment with the GLP-1 receptor agonist exenatide 2 mg once-weekly in chronic obese, antipsychotic-treated patients with schizophrenia spectrum disorder. Methods First, we compared baseline bone turnover markers (BTMs) of 45 chronic, obese, antipsychotic-treated patients with the Danish Health2006 study cohort as reference population, and we calculated bone mineral density (BMD) T- and Z-scores. Second, investigated effects of three months of GLP-1 receptor agonist exenatide 2 mg once-weekly (n=23), or placebo (n=22) on BTMs and BMD in these patients. Data were initially analyzed without covariates by two-way repeated measures ANOVA. All analyses were repeated with mean prolactin level as a covariate to evaluate the potential effect of prolactin. Results In women (n=24), all baseline BTM measurements of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were within reference values. In men (n=21), 5% displayed lower PINP and 14% displayed lower CTX. One patient displayed BMD Z-score <-2, and 23% of patients (17% of women and 29% of men) displayed -2.5
Published: 2019
Full Text: View/download PDF

39. Year in review in Intensive Care Medicine 2014: I. Cardiac dysfunction and cardiac arrest, ultrasound, neurocritical care, ICU-acquired weakness, nutrition, acute kidney injury, and miscellaneous

Author: J. Randall Curtis, Pierre Singer, Antoni Torres, Matteo Bassetti, Jan Bakker, Samir Jaber, Anders Perner, Elie Azoulay, Antoine Vieillard-Baron, Laurent Papazian, Michael Joannidis, Martin Smith, Gordon S. Doig, Marcio Soares, Giuseppe Citerio, Jean-François Timsit, Margaret S. Herridge, Mark J. Peters, Maurizio Cecconi, Dominique Benoit, Neurointensive Care Unit, Ospedale S. Gerardo, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Infectious Diseases Division, Università degli studi di Genova = University of Genoa (UniGe), Ghent University Hospital, Ghent, Belgium, Department of Anaesthesia, St. Georges Healthcare NHS Trust, Harborview Medical Center and The University of Washington, Northern Clinical School Intensive Care Research Unit, Interdepartmental Division of Critical Care Medicine, 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), Department of Intensive Care, University Clinic Innsbruck, Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Intensive Care [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, UCL Institute of Child Health and Great Ormond St Hospital, London, UK, General Intensive Care Department and Institute for Nutrition Research, Rabin Medical Center-Beilinson Hospital, The National Hospital for Neurology and Neurosurgery, Intensive Care Unit, Instituto Nacional de Câncer, Pulmonary Intensive Care Unit, Service de réanimation medico-chirurgicale [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Intensive Care, Internal Medicine, University of Genoa (UNIGE), INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Service de réanimation medico-chirurgicale, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Ambroise Paré [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Citerio, G, Bakker, J, Bassetti, M, Benoit, D, Cecconi, M, Curtis, J, Doig, G, Herridge, M, Jaber, S, Joannidis, M, Papazian, L, Perner, A, Peters, M, Singer, P, Smith, M, Soares, M, Torres, A, Vieillard Baron, A, Timsit, J, and Azoulay, E
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, Pain medicine, [SDV]Life Sciences [q-bio], Acute kidney injury, Neurointensive care, Disease, Year in Review 2014, Critical Care and Intensive Care Medicine, medicine.disease, 3. Good health, Intensive care, Anesthesiology, Review Intensive Care, Medicine, Renal replacement therapy, Cardiopulmonary resuscitation, business, Intensive care medicine, ComputingMilieux_MISCELLANEOUS
Abstract: Intensive Care Medicine is changing. New types of pa pers, such as “What’s New in Intensive Care?”, “Understanding the Disease” and “My Paper 20 Years Later”, form a stable proportion of the articles published in the 2014 issues. This diversification has been received with an extraordinary enthusiasm and appreciation by the worldwide readership, as evidenced by the massive number of hits and downloads. In this first of three 2014 “Year in Review” articles, we cover those papers published in Intensive Care Medicine during the past year which focus on cardiac arrest, ultrasonography in critically ill patients, neurocritical care, ICU-acquired weakness, nutrition, acute kidney injury, as well as a number of miscellaneous topics.
Published: 2015

40. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX

Author: Jean-François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Stéphanie Dimet, Camille Boulagnon-Rombi, Marc-Antoine Allard, Frédérique Penault-Llorca, Jaafar Bennouna, Pierre Laurent-Puig, Julien Taieb, Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Felix Keil, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Björn Jagdt, Alois Lang, Michael Fridrik, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Eric Van Cutsem, Hassan Rezaie Kalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Marc Ychou, Eveline Boucher, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara Matysiak Budnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans Guenter Derigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Dino Amadori, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Corrado Boni, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Alfredo Falcone, Domenico Cristi Corsi, Roberto Labianca, Stefania Salvagni, Silvana Chiara, Libero Ciuffreda, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel Valladares Ayerbes, Jaime Feliu Batlle, Silvia Gil, Albert Abad Esteve, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis Cirera Nogueras, Bernado Queralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos Pijaume Pericay, Manuel Constenla Figueiras, Inmaculada Guasch Jordan, Maria Jose Gome Reina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio Marcuello Gaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica Guillot Morales, Marta Llanos Muñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel Hernandez Busquier, Teresa Checa Ruiz, Adelaida Lacasta Muñoa, Miquel Nogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio Galan Brotons, Santiago Albiol Rodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita Centelles Ruiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, Leslie Samuel, UE 1373 Fourrages Environnement Ruminants Lusignan, Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Environnement et Agronomie ( E.A. ) -Biologie et Amélioration des Plantes ( BAP ) -Fourrages Environnement Ruminants Lusignan ( FERLUS ), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Service de Biostatistique, Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Vall d'Hebron University Hospital [Barcelona], Dpt of Internal Medicine, Section of Immunoallergology and Respiratory [Florence] Diseases, University of Florence, Carl Gustav Carus University Hospital, Erasme Hospital, Brussels, Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse, Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, Centre de recherche de Cancérologie et d'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 ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Nantes ( UN ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Klinikum Wels Grieskirchen, Oncology department [Salzburg], Salzburger Landesklinikum - Uniklinikum Salzburg ( SALK ), Institute of Chemical Reaction Engineering, Hamburg University of Technology, Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung ( AWI ), Department of Medical Oncology, Medical University Vienna, Department of Internal Medicine, Hospital of Steyr, Department Internal Medicine 3, Centre for Hematology and Medical Oncology, General Hospital Linz, Department Medicine LKH, Institut für Festköperfirschung, Institut des Sciences Moléculaires de Marseille ( ISM2 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Centrale de Marseille ( ECM ) -Aix Marseille Université ( AMU ), University Hospitals Leuven [Leuven], Katholieke Universiteit Leuven ( KU Leuven ), Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Institut de Biologie Computationnelle ( IBC ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Moléculaires ( ISM ), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique ( CNRS ), Faculty of Veterinary Medicine, Ghent University [Belgium] ( UGENT ), Medical Oncology, Antwerp University Hospital [Edegem], Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier de L'Ardenne (Libramont), Department of Cardiology [Sivas, Turkey], Cumhuriyet University [Sivas, Turkey], Department of Earth Sciences, Durham University, Department of Oncology, Rigshospitalet [Copenhagen], Odense Hospital, CP Kelco ApS, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Institut de Recherche en Cancérologie de Montpellier ( IRCM - U1194 Inserm - UM ), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Université du Québec à Montréal ( UQAM ), Université Panthéon-Sorbonne ( UP1 ), École nationale supérieure d'architecture de Nantes ( ENSA Nantes ), Department of Hepatogastroenterology and Oncology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France., Hôpital Ambroise Paré, CH Belfort-Montbéliard, Polyclinique Francheville, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Centre Hospitalier de Meaux, Service d'hématologie, Clinique Catherine de Sienne, Unité de recherche sur les Biopolymères, Interactions Assemblages ( BIA ), Institut National de la Recherche Agronomique ( INRA ), Université de la Méditerranée - Aix-Marseille 2, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), CHU Amiens-Picardie, Pôle oncologie médicale, Hôpital des Diaconesses, Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bretagne Occidentale - École de sages-femmes ( UBO UFR MSS ESF ), Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Service Gastro-Entérologie, CHU Besançon, Université de Franche-Comté ( UFC ) -Université de Franche-Comté ( UFC ), Centre Alexis Vautrin ( CAV ), Ecophysiologie Végétale, Agronomie et Nutritions ( EVA ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Recherche Agronomique ( INRA ), Image et ville ( IV ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Département informatique ( INFO ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Agence de l'Environnement et de la Maîtrise de l'Energie - ADEME, Service d'hépato-gastroentérologie, CHU Caen-Hôpital côte de nacre, Département de Médecine, Centre hospitalier de Libourne, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Fondation FondaMental, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Variabilité de réponse aux psychotropes ( VariaPsy - U1144 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ), Département d'oncologie digestive, Institut Bergonié - CRLCC Bordeaux, Hôpital St Joseph, Service de Gynécologie et d'Obstétrique ( CHU Lyon ), Hospices Civils de Lyon ( HCL ), Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 1 ( UM1 ), Service de gastro-entérologie - Hôpital Henri Mondor, Laboratoire Matière et Systèmes Complexes ( Laboratoire MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -UFR de Physique, France, Amériques, Espagne – Sociétés, pouvoirs, acteurs ( FRAMESPA ), Université Toulouse - Jean Jaurès ( UT2J ) -Centre National de la Recherche Scientifique ( CNRS ), Regional Hospital of Orleans, Histoire, Archéologie et littératures des Mondes chrétiens et musulmans médiévaux ( CIHAM ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -École des hautes études en sciences sociales ( EHESS ) -Université Jean Moulin - Lyon III ( UJML ) -Université d'Avignon et des Pays de Vaucluse ( UAPV ) -Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie des signaux intercellulaires ( NSI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Dept Med Genet, Hôpital Erasme (Bruxelles), Polyclinique de Limoges - site François Chénieux [Limoges], Clinique Médicale B, CHU Strasbourg, Service de gastro-entérologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Hôpital Européen [Fondation Ambroise Paré - Marseille], Asklepios Klinikum Uckermark GmbH, DESY, Notkestr 85, D-22607 Hamburg, Germany, NASA Ames Research Center ( ARC ), Department of Chemistry, Center for Structural Biology, Vanderbilt University [Nashville], Biostatistique et Processus Spatiaux ( BIOSP ), Institute of Ecology [Jena], Friedrich-Schiller-Universität Jena, University of Rostock [Germany], Universität Stuttgart [Stuttgart], Oneonta, Zentrum für Innere Medizin, Klinikum Schwäbisch Gmünd/Stauferklinik, Physiopathologie du stress pancréatique, Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, Institut de Mathématiques de Marseille ( I2M ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Science [Freiburg], University of Freiburg [Freiburg], Institut für Mathematik [Berlin], Technische Universität Berlin ( TUB ), Department of Information Engineering, Computer Science and Mathematics, Università degli Studi dell'Aquila [L'Aquila] ( UNIVAQ.IT ), Department of Animal Sciences, North Carolina Agricultural and Technical State University, FEEM, Romagna Cancer Registry, IRST, Luigi Pierantoni Hospital, Observatoire sociologique du changement ( OSC ), Sciences Po-Centre National de la Recherche Scientifique ( CNRS ), Dipartimento di Chimica, Fisica e Ambiente, Università degli Studi di Udine - University of Udine [Italie], Department of Nuclear Medicine, PET/CT Centre, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Clinica di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche [Ancona] ( UNIVPM ), Universidade Nova de Lisboa ( UNINOVA ), Ottawa Hospital Research Institute [Ottawa] ( OHRI ), Oncologia Medica, Ospedali Riuniti, Ospedale 'San Vincenzo', NIPE, CIPES, European Synchrotron Radiation Facility ( ESRF ), Departamento de Engenharia Informática, Faculdade de Engenharia [Porto] ( FEUP ), Universidade do Porto [Porto]-Universidade do Porto [Porto], 3Decide, Unité de recherche Amélioration, Génétique et Physiologie Forestières ( UAGPF ), Universidade Federal de Campina Grande [Campina Grande] ( UFCG ), Instituto de Engenharia de Sistemas e Computadores ( INESC ), Departamento de Ciências Biológicas, Universidade Regional do Cariri ( URCA Brasil ), Department of Biochemistry and Molecular Biology [Barcelona, Spain], Universitat de Barcelona ( UB ), Associated Unit to Consejo Superior de Investigaciones Científicas - CSIC [Barcelona, Spain], University of Barcelona-Institute of Biomedicine - IBUB [Barcelona, Spain], IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau ( CARE ), Institut de recherches sur la catalyse et l'environnement de Lyon ( IRCELYON ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'analyse et d'architecture des systèmes [Toulouse] ( LAAS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Institut National Polytechnique [Toulouse] ( INP ), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Instituto de Ciencia de Materiales de Madrid [Madrid] ( ICMM ), Interactions, Corpus, Apprentissages, Représentations ( ICAR ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique ( CNRS ), Institut d'Investigacions Biomèdiques August Pi i Sunyer ( IDIBAPS ), North Region Cancer Registry of Portugal, UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux ( EPOC ), Observatoire aquitain des sciences de l'univers ( OASU ), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Paediatrics and Intensive Care, Hospital Universitari Sant Joan de Deu, Laboratoire de Psychologie Sociale ( LPS ), Aix Marseille Université ( AMU ), Universitat de València ( UV ), Instituto de Cienca de Materiales de Madrid [Madrid] ( ICMM ), Biology, New Mexico State University, New Mexico State University, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department - Carnegie Mellon University, University of Pittsburgh, Laboratoire de Sciences Actuarielle et Financière ( SAF ), Université de Lyon-Université de Lyon, Instituto de Oncologia Corachan ( IDOC ), Laboratoire d'informatique de l'école normale supérieure ( LIENS ), École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Experimental Quantum Optics and Photonics Group, University of Strathclyde, Institut de recherches Asiatiques ( IrAsia ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Européen de Réalité Virtuelle ( CERV ), École Nationale d'Ingénieurs de Brest ( ENIB ), Sol Agro et hydrosystème Spatialisation ( SAS ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), Centre de recherche cerveau et cognition ( CERCO ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Géomatériaux et Environnement ( LGE ), Université Paris-Est Marne-la-Vallée ( UPEM ), Hôpital Ambroise Paré [AP-HP], Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université de Nantes (UN), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Salzburger Landesklinikum - Uniklinikum Salzburg (SALK), Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Biologie Computationnelle (IBC), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University [Belgium] (UGENT), Antwerp University Hospital [Edegem] (UZA), Hillerød Hospital, Copenhagen University Hospital-Copenhagen University Hospital, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Université Paris 1 Panthéon-Sorbonne (UP1), École nationale supérieure d'architecture de Nantes (ENSA Nantes), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bretagne Occidentale - École de sages-femmes (UBO UFR MSS ESF), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Alexis Vautrin (CAV), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Département informatique (INFO), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Libourne, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation FondaMental [Créteil], Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service de Gynécologie et d'Obstétrique (CHU Lyon), Hospices Civils de Lyon (HCL), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Hôpital privé Toulon Hyères : Sainte Marguerite, Clinique des Quatre Pavillons, Lormont, France, Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), NASA Ames Research Center (ARC), Biostatistique et Processus Spatiaux (BioSP), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], University of Rostock, State University of New York at Oneonta (SUNY Oneonta), State University of New York (SUNY), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Klinikum Deggendorf, Technische Universität Berlin (TU), Università degli Studi dell'Aquila (UNIVAQ), North Carolina A&T State University, University of North Carolina System (UNC)-University of North Carolina System (UNC), Observatoire sociologique du changement (OSC), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Università Politecnica delle Marche [Ancona] (UNIVPM), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ottawa Hospital Research Institute [Ottawa] (OHRI), European Synchrotron Radiation Facility (ESRF), Departamento de Engenharia Informática [Porto], Faculdade de Engenharia da Universidade do Porto (FEUP), Universidade do Porto-Universidade do Porto, Universidade Federal de Campina Grande [Campina Grande] (UFCG), Instituto de Engenharia de Sistemas e Computadores (INESC), Universidade Regional do Cariri (URCA Brasil), Universitat de Barcelona (UB), IRCELYON-Catalytic and Atmospheric Reactivity for the Environment (CARE), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitario de Valme, Anenida de Bellavista s/n, Sevilla 41014, Spain, Hospital Son Llatzer, Universitat de València (UV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hospital Universitari Son Espases, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Instituto de Oncologia Corachan (IDOC), Laboratoire d'informatique de l'école normale supérieure (LIENS), École normale supérieure - Paris (ENS Paris), Institut de recherches Asiatiques (IrAsia), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Sol Agro et hydrosystème Spatialisation (SAS), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Géomatériaux et Environnement (LGE), Université Paris-Est Marne-la-Vallée (UPEM), Fédération Francophone de Cancérologie Digestive (FFCD), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Department of Information Engineering, Computer Science and Mathematics = Dipartimento di Ingegneria e Scienze dell'Informazione e Matematica [L'Aquila] (DISIM), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département d'informatique - ENS Paris (DI-ENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institute of Biomedicine - IBUB [Barcelona, Spain]-University of Barcelona, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Environnement et Agronomie (E.A.)-Biologie et Amélioration des Plantes (BAP)-Fourrages Environnement Ruminants Lusignan (FERLUS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, University of Florence (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Ghent University [Belgium] (UGENT), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université du Québec à Montréal (UQAM), Université Panthéon-Sorbonne (UP1), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Franche-Comté (UFC)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Biostatistique et Processus Spatiaux (BIOSP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Technische Universität Berlin (TUB), Università degli Studi dell'Aquila [L'Aquila] (UNIVAQ.IT), Universidade Nova de Lisboa (NOVA), Faculdade de Engenharia [Porto] (FEUP), Unité de recherche Amélioration, Génétique et Physiologie Forestières (UAGPF), IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau (CARE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Emile, J, Julie, C, Le Malicot, K, Lepage, C, Tabernero, J, Mini, E, Folprecht, G, Van Laethem, J, Dimet, S, Boulagnon-Rombi, C, Allard, M, Penault-Llorca, F, Bennouna, J, Laurent-Puig, P, Taieb, J, Bidoli, P, Emile, J. -F., Julie, C., Le Malicot, K., Lepage, C., Tabernero, J., Mini, E., Folprecht, G., Van Laethem, J. -L., Dimet, S., Boulagnon-Rombi, C., Allard, M. -A., Penault-Llorca, F., Bennouna, J., Laurent-Puig, P., Taieb, J., Thaler, J., Greil, R., Gaenzer, J., Eisterer, W., Tschmelitsch, J., Keil, F., Samonigg, H., Zabernigg, A., Schmid, F., Steger, G., Steinacher, R., Andel, J., Jagdt, B., Lang, A., Fridrik, M., Fugger, R., Hofbauer, F., Woell, E., Geissler, D., Lenauer, A., Prager, M., D'Haens, G., Demolin, G., Kerger, J., Deboever, G., Ghillebert, G., Polus, M., Van Cutsem, E., Kalantari, H. R., Delaunoit, T., Goeminne, J. C., Peeters, M., Vergauwe, P., Houbiers, G., Humblet, Y., Janssens, J., Schrijvers, D., Vanderstraeten, E., Vermorken, J., Van Daele, D., Ferrante, M., Forget, F., Hendlisz, A., Yilmaz, M., Nielsen, S. E., Vestermark, L., Larsen, J., Zawadi, M. -A., Bouche, O., Mineur, L., Bennouna-Louridi, J., Dourthe, L. M., Ychou, M., Boucher, E., Pezet, D., Desseigne, F., Ducreux, M., Texereau, P., Miglianico, L., Rougier, P., Fratte, S., Levache, C. -B., Merrouche, Y., Ellis, S., Locher, C., Ramee, J. -F., Garnier, C., Viret, F., Chauffert, B., Cojean-Zelek, I., Michel, P., Lecaille, C., Borel, C., Seitz, J. -F., Smith, D., Lombard-Bohas, C., Andre, T., Gornet, J. -M., Fein, F., Coulon-Sfairi, M. -A., Kaminsky, M. -C., Lagasse, J. -P., Luet, D., Etienne, P. -L., Gasmi, M., Vanoli, A., Nguyen, S., Aparicio, T., Perrier, H., Stremsdoerfer, N., Laplaige, P., Arsene, D., Auby, D., Bedenne, L., Coriat, R., Denis, B., Geoffroy, P., Piot, G., Becouarn, Y., Bordes, G., Deplanque, G., Dupuis, O., Fruge, F., Guimbaud, R., Lecomte, T., Lledo, G., Sobhani, I., Asnacios, A., Azzedine, A., Desauw, C., Galais, M. -P., Gargot, D., Lam, Y. -H., Abakar-Mahamat, A., Berdah, J. -F., Catteau, S., Clavero-Fabri, M. -C., Codoul, J. -F., Legoux, J. -L., Goldfain, D., Guichard, P., Verge, D. P., Provencal, J., Vedrenne, B., Brezault-Bonnet, C., Cleau, D., Desir, J. -P., Fallik, D., Garcia, B., Gaspard, M. -H., Genet, D., Hartwig, J., Krummel, Y., Budnik, T. M., Palascak-Juif, V., Randrianarivelo, H., Rinaldi, Y., Aleba, A., Darut-Jouve, A., de Gramont, A., Hamon, H., Wendehenne, F., Matzdorff, A., Stahl, M. K., Schepp, W., Burk, M., Mueller, L., Geissler, M., Mantovani-Loeffler, L., Hoehler, T., Asperger, W., Kroening, H., von Weikersthal, L. F., Fuxius, S., Groschek, M., Meiler, J., Trarbach, T., Rauh, J., Ziegenhagen, N., Kretzschmar, A., Graeven, U., Nusch, A., von Wichert, G., Hofheinz, R. -D., Kleber, G., Schmidt, K. -H., Vehling-Kaiser, U., Baum, C., Schuette, J., Haag, G. M., Holtkamp, W., Potenberg, J., Reiber, T., Schliesser, G., Schmoll, H. -J., Schneider-Kappus, W., Abenhardt, W., Denzlinger, C., Henning, J., Marxsen, B., Derigs, H. G., Lambertz, H., Becker-Boost, I., Caca, K., Constantin, C., Decker, T., Eschenburg, H., Gabius, S., Hebart, H., Hoffmeister, A., Horst, H. -A., Kremers, S., Leithaeuser, M., Mueller, S., Wagner, S., Daum, S., Schlegel, F., Stauch, M., Heinemann, V., Maiello, E., Latini, L., Zaniboni, A., Amadori, D., Aprile, G., Barni, S., Mattioli, R., Martoni, A., Passalacqua, R., Nicolini, M., Pasquini, E., Rabbi, C., Aitini, E., Ravaioli, A., Barone, C., Biasco, G., Tamberi, S., Gambi, A., Verusio, C., Marzola, M., Lelli, G., Boni, C., Cascinu, S., Bidoli, P., Vaghi, M., Cruciani, G., Di Costanzo, F., Sobrero, A., Petrioli, R., Aglietta, M., Alabiso, O., Capuzzo, F., Falcone, A., Corsi, D. C., Labianca, R., Salvagni, S., Chiara, S., Ciuffreda, L., Ferrau, F., Giuliani, F., Lonardi, S., Gebbia, N., Mantovani, G., Sanches, E., Mellidez, J. C., Santos, P., Freire, J., Sarmento, C., Costa, L., Pinto, A. M., Barroso, S., Santo, J. E., Guedes, F., Monteiro, A., Sa, A., Furtado, I., Salazar, R., Aguilar, E. A., Herrero, F. R., Valera, J. S., Ayerbes, M. V., Batlle, J. F., Gil, S., Esteve, A. A., Garcia-Giron, C., Vivanco, G. L., Salvia, A. S., Orduna, V. A., Garcia, R. V., Gallego, J., Sureda, B. M., Remon, J., Safont Aguilera, M. J., Nogueras, L. C., Merino, B. Q., Castro, C. G., de Prado, P. M., Pericay, C. P., Figueiras, M. C., Jordan, I. G., Gome Reina, M. J., Garcia, A. L. -L., Garcia-Ramos, A. A., Cervantes, A., Martos, C. F., Gaspar, E. M., Montero, I. C., Emperador, P. E., Carbonero, A. L., Castillo, M. G., Garcia, T. G., Lopez, J. G., Flores, E. G., Morales, M. G., Munoz, M. L., Martin, A. L., Maurel, J., Camara, J. C., Garcia, R. D., Salgado, M., Busquier, I. H., Ruiz, T. C., Munoa, A. L., Aliguer, M. N., de Taranco, A. V. O., Urena, M. M., Gaspa, F. L., Ponce, J. J., Roig, C. B., Jimenez, P. V., Brotons, A. G., Rodriguez, S. A., Martinez, J. A., Ruiz, L. C., Ruiz, M. C., Bridgewater, J., Glynne-Jones, R., Tahir, S., Hickish, T., Cassidy, J., and Samuel, L.
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Medizin, Leucovorin, Prospective cohort study, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, FOLFOX, Organoplatinum Compounds/therapeutic use, Antineoplastic Combined Chemotherapy Protocols, tudy, Lymphocytes, Prospective Studies, Leucovorin/therapeutic use, Middle Aged, Prognosis, 3. Good health, Colorectal carcinoma, Fluorouracil, 030220 oncology & carcinogenesis, Predictive value of tests, Colonic Neoplasms, Biomarker (medicine), Lymphocytes/pathology, Female, Adjuvant, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fluorouracil/therapeutic use, Biomarkers, Tumor/analysis, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Predictive Value of Tests, Biomarker, Immune response, Internal medicine, medicine, Biomarkers, Tumor, Humans, Survival analysis, Aged, business.industry, medicine.disease, Survival Analysis, Surgery, 030104 developmental biology, Prospective cohort&nbsp, Multivariate Analysis, Colonic Neoplasms/diagnosis, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, business
Abstract: IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations of LI with patient recurrence and survival were analysed, and multivariable models were adjusted for treatment and relevant factors. Automated testing of LI was performed on virtual slides without access to clinical data.ResultsAmong the 1220 CC patients enrolled, LI was high, low and not evaluable in 241 (19.8%), 790 (64.8%) and 189 (15.5%), respectively. Primary objective was met with a 2-year recurrence rate of 14.4% versus 21.1% in patients with high and low LI, respectively (p = 0.02). Patients with high LI also had better disease free survival (DFS) and overall survival (OS). Tumour stage, grade, RAS status and BRAF status were with LI the only prognostic markers in multivariable analysis for OS. Subgroup analyses revealed that high LI had better DFS and OS in mismatch repair (MMR) proficient patients, and in patients without RAS mutation, but not in MMR deficient and RAS mutated patients.ConclusionAlthough this is the first validation with high level of evidence (IIB) of the prognostic value of a LI test in colon cancers, it still needs to be confirmed in independent series of colon cancer patients.
Published: 2017

