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114 results on '"Mount Sinai Hospital [Toronto, Canada] (MSH)"'

1. Hot topics in the mechanisms of pulmonary arterial hypertension disease: cancer-like pathobiology, the role of the adventitia, systemic involvement, and right ventricular failure

Author: Marlene Rabinovitch, Wolfgang M. Kuebler, Brian B. Graham, Norbert F. Voelkel, Grazyna Kwapiszewska, Elena A. Goncharova, Soni Savai Pullamsetti, Christophe Guignabert, Kurt R. Stenmark, Edda Spiekerkoetter, Harm Jan Bogaard, Division of Pulmonary and Critical Care Medicine [Stanford, CA, USA] (Cardiovascular Institute), Stanford University-Stanford Cardiovascular Institute-Wall Center for Pulmonary Vascular Disease [Stanford, CA, USA], Division of Pulmonary, Allergy and Critical Care Medicine [Pittsburgh, PA, États-Unis], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Department of Bioengineering [Pittsburgh, PA, USA], University of Pittsburgh (PITT), Université Paris-Saclay, Université Paris-Sud [Le Kremlin-Bicêtre] (Faculté de Médecine), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre chirurgical Marie Lannelongue, Department of Pediatrics [Denver, CO, USA] (School of Medicine), University of Colorado [Denver], Cardio Vascular Pulmonary Research Lab [Denver, CO, USA], Ludwig Boltzmann Institute for Lung Vascular Research [Graz], Stanford Cardiovascular Institute, Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), VU University Medical Center [Amsterdam], Pulmonary Sciences and Critical Care [Denver, CO, USA] (School of Medicine), Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, University of Giessen and Marburg Lung Center (UGMLC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Keenan Research Centre for Biomedical Science [Toronto, ON, Canada], Li Ka Shing Knowledge Institute [Toronto, ON, Canada]-St. Michael’s Hopsital [Toronto, ON, Canada], Department of Surgery [Toronto, ON, Canada], University of Toronto, Department of Physiology [Toronto, ON, Canada], Université de Toronto [Canada]-Mount Sinai Hospital [Toronto, Canada] (MSH)-Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], ES: NHLBI R01 HL128734, Department of Defense PR161256, Wall Center for Pulmonary Vascular Disease Stanford, Pulmonary Hypertension Association Career Development Grant. EAG: NIH/NHLBI R01HL130261, 2R01HL113178. CG: ANR-16-CE17-0014 (TAMIRAH), National Agency for Research (ANR), DEQ20150331712 (Equipe FRM 2015), Fondation de la Recherche Me´dicale (FRM), De´partement HospitaloUniversitaire Thorax Innovation (TORINO), Fonds de Dotation Recherche en Sante´ Respiratoire–(FRSR)–Fondation du Souffle (FdS), French Pulmonary Hypertension Association (HTAP France). KS: NIH/NHLBI: PPG P01 HL014985, 1R01HL125827, and DoD PR140977. GK: FWF P27848. MR: R01 HL074186, R01 HL087118, R01 HL122887, R01 HL138473, P01 HL108797, R24 HL123767, K12 HL120001. NV: none. HJB: Dutch Cardiovascular Alliance, PHAEDRA-IMPACT Consortium. BG: NHLBI P01HL014985, R03HL133306, and R01HL135872. SSP: The Max Planck Society, DFG, SFB 1213 (Project A01, A05), and the Excellence Cluster 147 CardioPulmonary System (ECCPS, EXC 147). WMK: HSFC G-16-00013171, DFG KU1218/9-1, DZHK, DZL, and ORF SCORR (RE07-086)., ANR-16-CE17-0014,TAMIRAH,Cibler l'activation anormale du récepteur des minéralocorticoïdes dans l'Hypertension Artérielle Pulmonaire : Une étude translationnelle vers un traitement(2016), Guignabert, Christophe, Cibler l'activation anormale du récepteur des minéralocorticoïdes dans l'Hypertension Artérielle Pulmonaire : Une étude translationnelle vers un traitement - - TAMIRAH2016 - ANR-16-CE17-0014 - AAPG2016 - VALID, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Toronto-Mount Sinai Hospital [Toronto, Canada] (MSH)-Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], Pulmonary medicine, and ACS - Pulmonary hypertension & thrombosis
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Neointima, medicine.medical_specialty, Systemic disease, lcsh:Diseases of the circulatory (Cardiovascular) system, vascular remodeling, [SDV]Life Sciences [q-bio], Disease, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 030204 cardiovascular system & hematology, Cardiorespiratory Medicine and Haematology, Cardiovascular, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Adventitia, right ventricle function and dysfunction, Medicine, 2.1 Biological and endogenous factors, Aetiology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Lung, lcsh:RC705-779, business.industry, Cancer, lcsh:Diseases of the respiratory system, Leading Edge Science, medicine.disease, experimental pulmonary hypertension, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Hot topics, Ventricle, lcsh:RC666-701, Cardiology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Right ventricular failure, Pro-Con debate, business
Abstract: International audience; In order to intervene appropriately and develop disease-modifying therapeutics for pulmonary arterial hypertension, it is crucial to understand the mechanisms of disease pathogenesis and progression. We herein discuss four topics of disease mechanisms that are currently highly debated, yet still unsolved, in the field of pulmonary arterial hypertension. Is pulmonary arterial hypertension a cancer-like disease? Does the adventitia play an important role in the initiation of pulmonary vascular remodeling? Is pulmonary arterial hypertension a systemic disease? Does capillary loss drive right ventricular failure? While pulmonary arterial hypertension does not replicate all features of cancer, anti-proliferative cancer therapeutics might still be beneficial in pulmonary arterial hypertension if monitored for safety and tolerability. It was recognized that the adventitia as a cell-rich compartment is important in the disease pathogenesis of pulmonary arterial hypertension and should be a therapeutic target, albeit the data are inconclusive as to whether the adventitia is involved in the initiation of neointima formation. There was agreement that systemic diseases can lead to pulmonary arterial hypertension and that pulmonary arterial hypertension can have systemic effects related to the advanced lung pathology, yet there was less agreement on whether idiopathic pulmonary arterial hypertension is a systemic disease per se. Despite acknowledging the limitations of exactly assessing vascular density in the right ventricle, it was recognized that the failing right ventricle may show inadequate vascular adaptation resulting in inadequate delivery of oxygen and other metabolites. Although the debate was not meant to result in a definite resolution of the specific arguments, it sparked ideas about how we might resolve the discrepancies by improving our disease modeling (rodent models, large-animal studies, studies of human cells, tissues, and organs) as well as standardization of the models. Novel experimental approaches, such as lineage tracing and better three-dimensional imaging of experimental as well as human lung and heart tissues, might unravel how different cells contribute to the disease pathology.
Published: 2019

2. Synaptoimmunology - roles in health and disease

Author: Robert Nisticò, Graham L. Collingridge, Dalila Mango, Celine S Nicolas, Zuner A. Bortolotto, Pierre Gressens, Stéphane Peineau, Eric W Salter, Marco Feligioni, Department of Biology [Rome, Italy], Università degli Studi di Roma Tor Vergata [Roma], Pharmacology of Synaptic Disease Lab [Rome, Italy], European Brain Research Institute [Rome, Italy] (EBRI), Department of Physiology [Toronto, ON, Canada], Mount Sinai Hospital [Toronto, Canada] (MSH)-Lunenfeld-Tanenbaum Research Institute [Toronto, Canada]-Université de Toronto [Canada], Centre for Synaptic Plasticity [Bristol, UK] (School of Physiology, Pharmacology & Neuroscience), University of Bristol [Bristol], Centre for the Developing Brain [London], King‘s College London-St Thomas' Hospital [London], Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM ERi 24 - GRAP, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), SP is supported by Medical Research Coucil (MR/K023098/1) and is holder of the chair of excellence 'Synaptic Plasticity' funded by Région Hauts de France., Université de Toronto [Canada]-Mount Sinai Hospital [Toronto, Canada] (MSH)-Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], BMC, BMC, University of Toronto-Mount Sinai Hospital [Toronto, Canada] (MSH)-Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], and Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Nervous system, medicine.medical_specialty, Neurology, [SDV]Life Sciences [q-bio], Review, Disease, Biology, Models, Biological, Synaptic Transmission, Synaptic plasticity, lcsh:RC346-429, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Immune system, Neuroinflammation, medicine, Animals, Humans, Microglia, Molecular Biology, lcsh:Neurology. Diseases of the nervous system, Brain Diseases, Settore BIO/14, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Health, Synapses, Psychopharmacology, Neuroscience, 030217 neurology & neurosurgery, Signal Transduction
Abstract: International audience; AbstractMounting evidence suggests that the nervous and immune systems are intricately linked. Many proteins first identified in the immune system have since been detected at synapses, playing different roles in normal and pathological situations. In addition, novel immunological functions are emerging for proteins typically expressed at synapses. Under normal conditions, release of inflammatory mediators generally represents an adaptive and regulated response of the brain to immune signals. On the other hand, when immune challenge becomes prolonged and/or uncontrolled, the consequent inflammatory response leads to maladaptive synaptic plasticity and brain disorders. In this review, we will first provide a summary of the cell signaling pathways in neurons and immune cells. We will then examine how immunological mechanisms might influence synaptic function, and in particular synaptic plasticity, in the healthy and pathological CNS. A better understanding of neuro-immune system interactions in brain circuitries relevant to neuropsychiatric and neurological disorders should provide specific biomarkers to measure the status of the neuroimmunological response and help design novel neuroimmune-targeted therapeutics.
Published: 2017

3. A 3D culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction

Author: Ben Mulcahy, Molly S. Shoichet, Howard J. Ginsberg, Hubrecht van den Dorpel, Christine T Nguyen, Mei Zhen, Tobias Fuehrmann, Elena Pegoraro, Bryan A. Stewart, Anne Bigot, Mohsen Afshar Bakooshli, Nisha Iyer, Randolph S. Ashton, Kayee Tung, Penney M. Gilbert, Henry Ahn, Ethan S. Lippmann, Donnelly Centre [Toronto, ON, Canada], University of Toronto, Institute of Biomaterials and Biomedical Engineering [Toronto, ON, Canada] (IBBME), Department of Biomedical Engineering [Madison, WI, USA], University of Wisconsin-Madison, Wisconsin Institute for Discovery [Madison], Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], Department of Cell and Systems Biology [Toronto, ON, Canada], Department of Surgery [Toronto, ON, Canada], Department of Biology [Mississauga, ON, Canada], University of Toronto at Mississauga, Department of Pharmaceutics [Utrecht, Netherlands] (UIPS), Utrecht University [Utrecht], Department of Chemical Engineering and Applied Chemistry (CHEM ENG), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Universita degli Studi di Padova, Department of Neurosciences [Padova, Italy], University of Padova [Padova, Italy], Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Department of Physiology [Toronto, ON, Canada], Université de Toronto [Canada]-Mount Sinai Hospital [Toronto, Canada] (MSH)-Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], Department of Molecular Genetics [Toronto], Department of Biochemistry [University of Toronto], Gestionnaire, HAL Sorbonne Université 5, Università degli Studi di Padova = University of Padua (Unipd), University of Toronto-Mount Sinai Hospital [Toronto, Canada] (MSH)-Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], and Centre de Recherche en Myologie
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], 0302 clinical medicine, Biology (General), Motor Neurons, neuromuscular junction, General Neuroscience, Skeletal, General Medicine, 3D co-culture, Stem Cells and Regenerative Medicine, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Muscle, Medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Stem cell, Research Article, Human, QH301-705.5, Science, regenerative medicine, acetylcholine receptor subunit epsilon, developmental biology, human, motor neuron, myasthenia gravis, skeletal muscle, stem cells, Coculture Techniques, Humans, Muscle Cells, Muscle, Skeletal, Neuromuscular Junction, Organ Culture Techniques, Biology, General Biochemistry, Genetics and Molecular Biology, Neuromuscular junction, 03 medical and health sciences, Calcium imaging, medicine, Acetylcholine receptor, [SDV.IB] Life Sciences [q-bio]/Bioengineering, General Immunology and Microbiology, Skeletal muscle, Motor neuron, medicine.disease, Myasthenia gravis, Electrophysiology, 030104 developmental biology, Neuroscience, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; Two-dimensional (2D) human skeletal muscle fiber cultures are ill-equipped to support the contractile properties of maturing muscle fibers. This limits their application to the study of adult human neuromuscular junction (NMJ) development, a process requiring maturation of muscle fibers in the presence of motor neuron endplates. Here we describe a three-dimensional (3D) co-culture method whereby human muscle progenitors mixed with human pluripotent stem cell-derived motor neurons self-organize to form functional NMJ connections. Functional connectivity between motor neuron endplates and muscle fibers is confirmed with calcium imaging and electrophysiological recordings. Notably, we only observed epsilon acetylcholine receptor subunit protein upregulation and activity in 3D co-cultures. Further, 3D co-culture treatments with myasthenia gravis patient sera shows the ease of studying human disease with the system. Hence, this work offers a simple method to model and evaluate adult human NMJ de novo development or disease in culture.
Published: 2019

4. Physiological and Pharmacological Mechanisms through which the DPP-4 Inhibitor Sitagliptin Regulates Glycemia in Mice

Author: Pierre Cattan, Julien Castel, Rémy Burcelin, Aurélie Waget, Daniel J. Drucker, Mattieu Armanet, Melis Karaca, Christophe Magnan, Jens J. Holst, Céline Garret, Thierry Sulpice, Gaëlle Payros, Myriam Masseboeuf, Adriano Maida, Cendrine Cabou, Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Cell Therapy Unit, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Biologie Fonctionnelle et Adaptative ( BFA ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Medicine, University of Toronto-Samuel Lunenfeld Research Institute-Mount Sinai Hospital ( MSH ), Physiogenex SAS, Prologue Biotech, PHYSIOGENEX S.A.S, Department of Biomedical Sciences, The panum Institute-University of Copenhagen ( KU ), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Toronto-Samuel Lunenfeld Research Institute-Mount Sinai Hospital [Toronto, Canada] (MSH), Physiogenex, Department of Biomedical Sciences [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Toronto-Mount Sinai Hospital [Toronto, Canada] (MSH)-Samuel Lunenfeld Research Institute, and University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)
Subjects: MESH : Insulin, medicine.medical_treatment, MESH : Vagus Nerve, MESH : Receptors, Glucagon, 0302 clinical medicine, Endocrinology, MESH: Dipeptides, MESH: Vagus Nerve, Glucose homeostasis, MESH: Animals, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH : Dipeptidyl-Peptidase IV Inhibitors, 0303 health sciences, Glucose tolerance test, MESH: Middle Aged, MESH: Dipeptidyl-Peptidase IV Inhibitors, medicine.diagnostic_test, MESH : Glucagon, MESH: Glucagon, digestive, oral, and skin physiology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH : Adult, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Glucagon-like peptide-1, 3. Good health, MESH : Pyrazines, MESH: Pyrazines, Sitagliptin, hormones, hormone substitutes, and hormone antagonists, medicine.drug, endocrine system, medicine.medical_specialty, MESH: Glucose Tolerance Test, MESH : Male, MESH : Dipeptides, MESH : Receptors, Gastrointestinal Hormone, Incretin, 030209 endocrinology & metabolism, MESH: Insulin, MESH : Mice, Inbred C57BL, Biology, Sitagliptin Phosphate, MESH : Glucose Tolerance Test, MESH: Receptors, Glucagon, 03 medical and health sciences, MESH: Mice, Inbred C57BL, Internal medicine, MESH : Mice, MESH : Triazoles, medicine, MESH : Middle Aged, MESH: Mice, Dipeptidyl peptidase-4, 030304 developmental biology, MESH: Humans, MESH: Receptors, Gastrointestinal Hormone, Insulin, MESH : Humans, MESH: Adult, MESH: Dipeptidyl Peptidase 4, MESH : Blood Glucose, MESH: Male, MESH: Triazoles, MESH : Dipeptidyl Peptidase 4, MESH: Blood Glucose, MESH : Animals
Abstract: International audience; Inhibition of dipeptidyl peptidase-4 (DPP-4) activity improves glucose homeostasis through a mode of action related to the stabilization of the active forms of DPP-4-sensitive hormones such as the incretins that enhance glucose-induced insulin secretion. However, the DPP-4 enzyme is highly expressed on the surface of intestinal epithelial cells; hence, the role of intestinal vs. systemic DPP-4 remains unclear. To analyze mechanisms through which the DPP-4 inhibitor sitagliptin regulates glycemia in mice, we administered low oral doses of the DPP-4 inhibitor sitagliptin that selectively reduced DPP-4 activity in the intestine. Glp1r(-/-) and Gipr(-/-) mice were studied and glucagon-like peptide (GLP)-1 receptor (GLP-1R) signaling was blocked by an i.v. infusion of the corresponding receptor antagonist exendin (9-39). The role of the dipeptides His-Ala and Tyr-Ala as DPP-4-generated GLP-1 and glucose-dependent insulinotropic peptide (GIP) degradation products was studied in vivo and in vitro on isolated islets. We demonstrate that very low doses of oral sitagliptin improve glucose tolerance and plasma insulin levels with selective reduction of intestinal but not systemic DPP-4 activity. The glucoregulatory action of sitagliptin was associated with increased vagus nerve activity and was diminished in wild-type mice treated with the GLP-1R antagonist exendin (9-39) and in Glp1r(-/-) and Gipr(-/-) mice. Furthermore, the dipeptides liberated from GLP-1 (His-Ala) and GIP (Tyr-Ala) deteriorated glucose tolerance, reduced insulin, and increased portal glucagon levels. The predominant mechanism through which DPP-4 inhibitors regulate glycemia involves local inhibition of intestinal DPP-4 activity, activation of incretin receptors, reduced liberation of bioactive dipeptides, and activation of the gut-to-pancreas neural axis.
Published: 2011

5. Glioma stem cells invasive phenotype at optimal stiffness is driven by MGAT5 dependent mechanosensing

Author: David Cornu, Julien Cambedouzou, Luc Bauchet, Jean-Philippe Hugnot, Ali Saleh, Hugues Duffau, Christine Fabre, James W. Dennis, Norbert Bakalara, Marta Martin-Fernandez, Cunjie Zhang, Thomas Iskratsch, Emilie Marhuenda, Retiveau, Nolwenn, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Queen Mary University of London (QMUL), Institut Européen des membranes (IEM), 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), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Mount Sinai Hospital [Toronto, Canada] (MSH), University of Toronto, Laboratoire Charles Coulomb (L2C), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and SATT AxLRMENRT fellowship (CBS2 Doctoral School)INSERM/INCA project PC201216 (Gliomatrack)
Subjects: 0301 basic medicine, Cancer Research, Glycosylation, Mechanotransduction, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Stiffness, Extracellular matrix, 0302 clinical medicine, Cell Movement, MESH: Cell Movement, Migration, RC254-282, biology, Brain Neoplasms, Chemistry, Mgat5, MESH: Glioblastoma, EMT, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cell biology, Phenotype, Oncology, MESH: N-Acetylglucosaminyltransferases, MESH: Brain Neoplasms, Neoplastic Stem Cells, Galectin, Stem cell, endocrine system, animal structures, Integrin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, N-Acetylglucosaminyltransferases, MESH: Phenotype, Focal adhesion, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neurosphere, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Epithelial–mesenchymal transition, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 3D-nanofibre scaffold, MESH: Humans, Research, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Neoplastic Stem Cells, Biomaterial, 030104 developmental biology, biology.protein, Glioblastoma, 030217 neurology & neurosurgery
Abstract: Background Glioblastomas stem-like cells (GSCs) by invading the brain parenchyma, remains after resection and radiotherapy and the tumoral microenvironment become stiffer. GSC invasion is reported as stiffness sensitive and associated with altered N-glycosylation pattern. Glycocalyx thickness modulates integrins mechanosensing, but details remain elusive and glycosylation enzymes involved are unknown. Here, we studied the association between matrix stiffness modulation, GSC migration and MGAT5 induced N-glycosylation in fibrillar 3D context. Method To mimic the extracellular matrix fibrillar microenvironments, we designed 3D-ex-polyacrylonitrile nanofibers scaffolds (NFS) with adjustable stiffnesses by loading multiwall carbon nanotubes (MWCNT). GSCs neurosphere were plated on NFSs, allowing GSCs migration and MGAT5 was deleted using CRISPR-Cas9. Results We found that migration of GSCs was maximum at 166 kPa. Migration rate was correlated with cell shape, expression and maturation of focal adhesion (FA), Epithelial to Mesenchymal Transition (EMT) proteins and (β1,6) branched N-glycan binding, galectin-3. Mutation of MGAT5 in GSC inhibited N-glycans (β1–6) branching, suppressed the stiffness dependence of migration on 166 kPa NFS as well as the associated FA and EMT protein expression. Conclusion MGAT5 catalysing multibranched N-glycans is a critical regulators of stiffness induced invasion and GSCs mechanotransduction, underpinning MGAT5 as a serious target to treat cancer.
Published: 2021

6. The gastric disease of Napoleon Bonaparte: brief report for the bicentenary of Napoleon’s death on St. Helena in 1821

Author: Jean-François Fléjou, Heather Dawson, Fátima Carneiro, Alessandro Lugli, Michael Vieth, Richard Kirsch, Magali Svrcek, Rachel S. van der Post, University of Bern, Universidade do Porto, Instituto de Investigação e Inovação em Saúde (I3S), Mount Sinai Hospital [Toronto, Canada] (MSH), Radboud University Medical Centre [Nijmegen, The Netherlands], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)
Subjects: Battle, History, Famous Persons, [SDV]Life Sciences [q-bio], Napoleon, media_common.quotation_subject, 610 Medicine & health, Autopsy, Disease, Ancient history, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Cause of Death, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Humans, Autopsy report, Molecular Biology, media_common, Brief Report, Interpretation (philosophy), History, 19th Century, Cell Biology, General Medicine, 3. Good health, Anniversaries and Special Events, Gastritis, 030220 oncology & carcinogenesis, Medical evidence, 570 Life sciences, biology, 030211 gastroenterology & hepatology, Bicentenary, Gastric cancer, Gastrointestinal Hemorrhage
Abstract: Contains fulltext : 245242.pdf (Publisher’s version ) (Open Access) After the defeat at the battle of Waterloo on June 18, 1815, Napoleon Bonaparte was sent into exile to the Island of St. Helena where he died 6 years later on May 5, 1821. One day after his death, Napoleon's personal physician, Dr. Francesco Antommarchi, performed the autopsy in the presence of Napoleon's exile companions and the British medical doctors. Two hundred years later, mysteries still surround the cause of his death and different hypotheses have been postulated in the medical and historical literature. The main reasons seem to be the presence of several autopsy reports, their interpretation and perhaps the greed for thrill and mystery. Therefore, for the bicentenary of Napoleon's death, an international consortium of gastrointestinal pathologists assembled to analyse Napoleon's autopsy reports based on the level of medical evidence and to investigate if the autopsy reports really do not allow a final statement.
Published: 2021

7. Infective Endocarditis Caused by Staphylococcus Aureus after Transcatheter Aortic Valve Replacement

Author: Fernando Alfonso, Marco Barbanti, Oliver Husser, Harindra C. Wijeysundera, Jean-Bernard Masson, Ignacio J. Amat-Santos, Samir R. Kapadia, Marina Urena, Francisco Campelo-Parada, Vinicius Esteves, Roger R. Godinho, Tarun Chakravarty, Marcos Antonio Marino, Stamatios Lerakis, Alexandre Siciliano Colafranceschi, Marouane Boukhris, Chekrallah Chamandi, Lisa Crusius, Tomasz Gasior, Azeem Latib, Norman Mangner, Utz Kappert, Josep Rodés-Cabau, José Armando Mangione, Francesco Rosato, Axel Linke, Sandro Sponga, Erika Muñoz-García, Valter Corriea de Lima, Susheel Kodali, Asim N. Cheema, Lars Søndergaard, Igor Vendramin, Alexandre Abizaid, Antonio L. Bartorelli, Annapoorna Kini, Rosana Hernández-Antolín, John G. Webb, Costanza Pellegrini, Didier Tchetche, Howard C. Herrmann, John Lisko, Claudia Fiorina, Mohamed Abdel-Wahab, Kim Won-Keun, Hélène Eltchaninoff, Alberto Alperi, Martin Landt, Dominique Himbert, Frédéric Maes, Victoria Vilalta, Luca Testa, Isaac Pascual, Luisa Salido, Jan Malte Sinning, Vicenç Serra, Guglielmo Mario Actis Dato, Antonio Miceli, Clement Servoz, David del Val, Rafael Romaguera, Maria-Cristina Ferreira, Eric Durand, Julio Andrea, Fabio Sandoli de Brito, Vincent Auffret, Philippe Gervais, Stefan Stortecky, Paolo Olivares, Francesco Giannini, Enrique Gutiérrez-Ibañes, Raj Makkar, Nikolaj Ihlemann, Wojtek Wojakowski, Hervé Le Breton, Abdullah Alkhodair, Juan C. Castillo, Ander Regueiro, David Holzhey, Luis Nombela-Franco, Henrique Barbosa Ribeiro, Saif Siddiqui, Université Laval [Québec] (ULaval), Universität Leipzig [Leipzig], Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], 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), CHU Toulouse [Toulouse], Clinique Pasteur, Clinique Pasteur [Toulouse], Mount Sinai Hospital [Toronto, Canada] (MSH), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), University Hospital Leipzig, Edwards Lifesciences, Fundación Alfonso Martín Escudero, Abbott Laboratories, Medtronic, Boston Scientific Corporation, UCL - (SLuc) Département cardiovasculaire, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Hôpital de Rangueil, Universität Leipzig, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, medicine.medical_specialty, Staphylococcus aureus, Prosthesis-Related Infections, Transcatheter aortic, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, medicine.disease_cause, Global Health, Prosthesis, Sepsis, Transcatheter Aortic Valve Replacement, 03 medical and health sciences, 0302 clinical medicine, Valve replacement, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Endocarditis, Humans, 030212 general & internal medicine, Hospital Mortality, Registries, 610 Medicine & health, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Incidence, Aortic Valve Stenosis, Endocarditis, Bacterial, Staphylococcal Infections, medicine.disease, 3. Good health, Surgery, Survival Rate, Infective endocarditis, Aortic Valve, Heart Valve Prosthesis, Etiology, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: International audience; Background - Staphylococcus aureus (SA) has been extensively studied as causative microorganism of surgical prosthetic-valve infective endocarditis (IE). However, scarce evidence exists on SA IE after transcatheter aortic valve replacement (TAVR). Methods - Data were obtained from the Infectious Endocarditis After TAVR International Registry, including patients with definite IE after TAVR from 59 centres in 11 countries. Patients were divided into 2 groups according to microbiologic etiology: non-SA IE vs SA IE. Results - SA IE was identified in 141 patients out of 573 (24.6%), methicillin-sensitive SA in most cases (115/141, 81.6%). Self-expanding valves were more common than balloon-expandable valves in patients presenting with early SA IE. Major bleeding and sepsis complicating TAVR, neurologic symptoms or systemic embolism at admission, and IE with cardiac device involvement (other than the TAVR prosthesis) were associated with SA IE (P < 0.05 for all). Among patients with IE after TAVR, the likelihood of SA IE increased from 19% in the absence of those risk factors to 84.6% if ≥ 3 risk factors were present. In-hospital (47.8% vs 26.9%; P < 0.001) and 2-year (71.5% vs 49.6%; P < 0.001) mortality rates were higher among patients with SA IE vs non-SA IE. Surgery at the time of index SA IE episode was associated with lower mortality at follow-up compared with medical therapy alone (adjusted hazard ratio 0.46, 95% CI 0.22-0.96; P = 0.038). Conclusions - SA IE represented approximately 25% of IE cases after TAVR and was associated with very high in-hospital and late mortality. The presence of some features determined a higher likelihood of SA IE and could help to orientate early antibiotic regimen selection. Surgery at index SA IE was associated with improved outcomes, and its role should be evaluated in future studies.
Published: 2022

8. Sequential design for microarray experiments

Author: Gilles Durrieu, Laurent Briollais, Durrieu, Gilles, Laboratoire de Mathématiques de Bretagne Atlantique (LMBA), Université de Brest (UBO)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS), Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), and University of Toronto-Mount Sinai Hospital [Toronto, Canada] (MSH)
Subjects: Statistics and Probability, [SDV]Life Sciences [q-bio], 01 natural sciences, Robust regression, 010104 statistics & probability, 03 medical and health sciences, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Statistics, Linear regression, 0101 mathematics, [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Mathematics, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], Microarray analysis techniques, Sample size, Design of experiments, Linear model, Regression analysis, [STAT.TH]Statistics [stat]/Statistics Theory [stat.TH], Dose-response, Sequential analysis, Sample size determination, Gene expression, Statistics, Probability and Uncertainty, Algorithm
Abstract: International audience; A critical aspect in the design of microarray studies is the determination of the sample size necessary to declare genes differentially expressed across different experimental conditions. In this article, we propose a sequential approach where the decision to stop the experiment depends on the accumulated microarray data. The study could stop whenever sufficient data have been accumulated to identify gene expression changes across several experimental conditions. The gene expression response is modeled by a robust linear regression model. We then construct a sequential confidence interval for the intercept of this model, which represents the median gene expression at a given experimental condition. We derive the stopping rule of the experiment for both continuous and discrete sequential approaches and give the asymptotic properties of the stopping variable. We demonstrate the desirable properties of our sequential approach, both theoretically and numerically. In our application to a study of hormone responsive breast cancer cell lines, we estimated the stopping variable for the sample size determination to be smaller than the actual sample size available to conduct the experiment. This means that we can obtain an accurate assessment of differential gene expression without compromising the cost and size of the study. Altogether, we anticipate that this approach could have an important contribution to microarray studies by improving the usual experimental designs and methods of analysis.
Published: 2005

9. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis

Author: Lucy Smyth, Andrea Mazzetti, Charles D. Pusey, Lorraine Harper, Donna Reidlinger, Gina Gregorini, William F. Clark, Pexivas Investigators Pexivas Investigators, Adeera Levin, Toshiko Ito-Ihara, Chen-Au Peh, Xavier Puéchal, Ulrich Specks, Carmel M. Hawley, Oliver Floßmann, Simon Carette, Alina Casian, Wojciech Szczeklik, Peter A. Merkel, Janak de Zoysa, Nader Khalidi, David Jayne, Samir Mehta, Biljana Brezina, Ron Wald, Michael Walsh, Luis Felipe Flores-Suárez, Carol A. McAlear, L. Guillevin, Louis Girard, Natalie Ives, Wladimir Szpirt, Vladimir Tesar, Elizabeth Broadhurst, Christian Pagnoux, Shouichi Fujimoto, McMaster University [Hamilton, Ontario], Royal Adelaide Hospital [Adelaide Australia], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Miyazaki, McMaster University, St. Joseph’s Healthcare, Royal Berkshire Hospital, St. Michael's Hospital, University of British Columbia (UBC), Università degli Studi di Brescia [Brescia], Mount Sinai Hospital [Toronto, Canada] (MSH), Mayo Clinic [Rochester], Charles University [Prague] (CU), Instituto Nacional de Enfermedades Respiratorias [México, Mexico], University of Cambridge [UK] (CAM), Addenbrooke's Hospital, and Cambridge University NHS Trust
Subjects: MESH: Combined Modality Therapy, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, Azathioprine, 030204 cardiovascular system & hematology, urologic and male genital diseases, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, MESH: Dose-Response Relationship, Drug, MESH: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, immune system diseases, Internal medicine, Medicine, MESH: Incidence, cardiovascular diseases, 030212 general & internal medicine, skin and connective tissue diseases, Anti-neutrophil cytoplasmic antibody, MESH: Aged, MESH: Kidney Diseases, MESH: Middle Aged, MESH: Humans, business.industry, MESH: Cyclophosphamide, MESH: Adult, Glomerulonephritis, General Medicine, MESH: Plasma Exchange, medicine.disease, MESH: Induction Chemotherapy, MESH: Male, respiratory tract diseases, 3. Good health, MESH: Kidney Failure, Chronic, MESH: Administration, Oral, Rituximab, Plasmapheresis, MESH: Immunosuppressive Agents, MESH: Rituximab, MESH: Glucocorticoids, business, Vasculitis, MESH: Female, medicine.drug
Abstract: BACKGROUND More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. METHODS We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of
Published: 2020

10. The autopsy of Napoleon Bonaparte: Anatomo-pathological assessment for the bicentenary of the death of Napoleon I on the island of Saint Helena in 1821

Author: Lugli, Alessandro, Carneiro, Fatima, Dawson, Heather, Fléjou, Jean-François, Kirsch, Richard, Van Der Post, Rachel, Vieth, Michael, Svrcek, Magali, University of Bern, Universidade do Porto, Mount Sinai Hospital [Toronto, Canada] (MSH), Radboud University Medical Centre [Nijmegen, The Netherlands], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Bicentenaire, Bicentennial, Napoleon I, Autopsie, [SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, All institutes and research themes of the Radboud University Medical Center, Cancer gastrique, Gastritis, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], Napoléon Ier, Autopsy, Gastrite, Gastric cancer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Napoleon Bonaparte died on 5 May 1821 on the island of St Helena after almost six years of exile. The next day, Dr Francesco Antommarchi, a Corsican doctor chosen by the Bonaparte family to treat the exiled emperor, performed the autopsy in the presence of sixteen people, including seven British doctors. Two hundred years after the event of 6 May 1821, the cause of Napoleon's death is still a mystery. Various hypotheses, such as arsenic intoxication, cardiac arrhythmia or, more recently, anaemia caused by gastrointestinal haemorrhage associated with chronic gastritis, have been put forward in the medical-historical literature. The main reasons for all these debates and misunderstandings are the presence of several autopsy reports, their often unscientific interpretation, as well as a certain taste for mystery. However, from a scientific point of view, the question arises as to whether autopsy reports are really conclusive as to the real cause of death. Thus, on the occasion of the bicentenary of Napoleon I's death in St. Helena, an international group of anatomo-pathologists specialising in digestive pathology set themselves the goal of analysing Napoleon I's autopsy reports according to their level of medical evidence (high, moderate and low). The autopsy reports of 1821 support the hypothesis of advanced malignant neoplasia of the stomach associated with gastric haemorrhage as the immediate cause of Napoleon I's death on 5 May 1821.; Napoléon Bonaparte est mort le 5 mai 1821 sur l’île de Sainte-Hélène après presque six années d’exil. Le lendemain, le docteur Francesco Antommarchi, médecin corse choisi par la famille Bonaparte pour soigner l’empereur exilé, procéda à l’autopsie en présence de seize personnes, dont sept médecins britanniques. Deux cents ans après cet événement du 6 mai 1821, des mystères entourent encore la cause de la mort de Napoléon. Différentes hypothèses, telle qu’une intoxication à l’arsenic, une arythmie cardiaque ou, plus récemment, une anémie causée par une hémorragie gastro-intestinale associée à une gastrite chronique, ont été avancées dans la littérature médico-historique. Les principales raisons de tous ces débats et malentendus sont la présence de plusieurs rapports d’autopsie, de leur interprétation souvent peu scientifique, de même qu’un certain goût pour le mystère. Toutefois, d’un point de vue scientifique, la question de savoir si les rapports d’autopsie permettent vraiment de conclure quant à la cause réelle du décès se pose. Ainsi, à l’occasion du bicentenaire de la mort de Napoléon 1er à Sainte Hélène, un groupe international d’anatomo-pathologistes spécialisés en pathologie digestive s’est donné pour objectif d’analyser les rapports d’autopsie de Napoléon 1er selon leur niveau d’évidence médicale (élevé, modéré et faible). Les rapports d’autopsie de 1821 sont en faveur de l’hypothèse d’une néoplasie maligne avancée de l’estomac associée à une hémorragie gastrique comme cause immédiate de la mort de Napoléon Ier le 5 mai 1821.
Published: 2021

11. Discovery of common and rare genetic risk variants for colorectal cancer

Author: Charles M. Connolly, Deborah A. Nickerson, Jian Gong, Sébastien Küry, Barbara Pardini, Brent W. Zanke, Andrea Gsur, Jochen Hampe, Coral Arnau-Collell, M. Henar Alonso, Elio Riboli, Annika Lindblom, Ulrike Peters, Gad Rennert, Tabitha A. Harrison, Lori C. Sakoda, Caroline McNeil, Flavio Lejbkowicz, Hyun Min Kang, David J. Hunter, Martha L. Slattery, Miguel Rodríguez-Barranco, Christina Bamia, Satu Männistö, Timothy J. Key, W. James Gauderman, Gonçalo R. Abecasis, Sanford D. Markowitz, Laurence N. Kolonel, Mark A. Jenkins, Yi Lin, Robin Myte, Hedy S. Rennert, Neil Murphy, Antonia Trichopoulou, Christopher I. Li, Ross L. Prentice, Sai Chen, Stephanie J. Weinstein, Kristin E. Anderson, Hua Ling, Mitul Shah, Philipp Hofer, Wen Yi Huang, Sergi Castellví-Bel, Susanna C. Larsson, Maria Dolores Chirlaque, Wei Zheng, Stephanie L. Schmit, Cecelia A. Laurie, Soo-Chin Lee, David Forman, Andrea N. Burnett-Hartman, Giovanna Masala, Sarah C. Nelson, Michael O. Woods, Charles Kooperberg, Qing Zhang, Sonja I. Berndt, Christopher S. Carlson, Katja Butterbach, Hyeong Rok Kim, Rebecca D. Jackson, David Van Den Berg, Michael C. Bassik, Amanda J. Cross, Sushma S. Thomas, Clemens Schafmayer, Anna H. Wu, Douglas F. Easton, Robert W. Haile, Ludmila Vodickova, Graham G. Giles, Yu Ru Su, Jenny Chang-Claude, Lorena Moreno, Peter C. Scacheri, Stefanie Brezina, Min-Ho Shin, Steven Gallinger, Bethany Van Guelpen, Daniel D. Buchanan, Roger L. Milne, Stephen J. Chanock, Tin Louie, Tameka Shelford, Emily White, Kala Visvanathan, Loic Le Marchand, Veronika Vymetalkova, Roxann G. Ingersoll, Temitope O. Keku, Stephanie A. Bien, Fredrick R. Schumacher, Wan-Ling Hsu, Amanda E. Toland, John S. Grove, Noralane M. Lindor, Faye Elliott, Leon Raskin, Heather Hampel, Joshua D. Smith, Vicente Martín, David V. Conti, Sjoerd G. Elias, Henk J. van Kranen, Manish Gala, Daniela Seminara, Syed H.E. Zaidi, Suzanne M. Leal, Tilman Kühn, Korbinian Weigl, Marc J. Gunter, Cornelia M. Ulrich, Peyton Greenside, Victor Moreno, John D. Potter, Michael Hoffmeister, Eric J. Jacobs, Catherine M. Tangen, Jihyoun Jeon, Fränzel J.B. Van Duijnhoven, Andrew T. Chan, Stephen B. Gruber, John A. Baron, Alicja Wolk, Edith J. M. Feskens, Demetrius Albanes, Amit Joshi, Bette J. Caan, Polly A. Newcomb, Stéphane Bézieau, Elizabeth M. Gillanders, Anshul Kundaje, Elizabeth A. Platz, Michael Wainberg, Sun-Seog Kweon, C. Roland Wolf, Gemma Ibáñez-Sanz, Shuji Ogino, Emiko Kobayashi, Richard B. Hayes, Patrick S. Parfrey, Katarina Cuk, Stephen N. Thibodeau, Kenneth Offit, David Duggan, Sophia Harlid, Pavel Vodicka, Juergen Boehm, Christa Stegmaier, Jeroen R. Huyghe, Joseph Vijai, Sang-Hee Cho, Elizabeth W. Pugh, Rachel Pearlman, Alessio Naccarati, Marilena Melas, Graham Casey, Jane Romm, Stephan Buch, Phyllis J. Goodman, Albert de la Chapelle, John L. Hopper, Zsofia K. Stadler, Corinne E. Joshu, Liesel M. FitzGerald, Wolfgang Lieb, Aung Ko Win, Keith R. Curtis, Hermann Brenner, Christopher K. Edlund, Li Hsu, Conghui Qu, Peter T. Campbell, Robert E. Schoen, Heiner Boeing, D. Timothy Bishop, Kimberly F. Doheny, Sabina Sieri, Barbara L. Banbury, Mathieu Lemire, Jane C. Figueiredo, Gregory Idos, Katerina Shulman, Thomas J. Hudson, Melissa C. Southey, Duncan C. Thomas, Paul D.P. Pharoah, Mila Pinchev, Vittorio Perduca, Rocky Fischer, Volker Arndt, William M. Grady, Nasa Sinnott-Armstrong, N. Charlotte Onland-Moret, David M. Levine, Li Li, Dallas R. English, Health Research Board - Ireland, Department of Medical Genetics, HMNC Brain Health, Case Western Reserve University [Cleveland], National Cancer Institute, NIH, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Service de Génétique, Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Division of Cancer Epidemiology, Cancer Genome Project, The Wellcome Trust Sanger Institute [Cambridge], Division of Signaling Biology, Ontario Cancer Institute, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), National Institute of Standards and Technology [Gaithersburg] (NIST), Ohio State University [Columbus] (OSU), Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Epidemiology Centre, Cancer Council Victoria, Division of Human Nutrition, Wageningen University and Research [Wageningen] (WUR), Division of Public Health Sciences, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Northern and Yorkshire Cancer Registry and Information Service, Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, London School of Hygiene and Tropical Medicine (LSHTM), Fraunhofer Institute for Manufacturing Engineering and Automation (Fraunhofer IPA), Fraunhofer (Fraunhofer-Gesellschaft), Centre for Molecular , Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne-Centre for Molecular, Melbourne School of Population Health, Department of Mathematics, University of Warwick, Warwick Mathematics Institute (WMI), University of Warwick [Coventry]-University of Warwick [Coventry], Department of Statistics, Penn State University, University of Pennsylvania [Philadelphia], Tata Memorial Centre, Cancer Epidemiology Unit, University of Oxford [Oxford], Thermo Fisher Scientific, Thermo Fisher Scientific Inc., Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, National University Health System, Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Dell-EMC, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Department of Pathology, Brigham and Women's Hospital [Boston], University Medical Center [Utrecht], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, Department of Epidemiology and Biostatistics, Imperial College London, Department of Visceral and Thoracic Surgery [Kiel, Germany], University Hospital Schleswig-Holstein [Kiel, Germany], Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, Department of Laboratory Medicine and Department of Pathology, Mayo Clinic College of Medicine, Department of Molecular Virology, Immunology and Medical Genetics [Colombus], Ohio State University [Columbus] (OSU)-College of Medicine and Public Health [Colombus], Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Dundee Technopole, CXR Biosciences Ltd, Karolinska Institutet [Stockholm], CINTRA / SEEE Nanyang Technological University, Nanyang Technological University [Singapour], Center for Astrophysical Sciences [Baltimore], Johns Hopkins University (JHU), Computer Science and Artificial Intelligence Laboratory (CSAIL), Massachusetts Institute of Technology (MIT), Department of Preventive Medicine, University of Southern California (USC), Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Medstar Research Institute, Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Wageningen University and Research Centre [Wageningen] (WUR), Mount Sinai Hospital (MSH), Fraunhofer Institute for Manufacturing Engineering and Automation [Stuttgart] (IPA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Czech Academy of Sciences [Prague] (ASCR), Huyghe, Jeroen R [0000-0001-6027-9806], Harrison, Tabitha A [0000-0002-4173-7530], Chen, Sai [0000-0003-3106-5643], Schmit, Stephanie L [0000-0001-5931-1194], Jeon, Jihyoun [0000-0001-7003-3412], Schumacher, Fredrick R [0000-0002-3073-7463], Nelson, Sarah C [0000-0002-2109-6465], Sinnott-Armstrong, Nasa A [0000-0003-4490-0601], Alonso, M Henar [0000-0003-0285-5451], Arndt, Volker [0000-0001-9320-8684], Bézieau, Stéphane [0000-0003-0095-1319], Bishop, D Timothy [0000-0002-8752-8785], Brezina, Stefanie [0000-0001-5238-6900], Buchanan, Daniel D [0000-0003-2225-6675], Chanock, Stephen J [0000-0002-2324-3393], de la Chapelle, Albert [0000-0001-9345-9248], Easton, Douglas F [0000-0003-2444-3247], Hampe, Jochen [0000-0002-2421-6127], Hayes, Richard B [0000-0002-0918-661X], Hofer, Philipp [0000-0003-2550-6019], Huang, Wen-Yi [0000-0002-4440-3368], Hudson, Thomas J [0000-0002-1376-4849], Jacobs, Eric J [0000-0002-8458-7659], Jenkins, Mark A [0000-0002-8964-6160], Joshi, Amit D [0000-0001-7581-6934], Küry, Sébastien [0000-0001-5497-0465], Larsson, Susanna C [0000-0003-0118-0341], Laurie, Cecelia A [0000-0001-6569-2501], Martín, Vicente [0000-0003-0552-2804], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger L [0000-0001-5764-7268], Naccarati, Alessio [0000-0001-5774-0905], Newcomb, Polly A [0000-0001-8786-0043], Pardini, Barbara [0000-0001-9571-4257], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul DP [0000-0001-8494-732X], Raskin, Leon [0000-0003-1195-7214], Rennert, Gad [0000-0002-8512-068X], Shin, Min-Ho [0000-0002-2217-5624], Toland, Amanda E [0000-0002-0271-1792], Vijai, Joseph [0000-0002-7933-151X], Weigl, Korbinian [0000-0003-4453-2036], Win, Aung Ko [0000-0002-2794-5261], Wolk, Alicja [0000-0001-7387-6845], Zheng, Wei [0000-0003-1226-070X], Bassik, Michael C [0000-0001-5185-8427], Moreno, Victor [0000-0002-2818-5487], Peters, Ulrike [0000-0001-5666-9318], and Apollo - University of Cambridge Repository
Subjects: Male, Nutrition and Disease, Colorectal cancer, IDENTIFIES 6, Genome-wide association study, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Genotype, ComputingMilieux_MISCELLANEOUS, Avaluació del risc per la salut, Genetics & Heredity, Genetics, 0303 health sciences, COLON-CANCER, 11 Medical And Health Sciences, Middle Aged, 3. Good health, Medical genetics, Female, RNA, Long Noncoding, Colorectal Neoplasms, Life Sciences & Biomedicine, Signal Transduction, EXPRESSION, medicine.medical_specialty, SUSCEPTIBILITY LOCI, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, Article, Health risk assessment, 03 medical and health sciences, QUALITY-CONTROL, Càncer colorectal, Journal Article, medicine, Life Science, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, METAANALYSIS, VLAG, Aged, 030304 developmental biology, Global Nutrition, [SDV.GEN]Life Sciences [q-bio]/Genetics, Wereldvoeding, Science & Technology, ORGAN SIZE, MUTATIONS, Haplotype, Case-control study, 06 Biological Sciences, medicine.disease, Genetic architecture, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human genome, LYSOPHOSPHATIDIC ACID, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract: To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P, Reporting Summary. Further information on experimental design is available in the Life Sciences Reporting Summary linked to this article.
Published: 2018

12. Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study

Author: Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andres, Gattinoni, Luciano, Larsson, Anders, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Nicolás Nin, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andre, Gattinoni, Luciano, Larsson, Ander, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L 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Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Pham, T, Pesenti, A, Bellani, G, Rubenfeld, G, Fan, E, Bugedo, G, Lorente, J, Fernandes, A, Van Haren, F, Bruhn, A, Rios, F, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Thompson, B, Wrigge, H, Brochard, L, Laffey, J, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), St. Michael's Hospital, University of Toronto, Groupe de recherche clinique CARMAS, 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, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano [Milano] (UNIMI), University of Milan, San Gerardo Hospital, Sunnybrook Health Sciences Center, Mount Sinai Hospital [Toronto, Canada] (MSH), Pontificia Universidad Católica de Chile (UC), University Hospital of Getafe, CIBER Enfermedades Respiratorias (CIBERES), Universidad Europea de Madrid, Hospital Garcia de Orta (EPE), Canberra Hospital, Medical School [Australian National University - ANU], Australian National University (ANU), University of Canberra, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Göttingen - Georg-August-Universität Göttingen, Uppsala University, Queen's University [Belfast] (QUB), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Università degli Studi di Bologna, Massachusetts General Hospital [Boston], University Hospital Leipzig, Department of Anaesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, 06112, Halle, National University of Ireland [Galway] (NUI Galway), Bayer GlaxoSmithKline, GSK Baxter International Boehringer Ingelheim Wellcome Trust, WT National Institute for Health Research, NIHR Queen's University Belfast, QUB Medical Research Council Canada, MRC European Society of Intensive Care Medicine, ESICM, Support statement: This work was supported by the European Society of Intensive Care Medicine. Funding information for this article has been deposited with the Crossref Funder Registry., Conflict of interest: T. Pham has nothing to disclose. A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work. G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work. G. Rubenfeld has nothing to disclose. E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work. G. Bugedo has nothing to disclose. J.A. Lorente has nothing to disclose. A.D. V. Fernandes has nothing to disclose. F. Van Haren has nothing to disclose. A. Bruhn has nothing to disclose. F. Rios has nothing to disclose. A. Esteban has nothing to disclose. L. Gattinoni has nothing to disclose. A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study. D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work, in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC, is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen’s University of Belfast (http://www.google.com/patents/US8962032), and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. M. Ranieri has nothing to disclose. B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work. H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work. L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work. J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work., LUNG SAFE Investigators and the European Society of Intensive Care Medicine Trials Group: Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J 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Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, and UCL - (SLuc) Service de soins intensifs
Subjects: Pulmonary and Respiratory Medicine, ARDS, Unidades de cuidados intensivos, [SDV]Life Sciences [q-bio], medicine.medical_treatment, mechanical ventilation, NO, law.invention, 03 medical and health sciences, Tratamiento médico, 0302 clinical medicine, law, Settore MED/41 - ANESTESIOLOGIA, Insuficiencia respiratoria, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Lung, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Respiration, Incidence (epidemiology), medicine.disease, Intensive care unit, Respiration, Artificial, 3. Good health, Intensive Care Units, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], medicine.anatomical_structure, 030228 respiratory system, Respiratory failure, Heart failure, Anesthesia, Artificial, ards, business, Respiratory Insufficiency, Enfermedad
Abstract: BackgroundCurrent incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).MethodsAn international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.Findings12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.InterpretationMore than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.
Published: 2021

13. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author: Samuel Kuperman, Leila Karhunen, Geòrgia Escaramís, Sébastien Guillaume, Kelly L. Klump, David C. Whiteman, Colin A. Hodgkinson, Stephanie H. Witt, Artemis Tsitsika, Hana Papezova, Renato Polimanti, P. Eline Slagboom, Peter Zill, Jakob Grove, Toni-Kim Clarke, Michael Soyka, Jennifer Jordan, Steven Gallinger, Philip Gorwood, Preben Bo Mortensen, Yuri Milaneschi, Ingrid Meulenbelt, Jen Chyong Wang, Markus M. Nöthen, Katrin Männik, Henry R. Kranzler, Michael M. Vanyukov, Anna Keski-Rahkonen, William G. Iacono, Raymond K. Walters, Stephanie Le Hellard, Bochao Danae Lin, Vesna Boraska Perica, Marion Roberts, Patrick F. Sullivan, Steven Crawford, Mark A. Frye, Melissa A. Munn-Chernoff, Hakon Hakonarson, Andreas Birgegård, Robert Culverhouse, Alexis C. Edwards, Jerome C. Foo, Alessandro Rotondo, Brenda W.J.H. Penninx, Laura M. Hack, Michael T. Lynskey, Mario Maj, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Julie K. O'Toole, Marta Tyszkiewicz-Nwafor, Matt McGue, Julien Bryois, Martina de Zwaan, Norbert Dahmen, Stefanie Heilmann-Heimbach, Deborah Kaminská, Benedetta Nacmias, Nicholas G. Martin, Anna R. Docherty, Christopher Hübel, Nancy L. Pedersen, Janet Treasure, William E. Copeland, Roger A.H. Adan, Jaakko Kaprio, Aarno Palotie, L. John Horwood, Maria La Via, Philippe Courtet, Virpi M. Leppä, Judy L. Silberg, Jason D. Boardman, Fazil Aliev, Wade H. Berrettini, Doo Sup Choi, Youl-Ri Kim, Konstantinos Hatzikotoulas, Harriet de Wit, Sandra A. Brown, Elisabeth Widen, Caroline Hayward, Nicholas J. Schork, Penelope A. Lind, Ralph E. Tarter, Jana Strohmaier, Allan S. Kaplan, Richard A. Grucza, Bradley T. Webb, Angela Favaro, Dalila Pinto, Helena Gaspar, Andrew W. Bergen, Beate Herpertz-Dahlmann, Robert Levitan, Wolfgang Gäbel, Xavier Estivill, Emma C. Johnson, Konstantinos Tziouvas, Lindsay A. Farrer, Lenka Foretova, Marc A. Schuckit, Joanna M. Biernacka, André Scherag, Robbee Wedow, Abraham A. Palmer, Amy E. Adkins, Franziska Degenhardt, Louisa Degenhardt, Jurjen J. Luykx, Marius Lahti-Pulkkinen, Brien P. Riley, Monika Ridinger, Matteo Cassina, Harry Brandt, Yiran Guo, Stephan Ripke, Palmiero Monteleone, Katri Räikkönen, Jonathan R. I. Coleman, Martin A. Kennedy, Stephen W. Scherer, Ioanna Tachmazidou, Catherine M. Olsen, Bernice Porjesz, Esther Walton, Yi-Ling Chou, Nicolas Ramoz, Tetsuya Ando, Andres Metspalu, Bertram Müller-Myhsok, Brion S. Maher, Sarah Bertelsen, Melanie L. Schwandt, Janiece E. DeSocio, Margaret Keyes, John F. Pearson, Dongbing Lai, Paul Lichtenstein, James MacKillop, George Dedoussis, Jari Lahti, Ulrike Schmidt, Stefan Ehrlich, Amanda G. Wills, Teemu Palviainen, David Goldman, Elena Tenconi, Dimitris Dikeos, Scott I. Vrieze, Sietske G. Helder, Katharina Buehren, Hongyu Zhao, Sara McDevitt, Jolanta Lissowska, Joseph M. Boden, Li-Shiun Chen, Susanne Lucae, Sara Marsal, Dan Rujescu, Claes Norring, Howard J. Edenberg, Victor M. Karpyak, Fragiskos Gonidakis, Per Hoffmann, Christopher S. Franklin, Karin Egberts, Johanna Giuranna, Stefan Herms, Leah Wetherill, Stephanie Zerwas, Anthony Batzler, Elliot C. Nelson, Jouke-Jan Hottenga, Marcella Rietschel, Ioanna Ntalla, Victor Hesselbrock, Sarah M. Hartz, Marie Navratilova, Falk Kiefer, Martien J H Kas, Richard J. Rose, Andrew C. Heath, Jin P. Szatkiewicz, Lenka Slachtova, Lisa Lilenfeld, Katherine A. Halmi, John P. Rice, Anjali K. Henders, Christian Dina, Norbert Wodarz, Satu Männistö, Hamdi Mbarek, Shuyang Yao, Vladimir Janout, Alison Goate, Bettina Konte, Alexandra Schosser, Danfeng Chen, Kirsty Kiezebrink, Euijung Ryu, Dana B. Hancock, James Mitchell, Sarah E. Medland, Ina Giegling, Valdo Ricca, Scott D. Gordon, Gabrielle Koller, Samuli Ripatti, Laura M. Thornton, Alison D. Murray, Morten Mattingsdal, Zeynep Yilmaz, Jens Treutlein, Kathleen K. Bucholz, Tim B. Bigdeli, Eric F. van Furth, Hermine H. Maes, Ken B. Hanscombe, Sandra Sanchez-Roige, Daniela Degortes, Monica Forzan, Manuel Mattheisen, Richard Sherva, Scott J. Crow, Mikael Landén, Wolfgang Herzog, Jeanette N. McClintick, Tõnu Esko, Louis Fox, Wolfgang Maier, Liselotte Petersen, Laura J. Bierut, Roseann E. Peterson, Gursharan Kalsi, Kathleen Mullan Harris, Margarita C T Slof-Op 't Landt, Tamara L. Wall, Patrik K. E. Magnusson, Unna N. Danner, Stephan Zipfel, Ulrich W. Preuss, Elisa Docampo, D. Blake Woodside, Alfonso Tortorella, Benjamin W. Domingue, Franziska Ritschel, Johan G. Eriksson, Anu Raevuori, Benjamin M. Neale, Marcus Ising, Annemarie A. van Elburg, Filip Rybakowski, Maureen Reynolds, Tracey D. Wade, Manfred M. Fichter, Monica Gratacos Mayora, Claudette Boni, Andreas J. Forstner, John Whitfield, Silviu Alin Bacanu, Matthew B. McQueen, Andrew M. McIntosh, Norbert Scherbaum, Tatiana Foroud, Gun Peggy Knudsen, Sven Cichon, Christian J. Hopfer, Josef Frank, Eleftheria Zeggini, Federica Tozzi, Nadia Micali, Danielle M. Dick, Pamela A. F. Madden, Christian R. Marshall, Johannes Hebebrand, Fernando Fernández-Aranda, Roel A. Ophoff, Roland Burghardt, Nathaniel Thomas, Leonid Padyukov, Nancy L. Saccone, Anu Loukola, Fabian Streit, James L. Kennedy, Jessica H. Baker, Peter McGuffin, Walter H. Kaye, Pei Hong Shen, Anne Farmer, Roger D. Cone, Ilka Boehm, Jacquelyn L. Meyers, Paolo Santonastaso, Maurizio Clementi, Susana Jiménez-Murcia, Gudrun Wagner, Anke Hinney, Richard Parker, James I. Hudson, Nathan A. Gillespie, Michael Strober, John I. Nurnberger, Sandro Sorbi, Dorret I. Boomsma, Beata Świątkowska, Janne Tidselbak Larsen, Kenneth S. Kendler, Hidetoshi Inoko, Jessica E. Salvatore, Hunna J. Watson, Jochen Seitz, Jacques Pantel, Karl Mann, Hang Zhou, Antonio Julià, Oliver S. P. Davis, Nancy Diazgranados, Krista Fischer, John K. Hewitt, Karen S. Mitchell, Joanna Hauser, Eric O. Johnson, Craig Johnson, E. Jane Costello, Agnieszka Słopień, Dong Li, Laramie E. Duncan, Arpana Agrawal, Grant W. Montgomery, Manuel Föcker, Thomas Werge, Lannie Ligthart, Andreas Karwautz, Raquel Rabionet, Kenneth Krauter, Joel Gelernter, James J. Crowley, Cynthia M. Bulik, Paola Giusti-Rodríguez, Laura M. Huckins, Gerome Breen, Michael C. Stallings, Daniel E. Adkins, Pierre J. Magistretti, John Kramer, Lars Alfredsson, Hartmut Imgart, Annette M. Hartmann, Ole A. Andreassen, Monika Dmitrzak-Weglarz, Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department Psychiatry [Chapel Hill], University of North Carolina System (UNC)-University of North Carolina System (UNC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], QIMR Berghofer Medical Research Institute, Karolinska Institutet [Stockholm], University Children's Hospital of Essen [Essen, Germany], University of Duisburg-Essen, Aarhus University [Aarhus], Stockholm County Council, University of Würzburg, Guy's Hospital [London], University Medical Center [Utrecht], University of Gothenburg (GU), Altrecht Center for Eating Disorders Rintveld [Zeist, The Netherlands] (Mental Health Institute), National Institute of Mental Health [Tokyo, Japan] (NIMH), National Center of Neurology and Psychiatry [Tokyo, Japan], University of Oslo (UiO), Norwegian Centre for Mental Disorders Research [Oslo] (NORMENT), University of Oslo (UiO)-Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB)-Oslo University Hospital [Oslo], Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Perelman School of Medicine, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Split, The Wellcome Trust Sanger Institute [Cambridge], RWTH Aachen University, Universitätsklinikum Frankfurt, Universita degli Studi di Padova, University Hospital Basel [Basel], Jülich Supercomputing Centre (JSC), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota System, University of Bristol [Bristol], Hannover Medical School [Hannover] (MHH), Harokopio University of Athens, Seattle University [Seattle], Virginia Commonwealth University (VCU), University of Athens Medical School [Athens], 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), Poznan University of Medical Sciences [Poland] (PUMS), Institute of Environmental Science and Technology [Barcelona] (ICTA), Universitat Autònoma de Barcelona (UAB), Massachusetts General Hospital [Boston], Stanford University, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Estonian Genome and Medicine, University of Tartu, Universitat Pompeu Fabra [Barcelona] (UPF), MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Ludwig-Maximilians-Universität München (LMU), Infectious diseases division, Department of internal medicine, University of Münster, Masaryk Memorial Cancer Institute, Masaryk Memorial Cancer Institute (RECAMO), Universitätsklinikum Bonn (UKB), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Medstar Research Institute, Universität Duisburg-Essen [Essen], National and Kapodistrian University of Athens (NKUA), Children’s Hospital of Philadelphia (CHOP ), The Center for Applied Genomics, Psychiatric Genetic Unit, Poznan University of Medical Sciences, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Heidelberg University Hospital [Heidelberg], Icahn School of Medicine at Mount Sinai [New York] (MSSM), School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Parkland-Klinik [Bad Wildungen-Reinhardshausen, Germany], Tokai University, Department of Epidemiology and Public Health [university of Ostrava], Lékařská fakulta / Faculty of Medicine [University of Ostrava], Ostravská univerzita / University of Ostrava-Ostravská univerzita / University of Ostrava, Vall d'Hebron University Hospital [Barcelona], Charles University [Prague] (CU), University of Eastern Finland, Medizinische Universität Wien = Medical University of Vienna, Centre de toxicomanie et de santé mentale [Toronto, ON, Canada], University of Helsinki, University of Aberdeen, Faculty of Science, J.E. Purkinje University, J. E. Purkinje University, Michigan State University System, Norwegian Institute of Public Health [Oslo] (NIPH), Haukeland University Hospital, University of Bergen (UiB), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), The Chicago School of Professional Psychology [Washington, District of Columbia, USA] (Washington DC Campus), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Department of Psychiatry, University of Napoli, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], University College Cork (UCC), Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, VA Boston Healthcare System, Università degli studi della Campania 'Luigi Vanvitelli', Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kartini Clinic [Portland, Oregon, USA], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Vanderbilt University School of Medicine [Nashville], The Hospital for sick children [Toronto] (SickKids), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Epidemiology and Biostatistics (MEB), University of Pisa - Università di Pisa, Division of Psychiatric Genomics, Institute of Medical Informatics, Biometry and Epidemiology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Leiden University Medical Center (LUMC), Center for Eating Disorders Ursula [Leiden, The Netherlands] (Rivierduinen), Medical University of Łódź (MUL), The Jackson Laboratory [Bar Harbor] (JAX), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), 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)-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), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Human Genetics, Internal Medicine [Tuebingen, Germany], Tuebingen University [Germany], Oregon Research Institute (ORI), University of Otago [Dunedin, Nouvelle-Zélande], The Center for Eating Disorders at Sheppard Pratt [Baltimore, MD, USA], Weill Medical College of Cornell University [New York], Eating Recovery Center [Denver, CO, USA], Centre for Addiction and Mental Health [Toronto, ON, Canada], University of California [San Diego] (UC San Diego), University of California, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Institute of Medical Science [Toronto], University of Toronto, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Genomics, Yale University School of Medicine, Indiana University School of Medicine, Indiana University System, Mayo Clinic [Rochester], Mayo Clinic, SUNY Downstate Medical Center, State University of New York (SUNY), University of Edinburgh, Department of Genomics, Life and Brain Center, University of Bonn, University of Utah School of Medicine [Salt Lake City], University of Heidelberg, Medical Faculty, Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], National Institutes of Health [Bethesda] (NIH), National Institute on Alcohol Abuse and Alcoholism [Bethesda, MD, USA] (NIAAA), Martin-Luther-University Halle-Wittenberg, Helsinki Institute of Life Science (HiLIFE), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Vrije Universiteit Amsterdam [Amsterdam] (VU), Mathematical Sciences Institute (MSI), Australian National University (ANU), University of Colorado [Boulder], VU University Medical Center [Amsterdam], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Universität Heidelberg [Heidelberg], Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Harvard University [Cambridge], University of Colorado Anschutz [Aurora], University of Vermont [Burlington], University of New South Wales [Sydney] (UNSW), University of Dusseldorf, Genetics and Pathology, Center for Human Genetic Research, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Heidelberg University, University of Iowa [Iowa City], Vienna University of Technology (TU Wien), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Indiana University System-Indiana University System, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Regensburg, Rush University Medical Center [Chicago], University of Utah, Duke University Medical Center, University of Illinois [Chicago] (UIC), University of Illinois System, Department of Medical and Molecular Genetics, Dpt of Neuroscience [New York], Laboratory of Neurogenetics, National Institutes of Health [Bethesda] (NIH)-National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, University of Connecticut (UCONN), University of Colorado [Denver], Research Triangle Institute International (RTI International), McMaster University [Hamilton, Ontario], CLinical Psychology, Department of Electrical and Computer Engineering [Montréal], McGill University = Université McGill [Montréal, Canada], Yale School of Public Health (YSPH), Analytic and Translational Genetics Unit, Flinders University [Adelaide, Australia], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Department of Public Health, Indiana University - Purdue University Indianapolis (IUPUI), National Institute of Mental Health (NIMH), University of Pennsylvania, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Università degli Studi di Padova = University of Padua (Unipd), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), King‘s College London-The Institute of Psychiatry, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Masaryk Memorial Cancer Institute (MMCI), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Università degli Studi di Firenze = University of Florence (UniFI), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Medical Research Council-Cardiff University, Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California (UC), University of California (UC)-University of California (UC), Yale School of Medicine [New Haven, Connecticut] (YSM), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Martinez Rico, Clara, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Kas lab, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Munn-Chernoff, M. A., Johnson, E. C., Chou, Y. -L., Coleman, J. R. I., Thornton, L. M., Walters, R. K., Yilmaz, Z., Baker, J. H., Hubel, C., Gordon, S., Medland, S. E., Watson, H. J., Gaspar, H. A., Bryois, J., Hinney, A., Leppa, V. M., Mattheisen, M., Ripke, S., Yao, S., Giusti-Rodriguez, P., Hanscombe, K. B., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Berrettini, W. H., Boehm, I., Boni, C., Boraska Perica, V., Buehren, K., Burghardt, R., Cassina, M., Cichon, S., Clementi, M., Cone, R. D., Courtet, P., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J. E., Dick, D. M., Dikeos, D., Dina, C., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L. E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Farmer, A., Favaro, A., Fernandez-Aranda, F., Fichter, M. M., Fischer, K., Focker, M., Foretova, L., Forstner, A. J., Forzan, M., Franklin, C. S., Gallinger, S., Giegling, I., Giuranna, J., Gonidakis, F., Gorwood, P., Gratacos Mayora, M., Guillaume, S., Guo, Y., Hakonarson, H., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S. G., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jimenez-Murcia, S., Julia, A., Kalsi, G., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, J. L., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K. L., Knudsen, G. P. S., La Via, M. C., Le Hellard, S., Levitan, R. D., Li, D., Lilenfeld, L., Lin, B. D., Lissowska, J., Luykx, J., Magistretti, P. J., Maj, M., Mannik, K., Marsal, S., Marshall, C. R., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, K., Monteleone, A. M., Monteleone, P., Nacmias, B., Navratilova, M., Ntalla, I., O'Toole, J. K., Ophoff, R. A., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Swiatkowska, B., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wagner, G., Walton, E., Widen, E., Zeggini, E., Zerwas, S., Zipfel, S., Bergen, A. W., Boden, J. M., Brandt, H., Crawford, S., Halmi, K. A., Horwood, L. J., Johnson, C., Kaplan, A. S., Kaye, W. H., Mitchell, J., Olsen, C. M., Pearson, J. F., Pedersen, N. L., Strober, M., Werge, T., Whiteman, D. C., Woodside, D. B., Grove, J., Henders, A. K., Larsen, J. T., Parker, R., Petersen, L. V., Jordan, J., Kennedy, M. A., Birgegard, A., Lichtenstein, P., Norring, C., Landen, M., Mortensen, P. B., Polimanti, R., Mcclintick, J. N., Adkins, A. E., Aliev, F., Bacanu, S. -A., Batzler, A., Bertelsen, S., Biernacka, J. M., Bigdeli, T. B., Chen, L. -S., Clarke, T. -K., Degenhardt, F., Docherty, A. R., Edwards, A. C., Foo, J. C., Fox, L., Frank, J., Hack, L. M., Hartmann, A. M., Hartz, S. M., Heilmann-Heimbach, S., Hodgkinson, C., Hoffmann, P., Hottenga, J. -J., Konte, B., Lahti, J., Lahti-Pulkkinen, M., Lai, D., Ligthart, L., Loukola, A., Maher, B. S., Mbarek, H., Mcintosh, A. M., Mcqueen, M. B., Meyers, J. L., Milaneschi, Y., Palviainen, T., Peterson, R. E., Ryu, E., Saccone, N. L., Salvatore, J. E., Sanchez-Roige, S., Schwandt, M., Sherva, R., Streit, F., Strohmaier, J., Thomas, N., Wang, J. -C., Webb, B. T., Wedow, R., Wetherill, L., Wills, A. G., Zhou, H., Boardman, J. D., Chen, D., Choi, D. -S., Copeland, W. E., Culverhouse, R. C., Dahmen, N., Degenhardt, L., Domingue, B. W., Frye, M. A., Gaebel, W., Hayward, C., Ising, M., Keyes, M., Kiefer, F., Koller, G., Kramer, J., Kuperman, S., Lucae, S., Lynskey, M. T., Maier, W., Mann, K., Mannisto, S., Muller-Myhsok, B., Murray, A. D., Nurnberger, J. I., Preuss, U., Raikkonen, K., Reynolds, M. D., Ridinger, M., Scherbaum, N., Schuckit, M. A., Soyka, M., Treutlein, J., Witt, S. H., Wodarz, N., Zill, P., Adkins, D. E., Boomsma, D. I., Bierut, L. J., Brown, S. A., Bucholz, K. K., Costello, E. J., de Wit, H., Diazgranados, N., Eriksson, J. G., Farrer, L. A., Foroud, T. M., Gillespie, N. A., Goate, A. M., Goldman, D., Grucza, R. A., Hancock, D. B., Harris, K. M., Hesselbrock, V., Hewitt, J. K., Hopfer, C. J., Iacono, W. G., Johnson, E. O., Karpyak, V. M., Kendler, K. S., Kranzler, H. R., Krauter, K., Lind, P. A., Mcgue, M., Mackillop, J., Madden, P. A. F., Maes, H. H., Magnusson, P. K. E., Nelson, E. C., Nothen, M. M., Palmer, A. A., Penninx, B. W. J. H., Porjesz, B., Rice, J. P., Rietschel, M., Riley, B. P., Rose, R. J., Shen, P. -H., Silberg, J., Stallings, M. C., Tarter, R. E., Vanyukov, M. M., Vrieze, S., Wall, T. L., Whitfield, J. B., Zhao, H., Neale, B. M., Wade, T. D., Heath, A. C., Montgomery, G. W., Martin, N. G., Sullivan, P. F., Kaprio, J., Breen, G., Gelernter, J., Edenberg, H. J., Bulik, C. M., and Agrawal, A.
Subjects: Netherlands Twin Register (NTR), Alcoholism/genetics, Schizophrenia/genetics, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, Medicine (miscellaneous), Genome-wide association study, Alcohol use disorder, Anorexia nervosa, Linkage Disequilibrium, ddc:616.89, [SCCO]Cognitive science, 0302 clinical medicine, Risk Factors, Tobacco Use Disorder/genetics, Substance-Related Disorders/genetics, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Factors de risc en les malalties, Bulimia nervosa, Feeding and Eating Disorders/genetics, eating disorders, genetic correlation, substance use, Tobacco Use Disorder, 3. Good health, Fenotip, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Alcoholism, Eating disorders, Phenotype, Schizophrenia, Drinking of alcoholic beverages, eating disorder, Consum d'alcohol, Major depressive disorder, medicine.symptom, Depressive Disorder, Major/genetics, eating disorders, genetic correlation, substance use, Clinical psychology, Substance abuse, Risk factors in diseases, Substance-Related Disorders, Polymorphism, Single Nucleotide, Article, Feeding and Eating Disorders, 03 medical and health sciences, SDG 3 - Good Health and Well-being, mental disorders, Genetics, medicine, Humans, Trastorns de la conducta alimentària, 030304 developmental biology, Genetic association, Pharmacology, Depressive Disorder, Major, Binge eating, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, [SCCO] Cognitive science, medicine.disease, Comorbidity, Twin study, 030227 psychiatry, Abús de substàncies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, business, Genètica, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genome-Wide Association Study
Abstract: Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; qwith binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to −0.23; qs
Published: 2021

14. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

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

15. Are there effects of consultation–liaison-psychiatry on length of stay in the general hospital? A path analysis

Author: Matthias Brunn, James J. Strain, Albert Diefenbacher, Centre d'Etudes Politiques Et sociaLes : Environnement, Santé, Territoires (CEPEL), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], and Mount Sinai Hospital [Toronto, Canada] (MSH)
Subjects: medicine.medical_specialty, Psychological intervention, 03 medical and health sciences, 0302 clinical medicine, Linear regression, Medicine, 030212 general & internal medicine, General hospital, Path analysis, Psychiatry, Path analysis (statistics), Suicidal ideation, Consultation-liaison psychiatry, Univariate analysis, Time-to-referral, business.industry, Retrospective cohort study, [SHS.SCIPO]Humanities and Social Sciences/Political science, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Liaison psychiatry, Length of stay, medicine.symptom, business
Abstract: Background and objectives Recently, several publications have addressed interactions between selected factors related to the role of consultation–liaison (CL) psychiatric interventions and length of stay (LOS) in the general hospital anew. Yet at present, recent available research is restricted in the scope of factors studied. This study aims at providing an analysis of factors associated with LOS in a large sample of patients, with a broad set of variables and by accounting for the complex relationships between them. Methods Retrospective cohort analysis of n = 3190 adult patients referred to the CL-psychiatry service of a general hospital. Univariate statistics and multiple regression were used to assess the association between patient characteristics and LOS. Path analysis was used to elucidate the mediating role of time-to-referral (TTR). Results Univariate analysis and multiple regression showed that TTR, age, and poor general functioning were associated with longer LOS. Diagnosis on Axis I + II (according to DSM), suicidal ideation and somatic diagnosis had no significant association with LOS. The four variables with the strongest total effect on LOS in the path analysis were TTR, the year of consultation, age and general functioning. Age had a higher indirect effect on LOS, while general functioning had a higher direct effect on LOS. Conclusions In the path model, TTR is a highly significant predictor of LOS and also a mediator of other predictors. This highlights the role of the CL-psychiatrist in the management of patients in the general hospital. Further research should investigate how referrals are prioritized by consultees and which different effects consultation recommendations might have on LOS.
Published: 2020

16. Human and mouse essentiality screens as a resource for disease gene discovery

Author: Cacheiro, Pilar, Muñoz-Fuentes, Violeta, Westerberg, Henrik, Scott, R. H., Siddiq, A., Sieghart, A., Smith, K. R., Sosinsky, A., Spooner, W., Stevens, H. E., Stuckey, A., Sultana, R., Thomas, E. R. A., Konopka, Tomasz, Thompson, S. R., Tregidgo, C., Tucci, A., Walsh, E., Watters, S. A., Welland, M. J., Williams, E., Witkowska, K., Wood, S. M., Zarowiecki, M., Hsu, Chih-Wei, Marschall, Susan, Lengger, Christoph, Maier, Holger, Seisenberger, Claudia, Bürger, Antje, Kühn, Ralf, Schick, Joel, Hörlein, Andreas, Oritz, Oskar, Giesert, Florian, Christiansen, Audrey, Beig, Joachim, Kenyon, Janet, Codner, Gemma, Fray, Martin, Johnson, Sara J, Cleak, James, Szoke-Kovacs, Zsombor, Lafont, David, Vancollie, Valerie E, McLaren, Robbie S B, Lanza, Denise G, Hughes-Hallett, Lena, Rowley, Christine, Sanderson, Emma, Galli, Antonella, Tuck, Elizabeth, Green, Angela, Tudor, Catherine, Siragher, Emma, Dabrowska, Monika, Mazzeo, Cecilia Icoresi, Beaudet, Arthur L, Griffiths, Mark, Gannon, David, Doe, Brendan, Cockle, Nicola, Kirton, Andrea, Bottomley, Joanna, Ingle, Catherine, Ryder, Edward, Gleeson, Diane, Ramirez-Solis, Ramiro, Heaney, Jason D, Birling, Marie-Christine, Pavlovic, Guillaume, Ayadi, Abdel, Hamid, Meziane, About, Ghina Bou, Champy, Marie-France, Jacobs, Hugues, Wendling, Olivia, Leblanc, Sophie, Vasseur, Laurent, Fuchs, Helmut, Chesler, Elissa J, Kumar, Vivek, White, Jacqueline K, Svenson, Karen L, Wiegand, Jean-Paul, Anderson, Laura L, Wilcox, Troy, Clark, James, Ryan, Jennifer, Denegre, James, Gailus-Durner, Valerie, Stearns, Tim, Philip, Vivek, Witmeyer, Catherine, Bates, Lindsay, Seavey, Zachary, Stanley, Pamela, Willet, Amelia, Roper, Willson, Creed, Julie, Moore, Michayla, Sorg, Tania, Dorr, Alex, Fraungruber, Pamelia, Presby, Rose, Mckay, Matthew, Nguyen-Bresinsky, Dong, Goodwin, Leslie, Urban, Rachel, Kane, Coleen, Murray, Stephen A, Prochazka, Jan, Novosadova, Vendula, Lelliott, Christopher J, Wardle-Jones, Hannah, Wells, Sara, Teboul, Lydia, Cater, Heather, Stewart, Michelle, Hough, Tertius, Wurst, Wolfgang, Dickinson, Mary E, Sedlacek, Radislav, Adams, David J, Seavitt, John R, Tocchini-Valentini, Glauco, Mammano, Fabio, Braun, Robert E, McKerlie, Colin, Herault, Yann, de Angelis, Martin Hrabě, Mallon, Ann-Marie, Bucan, Maja, Lloyd, K C Kent, Brown, Steve D M, Parkinson, Helen, Meehan, Terrence F, Smedley, Damian, Consortium, Genomics England Research, Consortium, International Mouse Phenotyping, Ambrose, J. C., Arumugam, P., Baple, E. L., Nutter, Lauryl M J, Bleda, M., Boardman-Pretty, F., Boissiere, J. M., Boustred, C. R., Brittain, H., Caulfield, M. J., Chan, G. C., Craig, C. E. H., Daugherty, L. C., de Burca, A., Peterson, Kevin A, Devereau, A., Elgar, G., Foulger, R. E., Fowler, T., Furió-Tarí, P., Hackett, J. M., Halai, D., Hamblin, A., Henderson, S., Holman, J. E., Haselimashhadi, Hamed, Hubbard, T. J. P., Ibáñez, K., Jackson, R., Jones, L. J., Kasperaviciute, D., Kayikci, M., Lahnstein, L., Lawson, K., Leigh, S. E. A., Leong, I. U. S., Flenniken, Ann M, Lopez, F. J., Maleady-Crowe, F., Mason, J., McDonagh, E. M., Moutsianas, L., Mueller, M., Murugaesu, N., Need, A. C., Odhams, C. A., Patch, C., Morgan, Hugh, Perez-Gil, D., Polychronopoulos, D., Pullinger, J., Rahim, T., Rendon, A., Riesgo-Ferreiro, P., Rogers, T., Ryten, M., Savage, K., Sawant, K., Cacheiro, Pilar [0000-0002-6335-8208], Muñoz-Fuentes, Violeta [0000-0003-3574-546X], Nutter, Lauryl MJ [0000-0001-9619-146X], Peterson, Kevin A [0000-0001-8353-3694], Haselimashhadi, Hamed [0000-0001-7334-2421], Konopka, Tomasz [0000-0003-3042-4712], Hsu, Chih-Wei [0000-0002-9591-9567], Lanza, Denise G [0000-0001-8750-6933], Heaney, Jason D [0000-0001-8475-8828], Fuchs, Helmut [0000-0002-5143-2677], Gailus-Durner, Valerie [0000-0002-6076-0111], Lelliott, Christopher J [0000-0001-8087-4530], Adams, David J [0000-0001-9490-0306], Mammano, Fabio [0000-0003-3751-1691], McKerlie, Colin [0000-0002-2232-0967], Herault, Yann [0000-0001-7049-6900], de Angelis, Martin Hrabě [0000-0002-7898-2353], Lloyd, KC Kent [0000-0002-5318-4144], Smedley, Damian [0000-0002-5836-9850], Apollo - University of Cambridge Repository, Queen Mary University of London (QMUL), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, The Jackson Laboratory [Bar Harbor] (JAX), Baylor College of Medicine (BCM), Baylor University, University of Pennsylvania, The Hospital for sick children [Toronto] (SickKids), Mount Sinai Hospital [Toronto, Canada] (MSH), MRC Harwell Institute [UK], Helmholtz Zentrum München = German Research Center for Environmental Health, Institut Clinique de la Souris (ICS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), French National Infrastructure for Mouse Phenogenomics (PHENOMIN), Institute of Molecular Genetics of the Czech Academy of Sciences (IMG / CAS), Czech Academy of Sciences [Prague] (CAS), The Wellcome Trust Sanger Institute [Cambridge], Technische Universität München = Technical University of Munich (TUM), Ludwig-Maximilians-Universität München (LMU), CNR - Italian National Research Council (CNR), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), University of California [Davis] (UC Davis), University of California (UC), J C Ambrose, P Arumugam, E L Baple, M Bleda, F Boardman-Pretty, J M Boissiere, C R Boustred, H Brittain, M J Caulfield, G C Chan, C E H Craig, L C Daugherty, A de Burca, A Devereau, G Elgar, R E Foulger, T Fowler, P Furió-Tarí, J M Hackett, D Halai, A Hamblin, S Henderson, J E Holman, T J P Hubbard, K Ibáñez, R Jackson, L J Jones, D Kasperaviciute, M Kayikci, L Lahnstein, K Lawson, S E A Leigh, I U S Leong, F J Lopez, F Maleady-Crowe, J Mason, E M McDonagh, L Moutsianas, M Mueller, N Murugaesu, A C Need, C A Odhams, C Patch, D Perez-Gil, D Polychronopoulos, J Pullinger, T Rahim, A Rendon, P Riesgo-Ferreiro, T Rogers, M Ryten, K Savage, K Sawant, R H Scott, A Siddiq, A Sieghart, K R Smith, A Sosinsky, W Spooner, H E Stevens, A Stuckey, R Sultana, E R A Thomas, S R Thompson, C Tregidgo, A Tucci, E Walsh, S A Watters, M J Welland, E Williams, K Witkowska, S M Wood, M Zarowiecki, Susan Marschall, Christoph Lengger, Holger Maier, Claudia Seisenberger, Antje Bürger, Ralf Kühn, Joel Schick, Andreas Hörlein, Oskar Oritz, Florian Giesert, Joachim Beig, Janet Kenyon, Gemma Codner, Martin Fray, Sara J Johnson, James Cleak, Zsombor Szoke-Kovacs, David Lafont, Valerie E Vancollie, Robbie S B McLaren, Lena Hughes-Hallett, Christine Rowley, Emma Sanderson, Antonella Galli, Elizabeth Tuck, Angela Green, Catherine Tudor, Emma Siragher, Monika Dabrowska, Cecilia Icoresi Mazzeo, Mark Griffiths, David Gannon, Brendan Doe, Nicola Cockle, Andrea Kirton, Joanna Bottomley, Catherine Ingle, Edward Ryder, Diane Gleeson, Ramiro Ramirez-Solis, Marie-Christine Birling, Guillaume Pavlovic, Abdel Ayadi, Meziane Hamid, Ghina Bou About, Marie-France Champy, Hugues Jacobs, Olivia Wendling, Sophie Leblanc, Laurent Vasseur, Elissa J Chesler, Vivek Kumar, Jacqueline K White, Karen L Svenson, Jean-Paul Wiegand, Laura L Anderson, Troy Wilcox, James Clark, Jennifer Ryan, James Denegre, Tim Stearns, Vivek Philip, Catherine Witmeyer, Lindsay Bates, Zachary Seavey, Pamela Stanley, Amelia Willet, Willson Roper, Julie Creed, Michayla Moore, Alex Dorr, Pamelia Fraungruber, Rose Presby, Matthew Mckay, Dong Nguyen-Bresinsky, Leslie Goodwin, Rachel Urban, Coleen Kane, Herault, Yann, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)
Subjects: 0301 basic medicine, Mutation rate, Cancer Research, [SDV]Life Sciences [q-bio], General Physics and Astronomy, methods [Genetic Association Studies], Disease, VARIANTS, Mice, Essential, 0302 clinical medicine, IMPC, Genetics research, Lethal allele, 2.1 Biological and endogenous factors, Aetiology, lcsh:Science, Organism, ComputingMilieux_MISCELLANEOUS, Disease gene, Mice, Knockout, 0303 health sciences, Multidisciplinary, Genes, Essential, genetics [Disease], Genomics, R/BIOCONDUCTOR PACKAGE, DATABASE, UPDATE, GENOME, [SDV] Life Sciences [q-bio], Knockout mouse, Identification (biology), ddc:500, International Mouse Phenotyping Consortium, Technology Platforms, Biotechnology, Knockout, Science, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Genetics, medicine, Animals, Humans, Genetic variation, Clinical genetics, Gene, Genetic Association Studies, 030304 developmental biology, Disease model, Prevention, Human Genome, General Chemistry, medicine.disease, Developmental disorder, Good Health and Well Being, 030104 developmental biology, Genomics England Research Consortium, Genes, lcsh:Q, Generic health relevance, 030217 neurology & neurosurgery, Rare disease
Abstract: The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery., Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.
Published: 2020
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17. Usefulness of Parasternal Intercostal Muscle Ultrasound during Weaning from Mechanical Ventilation