41. An integrated expression atlas of miRNAs and their promoters in human and mouse

Author: de Rie, Yoko, Abugessaisa, Yoko, Alam, Tanvir, Arner, Yoko, Arner, Peter, Ha, Haitham, Aström, Gaby, Babina, Magda, Bertin, Yoko, Burroughs, Yoko, Carlisle, Ailsa, Daub, Yoko, Detmar, Michael, Deviatiiarov, Yoko, Fort, Yoko, Gebhard, Claudia, Goldowitz, Daniel, Guhl, Sven, Ha, Thomas, Harshbarger, Yoko, Hasegawa, Yoko, Hashimoto, Yoko, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly, Hon, Yoko, Huang, Edward, Ishizu, Yoko, Kai, Chieko, Kasukawa, Yoko, Klinken, Peter, Lassmann, Yoko, Lecellier, Charles-Henri, Lee, Weonju, Lizio, Yoko, Makeev, Vsevolod, Mathelier, Anthony, Medvedeva, Yulia, Mejhert, Niklas, Mungall, Christopher, Noma, Yoko, Ohshima, Mitsuhiro, Okada-Hatakeyama, Yoko, Persson, Helena, Rizzu, Patrizia, Roudnicky, Filip, Sætrom, Pål, Sato, Hiroki, Severin, Yoko, Shin, Yoko, Swoboda, Rolf, Tarui, Yoko, Toyoda, Hiroo, Vitting-Seerup, Kristoffer, Winteringham, Louise, Yamaguchi, Yoko, Yasuzawa, Kayoko, Yoneda, Misako, Yumoto, Noriko, Zabierowski, Susan, Zhang, Peter, Wells, Christine, Summers, Kim, Kawaji, Hideya, Sandelin, Albin, Rehli, Michael, Hayashizaki, Yoshihide, Carninci, Piero, Forrest, Alistair, de Hoon, Michiel, de Rie, Derek, Abugessaisa, Imad, Arner, Erik, Ashoor, Haitham, Bertin, Nicolas, Burroughs, A Maxwell, Daub, Carsten, Deviatiiarov, Ruslan, Fort, Alexandre, Ha, Jayson, Ha, Akira, Ha, Kosuke, Hon, Chung Chau, Ishizu, Yuri, Kasukawa, Takeya, Lassmann, Timo, Lizio, Marina, Noma, Shohei, Ha, Mariko, Severin, Jessica, Shin, Jay, Tarui, Hiroshi, Ha, Yoshihide, Computat Biosci Res Ctr, Comp Elect & Math Sci & Engn Div, King Abdullah University of Science and Technology (KAUST), Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Dept Dermatol & Allergy, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Clinical Genetics, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institute of Genetics and Selection of Industrial Microorganisms, GosNIIGenetika, Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Oncology, Lund University [Lund]-Clinical Sciences, RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), University of Copenhagen = Københavns Universitet (KU), Cold Spring Harbor Laboratory, RIKEN Center for Life Science Technologies (RIKEN CLST), Ctr Life Sci Technol, Div Gen Technol, Tsurumi Ku, Karolinska Institutet [Stockholm], Department of Genetic Medicine and Development [Geneva], Université de Genève (UNIGE), Riken Omics Science Center, and Riken Yokohama Institute
Subjects: 0301 basic medicine, FANTOM Consortium, Cells, Biomedical Engineering, Bioengineering, Biology, Applied Microbiology and Biotechnology, Genome, Article, Promoter Regions, 03 medical and health sciences, Mice, Genetic, Transcription (biology), metabolism [MicroRNAs], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Gene expression, Transcriptional regulation, Gene silencing, Animals, Humans, genetics [MicroRNAs], Promoter Regions, Genetic, Cells, Cultured, Gene Library, Genetics, Cultured, Gene Expression Profiling, RNA, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, Gene expression profiling, MicroRNAs, 030104 developmental biology, Good Health and Well Being, genetics [Promoter Regions, Genetic], ddc:660, Molecular Medicine, Generic health relevance, Biotechnology, methods [Gene Expression Profiling]
Abstract: International audience; MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.
Published: 2017

42. Genome-wide linkage screen for testicular germ cell tumour susceptibility loci

Author: D. Timothy Bishop, Radka Lohynska, Robert Huddart, Douglas F. Easton, Ludmila Liubchenko, Katherine L. Nathanson, Michael R. Stratton, Barbara L. Weber, Kelly-Anne Phillips, Parry Guilford, Michael Friedlander, Hans Stoll, Stéphane Richard, Catherine Bonaïti-Pellié, T. Oliver, Wilma Ormiston, Katherine M. Tucker, Mark H. Greene, Joan Kramer, David Forman, Elizabeth A. Rapley, Lawrence H. Einhorn, Gedske Daugaard, Axel Heidenreich, Sergei Tjulandin, Walter P. Weber, Michael A.S. Jewett, David W. Hogg, Sophie D. Fosså, Peter Albers, Rachel Linger, Lajos Géczi, Lola Johnson, Darshna Dudakia, Mary L. McMaster, Ketil Heimdal, István Bodrogi, Victoria K. Cortessis, Edith Olah, Peter A. Daly, Gillian P. Crockford, Agnès Chompret, Sarah Hockley, Kaniewski, Nadine, Genetic Epidemiology Division, Cancer Research UK Clinical Centre, Saint James's University Hospital, Section of Cancer Genetics, Institute of cancer research, Academic Radiotherapy Unit, Dept of Medical Oncology, Division of Medicine, University of New South Wales [Sydney] (UNSW)-Prince of Wales Hospital Randwick, Dept of Haematology and Medical Oncology, Peter MacCallum Cancer Center, Princess Margaret Hospital, University of Toronto, Dept of Radiotherapy and Oncology, University hospital of Prague, Dept of Oncology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Génétique oncologique (GO - UMR 8125), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Service d'urologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Génétique épidémiologique et structures des populations humaines (Inserm U535), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dept of Urological Oncology, Phillips university, Department of Urology, Klinikum Kassel GmbH, Department of Molecular Genetics and Department of Chemotherapy, National Institute of Oncology, Department of Medical Oncology, St James's hospital, Cancer Genetics Laboratory, University of Otago [Dunedin, Nouvelle-Zélande], Departments of Clinical Cancer Research and genetics, Rikshospitalet-Radiumhospitalet Trust, Laboratory of Clinical Genetics, Institute of Clinical Oncology, Medical Oncology, University Hospital Basel [Basel], Cancer Epidemiology, University of Leeds-Cookridge Hospital, Barts and The London Queen Mary's School of Medicine, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Department of Preventive Medicine, Keck School of Medicine [Los Angeles], University of Southern California (USC)-University of Southern California (USC), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), and University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]
Subjects: Male, Genetic Linkage, MESH: Pedigree, Locus (genetics), Pedigree chart, Biology, MESH: Chromosomes, Human, X, Genetic Heterogeneity, 03 medical and health sciences, 0302 clinical medicine, Testicular Neoplasms, Gene mapping, Genetic linkage, Genetics, Genetic predisposition, Humans, Genetic Predisposition to Disease, Molecular Biology, Genetics (clinical), MESH: Genome, Human, 030304 developmental biology, MESH: Testicular Neoplasms, Chromosomes, Human, X, 0303 health sciences, MESH: Humans, Genome, Human, Genetic heterogeneity, MESH: Genetic Heterogeneity, MESH: Genetic Predisposition to Disease, Chromosome Mapping, Family aggregation, General Medicine, Neoplasms, Germ Cell and Embryonal, Human genetics, MESH: Male, Pedigree, 3. Good health, MESH: Lod Score, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, MESH: Neoplasms, Germ Cell and Embryonal, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Lod Score, MESH: Chromosome Mapping, MESH: Female, MESH: Linkage (Genetics)
Abstract: A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the disease.
Published: 2017

43. Targeting Influenza Virus Hemagglutinin to Xcr1(+) Dendritic Cells in the Absence of Receptor-Mediated Endocytosis Enhances Protective Antibody Responses

Author: Even Fossum, Bjarne Bogen, Vibeke Sundvold-Gjerstad, Marc Dalod, Anna Lysén, Arnar Gudjonsson, Espen S. Baekkevold, Sreekumar Balan, Lisa Richter, Catharina Arnold-Schrauf, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Immune Regulation [Oslo] (CIR), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, K.G. Jebsen Centre for Influenza Vaccine Research [Oslo, Norway], University of Oslo (UiO)-Oslo University Hospital [Oslo], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: 0301 basic medicine, Chemokine, biology, T cell, Immunology, Hemagglutinin (influenza), Chemotaxis, Receptor-mediated endocytosis, Virology, 3. Good health, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Immune system, biology.protein, medicine, Immunology and Allergy, [SDV.IMM]Life Sciences [q-bio]/Immunology, CD8, 030215 immunology, XCL1
Abstract: Targeting Ags to conventional dendritic cells can enhance Ag-specific immune responses. Although most studies have focused on the induction of T cell responses, the mechanisms by which targeting improves Ab responses are poorly understood. In this study we present data on the use of human XCL1 (hXCL1) and hXCL2 fusion vaccines in a murine model. We show that the human chemokines bound type 1 conventional dendritic cells (cDC1), and that immunization with influenza virus hemagglutinin fused to hXCL1 or hXCL2 induced full protection against influenza challenge. Surprisingly, the hXCL1- and hXCL2-fusion vaccines induced better long-term protection associated with stronger induction of neutralizing Abs, and more Ab-secreting cells in bone marrow. In contrast, murine Xcl1 fusion vaccines induced stronger CD8+ T cell responses compared with hXCL1. Further analysis revealed that although murine Xcl1 fusion vaccines induced chemotaxis and were rapidly endocytosed by cDC1, hXCL1 and hXCL2 fusion vaccines did not induce chemotaxis, were less efficiently endocytosed, and consequently, remained on the surface. This difference may explain the enhanced induction of Abs when targeting Ag to cDC1 using hXCL1 and hXCL2, and suggests that immune responses can be manipulated in directing Abs or T cells based on how efficiently the targeted Ag is endocytosed by the DC.
Published: 2017

44. Antibody-Directed Glucocorticoid Targeting to CD163 in M2-type Macrophages Attenuates Fructose-Induced Liver Inflammatory Changes