Author: Alexandre Demoule, Elise Morawiec, Julien Mayaux, Thomas Similowski, Martin Dres, Laurent Brochard, Bruno-Pierre Dubé, Stefannie Vorona, Ewan C. Goligher, Suela Demiri, dres, martin, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), St. Michael's Hospital, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], University of Toronto, Mount Sinai Hospital [Toronto, Canada] (MSH), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, medicine.medical_specialty, Weakness, Intraclass correlation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Diaphragm, Intercostal Muscles, Spontaneous breathing trial, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, Ultrasonography, Interventional, Mechanical ventilation, business.industry, Ultrasound, 030208 emergency & critical care medicine, Respiration, Artificial, Diaphragm (structural system), [SDV] Life Sciences [q-bio], Anesthesiology and Pain Medicine, medicine.anatomical_structure, 030228 respiratory system, Parasternal line, Cardiology, Female, medicine.symptom, business, Ventilator Weaning, Intercostal muscle
Abstract: Background The assessment of diaphragm function with diaphragm ultrasound seems to bring important clinical information to describe diaphragm work and weakness. When the diaphragm is weak, extradiaphragmatic muscles may play an important role, but whether ultrasound can also assess their activity and function is unknown. This study aimed to (1) evaluate the feasibility of measuring the thickening of the parasternal intercostal and investigate the responsiveness of this muscle to assisted ventilation; and (2) evaluate whether a combined evaluation of the parasternal and the diaphragm could predict failure of a spontaneous breathing trial. Methods First, an exploratory evaluation of the parasternal in 23 healthy subjects. Second, the responsiveness of parasternal to several pressure support levels were studied in 16 patients. Last, parasternal activity was compared in presence or absence of diaphragm dysfunction (assessed by magnetic stimulation of the phrenic nerves and ultrasound) and in case of success/failure of a spontaneous breathing trial in 54 patients. Results The parasternal was easily accessible in all patients. The interobserver reproducibility was good (intraclass correlation coefficient, 0.77 (95% CI, 0.53 to 0.89). There was a progressive decrease in parasternal muscle thickening fraction with increasing levels of pressure support (Spearman ρ = −0.61 [95% CI, −0.74 to −0.44]; P < 0.0001) and an inverse correlation between parasternal muscle thickening fraction and the pressure generating capacity of the diaphragm (Spearman ρ = −0.79 [95% CI, −0.87 to −0.66]; P < 0.0001). The parasternal muscle thickening fraction was higher in patients with diaphragm dysfunction: 17% (10 to 25) versus 5% (3 to 8), P < 0.0001. The pressure generating capacity of the diaphragm, the diaphragm thickening fraction and the parasternal thickening fraction similarly predicted failure or the spontaneous breathing trial. Conclusions Ultrasound assessment of the parasternal intercostal muscle is feasible in the intensive care unit and provides novel information regarding the respiratory capacity load balance. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Published: 2020

18. Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis

Author: Michael O. Woods, Fränzel J.B. van Duijnhoven, Tilman Kühn, Graham G. Giles, Temitope O. Keku, Konstantinos K. Tsilidis, Andrew T. Chan, Mingyang Song, Michael Hoffmeister, Gad Rennert, Tabitha A. Harrison, Anna H. Wu, Kenneth Offit, Mark A. Jenkins, Elizabeth A Platz, Sabina Sieri, Noralane M Lindor, John D. Potter, D Timothy Bishop, Barbara L. Banbury, Anne M. May, Sonja I. Berndt, José María Huerta, Antonia Trichopoulou, Paul D.P. Pharoah, Niki Dimou, Christopher I. Li, Roger L. Milne, Marc J. Gunter, Hermann Brenner, Martha L. Slattery, Catherine M. Tangen, Gianluca Severi, Richard M. Martin, Nabila Kazmi, Ruth C. Travis, Sanford D. Markowitz, Jeroen R. Huyghe, Heather Hampel, Ulrike Peters, John L. Hopper, Brigid M. Lynch, Krasimira Aleksandrova, Alicja Wolk, Merete Ellingjord-Dale, Li Li, Bethany Van Guelpen, Sergi Castellví-Bel, Edward Giovannucci, Steven J Gallinger, Annika Lindblom, Cornelia M. Ulrich, Stephen B. Gruber, Stephanie L. Schmit, Jenny Chang-Claude, Lorena Moreno, Victor Moreno, Nikos Papadimitriou, Stephen N. Thibodeau, Elio Riboli, Sophia Harlid, Polly A. Newcomb, Pavel Vodicka, Demetrius Albanes, Bas Bueno-de-Mesquita, Maria J. Sánchez, Sarah J Lewis, Timothy Robinson, Daniel D Buchanan, Loic Le Marchand, Carlo La Vecchia, Robert E Schoen, Neil Murphy, Giovanna Masala, Evelyn M. Monninkhof, Jane C. Figueiredo, Andrea Gsur, Jochen Hampe, Vittorio Perduca, Li Hsu, Emily White, Peter T. Campbell, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Epidemiology, German Institute of Human Nutrition, Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), The Cancer, Ageing and Somatic Mutation Programme [Cambridgeshire, UK], The Wellcome Trust Sanger Institute [Cambridge], Division of Cancer Epidemiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Melbourne, Harvard School of Public Health, Department of Internal Medicine, Epidemiology, Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Medical Department 1 [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Ohio State University [Columbus] (OSU), FESTO, Universität Stuttgart [Stuttgart], Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Genetics, HMNC Brain Health, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), University of Hawai‘i [Mānoa] (UHM), Chinese Center for Disease Control and Prevention, Department of Clinical Genetics, Karolinska University Hospital [Stockholm], Mayo Clinic, Case Western Reserve University [Cleveland], Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Cancer Epidemiology Centre, Cancer Council Victoria, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Memorial Sloane Kettering Cancer Center [New York], Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Department of Oncology, University of Cambridge [UK] (CAM), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Department of Community Medicine and Epidemiology, CHS National Cancer Control Center, School of Public Health [London, UK] (Faculty of Medicine), Andalusian School of Public Health [Granada], Istituto Nazionale dei Tumori, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Mayo Clinic [Rochester], University of Oxford [Oxford], WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Helmholtz Centre for Ocean Research [Kiel] (GEOMAR), Department of Medical Biosciences and Pathology, Umeå University, Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Karolinska Institutet [Stockholm], Nutrition and Metabolism Section, International Agency for Research on Cancer, [Papadimitriou,N, Dimou,N, Gunter,MJ, Murphy,N] Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Tsilidis,KK, Ellingjord-Dale,M, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Banbury,B, Harrison,TA, Hsu,L, Huyghe,JR, Li,CI, Newcomb,PA, Potter,JD, White,E, Peters,U] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Martin,RM, Kazmi,N] MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. [Martin,RM, Lewis,SJ, Robinson,TM] Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK. [Martin,RM] National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK. [Albanes,D, Berndt,SI] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MA, USA. [Aleksandrova,K] German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Bishop,DT] Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK. [Brenner,H, Hoffmeister,M] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Brenner,H] Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. [Brenner,H] German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. [Buchanan,DD, Giles,GG, Hopper,JL, Jenkins,MA, Lynch,B, Milne,R] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. [Buchanan,DD] Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Buchanan,DD] Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia [Bueno-de-Mesquita,B] Former senior scientist, Dept. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), BA Bilthoven, Netherlands. [Bueno-de-Mesquita,B] Former associate professor, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands. [Bueno-de-Mesquita,B] ormer visiting professor, Dept. of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary’s Campus, Norfolk Place, London, London, UK. [Bueno-de-Mesquita,B] Former academic Icon / visiting professor, Dept. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, Kuala Lumpur, Malaysia. [Campbell,PT] Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA. [Castellví-Bel,S, Moreno,L] Gastroenterology Department, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain. [Chan,AT, Song,M] Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chan,AT, Song,M] Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. [Chang-Claude,J, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Chang-Claude,J] University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany. [Figueiredo,JC] Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [Figueiredo,JC] Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gallinger,SJ] Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. [Giles,GG, Milne,R] Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia. [Giovannucci,E, Song,M] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. [Giovannucci,E, Song,M] Department of Nutrition, T.H. H, Chan School of Public Health, Boston, MA, USA. [Giovannucci,E] Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Gruber,SB, Schmit,SL] Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. [Gsur,A] Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria. [Hampe,J] Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany. [Hampel,H] Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. [Harlid,S] Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden. [Hopper,JL] Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea. [Hsu,L] Department of Biostatistics, University of Washington, Seattle, WA, USA. [Huerta,JM, Moreno,V, Sánchez,MJ] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Keku,TO] Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA. [La Vecchia,C, Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [La Vecchia,C] Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy. [Le Marchand,L] University of Hawaii Cancer Center, Honolulu, HI, USA. [Li,L] Department of Family Medicine, University of Virginia, Charlottesville, VA, USA. [Lindblom,A] Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. [Lindblom,A] Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. [Lindor,NM] Department of Health Science Research, Mayo Clinic, Scottsdale, AZ, USA. [Lynch,B] Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. [Markowitz,SD] Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, OH, USA. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [May,AM, Monninkhof,E] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, GA UTRECHT, Netherlands. [Milne,R] Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. [Moreno,V] Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Moreno,V] Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain. [Newcomb,PA] School of Public Health, University of Washington, Seattle, WA, USA. [Offit,K] Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. [Offit,K] Department of Medicine, Weill Cornell Medical College, New York, NY, USA. [Perduca,V, Severi,G] CESP, Fac. de médecine - Univ. ParisSud, Fac. de médecine - UVSQ I, Université Paris-Saclay, Villejuif, France. [Perduca,V, Severi,G] Gustave Roussy, Villejuif, France. [Perduca,V] Laboratoire de Mathématiques Appliquées MAP5 (UMR CNRS 8145), Université Paris Descartes, Paris, France. [Pharoah,PDP] Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Platz,EA] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. [Rennert,G] Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel. [Rennert,G] 7Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. [Rennert,G] Clalit National Cancer Control Center, Haifa, Israel. [Sánchez,MJ] Andalusian School of Public Health, Biomedical Research Institute ibs.GRANADA, University of Granada, Granada, Spain. [Schmit,SL] Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. [Schoen,RE] Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Slattery,ML] Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. [Tangen,CM] SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. [Thibodeau,SN] Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Ulrich,CM] Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. [van Duijnhoven,FJB] Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands. [Van Guelpen,B] Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden. [Van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Vodicka,P] Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic. [Vodicka,P] Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic. [Vodicka,P] Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic. [White,E, Peters,U] Department of Epidemiology, University of Washington, Seattle, WA, USA. [Wolk,A] Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. [Woods,MO] Memorial University of Newfoundland, Discipline of Genetics, St. John’s, Canada. [Wu,AH] University of Southern California, Preventative Medicine, Los Angeles, CA, USA., This work was supported by the National Cancer Institute, the International Agency for Research on Cancer and a Cancer Research UK program grant (C18281/A19169 to RMM, SJL & NK). RMM was supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funding sources for BCAC, CCFR, GECCO, and CORECT consortia are presented in detail in the appendix in the Supplementary material., Tsilidis, Konstantinos K [0000-0002-8452-8472], Martin, Richard M [0000-0002-7992-7719], Lewis, Sarah J [0000-0003-4311-6890], Robinson, Timothy M [0000-0003-0933-646X], Timothy Bishop, D [0000-0002-8752-8785], Buchanan, Daniel D [0000-0003-2225-6675], Chan, Andrew T [0000-0001-7284-6767], Giles, Graham G [0000-0003-4946-9099], Gsur, Andrea [0000-0002-9795-1528], Hampe, Jochen [0000-0002-2421-6127], Hampel, Heather [0000-0001-7558-9794], Harlid, Sophia [0000-0001-8540-6891], Harrison, Tabitha A [0000-0002-4173-7530], María Huerta, José [0000-0002-9637-3869], Huyghe, Jeroen R [0000-0001-6027-9806], Jenkins, Mark A [0000-0002-8964-6160], La Vecchia, Carlo [0000-0003-1441-897X], Masala, Giovanna [0000-0002-5758-9069], Milne, Roger [0000-0001-5764-7268], Moreno, Victor [0000-0002-2818-5487], Newcomb, Polly A [0000-0001-8786-0043], Perduca, Vittorio [0000-0003-0339-0473], Pharoah, Paul D P [0000-0001-8494-732X], Potter, John D [0000-0001-5439-1500], Rennert, Gad [0000-0002-8512-068X], Riboli, Elio [0000-0001-6795-6080], Schmit, Stephanie L [0000-0001-5931-1194], Schoen, Robert E [0000-0001-7153-2766], Van Guelpen, Bethany [0000-0002-9692-101X], Wolk, Alicja [0000-0001-7387-6845], Peters, Ulrike [0000-0001-5666-9318], Murphy, Neil [0000-0003-3347-8249], Apollo - University of Cambridge Repository, Tsilidis, Konstantinos K. [0000-0002-8452-8472], Martin, Richard M. [0000-0002-7992-7719], Lewis, Sarah J. [0000-0003-4311-6890], Timothy Bishop, D. [0000-0002-8752-8785], Buchanan, Daniel D. [0000-0003-2225-6675], Chan, Andrew T. [0000-0001-7284-6767], Giles, Graham G. [0000-0003-4946-9099], Harrison, Tabitha A. [0000-0002-4173-7530], Huyghe, Jeroen R. [0000-0001-6027-9806], Jenkins, Mark A. [0000-0002-8964-6160], Newcomb, Polly A. [0000-0001-8786-0043], Pharoah, Paul D. P. [0000-0001-8494-732X], Potter, John D. [0000-0001-5439-1500], Schmit, Stephanie L. [0000-0001-5931-1194], Schoen, Robert E. [0000-0001-7153-2766], and Pharoah, Paul DP [0000-0001-8494-732X]
Subjects: Oncology, Epidemiology, Colorectal cancer, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Accelerometry [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Molecular Epidemiology::Mendelian Randomization Analysis [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Epidemiology of cancer, Accelerometry, Odds Ratio, lcsh:Science, skin and connective tissue diseases, Cancer genetics, ComputingMilieux_MISCELLANEOUS, Cancer, 0303 health sciences, Biobank, 3. Good health, 030220 oncology & carcinogenesis, ICEP, Factores de riesgo, medicine.medical_specialty, Science, 631/67/2324, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Colorectal Neoplasms, Hereditary Nonpolyposis [Medical Subject Headings], Breast Neoplasms/genetics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Exercise [Medical Subject Headings], Humans, Epidemiologia, Exercise, VLAG, Cancer och onkologi, 45, 631/67/1347, Odds ratio, Mendelian Randomization Analysis, medicine.disease, Colorectal Neoplasms/genetics, 030104 developmental biology, Analyses, Risk factors, Check Tags::Female [Medical Subject Headings], Cancer and Oncology, lcsh:Q, Breast neoplasms, 0301 basic medicine, 631/67/1504/1885, Nutrition and Disease, General Physics and Astronomy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Risk Factors, Neoplasias colorrectales, Voeding en Ziekte, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], Multidisciplinary, article, Public Health, Global Health, Social Medicine and Epidemiology, Polymorphism, Single Nucleotide/genetics, Ejercicio físico, Neoplasias de la mama, Female, Colorectal Neoplasms, 631/67, 141, Breast Neoplasms, 45/23, Polymorphism, Single Nucleotide, Colorectal neoplasms, Càncer de mama, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], Cancer epidemiology, 631/67/68, Internal medicine, Mendelian randomization, medicine, Journal Article, Life Science, Genetic Predisposition to Disease, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], business.industry, General Chemistry, Physical fitness, Confidence interval, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Condició física
Abstract: Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI), International Agency for Research on Cancer, Cancer Research UK C18281/A19169, National Institute for Health Research (NIHR)
Published: 2020

19. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society

Author: Lyon, Alexander R., Dent, Susan, Stanway, Susanna, Earl, Helena, Brezden‐Masley, Christine, Cohen‐Solal, Alain, Tocchetti, Carlo G., Moslehi, Javid, Groarke, John D., Bergler‐Klein, Jutta, Khoo, Vincent, Tan, Li Ling, Anker, Markus S., Haehling, Stephan, Maack, Christoph, Pudil, Radek, Barac, Ana, Thavendirnathan, Paaladinesh, Ky, Bonnie, Neilan, Tomas G., Belenkov, Yury, Rosen, Stuart D., Iakobishvili, Zaza, Sverdlov, Aaron L., Hajjar, Ludhmila A., Macedo, Ariane V. S., Manisty, Charlotte, Ciardiello, Fortunato, Farmakis, Dimitrios, De Boer, Rudolf A., Skouri, Hadi, Suter, Thomas M., Cardinale, Daniela, Witteles, Ronald M., Fradley, Michael G., Herrmann, Joerg, Cornell, Robert F., Wechelaker, Ashutosh, Mauro, Michael J., Milojkovic, Dragana, Lavallade, Hugues, Ruschitzka, Frank, Coats, Andrew J. S., Seferovic, Petar M., Chioncel, Ovidiu, Thum, Thomas, Bauersachs, Johann, Andres, M. Sol, Wright, David J., López‐Fernández, Teresa, Plummer, Chris, Lenihan, Daniel, Imperial College London, Duke University [Durham], The Royal Marsden, University of Cambridge [UK] (CAM), Mount Sinai Hospital [Toronto, Canada] (MSH), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Naples Federico II = Università degli studi di Napoli Federico II, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Medizinische Universität Wien = Medical University of Vienna, Monash University [Melbourne], Shanghai Center for Plant Stress Biology [CAS] (PSC), Chinese Academy of Sciences [Beijing] (CAS), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Georg-August-University = Georg-August-Universität Göttingen, Hannover Medical School [Hannover] (MHH), Charles University [Prague] (CU), Georgetown University [Washington] (GU), University Health Network, University of Toronto, University of Pennsylvania, Massachusetts General Hospital [Boston], Sechenov First Moscow State Medical University, University College of London [London] (UCL), Tel Aviv University (TAU), University of Newcastle [Australia] (UoN), Universidade de São Paulo = University of São Paulo (USP), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, University of Cyprus [Nicosia] (UCY), University Medical Center Groningen [Groningen] (UMCG), American University of Beirut Faculty of Medicine and Medical Center (AUB), University of Bern, IRCCS Ospedale San Raffaele [Milan, Italy], Stanford University, Mayo Clinic [Rochester], Memorial Sloan Kettering Cancer Center (MSKCC), Hammersmith Hospital NHS Imperial College Healthcare, King's College Hospital (KCH), University hospital of Zurich [Zurich], University of Warwick [Coventry], Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), University of Belgrade [Belgrade], Emergency Institute for Cardiovascular Diseases 'Prof. Dr. C.C. Iliescu' [Bucharest, Romania], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Royal Brompton Hospital, Liverpool Heart and Chest Hospital NHS Trust [UK] (LH&CH), La Paz University Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), leboeuf, Christophe, Lyon, Alexander R, Dent, Susan, Stanway, Susanna, Earl, Helena, Brezden-Masley, Christine, Cohen-Solal, Alain, Tocchetti, Carlo G, Moslehi, Javid, Groarke, John D, Bergler-Klein, Jutta, Khoo, Vincent, Tan, Li Ling, Anker, Markus S, von Haehling, Stephan, Maack, Christoph, Pudil, Radek, Barac, Ana, Thavendirnathan, Paaladinesh, Ky, Bonnie, Neilan, Tomas G, Belenkov, Yury, Rosen, Stuart D, Iakobishvili, Zaza, Sverdlov, Aaron L, Hajjar, Ludhmila A, Macedo, Ariane V S, Manisty, Charlotte, Ciardiello, Fortunato, Farmakis, Dimitrio, De Boer, Rudolf A, Skouri, Hadi, Suter, Thomas M, Cardinale, Daniela, Witteles, Ronald M, Fradley, Michael G, Herrmann, Joerg, Cornell, Robert F, Wechelaker, Ashutosh, Mauro, Michael J, Milojkovic, Dragana, de Lavallade, Hugue, Ruschitzka, Frank, Coats, Andrew J S, Seferovic, Petar M, Chioncel, Ovidiu, Thum, Thoma, Bauersachs, Johann, Andres, M Sol, Wright, David J, López-Fernández, Teresa, Plummer, Chri, Lenihan, Daniel, Lyon, Alexander R., Brezden‐masley, Christine, Cohen‐solal, Alain, Tocchetti, Carlo G., Groarke, John D., Bergler‐klein, Jutta, Anker, Markus S., Haehling, Stephan, Neilan, Tomas G., Rosen, Stuart D., Sverdlov, Aaron L., Hajjar, Ludhmila A., Macedo, Ariane V. S., De Boer, Rudolf A., Suter, Thomas M., Witteles, Ronald M., Fradley, Michael G., Cornell, Robert F., Mauro, Michael J., Lavallade, Hugue, Coats, Andrew J. S., Seferovic, Petar M., Andres, M. Sol, Wright, David J., and López‐fernández, Teresa
Subjects: Male, Heart failure, Androgen Antagonists, Antineoplastic Agents, Middle Aged, Risk Assessment, Cardiotoxicity, Risk prediction, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardio-oncology, risk factor, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiovascular Diseases, Heart Disease Risk Factors, Risk Factors, Neoplasms, Humans, Female, Aged
Abstract: This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for CML targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies. This article is protected by copyright. All rights reserved.
Published: 2020

20. Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses

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

21. Prone position in ARDS patients: why, when, how and for whom

Author: John J. Marini, Antoine Vieillard-Baron, Laveena Munshi, Antonio Pesenti, Richard K. Albert, Jordi Mancebo, Luciano Gattinoni, Jeremy R. Beitler, Samir Jaber, Laurent Papazian, Claude Guérin, HAL UVSQ, Équipe, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Colorado Anschutz [Aurora], Columbia University College of Physicians and Surgeons, Georg-August-University = Georg-August-Universität Göttingen, 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), University of Minnesota System, Mount Sinai Hospital [Toronto, Canada] (MSH), University of Toronto, Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, 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, Hôpital Ambroise Paré [AP-HP], Hospital Universitari Sant Pau, Barcelona, University of Göttingen - Georg-August-Universität Göttingen, and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: ARDS, medicine.medical_specialty, Supine position, [SDV]Life Sciences [q-bio], Gravity, Review, Pulmonary compliance, Critical Care and Intensive Care Medicine, Ventilation/perfusion ratio, 03 medical and health sciences, Lung protective ventilation, Prone position, 0302 clinical medicine, Internal medicine, medicine, Humans, Lung Compliance, Contraindication, Respiratory Distress Syndrome, Acute respiratory distress syndrome, business.industry, 030208 emergency & critical care medicine, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030228 respiratory system, Ventilation/perfusion, Respiratory Mechanics, Breathing, Cardiology, business
Abstract: In ARDS patients, the change from supine to prone position generates a more even distribution of the gas–tissue ratios along the dependent–nondependent axis and a more homogeneous distribution of lung stress and strain. The change to prone position is generally accompanied by a marked improvement in arterial blood gases, which is mainly due to a better overall ventilation/perfusion matching. Improvement in oxygenation and reduction in mortality are the main reasons to implement prone position in patients with ARDS. The main reason explaining a decreased mortality is less overdistension in non-dependent lung regions and less cyclical opening and closing in dependent lung regions. The only absolute contraindication for implementing prone position is an unstable spinal fracture. The maneuver to change from supine to prone and vice versa requires a skilled team of 4–5 caregivers. The most frequent adverse events are pressure sores and facial edema. Recently, the use of prone position has been extended to non-intubated spontaneously breathing patients affected with COVID-19 ARDS. The effects of this intervention on outcomes are still uncertain. Electronic supplementary material The online version of this article (10.1007/s00134-020-06306-w) contains supplementary material, which is available to authorized users.
Published: 2020

22. Impact of foods and dietary supplements containing hydroxycinnamic acids on cardiometabolic biomarkers: A systematic review to explore inter-individual variability

Author: Egeria Scoditti, Christos Kontogiorgis, Cristina Andres-Lacueva, Emilie Combet, Mar Garcia-Aloy, Mireia Urpi-Sarda, Georgia-Eirini Deligiannidou, S.A. Palma-Duran, Marika Massaro, Eileen R. Gibney, Margherita Dall'Asta, Letizia Bresciani, Antonio González-Sarrías, Ana Rodriguez-Mateos, Daniela Martini, Christine Morand, Laura Chiavaroli, Pedro Mena, Daniele Del Rio, Viktorija Maksimova, Department of Veterinary Science, Nippon Veterinary and Life Science University, Department of Food & Drug, University of Parma, Department of Nutritional Sciences, Mount Sinai Hospital (MSH), University of Toronto, Grupo de Calidad, Seguridad y Bioactividad de Alimentos Vegetales, Centro de Edafologia y Biologia Aplicada del Segura, College of Medical, Veterinary and Life Sciences, University of Glasgow, Department of Medicine, Laboratory of Hygiene and Environmental Protection, Democritus University of Thrace (DUTH), Istituto di Fisiologia Clinica (IFC), CNR, Department of Applied Pharmacy, Faculty of Medical Sciences, University Goce Delcev (UGD), Department of Nutrition, Food Sciences and Gastronomy, University of Barcelona, XaRTA, INSA·UB, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable, Instituto de Salud Carlos III (ISC), UCD Institute of Food and Health, University College Dublin [Dublin] (UCD), School of Advanced Studies on Food and Nutrition, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), King’s College London, University of Parma = Università degli studi di Parma [Parme, Italie], Mount Sinai Hospital [Toronto, Canada] (MSH), Instituto de Salud Carlos III [Madrid] (ISC), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), King‘s College London, European Cooperation in Science and Technology (COST) FA1403-POSITIVe, European Cooperation in Science and Technology, Università degli studi di Parma = University of Parma (UNIPR), and Mena, P.
Subjects: 0301 basic medicine, Male, Future studies, Caffeoylquinic acids, Hydroxycinnamic acids, Effect modifier, Review, Coffee, Interindividual variability, law.invention, Basic medicine, 0302 clinical medicine, Randomized controlled trial, Other medical sciences, law, Coffees, Risk Factors, Compostos bioactius, 10. No inequality, Randomized Controlled Trials as Topic, 2. Zero hunger, Vegetarianisme, Nutrition and Dietetics, Biological Variation, Individual, Cardiometabolic health, Biological Variation, Middle Aged, Dietary supplements, 3. Good health, Artichoke, Cereals, Polyphenols, Potato, Adult, Aged, Biomarkers, Cardiovascular Diseases, Coumaric Acids, Female, Humans, Metabolic Diseases, Nutritional Status, Nutritive Value, Protective Factors, Risk Reduction Behavior, Young Adult, Diet, Dietary Supplements, Biological sciences, Cardiovascular diseases, Vegetarianism, Polifenols, Alimentation et Nutrition, lcsh:Nutrition. Foods and food supply, medicine.medical_specialty, 030209 endocrinology & metabolism, lcsh:TX341-641, Individual, Population health, Settore MED/49 - SCIENZE TECNICHE DIETETICHE APPLICATE, Bioactive compounds, 03 medical and health sciences, Internal medicine, medicine, Food and Nutrition, 030109 nutrition & dietetics, business.industry, artichoke, caffeoylquinic acids, cardiometabolic health, cereals, coffee, dietary supplements, hydroxycinnamic acids, interindividual variability, polyphenols, potato, Malalties cardiovasculars, Chemical sciences, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790., This article is based upon work from COST Action FA1403—POSITIVe “Interindividual variation in response to consumption of plant food bioactives and determinants involved” supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/).
Published: 2019

23. Updated Expert Consensus Statement on Platelet Function and Genetic Testing for Guiding P2Y12 Receptor Inhibitor Treatment in Percutaneous Coronary Intervention

Author: Derek So, Franz-Josef Neumann, Naveen L. Pereira, Gregg W. Stone, Lisa Gross, Robert F. Storey, Dietmar Trenk, David J. Moliterno, Jean-Philippe Collet, Marco Valgimigli, Dominick J. Angiolillo, Udaya S. Tantry, Matthew J. Price, Laurent Bonello, Young-Hoon Jeong, Dimitrios Alexopoulos, Francesco Franchi, Paul A. Gurbel, Roxana Mehran, Daniel Aradi, Deepak L. Bhatt, Thomas Cuisset, Dirk Sibbing, Jurriën M. ten Berg, Ron Waksman, Marc S. Sabatine, Ludwig-Maximilians-Universität München (LMU), Semmelweis University [Budapest], University of Athens Medical School [Athens], St. Antonius Hospital [Nieuwegein], VA Boston Healthcare System, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of North Florida [Jacksonville] (UNF), Gyeongsang National University, Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Kentucky, University Hospital Freiburg, Mayo Clinic, Scripps Clinic [San Diego, CA, USA], Harvard Medical School [Boston] (HMS), University of Ottawa [Ottawa], Columbia University [New York], University of Sheffield [Sheffield], Mount Sinai Hospital [Toronto, Canada] (MSH), University of Bern, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University of Florida [Gainesville] (UF), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and University of Kentucky (UK)
Subjects: medicine.medical_specialty, Acute coronary syndrome, OF-FUNCTION POLYMORPHISM, Prasugrel, medicine.medical_treatment, [SDV]Life Sciences [q-bio], GUIDED ANTIPLATELET THERAPY, 030204 cardiovascular system & hematology, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, PATIENTS SHOWING RESISTANCE, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, ASPIRIN AND/OR RESISTANCE, CLOPIDOGREL-TREATED PATIENTS, DUAL ANTIPLATELET, STENT THROMBOSIS, medicine, 030212 general & internal medicine, Intensive care medicine, thrombosis, business.industry, Standard treatment, P2Y(12) receptor inhibitor, ELEVATION MYOCARDIAL-INFARCTION, Percutaneous coronary intervention, BYPASS GRAFT-SURGERY, Guideline, Clopidogrel, medicine.disease, 3. Good health, genotyping, CYP2C19 GENOTYPE, Cardiology and Cardiovascular Medicine, business, Ticagrelor, platelet function testing, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y(12) receptor inhibitor is the standard treatment for patients undergoing percutaneous coronary intervention. The availability of different P2Y(12) receptor inhibitors (clopidogrel, prasugrel, ticagrelor) with varying levels of potency has enabled physicians to contemplate individualized treatment regimens, which may include escalation or de-escalation of P2Y(12)-inhibiting therapy. Indeed, individualized and alternative DAPT strategies may be chosen according to the clinical setting (stable coronary artery disease vs. acute coronary syndrome), the stage of the disease (early-vs. long-term treatment), and patient risk for ischemic and bleeding complications. A tailored DAPT approach may be potentially guided by platelet function testing (PFT) or genetic testing. Although the routine use of PFT or genetic testing in percutaneous coronary intervention-treated patients is not recommended, recent data have led to an update in guideline recommendations that allow considering selective use of PFT for DAPT de-escalation. However, guidelines do not expand on when to implement the selective use of such assays into decision making for personalized treatment approaches. Therefore, an international expert consensus group of key leaders from North America, Asia, and Europe with expertise in the field of antiplatelet treatment was convened. This document updates 2 prior consensus papers on this topic and summarizes the contemporary updated expert consensus recommendations for the selective use of PFT or genotyping in patients undergoing percutaneous coronary intervention. (c) 2019 by the American College of Cardiology Foundation.
Published: 2019