Author: Søren K. Moestrup, Jonas Heilskov Graversen, Erik Ilsø Christensen, Henrik Hager, Holger Jon Møller, Anders Etzerodt, Hendrik Vilstrup, Pia Svendsen, Rasmus Røge, Henning Grønbæk, Department of Pathology, Aarhus University Hospital, Department of Hepatology A, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, and DENARNAUD, Monique
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, lcsh:QH426-470, antibody-drug conjugates, steatohepatitis, Inflammation, dexamethasone, Biology, fructose, 03 medical and health sciences, Ballooning degeneration, 0302 clinical medicine, Fibrosis, Internal medicine, Genetics, medicine, Journal Article, lcsh:QH573-671, Molecular Biology, Dexamethasone, lcsh:Cytology, Fatty liver, medicine.disease, 3. Good health, macrophages, lcsh:Genetics, 030104 developmental biology, Endocrinology, inflammation, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular Medicine, 030211 gastroenterology & hepatology, Original Article, CD163, glucocorticoid, Steatohepatitis, medicine.symptom, Glucocorticoid, medicine.drug
Abstract: Increased consumption of high-caloric carbohydrates contributes substantially to endemic non-alcoholic fatty liver disease in humans, covering a histological spectrum from fatty liver to steatohepatitis. Hypercaloric intake and lipogenetic effects of fructose and endotoxin-driven activation of liver macrophages are suggested to be essential to disease progression. In the present study, we show that a low dose of an anti-CD163-IgG-dexamethasone conjugate targeting the hemoglobin scavenger receptor CD163 in Kupffer cells and other M2-type macrophages has a profound effect on liver inflammatory changes in rats on a high-fructose diet. The diet induced severe non-alcoholic steatohepatitis (NASH)-like changes within a few weeks but the antibody-drug conjugate strongly reduced inflammation, hepatocyte ballooning, fibrosis, and glycogen deposition. Non-conjugated dexamethasone or dexamethasone conjugated to a control IgG did not have this effect but instead exacerbated liver lipid accumulation. The low-dose anti-CD163-IgG-dexamethasone conjugate displayed no apparent systemic side effects. In conclusion, macrophage targeting by antibody-directed anti-inflammatory low-dose glucocorticoid therapy seems to be a promising approach for safe treatment of fructose-induced liver inflammation.
Published: 2017

45. Delineation of the 3p14.1p13 microdeletion associated with syndromic distal limb contractures

Author: Michel Francoise, Patrick Callier, Steven A. Vokes, Susanne Kjaergaard, Laurence Duplomb, Thomas Lee Dahm, Julien Thevenon, Nicole Monnier, Marie Hélène Aubriot-Lorton, Frédéric Huet, Tara Montgomery, Haley O. Tucker, Clémence Ragon, Nathalie Marle, Katherine Neas, Francine Mugneret, Pierre-Simon Jouk, Joël Lunardi, Klaus Dieterich, Laurence Faivre, Christel Thauvin-Robinet, Anne Laure Mosca-Boidron, Joanne Dixon, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Laboratoire de cytogénétique (CHU de Dijon), Centre de génétique et Centre de référence maladies rares et anomalies du développement et syndromes malformatifs du Centre Est, Département de Génétique et Procréation UF-Hôpital Couple Enfant de Grenoble-CHU Grenoble, Service de pédiatrie, Centre Hospitalier Wiliam Morey, Northern Genetics Service, Newcastle University [Newcastle], Department of Clinical Genetic, Rigshospitalet [Copenhagen], Central and Southern Regional Genetic Services, Wellington Hospital Private, Department of Pediatrics, Nordsjællands Hospital - Hillerød, Service de pédiatrie (CHU de Dijon), Service de Pathologie [CHU de Dijon], Section of Molecular Cell & Developmental Biology, Institute for Cellular and Molecular Biology-University of Texas at Austin [Austin], Graduate Program in Cell and Molecular Biology, University of Texas at Austin [Austin], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre Hospitalier Chalon-sur-Saône William Morey, Department of Clinical Genetics [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University of Texas at Austin [Austin]- Institute for Cellular and Molecular Biology, and Roux-Buisson, Nathalie
Subjects: Male, Pathology, medicine.medical_specialty, Contracture, [SDV]Life Sciences [q-bio], Locus (genetics), FOXP1, Biology, Mice, distal limb contractures, symbols.namesake, Exon, EIF4E3, Intellectual disability, Genetics, medicine, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 3p141p13 microdeletion, Genetics (clinical), Arthrogryposis, Chromosome Aberrations, Mice, Knockout, Sanger sequencing, Comparative Genomic Hybridization, [ SDV ] Life Sciences [q-bio], Extremities, Forkhead Transcription Factors, Syndrome, Microdeletion syndrome, medicine.disease, Blepharophimosis, Phenotype, Repressor Proteins, [SDV] Life Sciences [q-bio], array-CGH, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], symbols, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Chromosomes, Human, Pair 3, France, Carrier Proteins, intronic regulatory sequence
Abstract: International audience; Distal limb contractures (DLC) represent a heterogeneous clinical and genetic condition. Overall, 20–25% of the DLC are caused by mutations in genes encoding the muscle contractile apparatus. Large interstitial deletions of the 3p have already been diagnosed by standard chromosomal analysis, but not associated with a specific phenotype. We report on four patients with syndromic DLC presenting with a de novo 3p14.1p13 micro-deletion. The clinical features associated multiple contractures, feeding problems, developmental delay, and intellectual disability. Facial dysmorphism was constant with low-set posteriorly rotated ears and blepharophimosis. Review of previously reported cases with a precise mapping of the deletions, documented a 250 kb smallest region of overlap (SRO) necessary for DLC. This region contained one gene, EIF4E3, the first three exons of the FOXP1 gene, and an intronic enhancer of FOXP1 named hs1149. Sanger sequencing and locus quantification of hs1149, EIF4E3, and FOXP1 in a cohort of 11 French patients affected by DLC appeared normal. In conclusion, we delineate a new microdeletion syndrome involving the 3p14.1p13 locus and associated with DLC and severe developmental delay.
Published: 2014

46. A systematic literature review of evidence-based clinical practice for rare diseases: what are the perceived and real barriers for improving the evidence and how can they be overcome?