24. A reference map of the human protein interactome

Author: Madeleine F. Hardy, Bridget Teeking, Francisco J. Campos-Laborie, Dayag Sheykhkarimli, Dawit Balcha, Anjali Gopal, Marinella Gebbia, Ashyad Rayhan, Carles Pons, Gloria M. Sheynkman, Yves Jacob, Suzanne Gaudet, Aaron Richardson, Yoseph Kassa, Elodie Hatchi, Kerstin Spirohn, Dong-Sic Choi, Yu Xia, Eyal Simonovsky, David E. Hill, Hanane Ennajdaoui, Steven Deimling, Joseph N. Paulson, Natascha van Lieshout, Vincent Tropepe, Michael A. Calderwood, István Kovács, Gary D. Bader, Luke Lambourne, Sudharshan Rangarajan, Tiziana M. Cafarelli, Carl Pollis, Suet-Feung Chin, Alice Desbuleux, Andrew MacWilliams, Amélie Dricot, Jean-Claude Twizere, Patrick Aloy, Atina G. Cote, Marc Vidal, Jan Tavernier, Javier De Las Rivas, Cassandra D’Amata, Alexander O. Tejeda, Esti Yeger-Lotem, Liana Goehring, Joseph C. Mellor, Meaghan Daley, Irma Lemmens, Soon Gang Choi, Christian Bowman-Colin, Ghazal Haddad, Janusz Rak, Florian Goebels, Robert J. Weatheritt, Mariana Babor, Yang Wang, Thomas Rolland, Steffi De Rouck, Jochen Weile, Serena Landini, John Rasla, Sadie Schlabach, Nishka Kishore, Bridget E. Begg, Ruth Brignall, Quan Zhong, Tong Hao, David De Ridder, Claudia Colabella, Frederick P. Roth, Anupama Yadav, Mohamed Helmy, Katja Luck, Omer Basha, Dae-Kyum Kim, Benoit Charloteaux, Georges Coppin, Dylan Markey, Roujia Li, Miquel Duran-Frigola, Adriana San-Miguel, Wenting Bian, Miles W. Mee, Jennifer J. Knapp, Yun Shen, Murat Tasan, Xinping Yang, Dana-Farber Cancer Institute [Boston], Division of Medical Physics in Radiology [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Cancer Research UK Cambridge Institute (CRUK), University of Cambridge [UK] (CAM), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Harvard Medical School [Boston] (HMS), University of Toronto, Universidad de Salamanca, McGill University Health Center [Montreal] (MUHC), Mount Sinai Hospital [Toronto, Canada] (MSH), Université de Liège, Wigner Research Centre for Physics [Budapest], Hungarian Academy of Sciences (MTA), Northeastern University [Boston], Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Universiteit Gent = Ghent University [Belgium] (UGENT), Barcelona Institute of Science and Technology (BIST), Ben-Gurion University of the Negev (BGU), Università degli Studi di Perugia (UNIPG), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Canadian Institute for Advanced Research (CIFAR), Universiteit Gent = Ghent University (UGENT), Università degli Studi di Perugia = University of Perugia (UNIPG), and Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, Context (language use), Computational biology, Biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Genome, Interactome, Human genetics, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Human interactome, Proteome, 030217 neurology & neurosurgery, Function (biology), 030304 developmental biology
Abstract: Global insights into cellular organization and function require comprehensive understanding of interactome networks. Similar to how a reference genome sequence revolutionized human genetics, a reference map of the human interactome network is critical to fully understand genotype-phenotype relationships. Here we present the first human “all-by-all” binary reference interactome map, or “HuRI”. With ~53,000 high-quality protein-protein interactions (PPIs), HuRI is approximately four times larger than the information curated from small-scale studies available in the literature. Integrating HuRI with genome, transcriptome and proteome data enables the study of cellular function within essentially any physiological or pathological cellular context. We demonstrate the use of HuRI in identifying specific subcellular roles of PPIs and protein function modulation via splicing during brain development. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms underlying tissue-specific phenotypes of Mendelian diseases. HuRI thus represents an unprecedented, systematic reference linking genomic variation to phenotypic outcomes.
Published: 2019

25. The Management of Colorectal Cancer Liver Metastases: The Interventional Radiology Viewpoint

Author: Robert J. Lewandowski, Boris Guiu, Thomas Helmberger, Constantinos T. Sofocleous, Alban Denys, Philippe L. Pereira, David J. Breen, Edward Kim, Luigi Solbiati, Stephen B. Solomon, Samuel L. Rice, Reto Bale, Martijn Mejerjink, Nahum Goldberg, Thierry de Baere, Memorial Sloane Kettering Cancer Center [New York], Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Innsbruck Medical University [Austria] (IMU), University of Southampton, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Mount Sinai Hospital [Toronto, Canada] (MSH), Northwestern University Feinberg School of Medicine, Klinik Bogenhausen (Institut für Diagnostische und Interventionelle Radiologie), Heidelberg University Hospital [Heidelberg], Humanitas Clinical and Research Center [Rozzano, Milan, Italy], VU University Medical Center [Amsterdam], and VU University medical center
Subjects: Cancer Research, medicine.medical_specialty, Percutaneous, Colorectal cancer, Radiofrequency ablation, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiology, Interventional, 030218 nuclear medicine & medical imaging, law.invention, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, MESH: Colorectal Neoplasms, Liver Neoplasms, Radiation Oncology, law, medicine, Humans, Radiology, Nuclear Medicine and imaging, Radiation, medicine.diagnostic_test, business.industry, Cancer, Interventional radiology, Ablation, medicine.disease, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Radiology, Colorectal Neoplasms, business
Abstract: International audience; Comparison of Stereotactic Body Radiation Therapy and Radiofrequency Ablation in the Treatment of Intrahepatic Metastases” by Jackson et al is a thought-provoking addition to the literature concerning treatment of colorectal cancer metastasis (CLM). The benefits of hepatic CLM resection are well established; however, most patients are not candidates for resection. Local tumor ablation is a safe and effective alternative treatment for select patients. Considerable research has evaluated percutaneous ablation as treatment of CLM, including retrospective reviews with long-term follow-up and prospective randomized trials showing prolongation of progression-free and patient survival compared with chemotherapy alone.1, 2, 3 The National Comprehensive Cancer Network guidelines recommend ablation for patients with CLMs with or without surgery as long as all tumors can be effectively treated. Conversely, the evidence for stereotactic body radiation therapy (SBRT) in the treatment of any size of CLM is sparse; the National Comprehensive Cancer Network recommends that SBRT not be used indiscriminately when other treatment options are available.
Published: 2019

26. Genetic effects on the commensal microbiota in inflammatory bowel disease patients

Author: David Skurnik, Noah Zaitlen, Eric J. Tchetgen Tchetgen, Jacques Cosnes, Harry Sokol, Laurent Beaugerie, Dan Knights, Hugues Aschard, Vincent Laville, Rinse K. Weersma, Philippe Seksik, Ramnik J. Xavier, Mark S. Silverberg, Floris Imhann, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Harvard T.H. Chan School of Public Health, The Wharton School, University of Pennsylvania, University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), University of Groningen [Groningen], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of California (UC), Mount Sinai Hospital [Toronto, Canada] (MSH), Sorbonne Université (SU), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, 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), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania [Philadelphia], Service de Gastroentérologie et nutrition [CHU Saint-Antoine], 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), University of California, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), and Aschard, hugues
Subjects: Male, Cancer Research, Economics, Economic Models, Nod2 Signaling Adaptor Protein, Faecalibacterium prausnitzii, Social Sciences, Gut flora, QH426-470, Pathology and Laboratory Medicine, Inflammatory bowel disease, 0302 clinical medicine, [STAT.AP] Statistics [stat]/Applications [stat.AP], Medicine and Health Sciences, MESH: Nod2 Signaling Adaptor Protein, MESH: Genetic Variation, MESH: Models, Genetic, Genetics (clinical), [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Genetic Association Studies, Genetics, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], Clostridiales, [STAT.ME] Statistics [stat]/Methodology [stat.ME], MESH: Middle Aged, biology, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, Microbial Genetics, Genomics, Middle Aged, Colitis, Bacterial Pathogens, Medical Microbiology, MESH: CARD Signaling Adaptor Proteins, Female, Roseburia, Pathogens, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Research Article, Adult, MESH: Host Microbial Interactions, Microbial Genomics, Gastroenterology and Hepatology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, digestive system, Microbiology, Polymorphism, Single Nucleotide, MESH: Gastrointestinal Microbiome, MESH: Clostridiales, 03 medical and health sciences, Genetic variation, Genetic predisposition, medicine, Bacterial Genetics, Ulcerative Colitis, Humans, Genetic Predisposition to Disease, Microbiome, Molecular Biology, Microbial Pathogens, Ecology, Evolution, Behavior and Systematics, Genetic Association Studies, 030304 developmental biology, Genetic association, MESH: Humans, Host Microbial Interactions, Models, Genetic, Inflammatory Bowel Disease, Biology and Life Sciences, Genetic Variation, MESH: Adult, Bacteriology, biology.organism_classification, medicine.disease, MESH: Inflammatory Bowel Diseases, Inflammatory Bowel Diseases, MESH: Faecalibacterium prausnitzii, MESH: Male, digestive system diseases, Gastrointestinal Microbiome, CARD Signaling Adaptor Proteins, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Genetics of Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, 030217 neurology & neurosurgery
Abstract: Several bacteria in the gut microbiota have been shown to be associated with inflammatory bowel disease (IBD), and dozens of IBD genetic variants have been identified in genome-wide association studies. However, the role of the microbiota in the etiology of IBD in terms of host genetic susceptibility remains unclear. Here, we studied the association between four major genetic variants associated with an increased risk of IBD and bacterial taxa in up to 633 IBD cases. We performed systematic screening for associations, identifying and replicating associations between NOD2 variants and two taxa: the Roseburia genus and the Faecalibacterium prausnitzii species. By exploring the overall association patterns between genes and bacteria, we found that IBD risk alleles were significantly enriched for associations concordant with bacteria-IBD associations. To understand the significance of this pattern in terms of the study design and known effects from the literature, we used counterfactual principles to assess the fitness of a few parsimonious gene-bacteria-IBD causal models. Our analyses showed evidence that the disease risk of these genetic variants were likely to be partially mediated by the microbiome. We confirmed these results in extensive simulation studies and sensitivity analyses using the association between NOD2 and F. prausnitzii as a case study., Author summary In this study, we used observational data to explore associations between host genetics and the commensal microbiome in inflammatory bowel disease cases. Our analysis identified four associations involving two genes and four bacterial taxa and replicated two of these associations in independent cohorts. Then, we developed a counterfactual framework to assess the fitness of a few parsimonious gene-bacteria-IBD causal models. These analyses confirmed the robustness of the identified associations and highlighted microbiota mediation as a potential mechanism underlying the association between IBD and those genetic variants while ruling out reverse causation and arguing against a bacteria-IBD association resulting from a shared genetic effect.
Published: 2019

27. Targeting the delivery of dietary plant bioactives to those who would benefit most: from science to practical applications

Author: Nada Knežević, Anna Marja Aura, Baukje de Roos, María Teresa Garcia Conesa, Maria Rosário Bronze, Dragan Milenkovic, Arno Greyling, Tom Van de Wiele, Christine Morand, Aedin Cassidy, Jim Kaput, Ana Rodriguez-Mateos, Paul A. Kroon, Rikard Landberg, Eileen R. Gibney, Zohar Kerem, Claudine Manach, Francisco A. Tomás-Barberán, The Rowett Research Institute, University of Aberdeen, VTT Technical Research Centre of Finland (VTT), Instituto de Biologia Experimental e Tecnológica, Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Centro de Edafología y Biología Aplicada del Segura (CEBAS-CSIC), UCD Institute of Food and Health, University College Dublin (UCD), Unilever Research and Development, Vydiant, The Robert H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, Podravka d.d, Quadram Institute Bioscience, Division of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Department of Nutritional Sciences, Mount Sinai Hospital (MSH), King’s College London, Center for Microbial Ecology and Technology (CMET), Gent University, Instituto de Biologia Experimental e Tecnológica (IBET), Centro de Edafologia y Biologia aplicada del Segura (CEBAS - CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Chalmers University of Technology [Gothenburg, Sweden], Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Mount Sinai Hospital [Toronto, Canada] (MSH), King‘s College London, Universiteit Gent = Ghent University [Belgium] (UGENT), University of East Anglia [Norwich] (UEA), Quadram Institute Bioscience [Norwich, U.K.] (QIB), Biotechnology and Biological Sciences Research Council (BBSRC), Universiteit Gent = Ghent University (UGENT), and de Roos, B.
Subjects: Agriculture and Food Sciences, 0301 basic medicine, and promotion of well-being, Food industry, Phytochemicals, Medicine (miscellaneous), Review, Gut flora, Cardiovascular, Oral and gastrointestinal, 0302 clinical medicine, Stakeholders, Cost action, Marketing, Cancer, 2. Zero hunger, Potential impact, education.field_of_study, Nutrition and Dietetics, biology, Dietary intake, Diet, Vegetarian, Cardiometabolic diseases, 3. Good health, Cardiovascular Diseases, Alimentation et Nutrition, HEALTH, Healthy diet Cardiometabolic diseases Inter-individual variability in responses Stakeholders Food industry, BIOMARKERS, Population, 030209 endocrinology & metabolism, Health Promotion, METABOLISM, 03 medical and health sciences, Vegetarian, Metabolic Diseases, Inter-individual variability in responses, Food and Nutrition, Humans, Obesity, 3.3 Nutrition and chemoprevention, education, Metabolic and endocrine, Nutrition, Healthy diet, 030109 nutrition & dietetics, Nutrition & Dietetics, business.industry, Prevention, Clinical study design, Prevention of disease and conditions, biology.organism_classification, Diet, Business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Background A healthy diet and optimal lifestyle choices are amongst the most important actions for the prevention of cardiometabolic diseases. Despite this, it appears difficult to convince consumers to select more nutritious foods. Furthermore, the development and production of healthier foods do not always lead to economic profits for the agro-food sector. Most dietary recommendations for the general population represent a “one-size-fits-all approach” which does not necessarily ensure that everyone has adequate exposure to health-promoting constituents of foods. Indeed, we now know that individuals show a high variability in responses when exposed to specific nutrients, foods, or diets. Purpose This review aims to highlight our current understanding of inter-individual variability in response to dietary bioactives, based on the integration of findings of the COST Action POSITIVe. We also evaluate opportunities for translation of scientific knowledge on inter-individual variability in response to dietary bioactives, once it becomes available, into practical applications for stakeholders, such as the agro-food industry. The potential impact from such applications will form an important impetus for the food industry to develop and market new high quality and healthy foods for specific groups of consumers in the future. This may contribute to a decrease in the burden of diet-related chronic diseases., Key messages Individual differences in ADME (Absorption, Digestion, Metabolism and Excretion) is believed to underpin much of the inter-individual variation in responses.Recent developments in the area of food metabolome databases and fast improvements in innovative metabotyping technologies hold great promise for improved profiling of dietary intake, exposure to individual ingredients, foods and dietary patterns, as well as our ability to identify individual responsiveness.The food industry needs well-defined population clusters or targets in order to be able to design “personalized products”.There are indeed excellent industrial opportunities for foods that modulate gut microbiota, and thereby enable the delivery of food bioactive metabolites.It is currently not clear whether knowledge on individual nutrient needs, based on genetic or metagenomic data, would affect long-term dietary and health behaviours.Data to support the development of dietary recommendations may need to be generated by new n-of-1-based study designs in the future.
Published: 2019

28. Improving the reporting quality of intervention trials addressing the inter-individual variability in response to the consumption of plant bioactives: quality index and recommendations

Author: Marina Nikolić, Marika Massaro, Mar Garcia-Aloy, Geoffrey Istas, Christine Morand, Rocío García-Villalba, Lieselotte Cloetens, Noemi Tejera, Pedro Mena, Maria Rosaria Tumolo, Irena Krga, Mihail Chervenkov, Mireia Urpi-Sarda, Desislava Abadjieva, Antonio González-Sarrías, Francisco A. Tomás-Barberán, Laurent-Emmanuel Monfoulet, Banu Bayram, Margherita Dall'Asta, Aleksandra Konic Ristic, Karen F. Chambers, Rodrigo P. Feliciano, Egeria Scoditti, Institute for Medical Research, University of Belgrade [Belgrade], UCD Institute of Food and Health, University College Dublin [Dublin] (UCD), Laboratory of Food and Health, Centro de Edafologia y Biologia Aplicada del Segura, Department of Nutritional Sciences, Mount Sinai Hospital [Toronto, Canada] (MSH), King‘s College London, Department of Nutrition, Food Sciences and Gastronomy, University of Barcelona, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable, Instituto de Salud Carlos III [Madrid] (ISC), Human Nutrition Unit, Department of Food and Drugs, Università degli studi di Parma = University of Parma (UNIPR), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Biomedical Nutrition, Pure and Applied Biochemistry, Lund University [Lund], Department of Nutrition and Dietetics, Harokopio University, Institute for research on population and social policies (IRPPS), Faculty of Veterinary Medicine, University of Forestry (UF), Institute of Neurobioloy, Bulgarian Academy of Sciences, Istituto di Fisiologia Clinica (IFC), CNR, Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia [Norwich] (UEA), Institute of Biology and Immunology of Reproduction, Quadram Institute Bioscience [Norwich, U.K.] (QIB), Biotechnology and Biological Sciences Research Council (BBSRC), Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], European Cooperation in Science and Technology (COST) FA1403, Mount Sinai Hospital (MSH), King’s College London, Carlos III Institute, University of Parma, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Lund University, University of East Anglia, Quadram Institute Bioscience, University Düsseldorf, and University of Parma = Università degli studi di Parma [Parme, Italie]
Subjects: 0301 basic medicine, Intervention trials, Index (economics), Reporting quality, media_common.quotation_subject, Applied psychology, Phytochemicals, MEDLINE, Medicine (miscellaneous), 030209 endocrinology & metabolism, Settore MED/49 - SCIENZE TECNICHE DIETETICHE APPLICATE, Review, Guidelines, Recommendations, Inter-individual variation, 03 medical and health sciences, Consistency (database systems), Clinical trials · Reporting quality · Inter-individual variation · Quality index · Plant bioactive · Recommendations · Guidelines, 0302 clinical medicine, Clinical trials, Plant bioactive, Quality index, Humans, Quality (business), Data reporting, media_common, Consumption (economics), 030109 nutrition & dietetics, Nutrition and Dietetics, Diet, Vegetarian, Reproducibility of Results, Data Accuracy, Clinical trial, Biological Variation, Population, Research Design, Plants, Edible, Psychology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Purpose The quality of the study design and data reporting in human trials dealing with the inter-individual variability in response to the consumption of plant bioactives is, in general, low. There is a lack of recommendations supporting the scientific community on this topic. This study aimed at developing a quality index to assist the assessment of the reporting quality of intervention trials addressing the inter-individual variability in response to plant bioactive consumption. Recommendations for better designing and reporting studies were discussed. Methods The selection of the parameters used for the development of the quality index was carried out in agreement with the scientific community through a survey. Parameters were defined, grouped into categories, and scored for different quality levels. The applicability of the scoring system was tested in terms of consistency and effort, and its validity was assessed by comparison with a simultaneous evaluation by experts’ criteria. Results The “POSITIVe quality index” included 11 reporting criteria grouped into four categories (Statistics, Reporting, Data presentation, and Individual data availability). It was supported by detailed definitions and guidance for their scoring. The quality index score was tested, and the index demonstrated to be valid, reliable, and responsive. Conclusions The evaluation of the reporting quality of studies addressing inter-individual variability in response to plant bioactives highlighted the aspects requiring major improvements. Specific tools and recommendations favoring a complete and transparent reporting on inter-individual variability have been provided to support the scientific community on this field. Electronic supplementary material The online version of this article (10.1007/s00394-019-02069-3) contains supplementary material, which is available to authorized users., Key messages The reporting quality of human studies on inter-individual variation in response to plant bioactives is generally low and should be significantly improved.There is no specific guidance for reporting studies on inter-individual variation in response to plant bioactives.The assessment of reporting quality using a scale approach is considered a valuable tool in assessing compliance with the recommendations in the submission phase or during the reviewing process. It also provides a quantitative measure of the quality of studies to be used in meta-analysis.Eleven reporting criteria were developed and supported by detailed definitions and guidance for their scoring.The POSITIVe quality index was tested and demonstrated to be valid, reliable, and responsive.The use of the quality index and its supporting explanatory material (dictionary) as a guide for researchers, peer-reviewers, and journal editors will foster further complete and transparent reporting of data on inter-individual variability.The criteria used in the quality index can serve as additional guidance to inform the design and conduction of further studies on inter-individual variations in response to plant bioactives.Better reporting is expected to lead to a better understanding of the mechanisms and factors involved and thus better study designs with greater impact on policies and practice. Electronic supplementary material The online version of this article (10.1007/s00394-019-02069-3) contains supplementary material, which is available to authorized users.
Published: 2019
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29. Factors influencing the cardiometabolic response to (poly)phenols and phytosterols: a review of the COST Action POSITIVe activities

Author: Antonio González-Sarrías, Eileen R. Gibney, Emilie Combet, Dragan Milenkovic, Tatjana Ruskovska, Arno Greyling, Ana Rodriguez-Mateos, Baujke de Roos, Christine Morand, Francisco A. Tomás-Barberán, UCD School of Agriculture and Food Science, University College Dublin [Dublin] (UCD), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), College of Medical, Veterinary and Life Sciences, University of Glascow, University Goce Delcev (UGD), Unilever Research and Development, Food and Health, Centro de Edafologia y Biologia Aplicada del Segura, Rowett Research Institute, University of Aberdeen, Department of Nutritional Sciences, Mount Sinai Hospital (MSH), King’s College London, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Mount Sinai Hospital [Toronto, Canada] (MSH), King‘s College London, and European Cooperation in Science and Technology (COST) FA1403
Subjects: 0301 basic medicine, and promotion of well-being, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Review, Cardiovascular, Cardiovascular System, Oral and gastrointestinal, law.invention, Metabotype, 0302 clinical medicine, Randomized controlled trial, law, Medicine, Cost action, Data reporting, Cancer, 2. Zero hunger, Nutrition and Dietetics, Diet, Vegetarian, Phytosterol, Phytosterols, Biological Variation, Response, Plants, Cardiometabolic diseases, 3. Good health, Europe, Health, Plants, Edible, Population, Clinical Trials and Supportive Activities, 030209 endocrinology & metabolism, Variation, 03 medical and health sciences, Edible, Vegetarian, Clinical Research, Environmental health, Complementary and Integrative Health, Genetics, Humans, Metabolomics, Obesity, Microbiome, 3.3 Nutrition and chemoprevention, Metabolic and endocrine, Nutrition, 030109 nutrition & dietetics, Nutrition & Dietetics, business.industry, Dietary constituent, Prevention, Polyphenols, Plant, Prevention of disease and conditions, Diet, Clinical trial, Metabolism, Biological Variation, Population, Bioactive, Personalized nutrition, Gene expression, business
Abstract: Purpose Evidence exists regarding the beneficial effects of diets rich in plant-based foods regarding the prevention of cardiometabolic diseases. These plant-based foods are an exclusive and abundant source of a variety of biologically active phytochemicals, including polyphenols, carotenoids, glucosinolates and phytosterols, with known health-promoting effects through a wide range of biological activities, such as improvements in endothelial function, platelet function, blood pressure, blood lipid profile and insulin sensitivity. We know that an individual’s physical/genetic makeup may influence their response to a dietary intervention, and thereby may influence the benefit/risk associated with consumption of a particular dietary constituent. This inter-individual variation in responsiveness has also been described for dietary plant bioactives but has not been explored in depth. To address this issue, the European scientific experts involved in the COST Action POSITIVe systematically analyzed data from published studies to assess the inter-individual variation in selected clinical biomarkers associated with cardiometabolic risk, in response to the consumption of plant-based bioactives (poly)phenols and phytosterols. The present review summarizes the main findings resulting from the meta-analyses already completed. Results Meta-analyses of randomized controlled trials conducted within POSITIVe suggest that age, sex, ethnicity, pathophysiological status and medication may be responsible for the heterogeneity in the biological responsiveness to (poly)phenol and phytosterol consumption and could lead to inconclusive results in some clinical trials aiming to demonstrate the health effects of specific dietary bioactive compounds. However, the contribution of these factors is not yet demonstrated consistently across all polyphenolic groups and cardiometabolic outcomes, partly due to the heterogeneity in trial designs, low granularity of data reporting, variety of food vectors and target populations, suggesting the need to implement more stringent reporting practices in the future studies. Studies investigating the effects of genetic background or gut microbiome on variability were limited and should be considered in future studies. Conclusion Understanding why some bioactive plant compounds work effectively in some individuals but not, or less, in others is crucial for a full consideration of these compounds in future strategies of personalized nutrition for a better prevention of cardiometabolic disease. However, there is also still a need for the development of a substantial evidence-base to develop health strategies, food products or lifestyle solutions that embrace this variability., Key messages A balanced diet, rich in plant-based foods is known for the prevention of obesity, diabetes, and cardiovascular disease risk.(Poly)phenols and phytosterols displayed a range of biological effects of relevance to contribute to the cardiometabolic health benefits of plant foodsHowever, inter-individual variability in response to plant food bioactive consumption exists, and there is a need to understand the causes of this variation.Analysis of published RCTs examining impact of consumption of (poly)phenols and phytosterols on cardiometabolic risk factors demonstrated that a number of factors including age, sex, adiposity and health status could contribute to the effect demonstrated within these studies.Genome and microbiome studies will help identify what may be causing this variation.More studies, specifically designed to investigate individual variation are needed to fully understand the factors responsible for and the impact of this variationOnce fully understood, such variation should be used in directing personalised nutrition advice.
Published: 2019

30. Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches

Author: Yao, S., Kuja-Halkola, R., Martin, J., Lu, Y., Lichtenstein, P., Hubel, C., Almqvist, C., Magnusson, P. K., Bulik, C. M., Larsson, H., Norring, C., Birgegard, A., Yilmaz, Z., Watson, H., Baker, J., Thornton, L. M., Adan, R., Ando, T., Bergen, A., Berrettini, W., Boni, C., Boraska Perica, V., Brandt, H., Burghardt, R., Cassina, M., Cesta, C., Clementi, M., Coleman, J., Cone, R., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U., Davis, O., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J., Dick, D., Dikeos, D., Dmitrzak-Weglarz, M., Docampo, E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Favaro, A., Fernandez-Aranda, F., Fichter, M., Finan, C., Fischer, K., Focker, M., Foretova, L., Forzan, M., Franklin, C., Gaspar, H., Gonidakis, F., Gorwood, P., Gratacos, M., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S., Hendriks, J., Herpertz-Dahlmann, B., Herzog, W., Hilliard, C., Hinney, A., Huckins, L., Hudson, J., Huemer, J., Imgart, H., Inoko, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Jureus, A., Kalsi, G., Kaminska, D., Kaplan, A., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M., Kaye, W., Kennedy, J., Kennedy, M., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K., Knudsen, G. P., Koeleman, B., Koubek, D., La Via, M., Landen, M., Levitan, R., Li, D., Lilenfeld, L., Lissowska, J., Magistretti, P., Maj, M., Mannik, K., Martin, N., Mcdevitt, S., Mcguffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Mortensen, P., Munn-Chernoff, M., Nacmias, B., Nilsson, I., Ntalla, I., O'Toole, J., Pantel, J., Papezova, H., Parker, R., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Reichborn-Kjennerud, T., Ricca, V., Ripke, S., Ritschel, F., Roberts, M., Rotondo, A., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M., Slopien, A., Smith, T., Sorbi, S., Strengman, E., Strober, M., Sullivan, P., Szatkiewicz, J., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Thornton, L., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tziouvas, K., van Elburg, A., van Furth, E., Wade, T., Wagner, G., Walton, E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Alfredsson, L., Andreassen, O., Aschauer, H., Barrett, J., Bencko, V., Carlberg, L., Cichon, S., Cohen-Woods, S., Dina, C., Ding, B., Espeseth, T., Floyd, J., Gallinger, S., Gambaro, G., Giegling, I., Herms, S., Janout, V., Julia, A., Klareskog, L., Le Hellard, S., Leboyer, M., Lundervold, A., Marsal, S., Mattingsdal, M., Navratilova, M., Ophoff, R., Palotie, A., Pinto, D., Ripatti, S., Rujescu, D., Scherer, S., Scott, L., Sladek, R., Soranzo, N., Southam, L., Steen, V., Wichmann, H. -E., Widen, E., Breen, G., Bulik, C., Yao, S., Kuja-Halkola, R., Martin, J., Lu, Y., Lichtenstein, P., Hubel, C., Almqvist, C., Magnusson, P. K., Bulik, C. M., Larsson, H., Norring, C., Birgegard, A., Yilmaz, Z., Watson, H., Baker, J., Thornton, L. M., Adan, R., Ando, T., Bergen, A., Berrettini, W., Boni, C., Boraska Perica, V., Brandt, H., Burghardt, R., Cassina, M., Cesta, C., Clementi, M., Coleman, J., Cone, R., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U., Davis, O., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J., Dick, D., Dikeos, D., Dmitrzak-Weglarz, M., Docampo, E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Favaro, A., Fernandez-Aranda, F., Fichter, M., Finan, C., Fischer, K., Focker, M., Foretova, L., Forzan, M., Franklin, C., Gaspar, H., Gonidakis, F., Gorwood, P., Gratacos, M., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S., Hendriks, J., Herpertz-Dahlmann, B., Herzog, W., Hilliard, C., Hinney, A., Huckins, L., Hudson, J., Huemer, J., Imgart, H., Inoko, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Jureus, A., Kalsi, G., Kaminska, D., Kaplan, A., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M., Kaye, W., Kennedy, J., Kennedy, M., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K., Knudsen, G. P., Koeleman, B., Koubek, D., La Via, M., Landen, M., Levitan, R., Li, D., Lilenfeld, L., Lissowska, J., Magistretti, P., Maj, M., Mannik, K., Martin, N., Mcdevitt, S., Mcguffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Mortensen, P., Munn-Chernoff, M., Nacmias, B., Nilsson, I., Ntalla, I., O'Toole, J., Pantel, J., Papezova, H., Parker, R., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Reichborn-Kjennerud, T., Ricca, V., Ripke, S., Ritschel, F., Roberts, M., Rotondo, A., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M., Slopien, A., Smith, T., Sorbi, S., Strengman, E., Strober, M., Sullivan, P., Szatkiewicz, J., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Thornton, L., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tziouvas, K., van Elburg, A., van Furth, E., Wade, T., Wagner, G., Walton, E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Alfredsson, L., Andreassen, O., Aschauer, H., Barrett, J., Bencko, V., Carlberg, L., Cichon, S., Cohen-Woods, S., Dina, C., Ding, B., Espeseth, T., Floyd, J., Gallinger, S., Gambaro, G., Giegling, I., Herms, S., Janout, V., Julia, A., Klareskog, L., Le Hellard, S., Leboyer, M., Lundervold, A., Marsal, S., Mattingsdal, M., Navratilova, M., Ophoff, R., Palotie, A., Pinto, D., Ripatti, S., Rujescu, D., Scherer, S., Scott, L., Sladek, R., Soranzo, N., Southam, L., Steen, V., Wichmann, H. -E., Widen, E., Breen, G., Bulik, C., Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department Psychiatry [Chapel Hill], University of North Carolina System (UNC)-University of North Carolina System (UNC), Oregon Research Institute (ORI), Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Stockholm County Council, Analyse Phenotypique, Developpementale et Genetique des Comportements Addictifs, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), University of Split, Azienda Ospedaliera di Padova, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Nutrition-Dietetics, Harokopio University of Athens, University of Athens Medical School [Athens], MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Medstar Research Institute, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, National and Kapodistrian University of Athens (NKUA), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Weill Medical College of Cornell University [New York], Department of Genomics, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Universität Duisburg-Essen [Essen], Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Icahn School of Medicine at Mount Sinai [New York] (MSSM), School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Tokai University, Institute for Marine and Antarctic Studies [Horbat] (IMAS), University of Tasmania [Hobart, Australia] (UTAS), National Institute for Health and Welfare [Helsinki], Medizinische Universität Wien = Medical University of Vienna, University of California [San Diego] (UC San Diego), University of California, Psychiatric Neurogenetics Section, Centre for Addiction and Mental Health, School of Computing [Dublin], Dublin City University [Dublin] (DCU), University of Helsinki, University Medical Center [Utrecht], Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Oak Ridge National Laboratory [Oak Ridge] (ORNL), UT-Battelle, LLC, The M Sklodowska-Curie Cancer Center and Institute of Oncology, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Università degli studi della Campania 'Luigi Vanvitelli', Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Queensland Institute of Medical Research, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, Estonian Genome and Medicine, University of Tartu, Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, Università degli Studi di Salerno (UNISA), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Vanderbilt University School of Medicine [Nashville], Charles University [Prague] (CU), Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K, Norwegian Institute of Public Health [Oslo] (NIPH), Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Institute of Medical Informatics, Biometry and Epidemiology, The Scripps Translational Science Institute and The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, Leiden University Medical Center (LUMC), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, The Jackson Laboratory [Bar Harbor] (JAX), The Nofer Institute of Occupational Medicine, Università degli Studi di Perugia (UNIPG), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), 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)-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), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department Biostatistics University of North Carolina, Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Sachs' Children's Hospital, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Institute of Hygiene and Epidemiology, Charles University and General University Hospital-First Faculty of Medicine, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, 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), University of Oslo (UiO), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Department of Optics [Univ Palacký], Faculty of Science [Univ Palacký], Palacky University Olomouc-Palacky University Olomouc, Vall d'Hebron University Hospital [Barcelona], Rheumatology Unit, University of Bergen (UiB), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Masaryk Memorial Cancer Institute (RECAMO), Department of Psychiatry, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München (LMU)-Chair of Epidemiology, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Institute of Psychiatry-King‘s College London, Cardiff University-Medical Research Council, and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Adult, Male, Multifactorial Inheritance, Adolescent, behavioral disciplines and activities, Article, Feeding and Eating Disorders, Young Adult, [SCCO]Cognitive science, Polygenic risk score, Risk Factors, mental disorders, Humans, ADHD, Genetic epidemiology, Registries, Child, Sweden, [SDV.GEN]Life Sciences [q-bio]/Genetics, Eating disorder, Anorexia nervosa, Bulimia nervosa, Eating disorders, Attention Deficit Disorder with Hyperactivity, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; BACKGROUND:Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa.METHODS:We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472).RESULTS:Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes.CONCLUSIONS:We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.
Published: 2019

31. 4D Printing based piezoelectric composite for medical applications

Author: Sabrina Siddique, Jean-Fabien Capsal, Daniel Grinberg, Minh-Quyen Le, Pierre-Jean Cottinet, Richard Liang, Laboratoire de Génie Electrique et Ferroélectricité (LGEF), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Mount Sinai Hospital [Toronto, Canada] (MSH), and Florida State University [Tallahassee] (FSU)
Subjects: 0209 industrial biotechnology, Materials science, Polymers and Plastics, 02 engineering and technology, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 3. Good health, Electroactive materials, [SPI]Engineering Sciences [physics], 020901 industrial engineering & automation, Piezoelectric composite, Materials Chemistry, Physical and Theoretical Chemistry, Composite material, 0210 nano-technology, 4d printing
Abstract: International audience; Additive manufacturing (AM), otherwise known as three‐dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education, and medicine. Although a considerable amount of progress has been made in this field, additional research work is required to overcome various remaining challenges. Recently, one of the actively researched areas lies in the AM of smart materials and structures. Electroactive materials incorporated in 3D printing have given birth to 4D printing, where 3D printed structures can perform as actuating and/or sensing systems, making it possible to deliver electrical signals under external mechanical stimuli and vice versa. In this paper, we present a lightweight, low cost piezoelectric material based on the dispersion of inorganic ferroelectric submicron particles in a polymer matrix. We report on how the proposed material is compatible with the AM process. Finally, we discuss its potential applications for healthcare, especially in smart implants prostheses. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 109–115
Published: 2018

32. Sensitive tumour detection and classification using plasma cell-free DNA methylomes

Author: Zhen Zhao, Tiantian Li, Anna Goldenberg, Olena Kis, John Douglas Mcpherson, Tiago Medina, Jessica Liu, Mark Mansour, Scott V. Bratman, Signy Chow, Rayjean J. Hung, Neil E. Fleshner, Ayelet Borgida, Philippe L. Bedard, Mark D. Minden, Trevor J. Pugh, Yadon Wang, Anna Spreafico, Gordon Fehringer, Steven Gallinger, Michael H.A. Roehrl, Zhuo Chen, Rajat Singhania, Ankur Chakravarthy, David Roulois, Andrea Arruda, Michael M. Hoffman, Ilias Ettayebi, Geoffrey Liu, Ting Ting Wang, Natasha B. Leighl, Tracy Murphy, Catherine A. O’Brien, Dianne Chadwick, Philip C. Zuzarte, Grainne M. O'Kane, Shu Yi Shen, Daniel D. De Carvalho, Princess Margaret Hospital, University of Toronto, Mount Sinai Hospital [Toronto, Canada] (MSH), Memorial Sloane Kettering Cancer Center [New York], Ontario Institute for Cancer Research [Canada] (OICR), Ontario Institute for Cancer Research, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Toronto General Hospital Research Institute [Canada] (TGHRI), University of Toronto McLaughlin Centre [MC-2015-02], Canadian Institutes of Health Research [CIHR FDN 148430], Ontario Institute for Cancer Research (OICR), Canada Research Chair [950-231346], Princess Margaret Cancer Foundation, Canadian Cancer Society [CCSRI 701717, CCSRI 704716, CCSRI 703827, CCSRI 020214], Cancer Care Ontario Chair of Population Health, Canadian Institutes of Health Research (CIHR New Investigator Salary award) [201512MSH-360794-228629], province of Ontario, and Université de Rennes (UR)-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: 0301 basic medicine, Multidisciplinary, Somatic cell, Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, Plasma cell, Biology, medicine.disease, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, medicine.anatomical_structure, chemistry, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], DNA Mutational Analysis, DNA methylation, medicine, Epigenetics, Liquid biopsy, DNA
Abstract: The use of liquid biopsies for cancer detection and management is rapidly gaining prominence1. Current methods for the detection of circulating tumour DNA involve sequencing somatic mutations using cell-free DNA, but the sensitivity of these methods may be low among patients with early-stage cancer given the limited number of recurrent mutations2–5. By contrast, large-scale epigenetic alterations—which are tissue- and cancer-type specific—are not similarly constrained6 and therefore potentially have greater ability to detect and classify cancers in patients with early-stage disease. Here we develop a sensitive, immunoprecipitation-based protocol to analyse the methylome of small quantities of circulating cell-free DNA, and demonstrate the ability to detect large-scale DNA methylation changes that are enriched for tumour-specific patterns. We also demonstrate robust performance in cancer detection and classification across an extensive collection of plasma samples from several tumour types. This work sets the stage to establish biomarkers for the minimally invasive detection, interception and classification of early-stage cancers based on plasma cell-free DNA methylation patterns. An immunoprecipitation-based protocol is developed to analyse DNA methylation in small quantities of circulating cell-free DNA, and can detect and classify cancers in plasma samples from several tumour types.
Published: 2018

33. Measuring chordae tension during transapical neochordae implantation: Toward understanding objective consequences of mitral valve repair

Author: Daniel Grinberg, Jean-François Obadia, Pierre-Jean Cottinet, David Audigier, Sophie Thivolet, Minh-Quyen Le, Jean-Fabien Capsal, Laboratoire de Génie Electrique et Ferroélectricité (LGEF), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), hôpital Louis-Pradel, CHU de Lyon, 69500 Bron, France., Mount Sinai Hospital (MSH), Service de Cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Mount Sinai Hospital [Toronto, Canada] (MSH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Beating heart, medicine.medical_treatment, Hemodynamics, Biocompatible Materials, 030204 cardiovascular system & hematology, Prosthesis Design, Objective assessment, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Internal medicine, Mitral valve, medicine, Humans, Polytetrafluoroethylene, Aged, Aged, 80 and over, Heart Valve Prosthesis Implantation, Mitral valve repair, Mitral regurgitation, Mitral Valve Prolapse, business.industry, Tension (physics), Mitral Valve Insufficiency, Middle Aged, Original data, medicine.anatomical_structure, 030228 respiratory system, Heart Valve Prosthesis, Cardiology, Chordae Tendineae, Mitral Valve, Surgery, Cardiology and Cardiovascular Medicine, business, Echocardiography, Transesophageal
Abstract: International audience; OBJECTIVES:Complex structure of mitral valve and its central position in the heart limit assessment of mitral function to standardized calculated parameters assessed using medical imaging (echocardiography). Novel techniques, which allow mitral valve repair (MVr) in a beating heart, offer the opportunity for innovative objective assessment in physiologic and pathologic conditions. We report, to our knowledge, the first data of real-time chordal tension measurement during a transapical neochordae implantation.METHODS:Seven patients with severe degenerative mitral regurgitation due to posterior prolapse underwent transapical MVr using the NeoChord DS 1000 (NeoChord Inc, Minneapolis, Minn). During prolapse correction, the tension applied on the neochordae was measured in addition to hemodynamic and echocardiographic parameters.RESULTS:The traction applied on 1 chorda sustaining the P2 segment was measured at between 0.7 and 0.9 N, and oscillated with respiration. When several neochordae were set in tension, this initial tension was spread homogeneously on each chorda (mean sum of the amplitude of tension 0.98 ± 0.08 N). To achieve an optimal echocardiographic correction, a complementary synchronous traction on all chordae was required. During this adjustment, the sum of the tension decreased (mean 12 ± 2%; P = .018), suggesting that when normal physiology was restored, the valvular apparatus was in a low-stress state. This method allowed us to apply a precise and reproducible technique, leading to a good procedural success rate with a low morbidity and mortality rate.CONCLUSIONS:The tension applied on chordae during transapical implantation of neochordae for degenerative mitral regurgitation can be measured, providing original data about the objective consequences of MVr on the mitral apparatus.
Published: 2018

34. Comparison of five cell-free DNA isolation methods to detect the EGFR T790M mutation in plasma samples of patients with lung cancer

Author: Romain Senal, Marion Larrieux, Jérôme Solassol, Julie A. Vendrell, Alain Mangé, David Grand, Eleftherios P. Diamandis, Xavier Quantin, Patricia Audran, Service de Biopathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CRLCC Val d'Aurelle - Paul Lamarque, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Mount Sinai Hospital [Toronto, Canada] (MSH), University of Toronto, and University Health Network
Subjects: 0301 basic medicine, medicine.medical_treatment, Clinical Biochemistry, MESH: Reagent Kits, Diagnostic, EGFR T790M, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: ErbB Receptors, Targeted therapy, droplet digital PCR, 03 medical and health sciences, 0302 clinical medicine, medicine, Digital polymerase chain reaction, Lung cancer, ComputingMilieux_MISCELLANEOUS, circulating tumor DNA, MESH: Humans, Plasma samples, business.industry, MESH: Real-Time Polymerase Chain Reaction, Biochemistry (medical), General Medicine, medicine.disease, Isolation (microbiology), targeted therapy, 3. Good health, MESH: Lung Neoplasms, lung cancer, 030104 developmental biology, Cell-free fetal DNA, MESH: Gene Deletion, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Cancer research, MESH: Cell-Free Nucleic Acids, EGFR mutation, business, MESH: Exons, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2018

35. Direct Phosphorylation of SRC Homology 3 Domains by Tyrosine Kinase Receptors Disassembles Ligand-Induced Signaling Networks

Author: Noémie Lavoie, Patrick Laprise, Gerald D. Gish, Christian R. Landry, Nicolas Doucet, Kévin Jacquet, Sylvie Bourassa, François Otis, Sara L. Banerjee, Michel G. Tremblay, Ugo Dionne, François J.M. Chartier, Mani Jain, Normand Voyer, Nicolas Bisson, Yossef López de los Santos, David N. Bernard, Guy G. Poirier, Jean-Philippe Gagné, Université Laval [Québec] (ULaval), CHU de Québec–Université Laval, PROTEO, The Quebec Network for Research on Protein Function, Engineering, and Applications, Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS)-Université de Sherbrooke (UdeS)-Université Laval [Québec] (ULaval)-McGill University = Université McGill [Montréal, Canada]-University of Ottawa [Ottawa]-Université du Québec à Trois-Rivières (UQTR)-Université de Montréal (UdeM)-TransBiotech, Lévis-Concordia University [Montreal]-Université du Québec à Montréal = University of Québec in Montréal (UQAM), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Mount Sinai Hospital [Toronto, Canada] (MSH), and This work was funded by discovery grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) (418615-2012 and 2018-06293) and an operating grant from the Canadian Institutes for Health Research (CIHR) (130335) (to N.B.). N.B. was also supported by funds from the Canada Foundation for Innovation (30308 and 34963), holds a Canada Research Chair (Tier 2) in Cancer Proteomics, and previously received a salary award from the Fonds de Recherche du Québec-Santé (FRQ-S) with funds from the Quebec Breast Cancer Foundation. U.D. holds an Alexander-Graham-Bell Canada graduate scholarship and an FRQ-S doctoral award. N.L. is the recipient of a Frederick-Banting and Charles-Best Canada graduate scholarship and an FRQS M.Sc. award. D.N.B. is the recipient of an NSERC postgraduate scholarship. K.J. held a PROTEO scholarship and M.J. a MITACS scholarship. C.R.L. holds the Canada Research Chair in Evolutionary Cell and Systems Biology, and his work is supported by CIHR (299432 and 324265). N.D. holds an FRQ-S Research Scholar Junior 2 salary award and grants from the NIH (R01GM105978) and NSERC (2016-05557). P.L. holds an NSERC discovery grant (2015-04757) and is an FRQ-S Research Scholar. Work in G.G.P.’s lab is supported in part by CIHR (105888).
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], adaptor proteins, Cell Communication, Ligands, EPH receptors, Article, Receptor tyrosine kinase, src Homology Domains, 03 medical and health sciences, proteomics, Animals, Humans, Amino Acid Sequence, Active state, Phosphorylation, protein interaction networks, Phosphotyrosine, Molecular Biology, Adaptor Proteins, Signal Transducing, Oncogene Proteins, biology, tyrosine phosphorylation, Receptor, EphA4, Receptor Protein-Tyrosine Kinases, Signal transducing adaptor protein, Cell Biology, SRC homology domain, Cell biology, HEK293 Cells, 030104 developmental biology, Docking (molecular), biology.protein, Tyrosine, Drosophila, Signal transduction, tyrosine kinase receptors, signal transduction, HeLa Cells, Protein Binding, Proto-oncogene tyrosine-protein kinase Src
Abstract: International audience; Phosphotyrosine (pTyr) signaling has evolved into a key cell-to-cell communication system. Activated receptor tyrosine kinases (RTKs) initiate several pTyr-dependent signaling networks by creating the docking sites required for the assembly of protein complexes. However, the mechanisms leading to network disassembly and its consequence on signal transduction remain essentially unknown. We show that activated RTKs terminate downstream signaling via the direct phosphorylation of an evolutionarily conserved Tyr present in most SRC homology (SH) 3 domains, which are often part of key hub proteins for RTK-dependent signaling. We demonstrate that the direct EPHA4 RTK phosphorylation of adaptor protein NCK SH3s at these sites results in the collapse of signaling networks and abrogates their function. We also reveal that this negative regulation mechanism is shared by other RTKs. Our findings uncover a conserved mechanism through which RTKs rapidly and reversibly terminate downstream signaling while remaining in a catalytically active state on the plasma membrane.
Published: 2018

36. Diaphragm function and weaning from mechanical ventilation: an ultrasound and phrenic nerve stimulation clinical study

Author: Alexandre Demoule, Bruno-Pierre Dubé, Danielle Reuter, Martin Dres, Laurence Dangers, Elise Morawiec, Julien Mayaux, Thomas Similowski, Ewan C. Goligher, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Toronto, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Mount Sinai Hospital [Toronto, Canada] (MSH), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), and dres, martin
Subjects: medicine.medical_specialty, Phrenic nerve stimulation, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Diaphragm, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Spontaneous breathing trial, Diaphragm function, 03 medical and health sciences, 0302 clinical medicine, Weakness, Extubation, Liberation, Internal medicine, Ultrasound, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Medicine, Weaning, Ventilator, Mechanical ventilation, Receiver operating characteristic, business.industry, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, musculoskeletal system, Diaphragm (structural system), [SDV] Life Sciences [q-bio], 030228 respiratory system, Cardiology, business
Abstract: Background Diaphragm dysfunction is defined by a value of twitch tracheal pressure in response to magnetic phrenic stimulation (twitch pressure) amounting to less than 11 cmH2O. This study assessed whether this threshold or a lower one would predict accurately weaning failure from mechanical ventilation. Twitch pressure was compared to ultrasound measurement of diaphragm function. Methods In patients undergoing a first spontaneous breathing trial, diaphragm function was evaluated by twitch pressure and by diaphragm ultrasound (thickening fraction). Receiver operating characteristics curves were computed to determine the best thresholds predicting failure of spontaneous breathing trial. Results Seventy-six patients were evaluated, 48 (63%) succeeded and 28 (37%) failed the spontaneous breathing trial. The optimal thresholds of twitch pressure and thickening fraction to predict failure of the spontaneous breathing trial were, respectively, 7.2 cmH2O and 25.8%, respectively. The receiver operating characteristics curves were 0.80 (95% CI 0.70–0.89) for twitch pressure and 0.82 (95% CI 0.73–0.93) for thickening fraction. Both receiver operating characteristics curves were similar (p = 0.83). A twitch pressure value lower than 11 cmH2O (the traditional cutoff for diaphragm dysfunction) predicted failure of the spontaneous breathing trial with a sensitivity of 89% (95% CI 72–98%) and a specificity of 45% (95% CI 30–60%). Conclusions Failure of spontaneous breathing trial can be predicted with a lower value of twitch pressure than the value defining diaphragm dysfunction. Twitch pressure and thickening fraction had similar strong performance in the prediction of failure of the spontaneous breathing trial. Electronic supplementary material The online version of this article (10.1186/s13613-018-0401-y) contains supplementary material, which is available to authorized users.
Published: 2018

37. Glaucoma - Authors' reply

Author: Tin Aung, Jost B. Jonas, Robert Ritch, Rupert R A Bourne, Alain M. Bron, Songhomitra Panda-Jonas, Medical Faculty [Mannheim], Singapore Eye Research Institute [Singapore] (SERI), National University of Singapore (NUS), Anglia Ruskin University (ARU), 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), Université Bourgogne Franche-Comté [COMUE] (UBFC), Department of Ophthalmology, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and Mount Sinai Hospital [Toronto, Canada] (MSH)
Subjects: business.industry, MEDLINE, Glaucoma, 02 engineering and technology, General Medicine, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Text mining, 030221 ophthalmology & optometry, 0202 electrical engineering, electronic engineering, information engineering, medicine, Optometry, Humans, 020201 artificial intelligence & image processing, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2018

38. Antibiotic treatment of infections caused by carbapenem-resistant Gram-negative bacilli: an international ESCMID cross-sectional survey among infectious diseases specialists practicing in large hospitals

Author: Papst, Lea, Beović, Bojana, Pulcini, Céline, Durante-Mangoni, Emanuele, Rodríguez-Baño, Jesús, Kaye, Keith S, Daikos, George L, Raka, Lul, Paul, Mical, Esgap, Esgbis, ESGIE and the CRGNB treatment survey study group collaborators: Abbo, L, Abgueguen, P, Almirante, B, Azzini, Am, Bani-Sadr, F, Bassetti, M, Ben-Ami, R, Beović, B, Béraud, G, Botelho-Nevers, E, Bou, G, Boutoille, D, Cabié, A, Cacopardo, B, Cascio, A, Cassir, N, Castelli, F, Cecala, M, Charmillon, A, Chirouze, C, Cisneros, Jm, Colmenero, Jd, Coppola, N, Corcione, S, Daikos, Gl, Dalla Gasperina, D, De la Calle Cabrera, C, Delobel, P, Di Caprio, D, Durante Mangoni, E, Dupon, M, Ettahar, N, Falagas, Me, Falcone, M, Fariñas, Mc, Faure, E, Forestier, E, Foti, G, Gallagher, J, Gattuso, G, Gendrin, V, Gentile, I, Giacobbe, Dr, Gogos, Ca, Grandiere Perez, L, Hansmann, Y, Horcajada, Jp, Iacobello, C, Jacob, Jt, Justo, Ja, Kernéis, S, Komnos, A, Kotnik Kevorkijan, B, Lebeaux, D, Le Berre, R, Lechiche, C, Le Moing, V, Lescure, Fx, Libanore, M, Martinot, M, Merino de Lucas, E, Mondain, V, Mondello, P, Montejo, M, Mootien, J, Muñoz, P, Nir-Paz, R, Pan, A, Paño-Pardo, Jr, Patel, G, Paul, M, Pérez Rodríguez MT, Piroth, L, Pogue, J, Potoski, Ba, Pourcher, V, Pyrpasopoulou, A, Rahav, G, Rizzi, M, Rodríguez-Baño, J, Salavert, M, Scheetz, M, Sims, M, Spahija, G, Stefani, S, Stefos, A, Tamma, Pd, Tattevin, P, Tedesco, A, Torre-Cisneros, J, Tripolitsioti, P, Tsiodras, S, Uomo, G, Verdon, R, Viale, P, Vitrat, V, Weinberger, M, Wiener-Well, Y, Papst L., Beovic B., Pulcini C., Durante-Mangoni E., Rodriguez-Bano J., Kaye K.S., Daikos G.L., Raka L., Paul M., Abbo L., Abgueguen P., Almirante B., Azzini A.M., Bani-Sadr F., Bassetti M., Ben-Ami R., Beraud G., Botelho-Nevers E., Bou G., Boutoille D., Cabie A., Cacopardo B., Cascio A., Cassir N., Castelli F., Cecala M., Charmillon A., Chirouze C., Cisneros J.M., Colmenero J.D., Coppola N., Corcione S., Dalla Gasperina D., De la Calle Cabrera C., Delobel P., Di Caprio D., Durante Mangoni E., Dupon M., Ettahar N., Falagas M.E., Falcone M., Farinas M.C., Faure E., Forestier E., Foti G., Gallagher J., Gattuso G., Gendrin V., Gentile I., Giacobbe D.R., Gogos C.A., Grandiere Perez L., Hansmann Y., Horcajada J.P., Iacobello C., Jacob J.T., Justo J.A., Kerneis S., Komnos A., Kotnik Kevorkijan B., Lebeaux D., Le Berre R., Lechiche C., Le Moxing V., Lescure F.X., Libanore M., Martinot M., Merino de Lucas E., Mondain V., Mondello P., Montejo M., Mootien J., Munoz P., Nir-Paz R., Pan A., Pano-Pardo J.R., Patel G., Perez Rodriguez M.T., Piroth L., Pogue J., Potoski B.A., Pourcher V., Pyrpasopoulou A., Rahav G., Rizzi M., Salavert M., Scheetz M., Sims M., Spahija G., Stefani S., Stefos A., Tamma P.D., Tattevin P., Tedesco A., Torre-Cisneros J., Tripolitsioti P., Tsiodras S., Uomo G., Verdon R., Viale P., Vitrat V., Weinberger M., Wiener-Well Y., University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Monaldi Hospital, Hospital Virgen Macarena, University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, National and Kapodistrian University of Athens (NKUA), University Clinical Center of Kosova, Rambam Health Care Campus, Jackson Memorial Hospital, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Vall d'Hebron University Hospital [Barcelona], University of Verona (UNIVR), Centre Hospitalier Universitaire de Reims (CHU Reims), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Tel Aviv Sourasky Medical Centre, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hospital Universitario, A Coruña, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU de la Martinique [Fort de France], ARNAS 'Garibaldi, S. Luigi-Currò, Ascoli-Tomaselli', Università degli studi di Palermo - University of Palermo, Assistance Publique-Hôpitaux de Marseille (AP-HM), ASST Spedali Civili of Brescia, ARNAS Civico Palermo, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospital Universitario Virgen del Rocío [Sevilla], Hospital Regional Universitario de Málaga [Spain], Università degli studi della Campania 'Luigi Vanvitelli', University of Turin, University of Insubria, Varese, Hospital Clínic de Barcelona, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], AO San Sebastiano, CHU Bordeaux [Bordeaux], CH Valenciennes, Henry Dunant Hospital, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Hospital Marques de Valdecillas, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Métropole Savoie [Chambéry], Ospedale di Reggio Calabria, Children’s Hospital of Philadelphia (CHOP ), Carlo Poma Hospital Mantova (ASST Mantova ), CH Belfort-Montbéliard, University of Naples Federico II, AUO San Martino IST Ist Nazl Ric Canc, I-16132 Genoa, Italy, University of Patras [Patras], Centre Hospitalier Le Mans (CH Le Mans), CHU Strasbourg, IMIM-Hospital del Mar, Generalitat de Catalunya, Cannizzaro Hospital, Emory University School of Medicine, Emory University [Atlanta, GA], University of South Carolina [Columbia], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), General Hospital of Larissa, University medical centre Maribor (UKC Maribor), 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), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AP-HP - Hôpital Bichat - Claude Bernard [Paris], University of Ferrara at St. Anna Hospital, CH Colmar, Hospital General Universitario de Alicante, CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), AOU Policlinico 'G. Martino', Messina, Italy, Hospital Universitario Cruces = Cruces University Hospital, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Hospital General Universitario 'Gregorio Marañón' [Madrid], Hadassah Hebrew University Medical Center [Jerusalem], Azienda Istituti Ospitalieri di Cremona, Lozano Blesa Clinical Hospital [Zaragoza, Spain], Mount Sinai Hospital [Toronto, Canada] (MSH), Complejo Hospitalario de Vigo, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Detroit Medical Center, University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hippokration General Hospital, Sheba Medical Centre, Ramat Gan, Israel, ASST Papa Giovanni XXIII [Bergamo, Italy], Hospital Universitario La Fe, Valencia, Northwestern Hospital Chicago, Beaumont Hospital, Lagjia e Universitetit, Rruga 1, nr.32, 10000 Prishtina, Kosovo, parent, Università degli studi di Catania [Catania], Larissa University Hospital, Johns Hopkins University School of Medicine [Baltimore], CHU Pontchaillou [Rennes], Ospedale Fracastoro San Bonifacio [Verona], Hospital Reina Sofia, Cordoba, Agioi Anargiroi Hospital, Attikon University Hospital, Ospedale Cardarelli, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), CH Annecy Genevois, Assah Harofeh Medical Centre, Zerifin, Israel, Shaare Zedek Medical Centre, Jerusalem, Israel, National Institutes of Health (US), Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Red Española de Investigación en Patología Infecciosa, European Commission, Papst, Lea, Beović, Bojana, Pulcini, Céline, Durante-Mangoni, Emanuele, Rodríguez-Baño, Jesú, Kaye, Keith S, Daikos, George L, Raka, Lul, Paul, Mical, Papst, L., Beovic, B., Pulcini, C., Durante-Mangoni, E., Rodriguez-Bano, J., Kaye, K. S., Daikos, G. L., Raka, L., Paul, M., Abbo, L., Abgueguen, P., Almirante, B., Azzini, A. M., Bani-Sadr, F., Bassetti, M., Ben-Ami, R., Beraud, G., Botelho-Nevers, E., Bou, G., Boutoille, D., Cabie, A., Cacopardo, B., Cascio, A., Cassir, N., Castelli, F., Cecala, M., Charmillon, A., Chirouze, C., Cisneros, J. M., Colmenero, J. D., Coppola, N., Corcione, S., Dalla Gasperina, D., De la Calle Cabrera, C., Delobel, P., Di Caprio, D., Dupon, M., Ettahar, N., Falagas, M. E., Falcone, M., Farinas, M. C., Faure, E., Forestier, E., Foti, G., Gallagher, J., Gattuso, G., Gendrin, V., Gentile, I., Giacobbe, D. R., Gogos, C. A., Grandiere Perez, L., Hansmann, Y., Horcajada, J. P., Iacobello, C., Jacob, J. T., Justo, J. A., Kerneis, S., Komnos, A., Kotnik Kevorkijan, B., Lebeaux, D., Le Berre, R., Lechiche, C., Le Moxing, V., Lescure, F. X., Libanore, M., Martinot, M., Merino de Lucas, E., Mondain, V., Mondello, P., Montejo, M., Mootien, J., Munoz, P., Nir-Paz, R., Pan, A., Pano-Pardo, J. R., Patel, G., Perez Rodriguez, M. T., Piroth, L., Pogue, J., Potoski, B. A., Pourcher, V., Pyrpasopoulou, A., Rahav, G., Rizzi, M., Salavert, M., Scheetz, M., Sims, M., Spahija, G., Stefani, S., Stefos, A., Tamma, P. D., Tattevin, P., Tedesco, A., Torre-Cisneros, J., Tripolitsioti, P., Tsiodras, S., Uomo, G., Verdon, R., Viale, P., Vitrat, V., Weinberger, M., Wiener-Well, Y., Università degli studi di Verona = University of Verona (UNIVR), Assistance Publique - Hôpitaux de Marseille (APHM), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], and Università degli studi di Torino = University of Turin (UNITO)
Subjects: 0301 basic medicine, Acinetobacter baumannii, Carbapenem, Antibiotics, Drug Resistance, Drug resistance, Tigecycline, Carbapenem-resistant Gram-negative bacilli, Combination therapy, Enterobacteriaceae, Polymyxin, Pseudomonas aeruginosa, Survey, 0302 clinical medicine, Surveys and Questionnaires, polycyclic compounds, 030212 general & internal medicine, Anti-Bacterial Agents, Carbapenems, Cross Infection, Cross-Sectional Studies, Drug Resistance, Bacterial, Gram-Negative Bacteria, Gram-Negative Bacterial Infections, Hospitals, Humans, Microbial Sensitivity Tests, Microbiology (medical), Infectious Diseases, biology, Microbial Sensitivity Test, Bacterial, antibiotic management, carbapenem-resistant Gram-negative bacteria, General Medicine, 3. Good health, medicine.drug, Human, medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Fosfomycin, carbapenem-resistant Gram-negative bacteria, 03 medical and health sciences, Hospital, Internal medicine, Anti-Bacterial Agent, medicine, Gram-Negative Bacterial Infection, Cross-Sectional Studie, business.industry, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, Infectious disease (medical specialty), Carbapenem-resistant gram-negative bacilli, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, antibiotic management, business, Rifampicin
Abstract: ESGAP, ESGBIS, ESGIE and the CRGNB treatment survey study group., [Objectives] To explore contemporary antibiotic management of infections caused by carbapenem-resistant Gram-negative bacteria in hospitals., [Methods] Cross-sectional, internet-based questionnaire survey. We contacted representatives of all hospitals with more than 800 acute-care hospital beds in France, Greece, Israel, Italy, Kosovo, Slovenia, Spain and selected hospitals in the USA. We asked respondents to describe the most common actual practice at their hospital regarding management of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa through close-ended questions., [Results] Between January and June 2017, 115 of 141 eligible hospitals participated (overall response rate 81.6%, country-specific rates 66.7%–100%). Most were tertiary-care (99/114, 86.8%), university-affiliated (110/115, 89.1%) hospitals and most representatives were infectious disease specialists (99/115, 86.1%). Combination therapy was prescribed in 114/115 (99.1%) hospitals at least occasionally. Respondents were more likely to consider combination therapy when treating bacteraemia, pneumonia and central nervous system infections and for Enterobacteriaceae, P. aeruginosa and A. baumannii similarly. Combination of a polymyxin with a carbapenem was used in most cases, whereas combinations of a polymyxin with tigecycline, an aminoglycoside, fosfomycin or rifampicin were also common. Monotherapy was used for treatment of complicated urinary tract infections, usually with an aminoglycoside or a polymyxin. The intended goal of combination therapy was to improve the effectiveness of the treatment and to prevent development of resistance. In general, respondents shared the misconception that combination therapy is supported by strong scientific evidence., [Conclusions] Combination therapy was the preferred treatment strategy for infections caused by carbapenem-resistant Gram-negative bacteria among hospital representatives, even though high-quality evidence for carbapenem-based combination therapy is lacking., EDM received funding by NIH for project HHSN272201000039C. JRB received funding for research from Plan Nacional de I + D + i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001)—co-financed by European Development Regional Fund A way to achieve Europe, Operative Programme Intelligent Growth 2014–2020.
Published: 2018

39. Diffusion-weighted MR Imaging of the Pancreas: Current Status and Recommendations

Author: Riccardo Manfredi, Vilgrain, Christine Hoeffel, A Luciani, B Taouli, M Kanematsu, B Guiu, M Barral, Philippe Soyer, Dm Koh, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Mount Sinai Hospital [Toronto, Canada] (MSH), Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Royal Marsden NHS Foundation Trust, Service de Radiologie [Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Verona (UNIVR), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Gifu University Graduate School of Medicine, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Mount Sinai Hospital (MSH), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Università degli Studi di Verona, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Università degli studi di Verona = University of Verona (UNIVR)
Subjects: medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Contrast Media, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Image Interpretation, Computer-Assisted, medicine, Humans, Radiology, Nuclear Medicine and imaging, Stage (cooking), Diffusion-Weighted MR Imaging, Pancreas, Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA, business.industry, Pancreatic Diseases, Image Enhancement, Mr imaging, 3. Good health, diffusion-weighted ( DW diffusion weighted ) magnetic resonance (MR) imaging, Diffusion Magnetic Resonance Imaging, medicine.anatomical_structure, Radiology, business, Nuclear medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Advances in image quality over the past few years, mainly due to refinements in hardware and coil systems, have made diffusion-weighted ( DW diffusion weighted ) magnetic resonance (MR) imaging a promising technique for the detection and characterization of pancreatic conditions. DW diffusion weighted MR imaging can be routinely implemented in clinical protocols, as it can be performed relatively quickly, does not require administration of gadolinium-based contrast agents, and enables qualitative and quantitative assessment of tissue diffusivity (diffusion coefficients). In this review, acquisition parameters, postprocessing, and quantification methods applied to pancreatic DW diffusion weighted MR imaging will be discussed. The current common clinical uses of DW diffusion weighted MR imaging (ie, pancreatic lesion detection and characterization) and the less-common applications of DW diffusion weighted MR imaging used for the diagnosis of pancreatic parenchymal diseases will be reviewed. Also, the limitations of the technique, mainly image quality and reproducibility of diffusion parameters, as well as future directions for pancreatic DW diffusion weighted MR imaging will be discussed. The utility of apparent diffusion coefficient ( ADC apparent diffusion coefficient ) measurement for the characterization of pancreatic lesions is now well accepted but there are a number of limitations. Future well-designed, multicenter studies are needed to better determine the most appropriate use of ADC apparent diffusion coefficient in the area of pancreatic disease.
Published: 2015

40. Aberrant expression of kallikrein-related peptidase 7 is correlated to human melanoma aggressiveness by stimulating cell migration and invasion

Author: Delaunay, Tiphaine, Deschamps, Lydia, Haddada, Meriem, Walker, Francine, Soosaipillai, Antoninus, Soualmia, Feryel, El Amri, Chahrazade, Diamandis, Eleftherios P., Brattsand, Maria, Magdolen, Viktor, Darmoul, Dalila, Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de pathologie [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mount Sinai Hospital [Toronto, Canada] (MSH), Vieillissement Cellulaire Intégré et Inflammation (VCII), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Umeå University, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), HAL-UPMC, Gestionnaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-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)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Mount Sinai Hospital (MSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), and Technische Universität München [München] (TUM)
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Members of the tissue kallikrein-related peptidase (KLK) family not only regulate several important physiological functions, but aberrant expression has also been associated with various malignancies. Clinically, KLKs have been suggested as promising biomarkers for diagnosis and prognosis in many types of cancer. As of yet, expression of KLKs and their role in skin cancers are, however, poorly addressed. Malignant melanoma is an aggressive disease associated with poor prognosis. Hence, diagnostic biomarkers to monitor melanoma progression are needed. Herein, we demonstrate that although mRNAs of several KLKs are aberrantly expressed in melanoma cell lines, only the KLK7 protein is highly secreted in vitro. In line with these findings, ectopic expression of KLK7 in human melanomas and its absence in benign nevi was demonstrated by immunohistochemistry in vivo. Interestingly, overexpression of KLK7 induced a significant reduction in melanoma cell proliferation and colony formation. Moreover, KLK7 overexpression triggered an increase in cell motility and invasion associated with decreased expression of E-cadherin and an up-regulation of MCAM/CD146. Our results demonstrate, for the first time, that aberrant KLK7 expression leads to a switch from proliferative to invasive phenotype suggesting a potential role of KLK7 in melanoma progression. Thus, we hypothesize that KLK7 may represent a potential biomarker for melanoma progression.
Published: 2017

41. Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury in mice

Author: Sylvie Naveau, Virginie Puchois, Marie-Louise Noordine, Muriel Thomas, Anne-Marie Cassard, Cindy Hugot, Laura Wrzosek, Véronique Robert, Dominique Rainteau, Frédéric Cailleux, Dragos Ciocan, Gabriel Perlemuter, Madeleine Spatz, Gladys Ferrere, Williams Turpin, Lydie Humbert, Dominique Berrebi, Françoise Gaudin, UMR 996 - DHU Hépatinov, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Sud (Paris 11), Université Paris-Saclay, IFR 141 - Faculté de Pharmacie - Institut Paris-Sud d'Innovation Thérapeutique (IPSIT), UMR 996 - DHU Hepatinov, Division of Gastroenterology - Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital (MSH), UMR 996 - DHUHépatinov, Université Pierre et Marie Curie (Paris 6), Sorbonne Universités, ERL 1157 Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - 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), Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris), Département PM2 Plateforme de Métabolomique - Peptidomique et dosage de Médicam, Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris (AP-HP), ERL 1157 Inflammation-Immunopathology-Biotherapy Department (DHU i2B, U996 DHU Hépatinov, Institut Paris Saclay d’Innovation Thérapeutique (IPSIT), IFR 141 Institut Paris-Sud d’Innovation Thérapeutique (IPSIT) - Faculté de Pharmacie, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Hôpital Antoine Béclère, Assistance Publique - Hôpitaux de Paris (AP-HP), nstitutIFR 141 Paris-Sud d’Innovation Thérapeutique (IPSIT) - Faculté de Pharmac, U996 DHU Hepatinov, Institut IFR 141 Paris-Sud d’Innovation Thérapeutique (IPSIT) - Faculté de Pharmac, Mount Sinai Hospital [Toronto, Canada] (MSH), Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris sciences et lettres (PSL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-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)-École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Alcoholic liver disease, liver diseases, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Physiology, Alcoholic hepatitis, Biology, Microbiology, 03 medical and health sciences, bacteroides, medicine, microbiota, Gastrointestinal microbiome, Feces, fatty liver, Liver injury, Hepatology, Prebiotic, Fatty liver, fecal microbiota transplantation, dysbiosis, medicine.disease, alcohol drinking, 3. Good health, 030104 developmental biology, prebiotic, Steatosis, Dysbiosis, alcoholic
Abstract: Background & AimsAlcoholic liver disease (ALD) is a leading cause of liver failure and mortality. In humans, severe alcoholic hepatitis is associated with key changes to intestinal microbiota (IM), which influences individual sensitivity to develop advanced ALD. We used the different susceptibility to ALD observed in two distinct animal facilities to test the efficiency of two complementary strategies (fecal microbiota transplantation and prebiotic treatment) to reverse dysbiosis and prevent ALD.MethodsMice were fed alcohol in two distinct animal facilities with a Lieber DeCarli diet. Fecal microbiota transplantation was performed with fresh feces from alcohol-resistant donor mice to alcohol-sensitive receiver mice three times a week. Another group of mice received pectin during the entire alcohol consumption period.ResultsEthanol induced steatosis and liver inflammation, which were associated with disruption of gut homeostasis, in alcohol-sensitive, but not alcohol resistant mice. IM analysis showed that the proportion of Bacteroides was specifically lower in alcohol-sensitive mice (p
Published: 2017

42. Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders

Author: Joana Almeida, Christian R. Marshall, Hakon Hakonarson, Bárbara Oliveira, Anthony J. Griswold, Jacob A. S. Vorstman, Bhooma Thiruvahindrapuram, Suma Jacob, Judith Conroy, Alistair T. Pagnamenta, Christelle Cabrol, Jeremy R. Parr, Daniel H. Geschwind, Nancy J. Minshew, Xiao Xu, Richard Anney, Sven Bölte, Zhuozhi Wang, Emily L. Crawford, Elsa Delaby, Margaret A. Pericak-Vance, Joachim Hallmayer, Jonathan L. Haines, Dalila Pinto, Susana Mouga, Alexander Kolevzon, Elena Bacchelli, Frederico Duque, Bernie Devlin, Latha Soorya, Cátia Café, Kirsty Wing, Jennifer K. Lowe, Ana Tryfon, Stephen J. Guter, Geraldine Dawson, Tiago R. Magalhaes, Anthony J. Bailey, Michael Gill, Peter Szatmari, Steven Gallinger, Marion Pilorge, James S. Sutcliffe, Bridget A. Fernandez, Herman van Engeland, Catalina Betancur, Guiomar Oliveira, Andrew Green, Eftichia Duketis, Bernadette Rogé, Ann Le Couteur, Evdokia Anagnostou, Michelle Cotterchio, Daniele Merico, Giovanna Pellecchia, Jonathan Green, Regina Regan, Jillian P. Casey, Guiqing Cai, Gerard D. Schellenberg, Jennifer L. Howe, Elena Maestrini, Andrew D. Paterson, L. Alison McInnes, Patrick Bolton, Edwin H. Cook, Richard Delorme, Lambertus Klei, Thomas Bourgeron, Gillian Baird, Christine M. Freitag, Beth A. Dombroski, Andreas G. Chiocchetti, Sabine M. Klauck, Susan E. Folstein, Mafalda Barbosa, Anthony P. Monaco, Marion Leboyer, Nadia Bolshakova, Fritz Poustka, Richard Holt, Kerstin Wittemeyer, Wendy Roberts, Lonnie Zwaigenbaum, Louise Gallagher, Susan G. McGrew, Joseph D. Buxbaum, Graham Casey, Simon Wallace, Catherine Lord, Sean Brennan, Robert Ziman, Alison K. Merikangas, John I. Nurnberger, Christopher Gillberg, Ellen M. Wijsman, Astrid M. Vicente, Inȇs C. Conceição, Sean Ennis, Patricia Jiménez González, Hilary Coon, Raphael Bernier, John R. Gilbert, Ann P. Thompson, Susanne Thomson, Agatino Battaglia, Maretha de Jonge, Michael L. Cuccaro, Catarina Correia, Veronica J. Vieland, Stephen W. Scherer, Pauline Chaste, Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Seaver Autism Center-, The Mindich Child Health & Development Institute, Department of Psychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Seaver Autism Center for Research and Treatment, Friedman Brain Institute, The Mindich Child Health and Development Institute, The Icahn Institute for Genomics and Multiscale Biology, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Trinity College Dublin-St. James's Hospital, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), McLaughlin Centre, University of Toronto, BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Department of Neurology, University of California [Los Angeles] (UCLA), University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, Fisico-Quimica Biologica, Universidade Federal do Rio de Janeiro (UFRJ), John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Pathology and Laboratory Medicine, University of Pennsylvania [Philadelphia], Department of Pathology, Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Prevention & Cancer Control, Cancer Care Ontario, Department of Preventive Medicine, University of Southern California (USC), Department of Pediatrics, University of Alberta, School of Education, University of Birmingham [Birmingham], University of Oxford [Oxford]-Warneford Hospital, Octogone Unité de Recherche Interdisciplinaire (Octogone), Université Toulouse - Jean Jaurès (UT2J), Autism Research Unit, The Hospital for sick children [Toronto] (SickKids)-University of Toronto, Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Institute for Biomedical Imaging and Life Science, University of Coimbra [Portugal] (UC), Vanderbilt University [Nashville], Center for Autism and the Developing Brain (CADB), Weill Medical College of Cornell University [New York], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institute of Health and Society, Newcastle University [Newcastle], Department of Child and Adolescent Psychiatry, Newcastle University [Newcastle]-Institute of Health & Society (Child & Adolescent Psychiatry), Child Developmental and Behavioral Unit, Hospital Nacional de Niños Dr Sáenz Herrera, Institute for Juvenile Research-University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Manchester Academic Health Sciences Centre, Gillberg Neuropsychiatry Centre [Göteborg, Sueden], Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU), Institute of Child Health, University College of London [London] (UCL), Memorial University of Newfoundland [St. John's], Disciplines of Genetics and Medicine, Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Institute of Psychiatry, King‘s College London, Institute of psychiatry, University of Washington [Seattle], Paediatric Neurodisability, King‘s College London-King's Health Partners, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, University of British Columbia (UBC), Bloorview Research Institute, Division of Medical Genetics [Seattle], Departments of Biostatistics and Medicine, Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, Institute of Neuroscience [Newcastle] (ION), Institutes of Neuroscience and Health and Society, Indiana University School of Medicine, Indiana University System-Indiana University System, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Utah Autism Research Program, University of Utah Psychiatry Department, University of Miami School of Medicine, Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris [Pisa], Department of Psychiatry and Behavioral Sciences [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford School of Medicine [Stanford], Institute for Juvenile Research, University of Illinois [Chicago] (UIC), Department of Neuroscience, Main funders of the Autism Genome Project: Autism Speaks (USA), the Health Research Board (Ireland, AUT/2006/1, AUT/2006/2, PD/2006/48), the Medical Research Council (UK), the Hilibrand Foundation (USA), Genome Canada, the Ontario Genomics Institute, and the Canadian Institutes of Health Research (CIHR), Autism Genome Project Consortium, Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), University of Pennsylvania, University of Oxford-Warneford Hospital, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), Betancur, Catalina, Instituto Nacional de Saude Dr Ricardo Jorge, Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement (LAMBE - UMR 8587), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Università di Bologna [Bologna] (UNIBO), Mount Sinai Hospital (MSH), University of Toronto-The Hospital for Sick Children, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Gillberg Neuropsychiatry Centre, University of Gothenburg (GU), Stanford University Medical School, Stanford University School of Medicine [Stanford], Stanford University [Stanford], Université de Toulouse (UT)-Université de Toulouse (UT), Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JA, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, Conceição IC, Chiocchetti AG, Casey JP, Cai G, Cabrol C, Bolshakova N, Bacchelli E, Anney R, Gallinger S, Cotterchio M, Casey G, Zwaigenbaum L, Wittemeyer K, Wing K, Wallace S, van Engeland H, Tryfon A, Thomson S, Soorya L, Rogé B, Roberts W, Poustka F, Mouga S, Minshew N, McInnes LA, McGrew SG, Lord C, Leboyer M, Le Couteur AS, Kolevzon A, Jiménez González P, Jacob S, Holt R, Guter S, Green J, Green A, Gillberg C, Fernandez BA, Duque F, Delorme R, Dawson G, Chaste P, Café C, Brennan S, Bourgeron T, Bolton PF, Bölte S, Bernier R, Baird G, Bailey AJ, Anagnostou E, Almeida J, Wijsman EM, Vieland VJ, Vicente AM, Schellenberg GD, Pericak-Vance M, Paterson AD, Parr JR, Oliveira G, Nurnberger JI, Monaco AP, Maestrini E, Klauck SM, Hakonarson H, Haines JL, Geschwind DH, Freitag CM, Folstein SE, Ennis S, Coon H, Battaglia A, Szatmari P, Sutcliffe JS, Hallmayer J, Gill M, Cook EH, Buxbaum JD, Devlin B, Gallagher L, Betancur C, and Scherer SW.
Subjects: Male, INTELLECTUAL DISABILITY, pathways, Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Bioinformatics, DUPLICATIONS, Intellectual disability, Gene Regulatory Networks, Genetics(clinical), Copy-number variation, 10. No inequality, Child, GDI1, Genetics (clinical), Sequence Deletion, COPY NUMBER VARIANTS, Genetics, gene networks, Copy Number Variation, 3. Good health, Pedigree, Fragile X syndrome, Multigene Family, Female, Metabolic Networks and Pathways, de novo, DNA Copy Number Variations, autism, Biology, rare CNV, PHENOTYPE ONTOLOGY, Article, Structural variation, mental disorders, medicine, Humans, ddc:610, FRAGILE-X-SYNDROME, GENOME-WIDE ASSOCIATION, Gene, [SDV.GEN]Life Sciences [q-bio]/Genetics, HDAC4, SETD5, medicine.disease, CHD2, inherited, STRUCTURAL VARIATION, DELETIONS, DE-NOVO MUTATIONS, Child Development Disorders, Pervasive, Autism
Abstract: International audience; Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
Published: 2014
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43. Application of quantile regression to recent genetic and -omic studies

Author: Laurent Briollais, Gilles Durrieu, Samuel Lunenfeld Research Institute, University of Toronto-Mount Sinai Hospital [Toronto, Canada] (MSH), Laboratoire de Mathématiques de Bretagne Atlantique (LMBA), and Université de Brest (UBO)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Proteomics, Gene Expression, Genomics, Biology, Bioinformatics, Machine learning, computer.software_genre, 01 natural sciences, Robust regression, 010104 statistics & probability, 03 medical and health sciences, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Genetics, Animals, Humans, Metabolomics, Computer Simulation, 0101 mathematics, Genetics (clinical), Statistical software, Oligonucleotide Array Sequence Analysis, 030304 developmental biology, Genetic association, 0303 health sciences, business.industry, Regression analysis, [STAT.TH]Statistics [stat]/Statistics Theory [stat.TH], Regression, omics, Quantile regression, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Expression quantitative trait loci, Regression Analysis, Artificial intelligence, business, computer
Abstract: This paper provides a review of recent applications of quantile regression to the fields of genetic and the emerging -omic studies. It begins with a general background about this statistical approach following the seminal paper of Koenker and Bassett (Econometrica 46:33-50, 1978). Applications are described, as diverse as genetic association studies, penetrance estimation, gene expression, CGH array experiments, RNAseq experiments, methylation data and proteomics. This paper also introduces recent extensions of quantile regression with a particular focus on the Copula-quantile regression, an approach we recently proposed for sib-pair analysis. A real data example from eQTL analysis is then presented and the [Formula: see text] codes, which run the analyses are provided. Finally, we conclude with some statistical software presentation and some general statements about the potential and interests of quantile regression in modern biological experiments.
Published: 2014

44. Occupational prestige, social mobility and the association with lung cancer in men

Author: Behrens, Thomas, Groß, Is, Siemiatycki, Jack, Conway, David I., Olsson, Ann, Stücker, Isabelle, Guida, Florence, Jöckel, Karl-Heinz, Pohlabeln, Hermann, Ahrens, Wolfgang, Brüske, Irene, Wichmann, Heinz-Erich, Gustavsson, Per, Consonni, Dario, Merletti, Franco, Richiardi, Lorenzo, Simonato, Lorenzo, Fortes, Cristina, Parent, Marie-Elise, McLaughlin, John, Demers, Paul, Landi, Maria Teresa, Caporaso, Neil, Zaridze, David, Szeszenia-Dabrowska, Neonila, Rudnai, Peter, Lissowska, Jolanta, Fabianova, Eleonora, Tardón, Adonina, Field, John K, Dumitru, Rodica Stanescu, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Kromhout, Hans, Vermeulen, Roel, Boffetta, Paolo, Straif, Kurt, Schüz, Joachim, Hovanec, Jan, Kendzia, Benjamin, Pesch, Beate, Brüning, Thomas, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Montreal University Hospital Research Center (CRCHUM), Université de Montréal, University of Glasgow, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation mondiale de la santé (OMS/WHO), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Centre de recherche en Épidémiologie et Santé des Populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) - Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine) - Institut National de la Santé et de la Recherche Médicale (INSERM) - AP-HP Hôpital Paul Brousse [Paris], University of Duisburg-Essen [Germany], Leibniz Institute for Prevention Research and Epidemiology, University of Bremen, Helmholtz Zentrum München, Technical University Munich [Munich] (TUM), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Unit of Cancer Epidemiology, Université de Turin - CERMS and Centre for Oncologic Prevention, University of Padova (ITALY), University of Padova, Istituto dermopatico dell'immacolata (IDI-IRCCS), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS) - Réseau International des Instituts Pasteur - Institut Armand Frappier, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Occupational Cancer Research Centre, National Cancer Institute (NIH), Institute of Carcinogenesis, Russian Cancer Research Centre, The Nofer Institute of Occupational Medicine, National Institutes of Environmental Health Sciences, National Institutes of Health (NIH), The M Sklodowska-Curie Cancer Center and Institute of Oncology, Regional Authority of Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), University of Liverpool [Liverpool], University of Liverpool, National Institute of Public Health, Institute of Hygiene and Epidemiology, Charles University and General University Hospital - First Faculty of Medicine, Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Palacky University, Institute for Risk Assessment Sciences, Utrecht University [Utrecht], International Prevention Research Institute (IPRI), Icahn School of Medicine at Mount Sinai [New York], This work was supported by the German Social Accident Insurance (grant number FP 271). Grant sponsors of the individual studies were the Canadian Institutes of Health Research and Guzzo-SRC Chair in Environment and Cancer, the Fondation de France, the German Federal Ministry of Education, Science, Research, and Technology and the Ministry of Labour and Social Affairs, EC’s INCO-COPERNICUS Program, Polish State Committee for Science Research, Roy Castle Foundation, NIH/NCI/DCEG Intramural Research Program, Lombardy Region, INAIL and the European Union Nuclear Fission Safety Program, Italian Association for Cancer Research, Region Piedmont, Compagnia di San Paolo, Europe Against Cancer Program, the Swedish Council for Work Life Research and the Swedish EPA, the University of Oviedo, the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101), CIBERESP, and FISS-PI060604., LS IRAS EEPI EXAS (Arb.hyg+bl.st.kar.), LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-I&I RA, dIRAS RA-2, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Duisburg-Essen [Essen], Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Helmholtz Zentrum München = German Research Center for Environmental Health, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Université de Turin-CERMS and Centre for Oncologic Prevention, Università degli Studi di Padova = University of Padua (Unipd), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Mount Sinai Hospital [Toronto, Canada] (MSH), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Regional Authority of Public Health [Slovaquia] (RAPH), Ministry of Health of the Slovak Republic [Slovaquia], Charles University [Prague] (CU)-First Faculty of Medicine, Masaryk University [Brno] (MUNI), Department of Optics [Univ Palacký], Faculty of Science [Univ Palacký], Palacky University Olomouc-Palacky University Olomouc, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Courcelles, Michel, Behrens, T., Groß, I., Siemiatycki, J., Conway, D.I., Olsson, A., Stücker, I., Guida, F., Jöckel, K.-H., Pohlabeln, H., Ahrens, W., Brüske, I., Wichmann, H.-E., Gustavsson, P., Consonni, D., Merletti, F., Richiardi, L., Simonato, L., Fortes, C., Parent, M.-E., McLaughlin, J., Demers, P., Landi, M.T., Caporaso, N., Zaridze, D., Szeszenia-Dabrowska, N., Rudnai, P., Lissowska, J., Fabianova, E., Tardón, A., Field, J.K., Dumitru, R.S., Bencko, V., Foretova, L., Janout, V., Kromhout, H., Vermeulen, R., Boffetta, P., Straif, K., Schüz, J., Hovanec, J., Kendzia, B., Pesch, B., Brüning, T., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Helmholtz-Zentrum München (HZM), Universita degli Studi di Padova, and Charles University and General University Hospital-First Faculty of Medicine
Subjects: Adult, Male, Cancer Research, Occupational history, Lung Neoplasms, [SDV]Life Sciences [q-bio], socio-economic status, Socio-economic status, Medizin, Young Adult, Life Course, Occupational History, Synergy, Social Prestige, Socio-economic Status, Transitions, Social prestige, SYNERGY, Life course, Risk Factors, Occupational Exposure, Genetics, Odds Ratio, Humans, Occupational prestige, social mobility and the association with lung cancer in men, Aged, Aged, 80 and over, Smoking, Middle Aged, Social Mobility, [SDV] Life Sciences [q-bio], Oncology, Socioeconomic Factors, Case-Control Studies, transitions, occupational history, social prestige, Research Article
Abstract: BACKGROUND: The nature of the association between occupational social prestige, social mobility, and risk of lung cancer remains uncertain. Using data from the international pooled SYNERGY case–control study, we studied the association between lung cancer and the level of time-weighted average occupational social prestige as well as its lifetime trajectory. METHODS: We included 11,433 male cases and 14,147 male control subjects. Each job was translated into an occupational social prestige score by applying Treiman’s Standard International Occupational Prestige Scale (SIOPS). SIOPS scores were categorized as low, medium, and high prestige (reference). We calculated odds ratios (OR) with 95 % confidence intervals (CI), adjusting for study center, age, smoking, ever employment in a job with known lung carcinogen exposure, and education. Trajectories in SIOPS categories from first to last and first to longest job were defined as consistent, downward, or upward. We conducted several subgroup and sensitivity analyses to assess the robustness of our results. RESULTS: We observed increased lung cancer risk estimates for men with medium (OR = 1.23; 95 % CI 1.13–1.33) and low occupational prestige (OR = 1.44; 95 % CI 1.32–1.57). Although adjustment for smoking and education reduced the associations between occupational prestige and lung cancer, they did not explain the association entirely. Traditional occupational exposures reduced the associations only slightly. We observed small associations with downward prestige trajectories, with ORs of 1.13, 95 % CI 0.88–1.46 for high to low, and 1.24; 95 % CI 1.08–1.41 for medium to low trajectories. CONCLUSIONS: Our results indicate that occupational prestige is independently associated with lung cancer among men. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2432-9) contains supplementary material, which is available to authorized users.
Published: 2016

45. Amotl1 mediates sequestration of the Hippo effector Yap1 downstream of Fat4 to restrict heart growth

Author: Chiara V. Ragni, Jean-François Le Garrec, Jean-Christophe Olivo-Marin, Laurent Guillemot, Tatiana P. Resende, Alain Trouvé, Sigolène M. Meilhac, Helen McNeill, Lisa Kitasato, Nicolas Diguet, Marta Novotova, Nicolas Charon, Alexandre Dufour, Sorin Pop, Caroline Badouel, URA 2578, Centre National de le Recherche Scientifique, UPMC - Institut de Formation Doctorale (IFD ), Université Pierre et Marie Curie - Paris 6 (UPMC), Département de Biologie du Développement et Cellules souches - Department of Developmental and Stem Cell Biology, Institut Pasteur [Paris], Institute of Molecular Physiology and Genetics, Slovak Academy of Science [Bratislava] (SAS), Universidade do Porto, Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Mathématiques et de Leurs Applications (CMLA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), This work was supported by grants from VEGA [2/0110/15] to M.N. and from the Institut Pasteur [PTR335], ANR [11-JSV2-00601], FRM [DPC20111122997], CNRS [PEPS BMI] to S.M.M. C.V.R. was funded by the MESR and ARC, N.D. and L.K. by the Fondation Lefoulon-Delalande, L.K. by the Institut Servier and S.M.M. is an INSERM research scientist. T.P.R. is funded by the FCT [SFRH/BPD/80588/2011] and INEB [NORTE-07-0124-FEDER-000005] to P. Pinto-do-Ó., ANR-11-JSV2-0006,cardiopol,Polarité des cellules du myocarde au cours de la formation des chambres cardiaques(2011), Institut Pasteur [Paris] (IP), Bases Génétiques, Moléculaires et Cellulaires du Développement (BGMCD), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institute of Molecular Physiology and Genetics (IMPG), Universidade do Porto = University of Porto, and Analyse d'Images Quantitative (AIQ)
Subjects: 0301 basic medicine, animal structures, Science, Heart growth, General Physics and Astronomy, Cardiomegaly, Cell Cycle Proteins, Biology, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Mice, Downregulation and upregulation, Animals, Transcription factor, Angiopoietin-Like Protein 1, Adaptor Proteins, Signal Transducing, Cell Proliferation, YAP1, Hippo signaling pathway, Multidisciplinary, Kinase, Cadherin, Effector, fungi, Gene Expression Regulation, Developmental, Membrane Proteins, Heart, YAP-Signaling Proteins, General Chemistry, Desmosomes, Cadherins, Phosphoproteins, Cell biology, Rats, body regions, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, 030104 developmental biology, Animals, Newborn, sense organs, Protein Binding, Signal Transduction
Abstract: Although in flies the atypical cadherin Fat is an upstream regulator of Hippo signalling, the closest mammalian homologue, Fat4, has been shown to regulate tissue polarity rather than growth. Here we show in the mouse heart that Fat4 modulates Hippo signalling to restrict growth. Fat4 mutant myocardium is thicker, with increased cardiomyocyte size and proliferation, and this is mediated by an upregulation of the transcriptional activity of Yap1, an effector of the Hippo pathway. Fat4 is not required for the canonical activation of Hippo kinases but it sequesters a partner of Yap1, Amotl1, out of the nucleus. The nuclear translocation of Amotl1 is accompanied by Yap1 to promote cardiomyocyte proliferation. We, therefore, identify Amotl1, which is not present in flies, as a mammalian intermediate for non-canonical Hippo signalling, downstream of Fat4. This work uncovers a mechanism for the restriction of heart growth at birth, a process which impedes the regenerative potential of the mammalian heart., Growth of the mammalian heart is controlled by Hippo signalling but how this is regulated is unclear. Here, the authors show that Fat4 (an atypical cadherin) acts upstream of Hippo signalling and Fat4 mutant mice have thicker myocardium, which is mediated by the scaffold Amot1 and transcription factor Yap1.
Published: 2016

46. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Author: John R. B. Perry, James B. Meigs, José Dupuis, Luigi Ferrucci, Johan G. Eriksson, Vilmundur Gudnason, Eric J.G. Sijbrands, Jeanette S. Andrews, Jonna L. Grimsby, Lawrence F. Bielak, Peter Kovacs, Panos Deloukas, Marijana Peričić, Johannes H. Smit, Ruth J. F. Loos, Gonneke Willemsen, Eric Boerwinkle, Ben A. Oostra, Manuel Serrano-Ríos, Alena Stančáková, Meena Kumari, Antti Jula, Michael Marmot, Caroline S. Fox, Simon Heath, Guo Li, Ola Hansson, Gerard Waeber, Anne U. Jackson, Nicholas L. Smith, Markku Laakso, George Dedoussis, Aarno Palotie, Sara M. Willems, John F. Peden, Elisabeth Widen, Caroline Hayward, Alan F. Wright, Claes Ladenvall, May E. Montasser, María Teresa Martínez-Larrad, Peter Vollenweider, Louis Pérusse, Tamara B. Harris, Wen Hong L. Kao, Danijela Budimir, Denis Rybin, David B. Savage, Michael A. Province, Alisa K. Manning, Bruna Gigante, Najaf Amin, Lenore J. Launer, Naveed Sattar, Lori L. Bonnycastle, Göran Hallmans, Jeffrey R. O'Connell, Stéphane Lobbens, Jacques S. Beckmann, Gemma Cadby, J. Wouter Jukema, Maria Dimitriou, Michael Stumvoll, Max Vikström, Rona J. Strawbridge, Hugh Watkins, Lyle J. Palmer, Johanna Kuusisto, Aimo Ruokonen, Hanieh Yaghootkar, Yan V. Sun, Inês Barroso, Amy J. Swift, Nancy L. Pedersen, Lars Lind, Mladen Boban, Nita G. Forouhi, Ken K. Ong, Ivana Kolcic, Anke Tönjes, Timothy M. Frayling, Paul W. Franks, Narisu Narisu, Karin Leander, Serge Hercberg, Diana Zelenika, Sharon L.R. Kardia, Min A. Jhun, Marjo-Riitta Järvelin, Stella Trompet, Jaakko Kaprio, Toshiko Tanaka, David S. Siscovick, Toby Johnson, Cornelia M. van Duijn, Veikko Salomaa, Jose C. Florez, James F. Wilson, Leena Peltonen, Pilar Galan, Robert Clarke, Andrew A. Hicks, Claudia Langenberg, Anders Hamsten, David Couper, Albert Hofman, Dawn M. Waterworth, John Blangero, James S. Pankow, Nabila Bouatia-Naji, Sirkka Keinänen-Kiukaanniemi, Mark I. McCarthy, Valeriya Lyssenko, Leif Groop, Brenda W.J.H. Penninx, Ching-Ti Liu, Anuj Goel, Marina Pehlić, Michael Boehnke, Mika Kivimäki, Maria Sabater-Lleal, Emil Rehnberg, Ingrid B. Borecki, Ozren Polasek, Eco J. C. de Geus, Peter P. Pramstaller, Igor Rudan, Richard M. Watanabe, Pierre Meneton, Iva Miljkovic, Vincent Mooser, G. Mark Lathrop, John Beilby, Laura J. Rasmussen-Torvik, Arturo Corbató-Anchuelo, Yvonne Böttcher, Richard N. Bergman, Daniel R. Barnes, Paul C. D. Johnson, Mustafa Atalay, Aroon D. Hingorani, Olga D. Carlson, Perttu Salo, Jacqueline C.M. Witteman, Udo Seedorf, Timo Saaristo, Jian'an Luan, Nicholas J. Wareham, Gudny Eiriksdottir, Matti Uusitupa, Yongmei Liu, Jaakko Tuomilehto, Yurii S. Aulchenko, Peter Schwarz, Robert A. Scott, Lina Zgaga, Joseph Hung, Reedik Mägi, Maria Grazia Franzosi, Eric J. Brunner, Claude Bouchard, Ian Ford, Francis S. Collins, Ulf de Faire, Benjamin F. Voight, Erik Ingelsson, Mario A. Morken, Stefania Bandinelli, Nicole L. Glazer, Dmitry Shungin, Lars Lannfelt, André G. Uitterlinden, Tatijana Zemunik, Markus Perola, Kenneth Rice, Veronique Vitart, Kerrin S. Small, Jouke-Jan Hottenga, Han Chen, Jerome I. Rotter, Philippe Froguel, Karen L. Mohlke, Marie-Claude Vohl, Dorret I. Boomsma, Harry Campbell, Peter S. Chines, Pau Navarro, Vasiliki Lagou, Albert V. Smith, Kathleen Stirrups, Josephine M. Egan, Alan R. Shuldiner, Katri Räikkönen, Inga Prokopenko, Ping An, Rainer Rauramaa, Beverley Balkau, Thor Aspelund, Eleanor Wheeler, Mariza de Andrade, Richa Saxena, Jari Lahti, Cécile Lecoeur, Timo A. Lakka, Jennie Hui, Michael R. Erdos, Stavroula Kanoni, Kirsten Ohm Kyvik, Bengt Sennblad, Sarah H. Wild, Patricia A. Peyser, Patrik K. E. Magnusson, Claire Bellis, Elodie Eury, Jaana Lindström, Boston University [Boston] (BU), Broad Institute of Harvard and MIT, Partenaires INRAE, Massachusetts General Hospital, Massachusetts General Hospital [Boston], Department of Genetics [Boston], Harvard Medical School [Boston] (HMS), Department of Medicine, Université de Sherbrooke (UdeS), Addenbrooke's Hospital, Harvard Medical School [Boston] (HMS)-Beth Israel Deaconess Medical Center [Boston] (BIDMC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Université Lille Nord de France (COMUE), Department of Epidemiology, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-Center for Social Epidemiology and Population Health, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford [Oxford], The Wellcome Trust Centre for Human Genetics [Oxford], The Netherlands Cancer Institute, Ontario Institute for Cancer Research, Mount Sinai Hospital [Toronto, Canada] (MSH), VU University Amsterdam, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Michigan System, Queen Mary University of London (QMUL), The Wellcome Trust Sanger Institute [Cambridge], Lund University [Lund], Diabetes Centre, Lund University, University of Helsinki, Wake Forest School of Medicine, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, University of Maryland School of Medicine, University of Maryland System, University of Edinburgh, University of Exeter, Department of Twin Research and Genetic Epidemiology, King's College London, London, Northwestern University [Evanston], National Institute of Health and Welfare, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Lund University Diabetes Centre, Umeå University, National Institutes of Health, Centre for Medical Systems Biology, Netherlands Genomics Initiative, Washington University in Saint Louis (WUSTL), Department of Health Sciences Research, Mayo Clinic, Wake Forest University, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland, Institute of Biomedicine, Physiology, University of Eastern Finland, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR S 1018, Université Paris-Sud - Paris 11 (UP11), Azienda Sanitaria Firenze, Department of Medical Genetics, Université de Lausanne (UNIL), Centre Hospitalier Universitaire Vaudois (CHUV), Queen Elizabeth II Medical Centre, Research Institute, University of Southern California (USC), University of Split, The University of Texas Health Science Center at Houston (UTHealth), Leipzig University, Pennington Biomedical Research Center, Department of Epidemiology & Public Health, University College of London [London] (UCL), San Carlos Clinical Hospital, University of North Carolina, Harokopio University, National Institute on Aging, Folkhälsan Research Centre, Vaasa Central Hospital, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatry, EMGO - Lifestyle, overweight and diabetes, Epidemiology, Immunology, Erasmus School of Social and Behavioural Sciences, Clinical Genetics, Ophthalmology, Internal Medicine, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Multiple Tissue Human Expression Resource (MUTHER) Consortium, Ahmadi, K.R., Ainali, C., Barrett, A., Bataille, V., Bell, J.T., Buil, A., Deloukas, P., Dermitzakis, E.T., Dimas, A.S., Durbin, R., Glass, D., Grundberg, E., Hassanali, N., Hedman, Å.K., Ingle, C., Knowles, D., Krestyaninova, M., Lindgren, C.M., Lowe, C.E., McCarthy, M.I., Meduri, E., di Meglio, P., Min, J.L., Montgomery, S.B., Nestle, F.O., Nica, A.C., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, S.Y., Small, K.S., Soranzo, N., Spector, T.D., Surdulescu, G., Travers, M.E., Tsaprouni, L., Tsoka, S., Wilk, A., Yang, T.P., Zondervan, K.T., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Morris, A.P., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Langenberg, C., Hofmann, O.M., Dupuis, J., Qi, L., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Couper, D.J., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Klopp, N., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Perry, J.R., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Mohlke, K.L., Morris, A.D., Palmer, C.N., Pramstaller, P.P., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Wareham, N.J., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Hu, F.B., Meigs, J.B., Pankow, J.S., Pedersen, O., Wichmann, H.E., Barroso, I., Florez, J.C., Frayling, T.M., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA)
Subjects: Blood Glucose, Netherlands Twin Register (NTR), medicine.medical_treatment, [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Type 2 diabetes, SUSCEPTIBILITY, Body Mass Index, GLUCOSE, Blood Glucose/metabolism, Cholesterol, HDL/metabolism, Diabetes Mellitus, Type 2/genetics, Genome-Wide Association Study, Humans, Insulin/metabolism, Insulin Resistance/genetics, Polymorphism, Single Nucleotide, 0302 clinical medicine, Insulin, 2. Zero hunger, Genetics, 0303 health sciences, COMMON VARIANTS, 3. Good health, ENVIRONMENT INTERACTION, OBESITY, CORONARY-ARTERY-DISEASE, medicine.medical_specialty, 030209 endocrinology & metabolism, Accounting, Biology, Article, 03 medical and health sciences, Insulin resistance, SDG 3 - Good Health and Well-being, Internal medicine, Diabetes mellitus, medicine, 030304 developmental biology, Genetic association, Glycemic, loci, SNP, insulin, business.industry, Cholesterol, HDL, medicine.disease, Obesity, POLYMORPHISM, ASSOCIATION ANALYSIS, Endocrinology, Diabetes Mellitus, Type 2, TYPE-2 DIABETES RISK, Insulin Resistance, business
Abstract: Group Authors : DIAGRAM Consortium MUTHER Consortium variants influencing fasting glycemic traits and insulin resistance Seuls les 100 premiers auteurs ont été conservés dans la publication. La liste complète des auteurs et des des affiliations est disponible sur la publication https://www.nature.com/articles/ng.2274.pdf p. 667-669.; International audience; Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
Published: 2012

47. Assessment of evidence for a protective role of vitamin D in multiple sclerosis

Author: Heather Hanwell, Brenda Banwell, Department of Nutritional Sciences, Mount Sinai Hospital [Toronto, Canada] (MSH), Department of Paediatrics, and University of Toronto
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, Genes, MHC Class II, Primary disease, Disease activity, Mice, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Risk Factors, Internal medicine, medicine, Vitamin D and neurology, Animals, Humans, Vitamin D, Child, Molecular Biology, 030304 developmental biology, 0303 health sciences, Vitamin d supplementation, Hill's Criteria, business.industry, Multiple sclerosis, Infant, Newborn, Vitamin D Deficiency, medicine.disease, Early life, 3. Good health, Clinical trial, Sunlight, Molecular Medicine, Female, Bradford Hill criteria, Familial Hypophosphatemic Rickets, Seasons, business, 030217 neurology & neurosurgery
Abstract: International audience; Evidence for a role of vitamin D insufficiency in determining risk in Multiple Sclerosis (MS) is supported by studies in both pediatric- and adult-onset patients. The potential role of vitamin D in modulating MS disease activity is an area of active clinical trials research, and the possibility of primary disease prevention with vitamin D supplementation in early life is an emerging concept. With Sir Austin Bradford Hill's criteria as a framework, the present review assesses the evidence for a causal relationship between vitamin D insufficiency and the pathobiology of MS, and discusses rationale for future clinical trials with vitamin D.
Published: 2011

48. Expanded CTG repeat demarcates a boundary for abnormal CpG methylation in myotonic dystrophy patient tissues

Author: Christopher E. Pearson, Masayuki Nakamori, Stéphanie Tomé, Arturo López Castel, Geneviève Gourdon, Charles A. Thornton, David Chitayat, The Hospital for sick children [Toronto] (SickKids), University of Rochester [USA], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), 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), University of Toronto, Mount Sinai Hospital [Toronto, Canada] (MSH), and TOME, Stéphanie
Subjects: Adult, Male, musculoskeletal diseases, CCCTC-Binding Factor, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Mice, Transgenic, Locus (genetics), Protein Serine-Threonine Kinases, Biology, Myotonic dystrophy, Myotonin-Protein Kinase, Mice, Young Adult, Transcription (biology), Genetics, medicine, Animals, Humans, Myotonic Dystrophy, Allele, Molecular Biology, Alleles, Genetics (clinical), Aged, 80 and over, Base Sequence, Articles, General Medicine, Methylation, DNA Methylation, Middle Aged, medicine.disease, Molecular biology, Repressor Proteins, [SDV] Life Sciences [q-bio], Organ Specificity, CTCF, DNA methylation, Female, Microsatellite Instability, Trinucleotide Repeat Expansion, Trinucleotide repeat expansion
Abstract: International audience; Myotonic dystrophy (DM1) affects multiple organs, shows age-dependent progression and is caused by CTG expansions at the DM1 locus. We determined the DM1 CpG methylation profile and CTG length in tissues from DM1 foetuses, DM1 adults, non-affected individuals and transgenic DM1 mice. Analysis included CTCF binding sites upstream and downstream of the CTG tract, as methylation-sensitive CTCF binding affects chromatinization and transcription of the DM1 locus. In humans, in a given foetus, expansions were largest in heart and smallest in liver, differing by 40-400 repeats; in adults, the largest expansions were in heart and cerebral cortex and smallest in cerebellum, differing by up to 5770 repeats in the same individual. Abnormal methylation was specific to the mutant allele. In DM1 adults, heart, liver and cortex showed high-to-moderate methylation levels, whereas cerebellum, kidney and skeletal muscle were devoid of methylation. Methylation decreased between foetuses and adults. Contrary to previous findings, methylation was not restricted to individuals with congenital DM1. The expanded repeat demarcates an abrupt boundary of methylation. Upstream sequences, including the CTCF site, were methylated, whereas the repeat itself and downstream sequences were not. In DM1 mice, expansion-, tissue- and age-specific methylation patterns were similar but not identical to those in DM1 individuals; notably in mice, methylation was present up- and downstream of the repeat, but greater upstream. Thus, in humans, the CpG-free expanded CTG repeat appears to maintain a highly polarized pattern of CpG methylation at the DM1 locus, which varies markedly with age and tissues.
Published: 2010

49. High kallikrein-related peptidase 6 in non-small cell lung cancer cells: an indicator of tumour proliferation and poor prognosis

Author: Heuzé-Vourc’h Nathalie, Brillet Benjamin, Laurent Briollais, Guyetant Serge, Planque Chris, Jourdan Marie-Lise, Coco Catherine, Parent Christelle, Blechet Claire, Reverdiau Pascale, Courty Yves, Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Nutrition, croissance et cancer (U 1069) (N2C), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Nocchi, Estelle, and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Pathology, Lung Neoplasms, Cyclin E, NSCLC, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Lung, Cyclin, Aged, 80 and over, 0303 health sciences, KLK6, Middle Aged, Cell cycle, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, Molecular Oncology, c-Myc, 030220 oncology & carcinogenesis, Molecular Medicine, Female, Kallikreins, cell cycle, Adult, Cyclin-Dependent Kinase Inhibitor p21, medicine.medical_specialty, Biology, survival, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, cyclin, Cell Line, Tumor, medicine, Humans, Lung cancer, Aged, 030304 developmental biology, Cell growth, Cancer, Cell Biology, Kallikrein, medicine.disease, respiratory tract diseases, cell proliferation, kallikrein-related peptidase, Cancer research, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Kallikrein related peptidase, overexpression
Abstract: International audience; The human kallikrein-related peptidases (KLK) are serine proteases whose concentrations are often abnormal in common human malignancies and contribute to neoplastic progression through multifaceted roles. However, little attention has been paid to their synthesis and involvement in the development and dissemination of lung cancer, the leading cause of cancer mortality worldwide. We have analysed the production of KLK6 in normal lung and tumour tissues from patients with non-small cell lung cancer (NSCLC). KLK6 immunoreactivity was restricted to epithelial cells of the normal bronchi, but most of the cancer samples were moderately or highly immunoreactive, regardless of the histological subtype. In contrast, little or no KLK6 was detected in NSCLC cells. We have developed NSCLC lines expressing wild-type KLK6 in order to investigate the role of KLK6 in lung cancer biology, and analysed its impact on proliferation. Ectopic KLK6 dramatically enhanced NSCLC cell growth and KLK6-producing NSCLC cells had accelerated cell cycles, between the G1 and S phases. This was accompanied by a marked increase in cyclin E and decrease in p21. KLK6 production was also associated with enhanced synthesis of c-Myc, which is known to promote cell-cycle progression. Finally, examination of specimens from patients with NSCLC revealed that KLK6 mRNA is overexpressed in tumour tissue, and high KLK6 concentrations were associated with lower survival rates. We conclude that a high concentration of KLK6 is an indicator of tumour proliferation and an independent predictive factor in NSCLC.
Published: 2009

50. Electrophysiological studies of malaria parasite-infected erythrocytes: Current status

Author: Patrick Verloo, Ajay Pillai, Henry M. Staines, Abdulnaser Alkhalil, Sanjay A. Desai, Florian Lang, Richard J.W. Allen, Serge Thomas, Sherin J. Rouhani, Kempaiah Rayavara, Kevin J. Saliba, Eugene K. Oteng, Hugo R. de Jonge, Elvira T. Derbyshire, Kiaran Kirk, Godfrey Lisk, Stéphane Egée, Tsione Solomon, Stephan M. Huber, Hagai Ginsburg, David R.C. Hill, Crystal Shen, School of Geographical Sciences [Bristol], University of Bristol [Bristol], Institut d'Informatique et de Mathématiques Appliquées de Grenoble (IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry [Netherlands] (DB), Department of Biochemistry-Medical Faculty, Erasmus University Medical Centre-Erasmus University Rotterdam, Department of Clinical Genetics (DCG), Erasmus University Medical Centre, Mer et santé (MS), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Development and Fetal Health, Mount Sinai Hospital [Toronto, Canada] (MSH), Laboratoire d'Informatique, de Modélisation et d'optimisation des Systèmes (LIMOS), SIGMA Clermont (SIGMA Clermont)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Ecole Nationale Supérieure des Mines de St Etienne-Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Technische Hoschschule, University of Applied Sciences [Darmstadt], Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute [Boston]-Department of Cancer Biology, Department of Genetics [Boston], Harvard Medical School [Boston] (HMS), School of Engineering and Science, University of the West of Scotland (UWS), System validation - Research and applications (VASY), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'Informatique de Grenoble (LIG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF), Recherches en cancérologie, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), School of Science, Huzhou Tearchers College, National ICT Australia [Sydney] (NICTA), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-SIGMA Clermont (SIGMA Clermont)-Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), and Biochemistry
Subjects: MESH: Oxidation-Reduction, Cell Membrane Permeability, Erythrocytes, Patch-Clamp Techniques, Plasmodium, Ion Channels, MESH: Furosemide, 0302 clinical medicine, Furosemide, Parasite hosting, MESH: Animals, MESH: Cell Membrane Permeability, MESH: Membrane Transport Modulators, Malaria, Falciparum, Membrane Transport Modulators, MESH: Plasmodium falciparum, Confusion, MESH: Dantrolene, 0303 health sciences, biology, MESH: Erythrocytes, MESH: Malaria, Falciparum, 3. Good health, Infectious Diseases, medicine.symptom, Oxidation-Reduction, MESH: Anions, Anions, Plasmodium falciparum, 030231 tropical medicine, Dantrolene, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, MESH: Patch-Clamp Techniques, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Humans, Membrane transport, biology.organism_classification, medicine.disease, Electrophysiology, Nitrobenzoates, MESH: Nitrobenzoates, MESH: Ion Channels, Immunology, Parasitology, Malaria
Abstract: International audience; The altered permeability characteristics of erythrocytes infected with malaria parasites have been a source of interest for over 30 years. Recent electrophysiological studies have provided strong evidence that these changes reflect transmembrane transport through ion channels in the host erythrocyte plasma membrane. However, conflicting results and differing interpretations of the data have led to confusion in this field. In an effort to unravel these issues, the groups involved recently came together for a week of discussion and experimentation. In this article, the various models for altered transport are reviewed, together with the areas of consensus in the field and those that require a better understanding.
Published: 2007

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