Author: Valérie Salamon, Jacques Demotes-Mainard, Ana Rath, Martine Laville, Rita Banzi, Vittorio Bertele, Michaela Eikermann, Silvio Garattini, Snezana Djurisic, Sandra Peixoto, Virginie Hivert, Christian Gluud, Janus Christian Jakobsen, Berenice Segrestin, Edmund Neugebauer, Christine Kubiak, Jørn Wetterslev, Plateforme d'information et de services pour les maladies rares et les médicaments orphelins (Orphanet), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Broussais-Institut National de la Santé et de la Recherche Médicale (INSERM), EURORDIS-Rare Diseases Europe (Bureau de Paris), EURORDIS - Plateforme Maladies Rares [Paris], Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Brandenburg Medical School [Witten, Germany], Witten/Herdecke University, Institute for Research in Operative Medicine [Cologne, Germany], Universität Witten - Herdecke [Germany], IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri' [Milan, Italy], Copenhagen Trial Unit -CTU [Copenhagen, Denmark] (Centre for Clinical Intervention Research), Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital-Copenhagen University Hospital, Department of Cardiology [Holbæek, Denmark], Holbæk Hospital [Denmark], European Clinical Research Infrastructures Network [Paris] (ECRIN), Ecrin, European Project: 284395,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2011-1,ECRIN-IA(2012), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Broussais-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Rigshospitalet [Copenhagen]-Copenhagen University Hospital, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), BMC, BMC, European Clinical Research Infrastructures Network - Integrating Activity - ECRIN-IA - - EC:FP7:INFRA2012-01-01 - 2017-12-31 - 284395 - VALID, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Research design, Pathology, medicine.medical_specialty, Evidence-based medicine, Evidence-based practice, Databases, Factual, International Cooperation, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Context (language use), Review, Assessment, Health informatics, Evidence-based clinical practice, 03 medical and health sciences, 0302 clinical medicine, Stakeholder Participation, medicine, Humans, Multicenter Studies as Topic, Pharmacology (medical), 030212 general & internal medicine, Registries, Medical education, lcsh:R5-920, Clinical Trials as Topic, Specific barriers, business.industry, Clinical study design, Patient Selection, ECRIN, Randomised clinical trials, 3. Good health, Rare diseases, [SDV] Life Sciences [q-bio], Clinical research, Systematic review, Research Design, business, lcsh:Medicine (General), 030217 neurology & neurosurgery, European Clinical Infrastructure Networks
Abstract: Background Evidence-based clinical practice is challenging in all fields, but poses special barriers in the field of rare diseases. The present paper summarises the main barriers faced by clinical research in rare diseases, and highlights opportunities for improvement. Methods Systematic literature searches without meta-analyses and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. Results Barriers specific to rare diseases comprise the difficulty to recruit participants because of rarity, scattering of patients, limited knowledge on natural history of diseases, difficulties to achieve accurate diagnosis and identify patients in health information systems, and difficulties choosing clinically relevant outcomes. Conclusions Evidence-based clinical practice for rare diseases should start by collecting clinical data in databases and registries; defining measurable patient-centred outcomes; and selecting appropriate study designs adapted to small study populations. Rare diseases constitute one of the most paradigmatic fields in which multi-stakeholder engagement, especially from patients, is needed for success. Clinical research infrastructures and expertise networks offer opportunities for establishing evidence-based clinical practice within rare diseases. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2287-7) contains supplementary material, which is available to authorized users.
Published: 2016

47. A map of direct TF–DNA interactions in the human genome

Author: Benoit Ballester, Aziz Khan, Anthony Mathelier, Jeanne Chèneby, Marius Gheorghe, Geir Kjetil Sandve, Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Informatics [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Institute for Cancer Research [Oslo], Oslo University Hospital [Oslo], and Spinelli, Lionel
Subjects: Chromatin Immunoprecipitation, ChIP-eat software, Interaction, Sequence analysis, [SDV]Life Sciences [q-bio], genetic processes, ReMap database, Single-nucleotide polymorphism, Plasma protein binding, Computational biology, Biology, Genome, chemistry.chemical_compound, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Humans, natural sciences, Transcription factor, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Binding Sites, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Human genome, Genome, Human, UniBind, Protein interaction, Chromosome Mapping, Computational Biology, High-Throughput Nucleotide Sequencing, DNA, Sequence Analysis, DNA, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV] Life Sciences [q-bio], chemistry, 030220 oncology & carcinogenesis, Methods Online, Corrigendum, Chromatin immunoprecipitation, Algorithms, 030217 neurology & neurosurgery, Protein Binding, Transcription Factors
Abstract: Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is the most popular assay to identify genomic regions, called ChIP-seq peaks, that are bound in vivo by transcription factors (TFs). These regions are derived from direct TF–DNA interactions, indirect binding of the TF to the DNA (through a co-binding partner), nonspecific binding to the DNA, and noise/bias/artifacts. Delineating the bona fide direct TF–DNA interactions within the ChIP-seq peaks remains challenging. We developed a dedicated software, ChIP-eat, that combines computational TF binding models and ChIP-seq peaks to automatically predict direct TF–DNA interactions. Our work culminated with predicted interactions covering >2% of the human genome, obtained by uniformly processing 1983 ChIP-seq peak data sets from the ReMap database for 232 unique TFs. The predictions were a posteriori assessed using protein binding microarray and ChIP-exo data, and were predominantly found in high quality ChIP-seq peaks. The set of predicted direct TF–DNA interactions suggested that high-occupancy target regions are likely not derived from direct binding of the TFs to the DNA. Our predictions derived co-binding TFs supported by protein-protein interaction data and defined cis-regulatory modules enriched for disease- and trait-associated SNPs. We provide this collection of direct TF–DNA interactions and cis-regulatory modules through the UniBind web-interface (http://unibind.uio.no).
Published: 2019

48. SCRIB and PUF60 Are Primary Drivers of the Multisystemic Phenotypes of the 8q24.3 Copy-Number Variant

Author: Jacques S. Beckmann, Christelle Golzio, Nicholas Katsanis, Andrew Dauber, Małgorzata J.M. Nowaczyk, Susan Zeesman, Joel N. Hirschhorn, Francine M. Jodelka, Jill A. Rosenfeld, Danielle Martinet, Bruno Leheup, Cécile Guenot, Michelle L. Hastings, Susanne Kjaergaard, Sébastien Jacquemont, Janice Zunich, Maria Kibaek, UL, NGERE, Division of Endocrinology, Children's Hospital Boston, Harvard Medical School, Harvard Medical School [Boston] (HMS), Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Center for Human Disease Modeling, Duke University [Durham], Service de Génétique Médicale [CHUV Lausanne], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Service de Génétique Clinique [CHUV Lausanne], Department of Cell Biology and Anatomy [Chicago Medical School · Rosalind Franklin University], Chicago Medical School [Rosalind Franklin University], Rosalind Franklin University-Rosalind Franklin University, Department of Pediatrics [Odense University Hospital], Odense University Hospital, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Service de Génétique Médicale [CHRU Nancy], 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), McMaster University [Hamilton, Ontario], PerkinElmer, Inc., Indiana University School of Medicine, Indiana University System-Indiana University System, and Dept of Genetics, Harvard Medical School
Subjects: Male, Microcephaly, Developmental Disabilities, [SDV]Life Sciences [q-bio], medicine.disease_cause, 0302 clinical medicine, Genetics(clinical), Copy-number variation, Child, Zebrafish, Genetics (clinical), Genetics, 0303 health sciences, Mutation, Chromosome Mapping, RNA-Binding Proteins, Phenotype, [SDV] Life Sciences [q-bio], Child, Preschool, Gene Knockdown Techniques, RNA splicing, Female, RNA Splicing Factors, Erratum, Chromosomes, Human, Pair 8, SCRIB, Adolescent, DNA Copy Number Variations, Biology, Article, 03 medical and health sciences, Intellectual Disability, medicine, Animals, Humans, Allele, Alleles, 030304 developmental biology, Tumor Suppressor Proteins, Membrane Proteins, medicine.disease, Human genetics, Genetic architecture, Repressor Proteins, Gene Deletion, 030217 neurology & neurosurgery, HeLa Cells
Abstract: International audience; Copy-number variants (CNVs) represent a significant interpretative challenge, given that each CNV typically affects the dosage of multiple genes. Here we report on five individuals with coloboma, microcephaly, developmental delay, short stature, and craniofacial, cardiac, and renal defects who harbor overlapping microdeletions on 8q24.3. Fine mapping localized a commonly deleted 78 kb region that contains three genes: SCRIB, NRBP2, and PUF60. In vivo dissection of the CNV showed discrete contributions of the planar cell polarity effector SCRIB and the splicing factor PUF60 to the syndromic phenotype, and the combinatorial suppression of both genes exacerbated some, but not all, phenotypic components. Consistent with these findings, we identified an individual with microcephaly, short stature, intellectual disability, and heart defects with a de novo c.505C>T variant leading to a p.His169Tyr change in PUF60. Functional testing of this allele in vivo and in vitro showed that the mutation perturbs the relative dosage of two PUF60 isoforms and, subsequently, the splicing efficiency of downstream PUF60 targets. These data inform the functions of two genes not associated previously with human genetic disease and demonstrate how CNVs can exhibit complex genetic architecture, with the phenotype being the amalgam of both discrete dosage dysfunction of single transcripts and also of binary genetic interactions.
Published: 2013

49. The Kinase PKCα Selectively Upregulates Interleukin-17A during Th17 Cell Immune Responses

Author: Meisel, Marlies, Hermann-Kleiter, Natascha, Hinterleitner, Reinhard, Gruber, Thomas, Wachowicz, Katarzyna, Pfeifhofer-Obermair, Christa, Fresser, Friedrich, Leitges, Michael, Soldani, Cristiana, Viola, Antonella, Kaminski, Sandra, Baier, Gottfried, Experimental Cell Genetics, Department for Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Austria., Biotechnology center of Oslo, Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Istituto Clinico Humanitas [Milan] (IRCCS Milan), and Humanitas University [Milan] (Hunimed)
Subjects: Encephalomyelitis, Autoimmune, Experimental, Protein Kinase C-alpha, Knockout, Immunology, Smad Proteins, Article, Substrate Specificity, Experimental, Mice, Transforming Growth Factor beta, Receptors, Immunology and Allergy, Animals, Encephalomyelitis, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Interleukin-17, Peptide Fragments, Gene Expression Regulation, Myelin-Oligodendrocyte Glycoprotein, Receptors, Transforming Growth Factor beta, Signal Transduction, Th17 Cells, Infectious Diseases, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Autoimmune
Abstract: Summary Transforming growth-factor β (TGFβ) has been implicated in T helper 17 (Th17) cell biology and in triggering expression of interleukin-17A (IL-17A), which is a key Th17 cell cytokine. Deregulated TGFβ receptor (TGFβR) signaling has been implicated in Th17-cell-mediated autoimmune pathogenesis. Nevertheless, the full molecular mechanisms involved in the activation of the TGFβR pathway in driving IL-17A expression remain unknown. Here, we identified protein kinase C α (PKCα) as a signaling intermediate specific to the Th17 cell subset in the activation of TGFβRI. We have shown that PKCα physically interacts and functionally cooperates with TGFβRI to promote robust SMAD2-3 activation. Furthermore, PKCα-deficient (Prkca−/−) cells demonstrated a defect in SMAD-dependent IL-2 suppression, as well as decreased STAT3 DNA binding within the Il17a promoter. Consistently, Prkca−/− cells failed to mount appropriate IL-17A, but not IL-17F, responses in vitro and were resistant to induction of Th17-cell-dependent experimental autoimmune encephalomyelitis in vivo., Graphical Abstract Highlights PKCα-deficient mice are resistant to EAE induction ► PKCα function is specific to the Th17 cell subset ► PKCα is a positive regulator of IL-17A transcription ► PKCα directly regulates TGFβRI-mediated phosphorylation of SMAD2-3
Published: 2013

50. Nomogram-based prediction of overall survival in patients with metastatic urothelial carcinoma receiving first-line platinum-based chemotherapy: Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC)

Author: Salvatore Lo Vullo, Günter Niegisch, Yu-Ning Wong, Jack Baniel, Sylvain Ladoire, Luigi Mariani, Lauren C. Harshman, Ugo De Giorgi, Daniel W. Bowles, Simon J. Crabb, Sumanta K. Pal, Rafael Morales-Barrera, Guru Sonpavde, Thomas Powles, Andrea Necchi, Christine Theodore, Ajjai Alva, Jonathan E. Rosenberg, Joaquim Bellmunt, Linda Cerbone, Simon Chowdhury, Ulka N. Vaishampayan, Cora N. Sternberg, Evan Y. Yu, Neeraj Agarwal, Aristotelis Bamias, Dominik Berthold, Matthew D. Galsky, Gedske Daugaard, Daniele Giardiello, Ali Reza Golshayan, Matthew I. Milowsky, Sandy Srinivas, Srikala S. Sridhar, Necchi, A, Sonpavde, G, Lo Vullo, S, Giardiello, D, Bamias, A, Crabb, Sj, Harshman, Lc, Bellmunt, J, De Giorgi, U, Sternberg, Cn, Cerbone, L, Ladoire, S, Wong, Yn, Yu, Ey, Chowdhury, S, Niegisch, G, Srinivas, S, Vaishampayan, Un, Pal, Sk, Agarwal, N, Alva, A, Baniel, J, Golshayan, Ar, Morales-Barrera, R, Bowles, Dw, Milowsky, Mi, Theodore, C, Berthold, Dr, Daugaard, G, Sridhar, S, Powles, T, Rosenberg, Je, Galsky, Md, Mariani, L, Fondazione IRCCS Istituto Nazionale dei Tumori, UAB Comprehensive Cancer Center UAB Comprehensive Cancer Center [Birmingham, AL, USA], University of Alabama at Birmingham [ Birmingham] (UAB), National and Kapodistrian University of Athens (NKUA), University of Southampton, Dana-Farber Cancer Institute [Boston], Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), San Camillo Forlanini Hospital [Rome], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Fox Chase Cancer Center, University of Washington [Seattle], Guy's and St Thomas' Hospital [London], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Karmanos Cancer Institute, City of Hope Comprehensive Cancer Center [Duarte], University of Utah School of Medicine [Salt Lake City], University of Michigan [Ann Arbor], University of Michigan System, Rabin Medical Center - Beilinson and Hasharon Hospitals [Petach-Tikva, Israel], Medical University of South Carolina [Charleston] (MUSC), Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Service d'Oncologie Médicale, Service d'Oncologie Médicale, Hôpital Foch, Suresnes, Dept of Oncology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Barts & The London School of Medicine, Memorial Sloane Kettering Cancer Center [New York], and Icahn School of Medicine at Mount Sinai [New York] (MSSM)
Subjects: Oncology, Male, medicine.medical_specialty, Urologic Neoplasms, Metastatic Urothelial Carcinoma, Internationality, Urology, Population, 030232 urology & nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Nomogram, Article, Carboplatin, 03 medical and health sciences, chemistry.chemical_compound, Random Allocation, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Overall survival, education, Survival analysis, Aged, Retrospective Studies, 2. Zero hunger, education.field_of_study, Carcinoma, Transitional Cell, Performance status, business.industry, Proportional hazards model, Combination chemotherapy, Middle Aged, Prognosis, Survival Analysis, 3. Good health, Platinum chemotherapy, Nomograms, chemistry, 030220 oncology & carcinogenesis, Urothelial carcinoma, Female, Cisplatin, business
Abstract: IF 16.265; International audience; BACKGROUND:The available prognostic models for overall survival (OS) in patients with metastatic urothelial carcinoma (UC) have been derived from clinical trial populations of cisplatin-treated patients.OBJECTIVE:To develop a new model based on real-world patients.DESIGN, SETTING, AND PARTICIPANTS:Individual patient-level data from 29 centers were collected, including metastatic UC and first-line cisplatin- or carboplatin-based chemotherapy administered between January 2006 and January 2011.INTERVENTION:First-line, platinum-based, combination chemotherapy.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The population was randomly split into a development and a validation cohort. Generalized boosted regression modelling was used to screen out irrelevant variables and address multivariable analyses. Two nomograms were built to estimate OS probability, the first based on baseline factors and platinum agent, the second incorporating objective response (OR). The performance of the above nomograms and that of other available models was assessed. We plotted decision curves to evaluate the clinical usefulness of the two nomograms.RESULTS AND LIMITATIONS:A total of 1020 patients were analyzed (development: 687, validation: 333). In a platinum-stratified Cox model, significant variables for OS were performance status (p
Published: 2016

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

142 results on '"Copenhagen University Hospital-Copenhagen University Hospital"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources