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3,254 results on '"Campbell family"'

1. Tamoxifen Therapy for Myotubular Myopathy (TAM4MTM)

Author: Canadian Institutes of Health Research (CIHR), Cures Within Reach, The Joshua Frase Foundation USA, Will Cure USA, Mogford Campbell Family Chair Fund, Myotubular Trust, Great Ormond Street Hospital Charity, Sparks, and James Dowling, Staff clinician and senior scientist
Published: 2024

2. Non-invasive Brain Stimulation Using Transcranial Direct Current Stimulation for Neuropsychiatric Symptoms of Dementia

Author: Sanjeev Kumar, Medical Head of Geriatric Clinical Research, Centre for Addiction and Mental Health; Clinician Scientist and Staff Psychiatrist, Campbell Family Mental Health Research Institute; Assistant Professor of Psychiatry, University of Toronto.
Published: 2024

3. Presynaptic Imaging in Major Depressive Episodes After COVID-19 (PCOV)

Author: Jeff Meyer, Scientist and Head, Neurochemical Imaging Program in Mood and Anxiety Disorders, Brain Health Imaging Centre, Campbell Family Mental Health Research Institute
Published: 2023

4. Land conveyances between the Johnson and Campbell families, Fayette County, Alabama, August 2, 1880

Author: Johnson (Family : Fayette County, Ala.), Campbell (Family : Fayette County, Ala.), Johnson (Family : Fayette County, Ala.), and Campbell (Family : Fayette County, Ala.)

5. Land conveyances between the Johnson and Campbell families, Fayette County, Alabama, August 2, 1880

Author: Johnson (Family : Fayette County, Ala.), Campbell (Family : Fayette County, Ala.), Johnson (Family : Fayette County, Ala.), and Campbell (Family : Fayette County, Ala.)

6. Campbell Family Papers

Author: Campbell family and Campbell family
Subjects: Account books., Farms and farming., General stores., Geology., Lawyers - letters and papers., Marietta College, Petroleum industry and trade., Plantations., Geology, Géologie., Magasins généraux., Pétrole Industrie et commerce., Plantations., geology., plantations., general stores (built works), Account books, General stores, Geology, Petroleum industry and trade, Plantations
Abstract: The "View now" link directs to the finding aid only. Please email wvrhcref@westvirginia.libanswers.com or call 304-293-3536 for more information about accessing collection A&M 1321 Campbell Family Papers, 1847-1901. Account book, 1856-1901, of James Wilson Campbell. Includes estate settlement of his father, James L. Campbell, Cattle pedigrees, and various accounts, including some kept in James L.'s hand. Correspondence, 1866-1899 concerns family affairs, business, and there is one letter from a cousin at Marietta College, 1866, telling of geological field trip through the Wood, Ritchie, Pleasants, oil district of W. Va. School notes on mathematics and surveying of James Wilson Campbell, ca. 1854-1859; Misc. papers, notes, accounts, etc.

7. Campbell Family Papers

Author: Campbell family and Campbell family
Subjects: Account books., Campbell family, Campbell, James L., Campbell, James Wilson., Farms and farming., General stores., Plantations., Magasins généraux., Plantations., plantations., general stores (built works), Account books, General stores, Plantations
Abstract: The "View now" link directs to the finding aid only. Please email wvrhcref@westvirginia.libanswers.com or call 304-293-3536 for more information about accessing collection A&M 1265 Campbell Family Papers, 1795-1873. Financial and farm records of James Campbell who owned a plantation near Arden, Berkeley County on which he also operated a store. The collection also includes a ledger and some loose financial papers of James L. Campbell who ran the family homestead.

8. Comparative efficacy and acceptability of psychotherapies for post-traumatic stress disorder in children and adolescents: a systematic review and network meta-analysis

Author: John R. Weisz, Jürgen Barth, Cinzia Del Giovane, Teng Teng, Peng Xie, Pim Cuijpers, Yajie Xiang, Yuanliang Jiang, Xuemei Li, Xueer Liu, Andrea Cipriani, Arun V. Ravindran, Kang Du, Donna M. Gillies, Xinyu Zhou, Li Fan, Yuqing Zhang, David Cohen, Chongqing University [Chongqing], University of Oxford [Oxford], University of Bern, Harvard University [Cambridge], Vrije Universiteit Amsterdam [Amsterdam] (VU), University hospital of Zurich [Zurich], Institut des Systèmes Intelligents et de Robotique (ISIR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), 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), The University of Sydney, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), University of Toronto, and University of Zurich
Subjects: Adolescent, Efficacy, Network Meta-Analysis, child & adolescent psychiatry, traumatic stress disorder, 610 Medicine & health, Child and Adolescent Mental Health, Stress Disorders, Post-Traumatic, 03 medical and health sciences, 0302 clinical medicine, Acceptability, 360 Social problems & social services, Behavior Therapy, Medicine, Humans, 030212 general & internal medicine, Child, Psychological treatment, Post-traumatic stress disorder (PTSD), Cognitive Behavioral Therapy, business.industry, Traumatic stress, PTSD, medicine.disease, 3. Good health, 030227 psychiatry, Clinical Practice, Psychotherapy, Psychiatry and Mental health, 10034 Institute of Complementary Medicine, Post, Supportive psychotherapy, Meta-analysis, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cognitive processing therapy, Anxiety, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Clinical psychology
Abstract: BackgroundAvailable evidence on the comparative efficacy and acceptability of psychotherapies for post-traumatic stress disorder (PTSD) in children and adolescents remains uncertain.ObjectiveWe aimed to compare and rank the different types and formats of psychotherapies for PTSD in children and adolescents.MethodsWe searched eight databases and other international registers up to 31 December 2020. The pairwise meta-analyses and frequentist network meta-analyses estimated pooled standardised mean differences (SMDs) and ORs with random-effects model. Efficacy at post-treatment and follow-up, acceptability, depressive and anxiety symptoms were measured.FindingsWe included 56 randomised controlled trials with 5327 patients comparing 14 different types of psychotherapies and 3 control conditions. For efficacy, cognitive processing therapy (CPT), behavioural therapy (BT), individual trauma-focused cognitive–behavioural therapy (TF-CBT), eye movement desensitisation and reprocessing, and group TF-CBT were significantly superior to all control conditions at post-treatment and follow-up (SMDs between −2.42 and −0.25). Moreover, CPT, BT and individual TF-CBT were more effective than supportive therapy (SMDs between −1.92 and −0.49). Results for depressive and anxiety symptoms were similar to the findings for the primary outcome. Most of the results were rated as ‘moderate’ to ‘very low’ in terms of confidence of evidence.ConclusionsCPT, BT and individual TF-CBT appear to be the best choices of psychotherapy for PTSD in young patients. Other types and different ways of delivering psychological treatment can be alternative options. Clinicians should consider the importance of each outcome and the patients’ preferences in real clinical practice.
Published: 2021
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9. De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder

Author: Jonathan A. Bernstein, Leah J. Rowe, Kimberly Foss, Samin A. Sajan, Kun Xia, Juliane Hoyer, Anita E. Beck, Shayna Svihovec, Vincent Gatinois, Lance H. Rodan, Roksana Sasanfar, Christiane Zweier, Alban Ziegler, Sonal Mahida, Kristin G. Monaghan, Charlotte W. Ockeloen, André Reis, Milen Velinov, Janson White, Evan E. Eichler, Nasim Vasli, Jennifer Friedman, Constance Smith-Hicks, Gilles Morin, Rachel Westman, Sandra Yang, Joshua Scheck, Christian Thiel, John B. Vincent, Deborah A. Nickerson, Michelle E. Ernst, Jacqueline Harris, Natasha Zeid, Bernt Popp, Francesca Mattioli, Zehra Agha, Ellen van Binsbergen, Julian A. Martinez-Agosto, Karen W. Gripp, Gwenaël Le Guyader, Catherine Vincent-Delorme, Lori-Anne Schillaci, Jennefer N. Kohler, Kimberly A. Aldinger, Laurence J. Walsh, Jessica X. Chong, David Geneviève, Rami Abou Jamra, Amy Yang, Cigdem I. Akman, Sha Tang, Ricardo Harripaul, Rick Person, Marleen Simon, Hui Guo, Muhammad Ayub, Laura S. Farach, Patricia Blanchet, Austin Larson, Marie Vincent, Luis Rohena, Michael J. Bamshad, Raheel Qamar, Gregory M. Enns, Joshua Rotenberg, Katelyn Payne, William J. Sunderland, Anne C.-H. Tsai, Annika M. Dries, Michèle Mathieu-Dramard, Dominique Bonneau, Ghayda M. Mirzaa, Bénédicte Gérard, Elise Schaefer, Amélie Piton, Patricia G Wheeler, Division of Medical Genetics [Seattle], University of Washington [Seattle], Détoxication et réparation tissulaire, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Center for Integrative Brain Research [Seattle, WA, USA], University of Washington [Seattle]-Seattle Children's Research Institute, Central South University [Changsha], Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Center for Integrative Brain Research, Ambry Genetics [Aliso Viejo, CA, USA], China Agricultural University (CAU), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Kennedy Krieger Institute [Baltimore], Institute of Human Genetics [Erlangen, Allemagne], Universität Leipzig, Yale University [New Haven], Oregon Health and Science University [Portland] (OHSU), McGovern Medical School [Houston, Texas], Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Indiana University [South Bend], The University of Texas at San Antonio (UTSA), New York State Psychiatric Institute, Columbia University [New York], Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Strasbourg, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University Medical Center [Utrecht], Stanford University School of Medicine [CA, USA], Memorial Hermann Heart and Vascular Institute [Houston, TX, USA], University of Central Florida [Orlando] (UCF), Department of Pediatrics [Univ California San Diego] (UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), University of California (UC)-University of California (UC), University of Colorado Anschutz [Aurora], Department of Chemistry and Biochemistry [Bern], University of Bern, Columbia University Irving Medical Center (CUIMC), Signal Processing Lab [Boise - Idaho], Boise State University, University Hospitals Case Medical Center (CLEVELAND - UHCMC), University Hospitals Case Medical Center, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Psychology [University North Carolina Wilmington], University of North Carolina [Wilmington] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie et immunologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Unité de génétique médicale et oncogénétique [CHU Amiens Picardie], CHU Amiens-Picardie, Institut d'histoire du temps présent (IHTP), Centre National de la Recherche Scientifique (CNRS), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Queen's University [Kingston, Canada], Department of Molecular Genetics [Toronto], University of Toronto, GeneDx [Gaithersburg, MD, USA], Department of Genome Sciences [Seattle] (GS), Department of Pediatrics [Stanford], Stanford Medicine, Stanford University-Stanford University, Stanford School of Medicine [Stanford], Stanford University, University of California (UC), COMSATS Institute of Information Technology [Islamabad] (CIIT), Boston Children's Hospital, University of California [Los Angeles] (UCLA), Radboud University Medical Center [Nijmegen], Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Psychiatry, Seattle University [Seattle], 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), Universität Leipzig [Leipzig], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Pediatrics [san Diego], UC San Diego School of Medicine, Université Paris Diderot - Paris 7 (UPD7)-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), and University of California
Subjects: 0301 basic medicine, Proband, Male, Adolescent, Autism Spectrum Disorder, autism spectrum disorders, Nerve Tissue Proteins, Neuroimaging, 030105 genetics & heredity, Biology, Article, 03 medical and health sciences, Neurodevelopmental disorder, ZNF292, Intellectual disability, mental disorders, Exome Sequencing, medicine, Humans, Genetic Predisposition to Disease, Child, Genetics (clinical), Exome sequencing, Genetics, Zinc finger, next generation sequencing, Genetic heterogeneity, High-Throughput Nucleotide Sequencing, medicine.disease, Phenotype, 3. Good health, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Autism spectrum disorder, intellectual disability, Neurodevelopmental Disorders, Child, Preschool, next-generation sequencing, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Carrier Proteins, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract: Contains fulltext : 218267.pdf (Publisher’s version ) (Closed access) PURPOSE: Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous neurodevelopmental disorders. We sought to delineate the clinical, molecular, and neuroimaging spectrum of a novel neurodevelopmental disorder caused by variants in the zinc finger protein 292 gene (ZNF292). METHODS: We ascertained a cohort of 28 families with ID due to putatively pathogenic ZNF292 variants that were identified via targeted and exome sequencing. Available data were analyzed to characterize the canonical phenotype and examine genotype-phenotype relationships. RESULTS: Probands presented with ID as well as a spectrum of neurodevelopmental features including ASD, among others. All ZNF292 variants were de novo, except in one family with dominant inheritance. ZNF292 encodes a highly conserved zinc finger protein that acts as a transcription factor and is highly expressed in the developing human brain supporting its critical role in neurodevelopment. CONCLUSION: De novo and dominantly inherited variants in ZNF292 are associated with a range of neurodevelopmental features including ID and ASD. The clinical spectrum is broad, and most individuals present with mild to moderate ID with or without other syndromic features. Our results suggest that variants in ZNF292 are likely a recurrent cause of a neurodevelopmental disorder manifesting as ID with or without ASD.
Published: 2019
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10. Alcohol, tobacco and health care costs: a population-wide cohort study (n = 606 947 patients) of current drinkers based on medical and administrative health records from Catalonia

Author: Joan Colom, Lidia Segura, Peter J. Anderson, Kevin D. Shield, Antoni Gual, Emili Vela, Juergen Rehm, Montserrat Bustins, Laia Miquel, Health promotion, RS: CAPHRI - R6 - Promoting Health & Personalised Care, Family Medicine, Instituto de Salud Carlos III, European Commission, Lundbeck Foundation, [Miquel L] Grup de Recerca en Addiccions Clínic, Institut Clínic de Neurociències, Barcelona, Spain. Universitat de Barcelona, Barcelona, Spain. Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Barcelona, Spain. Spanish Network of Addictive Disorders (RTA), Madrid, Spain. [Rehm J] Institute for Mental Health Policy Research, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. Department of Psychiatry, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, Canada. WHO/PAHO Collaborating Centre in Addiction and Mental Health, Toronto, ON, Canada. Epidemiological Research Unit, Klinische Psychologie & Psychotherapie, Technische Universität Dresden, Dresden, Germany. Campbell Family Mental Health Research Institute, Toronto, ON, Canada. [Shield KD] WHO/PAHO Collaborating Centre in Addiction and Mental Health, Toronto, ON, Canada. Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France. [Vela E] Grup de Recerca en Addiccions Clínic, Institut Clínic de Neurociències, Barcelona, Spain. Universitat de Barcelona, Barcelona, Spain. [Bustins M] Divisió d'Anàlisi de la Demanda i l'Activitat, Servei Català de la Salut, Departament de Salut, Generalitat de Catalunya, Barcelona, Spain. [Segura L, Colom J] Subdirecció General de Drogodependències, Agència de Salut Pública de Catalunya, Departament de Salut, Generalitat de Catalunya, Barcelona, Spain, and Departament de Salut
Subjects: Male, Public health medicine, Psychological intervention, 030508 substance abuse, Alcohol drinking, Disease, DISEASE, Cohort Studies, 0302 clinical medicine, Tabaquisme, Health care, Chemically-Induced Disorders::Substance-Related Disorders::Tobacco Use Disorder [DISEASES], trastornos inducidos químicamente::trastornos relacionados con sustancias::tabaquismo [ENFERMEDADES], Medicine, 030212 general & internal medicine, Other subheadings::Other subheadings::/economics [Other subheadings], health care economics and organizations, Primary health care, Aged, 80 and over, education.field_of_study, Smokers, Smoking, BRIEF INTERVENTION, Middle Aged, DRINKING PATTERNS, Alcoholism, economía y organizaciones para la atención de la salud::economía::costes y análisis de costes::costes de la atención a la salud [ATENCIÓN DE SALUD], Alcoholisme, Catalunya - Assistència sanitària - Cost, Cost of illness, Female, Chemically-Induced Disorders::Substance-Related Disorders::Alcohol-Related Disorders::Alcoholism [DISEASES], Health care costs, 0305 other medical science, Cohort study, Adult, Catalonia, Adolescent, Population, Pharmacy, Socioeconomic factors, Young Adult, 03 medical and health sciences, Sex Factors, trastornos inducidos químicamente::trastornos relacionados con sustancias::trastornos relacionados con el alcohol::alcoholismo [ENFERMEDADES], Cataluña, Environmental health, Tobacco, Humans, education, Aged, Otros calificadores::Otros calificadores::/economía [Otros calificadores], Ethanol, business.industry, Public Health, Environmental and Occupational Health, CONSUMPTION, Emergency department, GLOBAL BURDEN, Tobacco use, Spain, Health Care Economics and Organizations::Economics::Costs and Cost Analysis::Health Care Costs [HEALTH CARE], Brief intervention, business
Abstract: [Background] Most cost of illness studies are based on models where information on exposure is combined with risk information from meta-analyses, and the resulting attributable fractions are applied to the number of cases. [Methods] This study presents data on alcohol and tobacco use for 2011 and 2012 obtained from a routine medical practice in Catalonia of 606 947 patients, 18 years of age and older, as compared with health care costs for 2013 (all costs from the public health care system: primary health care visits, hospital admissions, laboratory and medical tests, outpatient visits to specialists, emergency department visits and pharmacy expenses). Quasi-Poisson regressions were used to assess the association between alcohol consumption and smoking status and health care costs (adjusted for age and socio-economic status). [Results] Resulting health care costs per person per year amounted to 1290 Euros in 2013, and were 20.1% higher for men than for women. Sex, alcohol consumption, tobacco use and socio-economic status were all associated with health care costs. In particular, alcohol consumption had a positive dose–response association with health care costs. Similarly, both smokers and former smokers had higher health care costs than did people who never smoked. [Conclusions] Alcohol and tobacco use had modest and large impacts respectively on health care costs, confirming the results of previous ecological modelling analyses. Reductions of alcohol consumption and smoking through public policies and via early identification and brief interventions would likely be associated with reductions in health care costs., This work was supported by a grant from Lundbeck Denmark received by A.G. (CP041374). This work also received funding from the RD12/0028/0016 project, Plan Nacional de I + D+I and was financed jointly with ISCII-Subdireccio´n General de Evaluacio´n y Fondo Europeo de Desarrollo Regional (FEDER). This grant was received by AG. http://www.redrta.es/.
Published: 2018
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11. Ptchd1 deficiency induces excitatory synaptic and cognitive dysfunctions in mouse

Author: Ung, D., Iacono, G, Méziane, H, Blanchard, E., Papon, M-A, Selten, M, van Rhijn, J-R, Montjean, R, Rucci, J, Martin, Stéphane, Fleet, A, Birling, M-C, Marouillat, S, Roepman, R, Selloum, M, Lux, A., Thépault, R-A, Hamel, P, Mittal, K, Vincent, J., Dorseuil, O, Stunnenberg, H, Billuart, P, Nadif Kasri, N, Hérault, Y., Laumonnier, F, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Radboud university [Nijmegen], 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), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Donders Institute for Brain, Cognition and Behaviour, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), University of Toronto, Radboud University Medical Center [Nijmegen], Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Martin, Stephane, Radboud University [Nijmegen], and Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: Male, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Hippocampus, Synaptic Transmission, Mice, [SCCO]Cognitive science, Cognition, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Basic Helix-Loop-Helix Transcription Factors, Animals, Cognitive Dysfunction, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Neurons, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Membrane Proteins, [SCCO] Cognitive science, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Synapses, Original Article, Disks Large Homolog 4 Protein, Guanylate Kinases, Signal Transduction
Abstract: Contains fulltext : 193089.pdf (Publisher’s version ) (Open Access) Synapse development and neuronal activity represent fundamental processes for the establishment of cognitive function. Structural organization as well as signalling pathways from receptor stimulation to gene expression regulation are mediated by synaptic activity and misregulated in neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been described in male patients with X-linked ID and/or ASD. The structure of PTCHD1 protein is similar to the Patched (PTCH1) receptor; however, the cellular mechanisms and pathways associated with PTCHD1 in the developing brain are poorly determined. Here we show that PTCHD1 displays a C-terminal PDZ-binding motif that binds to the postsynaptic proteins PSD95 and SAP102. We also report that PTCHD1 is unable to rescue the canonical sonic hedgehog (SHH) pathway in cells depleted of PTCH1, suggesting that both proteins are involved in distinct cellular signalling pathways. We find that Ptchd1 deficiency in male mice (Ptchd1(-/y)) induces global changes in synaptic gene expression, affects the expression of the immediate-early expression genes Egr1 and Npas4 and finally impairs excitatory synaptic structure and neuronal excitatory activity in the hippocampus, leading to cognitive dysfunction, motor disabilities and hyperactivity. Thus our results support that PTCHD1 deficiency induces a neurodevelopmental disorder causing excitatory synaptic dysfunction.
Published: 2018
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12. System-Wide Modulation of HECT E3 Ligases with Selective Ubiquitin Variant Probes

Author: Emmanuel Lemichez, Brenda A. Schulman, Zhenyue Hao, Sachdev S. Sidhu, Nan Li, Ryan Murchie, Wei Zhang, Maria A. Sartori, Kuen-Phon Wu, Jason Moffat, John R. Walker, Avinash Persaud, Yi Sheng, Alban Ordureau, Jicheng Hu, Chong Jiang, Manjeet Mukherjee, Kevin R. Brown, Yufeng Tong, Yanjun Li, Junjie Chen, Anne Doye, Peter Y. Mercredi, Daniela Rotin, Hari B. Kamadurai, J. Wade Harper, Donnelly Center Cellular and Biomolecular Research [Univ. Toronto], University of Toronto, St Jude Children's Research Hospital, Department of Cell Biology, Harvard Medical School [Boston] (HMS), Program in Cell Biology [Toronto], The Hospital for sick children [Toronto] (SickKids)-Department of Biochemistry [University of Toronto], University of Toronto-University of Toronto, Structural Genomics Consortium, The University of Texas M.D. Anderson Cancer Center [Houston], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of York [York, UK], Campbell Family Institute for Breast Cancer Research, University Health Network, Department of Pharmacology and Toxicology [Toronto], Department of Molecular Genetics [Toronto], The Donnelly Centre for Cellular and Biomolecular Research [Toronto, ON, Canada] (CCBR), J.W.H. was supported by NIH (R37NS083524 and GM095567). A.O. was supported by an Edward R. and Anne G. Lefler Center postdoctoral fellowship. J.W.H. is a consultant for Millennium: the Takada Oncology Company and Biogen. D.R. holds a Canada Research Chair (Tier 1 in Biochemistry and Signal Transduction) and was supported by CIHR (MOP#130422). B.A.S. is an investigator of the Howard Hughes Medical Institute (HHMI) and was supported by ALSAC, NIH R37GM065930 and P30CA021765. NECAT and APS were supported by NIH P41 GM103403 and DOE Contract DE-AC02-06CH11357. W.Z. was supported by a CIHR postdoctoral fellowship. S.S.S. and J.M. were supported by CIHR (MOP#111149 and 136956). The Structural Genomics Consortium (SGC) is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative (EU/EFPIA) (ULTRA-DD grant no. 115766), Janssen, Merck & Co., Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, São Paulo Research Foundation-FAPESP, Takeda, and the Wellcome Trust., and We thank members of the Sidhu and Schulman groups for helpful comments. We thank Andrew Vorobyov, Eva Chou, Yogesh Hooda, Jun Gu, and Aiping Dong for technical assistance. We are indebted to Pankaj Garg, Andreas Ernst, Abiodun Ogunjimi, Clare Jeon, Satra Nim, Frank Sicheri, and Hongrui Wang for reagents and advice.
Subjects: Models, Molecular, 0301 basic medicine, Subfamily, [SDV]Life Sciences [q-bio], MESH: Catalytic Domain, NEDD4, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: Ubiquitin/chemistry, MESH: Ubiquitin/metabolism, Madin Darby Canine Kidney Cells, MESH: Dogs, Ubiquitin, Cell Movement, Catalytic Domain, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, MESH: Cell Movement, chemistry.chemical_classification, MESH: Organoids/metabolism, biology, MESH: Ubiquitin-Protein Ligases/chemistry, Cell migration, Cell biology, MESH: Ubiquitin/genetics, Organoids, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Models, Molecular, MESH: HCT116 Cells, Ubiquitin-Protein Ligases, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, macromolecular substances, Cell Line, 03 medical and health sciences, Dogs, Peptide Library, Animals, Humans, Molecular Biology, NEDD4L, DNA ligase, MESH: Humans, MESH: Organoids/cytology, MESH: Madin Darby Canine Kidney Cells, MESH: Ubiquitin-Protein Ligases/metabolism, Cell Biology, HCT116 Cells, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Cell Line, 030104 developmental biology, chemistry, biology.protein, MESH: Peptide Library, Genetic screen
Abstract: Comment in : A Billion Ubiquitin Variants to Probe and Modulate the UPS. [Mol Cell. 2016]; International audience; HECT-family E3 ligases ubiquitinate protein substrates to control virtually every eukaryotic process and are misregulated in numerous diseases. Nonetheless, understanding of HECT E3s is limited by a paucity of selective and potent modulators. To overcome this challenge, we systematically developed ubiquitin variants (UbVs) that inhibit or activate HECT E3s. Structural analysis of 6 HECT-UbV complexes revealed UbV inhibitors hijacking the E2-binding site and activators occupying a ubiquitin-binding exosite. Furthermore, UbVs unearthed distinct regulation mechanisms among NEDD4 subfamily HECTs and proved useful for modulating therapeutically relevant targets of HECT E3s in cells and intestinal organoids, and in a genetic screen that identified a role for NEDD4L in regulating cell migration. Our work demonstrates versatility of UbVs for modulating activity across an E3 family, defines mechanisms and provides a toolkit for probing functions of HECT E3s, and establishes a general strategy for systematic development of modulators targeting families of signaling proteins.
Published: 2016
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13. Contribution of alcohol use disorders to the burden of dementia in France 2008–13: a nationwide retrospective cohort study

Author: Omer S. M. Hasan, Carole Dufouil, Frédéric Planchet, Sylvain Baillot, Quentin Guibert, Stéphane Luchini, Michaël Schwarzinger, Bruce G. Pollock, Jürgen Rehm, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Translational Health Economics Network (THEN), Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Department of Psychiatry, University of Toronto, Dalla Lana School of Public Health, University of Toronto, Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Equipe HEALTHY (U1219 Inserm - UB - Bordeaux population Health Centre Recherche), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux University Hospital, Institute of Medical Science, University of Toronto, University of Toronto, Institute for Clinical Psychology and Psychotherapy, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Translational Health Economics Network, (THEN), Laboratoire de Sciences Actuarielle et Financière (SAF), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Groupement de Recherche en Économie Quantitative d'Aix-Marseille (GREQAM), École des hautes études en sciences sociales (EHESS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), and École Centrale de Marseille (ECM)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: Male, Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Disease, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Intervention (counseling), mental disorders, medicine, Dementia, Humans, 030212 general & internal medicine, Risk factor, education, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, business.industry, Proportional hazards model, lcsh:Public aspects of medicine, Hazard ratio, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Retrospective cohort study, Middle Aged, medicine.disease, 3. Good health, Alcoholism, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: Dementia is a prevalent condition, affecting 5-7% of people aged 60 years and older, and a leading cause of disability in people aged 60 years and older globally. We aimed to examine the association between alcohol use disorders and dementia risk, with an emphasis on early-onset dementia (1·7) in sensitivity analyses on dementia case definition (including Alzheimer's disease) or older study populations. Also, alcohol use disorders were significantly associated with all other risk factors for dementia onset (all p
Published: 2018
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14. Towards new recommendations to reduce the burden of alcohol-induced hypertension in the European Union

Author: Bernd Schulte, Nuria Bastida Bastus, Lidia Segura-García, Gerrit Gmel, Carlos Brotons, Robyn Burton, Joan Colom, Jose Angel Arbesu Prieto, Lars Møller, Iain Armstrong, Jakob Manthey, Michael Bachmann, Cristina Sierra, Manuel Cardoso, Emanuele Scafato, Peter J. Anderson, Daniel A. Duprez, Henri-Jean Aubin, Jürgen Rehm, Kevin D. Shield, Reinhold Kreutz, Konstantin Vyshinskiy, Ľubomír Okruhlica, Marcin Wojnar, Ludwig Kraus, Helena Liira, José Zarco, Antoni Gual, Michael Roerecke, Family Medicine, RS: CAPHRI - R6 - Promoting Health & Personalised Care, Universitat de Barcelona, [Rehm J] Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, Toronto, Canada. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada. Addiction Policy, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. Institute of Medical Science, University of Toronto, Faculty of Medicine, Medical Sciences Building, Toronto, Canada. Department of Psychiatry, University of Toronto, Toronto, Canada. Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany. [Anderson P] Substance Use, Policy and Practice, Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK. Alcohol and Health, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands. [Arbesu Prieto JA] Primary Care Center La Eria, Oviedo, Spain. Primary Care Spanish Society SEMERGEN, Madrid, Spain. [Armstrong I] Health and Wellbeing Directorate, Public Health England, London, UK. [Aubin HJ] CESP, University Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, APHP, Hôpitaux Universitaires Paris-Sud, Villejuif, France. [Bachmann M] Copentown Healthcare Consultants, Cape Town, South Africa. [Colom J, Segura-Garcia L] Programa d’Abús de Substàncies, Agència Pública de Salut de Catalunya, Departament de Salut, Generalitat de Catalunya, Barcelona, Spain, Departament de Salut, Clinicum, Department of General Practice and Primary Health Care, and University of Helsinki
Subjects: Otros calificadores::Otros calificadores::/prevención & control [Otros calificadores], Cost effectiveness, Psychological intervention, lcsh:Medicine, SYSTEMIC HYPERTENSION, Disease, Guideline, 030204 cardiovascular system & hematology, Recommendations, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, Environmental Health::Health::Health Services::Primary Health Care [PUBLIC HEALTH], RESISTANT HYPERTENSION, COST-EFFECTIVENESS, 0302 clinical medicine, Risk Factors, Alcoholisme - Estudi de casos, Medicine, 030212 general & internal medicine, media_common, Public health, European Union countries, HIGH BLOOD-PRESSURE, General Medicine, GENERAL-PRACTITIONERS, 3. Good health, Management, Substance abuse, Europe, Alcoholism, SERVICES TASK-FORCE, Atenció primària - Unió Europea, Systematic review, DIFFERENT DIMENSIONS, Alcoholisme, Hypertension, Hipertensió - Estudi de casos, Blood pressure, Screening, Hipertensió, Chemically-Induced Disorders::Substance-Related Disorders::Alcohol-Related Disorders::Alcoholism [DISEASES], Alcohol use, enfermedades cardiovasculares::enfermedades vasculares::hipertensión [ENFERMEDADES], medicine.medical_specialty, Alcohol Drinking, PRIMARY-HEALTH-CARE, Guidelines as Topic, Cardiovascular Diseases::Vascular Diseases::Hypertension [DISEASES], Països de la Unió Europea, Other subheadings::Other subheadings::/prevention & control [Other subheadings], 03 medical and health sciences, Unión Europea, USE DISORDERS, trastornos inducidos químicamente::trastornos relacionados con sustancias::trastornos relacionados con el alcohol::alcoholismo [ENFERMEDADES], Environmental health, Humans, media_common.cataloged_instance, European Union, European union, BRIEF INTERVENTIONS, business.industry, lcsh:R, Blood Pressure Determination, medicine.disease, Salut pública, 3121 General medicine, internal medicine and other clinical medicine, Economic evaluation, Physical therapy, salud ambiental::salud::servicios de salud::atención primaria de la salud [SALUD PÚBLICA], business, Primary healthcare
Abstract: Consumo de alcohol; Presión sanguínea; Atención primaria; Recomendaciones Consum d'alcohol; Pressió sanguínea; Atenció primària; Recomanacions Alcohol use; Blood pressure; Primary healthcare; Recommendations Background: Hazardous and harmful alcohol use and high blood pressure are central risk factors related to premature non-communicable disease (NCD) mortality worldwide. A reduction in the prevalence of both risk factors has been suggested as a route to reach the global NCD targets. This study aims to highlight that screening and interventions for hypertension and hazardous and harmful alcohol use in primary healthcare can contribute substantially to achieving the NCD targets. Methods: A consensus conference based on systematic reviews, meta-analyses, clinical guidelines, experimental studies, and statistical modelling which had been presented and discussed in five preparatory meetings, was undertaken. Specifically, we modelled changes in blood pressure distributions and potential lives saved for the five largest European countries if screening and appropriate intervention rates in primary healthcare settings were increased. Recommendations to handle alcohol-induced hypertension in primary healthcare settings were derived at the conference, and their degree of evidence was graded. Results: Screening and appropriate interventions for hazardous alcohol use and use disorders could lower blood pressure levels, but there is a lack in implementing these measures in European primary healthcare. Recommendations included (1) an increase in screening for hypertension (evidence grade: high), (2) an increase in screening and brief advice on hazardous and harmful drinking for people with newly detected hypertension by physicians, nurses, and other healthcare professionals (evidence grade: high), (3) the conduct of clinical management of less severe alcohol use disorders for incident people with hypertension in primary healthcare (evidence grade: moderate), and (4) screening for alcohol use in hypertension that is not well controlled (evidence grade: moderate). The first three measures were estimated to result in a decreased hypertension prevalence and hundreds of saved lives annually in the examined countries. Conclusions: The implementation of the outlined recommendations could contribute to reducing the burden associated with hypertension and hazardous and harmful alcohol use and thus to achievement of the NCD targets. Implementation should be conducted in controlled settings with evaluation, including, but not limited to, economic evaluation. The workshop entitled “Screening and intervention for harmful alcohol use as a tool to improve the management of hypertension in primary care”, held on November 12, 2015, in Barcelona, Spain, was financially supported by Lundbeck (in providing travel allowances for some participants). An agenda of the workshop can be found in Additional file 1: Appendix 1.
Published: 2017

15. Data publication with the structural biology data grid supports live analysis

Author: Emil F. Pai, Qing R. Fan, Yousif Shamoo, Kevin D. Corbett, Dominika Borek, Tom Kirchhausen, James S. Fraser, Elizabeth Ransey, Stephanie M. Socias, Peter A. Meyer, Enrico Di Cera, Oleg V. Tsodikov, Jason S. McLellan, C. S. Raman, James Withrow, Mercè Crosas, Karen S. Anderson, Carlo Petosa, Filipe R. N. C. Maia, Gabrielle Rudenko, Yorgo Modis, Peng Gong, Walter J. Chazin, Zongchao Jia, Zbyszek Otwinowski, Adrian R. Ferré-D'Amaré, Yunsun Nam, Stephen C. Harrison, Sirano Dhe-Paganon, Joseph Schlessinger, Catherine L. Drennan, Kenneth D. Westover, Holger Sondermann, Richard H. G. Baxter, Marc Kvansakul, Ekaterina E. Heldwein, J. Christopher Fromme, Sean Crosson, Michael K. Rosen, Antonina Roll-Mecak, Robert J. Keenan, Tamir Gonen, Andrew C. Kruse, Ian Foster, Kanagalaghatta R. Rajashankar, Titus J. Boggon, Ming Lei, K. Christopher Garcia, Alexandre M. J. J. Bonvin, Michael S. Cosgrove, Amedeo Caflisch, Michael J. Eck, Brandt F. Eichman, Thomas U. Schwartz, Chung-I Chang, Rachelle Gaudet, Yizhi Jane Tao, Emily C. Tjon, Pedro Pereira, Jason Key, David B. Neau, Stephen C. Blacklow, Kay Diederichs, Hao Wu, Tom A. Rapoport, Alejandro Buschiazzo, Tom J. Brett, Piotr Sliz, Chris Botka, Niraj H. Tolia, Department of Biological Chemistry and Molecular Pharmacology [Boston] (DBCMP), Harvard Medical School [Boston] (HMS), Laboratory of molecular and structural microbiology, Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Shanghai Institutes for Biological Sciences (Institute of Biochemistry and Cell Biology), Chinese Academy of Sciences [Beijing] (CAS), NE-CAT and department of chemistry and chemical biology [Argonne], Cornell University, Departments of pharmacology and molecular biophysics and biochemistry [New Haven], Yale University School of Medicine, Department of Chemistry and Molecular Biophysics & Biochemistry [New Haven], Yale University [New Haven], Bijovet center [Utrecht], Utrecht University [Utrecht], Department of Biophysics and Biochemistry [Dallas], University of Texas Southwestern Medical Center [Dallas], Department of Internal Medicine [St Louis], Washington University School of Medicine, Department of Biochemistry [Zurich], University of Zürich [Zürich] (UZH), Institute of Biological Chemistry (IBC Sinica), Academia Sinica, Departments of biochemistry and chemistry [Nashville], Vanderbilt University [Nashville], Ludwig Institute for Cancer Research, University of California [San Diego] (UC San Diego), University of California, SUNY Upstate Medical University, State University of New York (SUNY), University of Chicago, Dana-Farber Cancer Institute [Boston], Saint Louis University School of Medicine [St Louis], Massachusetts Institute of Technology (MIT), Department of Biological Chemistry and Molecular Pharmacology (DBCMP), Columbia University [New York], National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Weill Institute for Cell and Molecular Biology, Howard Hughes Medical Institute [Stanford], Stanford University School of Medicine [CA, USA], Harvard University [Cambridge], Wuhan Institute of Virology, Howard Hughes Medical Institute [Boston], Tufts University School of Medicine [Boston], Queen's University [Kingston], La Trobe University [Melbourne], Geisel School of Medicine at Dartmouth, University of Cambridge [UK] (CAM), University of Texas at Dallas [Richardson] (UT Dallas), Campbell Family Institute for Breast Cancer Research, University Health Network, University of Toronto, Instituto de Biologia Molecular e Celular (IBMC), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), University of Maryland [Baltimore County] (UMBC), University of Maryland System, National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch (UTMB), Rice University [Houston], University of Washington School of Medicine, University of Kentucky, Boston Children's Hospital, Department of Computer Science, University of Chicago, University of California [San Francisco] (UCSF), Uppsala University, Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Howard Hughes Medical Institute [Ashburn], Fachbereich Biologie, University of Konstanz, Institute for Quantitative Social Sciences, Development of the Structural Biology Data Grid is funded by The Leona M. and Harry B. Helmsley Charitable Trust 2016PG-BRI002 to PS and MC. Development of citation workflows is supported NSF 1448069 (to PS). DAA is being developed as a pilot project of the National Data Service, with additional funds to support storage and technology development, including NIH P41 GM103403 (NE-CAT) and 1S10RR028832 (HMS) and DOE DE-AC02-06CH11357, NIH 1U54EB020406-01, Big Data for Discovery Science Center, and NIST 60NANB15D077 (Globus Project), Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemistry, Drennan, Catherine L., Schwartz, Thomas, Sub NMR Spectroscopy, NMR Spectroscopy, Instituto de Investigação e Inovação em Saúde, Molecular and structural microbiology / Microbiología Molecular y Estructural [Montevideo], Cornell University [New York], Universität Zürich [Zürich] = University of Zurich (UZH), Howard Hughes Medical Institute (HHMI), Queen's University [Kingston, Canada], Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), University of Zurich, Sliz, Piotr, Yale School of Medicine [New Haven, Connecticut] (YSM), University of California (UC), Harvard University, Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Kentucky (UK), University of California [San Francisco] (UC San Francisco), Harrison, Seamus Conor [0000-0003-1480-1143], Modis, Yorgo [0000-0002-6084-0429], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Chemistry(all), Experiences, General Physics and Astronomy, computer.software_genre, Crystallography, X-Ray, Biochemistry, Software, Structural Biology, Databases, Genetic, Structure models, Macromolecular crystallography, media_common, Strukturbiologi, Uncategorized, Multidisciplinary, Crystallography, Data grid, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Publications, X-ray scattering, 1.5 Resources and infrastructure (underpinning), 3100 General Physics and Astronomy, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Networking and Information Technology R&D, Networking and Information Technology R&D (NITRD), The Internet, Data mining, Macromolecular Substances, media_common.quotation_subject, Science, 610 Medicine & health, 1600 General Chemistry, Biology, Physics and Astronomy(all), General Biochemistry, Genetics and Molecular Biology, Article, Synchrotron, 03 medical and health sciences, Databases, Genetic, Underpinning research, 1300 General Biochemistry, Genetics and Molecular Biology, ddc:570, 10019 Department of Biochemistry, Quality (business), Internet, business.industry, Biochemistry, Genetics and Molecular Biology(all), Data quality, Experimental data, General Chemistry, Data science, 030104 developmental biology, Data access, Protein data-bank, Paradigm shift, X-Ray, 570 Life sciences, biology, Resolution, business, computer, Department of Biochemistry, Genetics and Molecular Biology(all)
Abstract: Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis., The validation and analysis of X-ray crystallographic data is essential for reproducibility and the development of crystallographic methods. Here, the authors describe a repository for crystallographic datasets and demonstrate some of the ways it could serve the crystallographic community.
Published: 2016
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16. Data publication with the structural biology data grid supports live analysis

Author: Pa, Meyer, Socias S, Key J, Ransey E, Ec, Tjon, Alejandro Buschiazzo, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Ks, Anderson, Rh, Baxter, Sc, Blacklow, Tj, Boggon, Am, Bonvin, Borek D, Tj, Brett, Caflisch A, Ci, Chang, Department of Biological Chemistry and Molecular Pharmacology [Boston] (DBCMP), Harvard Medical School [Boston] (HMS), Molecular and structural microbiology = Microbiología Molecular y Estructural [Montevideo], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Shanghai Institutes for Biological Sciences (Institute of Biochemistry and Cell Biology), Chinese Academy of Sciences [Beijing] (CAS), NE-CAT and department of chemistry and chemical biology [Argonne], Cornell University, Departments of pharmacology and molecular biophysics and biochemistry [New Haven], Yale University School of Medicine, Department of Chemistry and Molecular Biophysics & Biochemistry [New Haven], Yale University [New Haven], Bijovet center [Utrecht], Utrecht University [Utrecht], Department of Biophysics and Biochemistry [Dallas], University of Texas Southwestern Medical Center [Dallas], Department of Internal Medicine [St Louis], Washington University School of Medicine, Department of Biochemistry [Zurich], University of Zürich [Zürich] (UZH), Institute of Biological Chemistry (IBC Sinica), Academia Sinica, Departments of biochemistry and chemistry [Nashville], Vanderbilt University [Nashville], Ludwig Institute for Cancer Research, University of California [San Diego] (UC San Diego), University of California, SUNY Upstate Medical University, State University of New York (SUNY), University of Chicago, Dana-Farber Cancer Institute [Boston], Saint Louis University School of Medicine [St Louis], Massachusetts Institute of Technology (MIT), Department of Biological Chemistry and Molecular Pharmacology (DBCMP), Columbia University [New York], National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Weill Institute for Cell and Molecular Biology, Howard Hughes Medical Institute [Stanford], Stanford University School of Medicine [CA, USA], Harvard University [Cambridge], Wuhan Institute of Virology, Howard Hughes Medical Institute [Boston], Tufts University School of Medicine [Boston], Queen's University [Kingston], La Trobe University [Melbourne], Geisel School of Medicine at Dartmouth, University of Cambridge [UK] (CAM), University of Texas at Dallas [Richardson] (UT Dallas), Campbell Family Institute for Breast Cancer Research, University Health Network, University of Toronto, Instituto de Biologia Molecular e Celular (IBMC), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), University of Maryland [Baltimore County] (UMBC), University of Maryland System, National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch (UTMB), Rice University [Houston], University of Washington School of Medicine, University of Kentucky, Boston Children's Hospital, Department of Computer Science, University of Chicago, University of California [San Francisco] (UCSF), Uppsala University, Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Howard Hughes Medical Institute [Ashburn], Fachbereich Biologie, University of Konstanz, Institute for Quantitative Social Sciences, Development of the Structural Biology Data Grid is funded by The Leona M. and Harry B. Helmsley Charitable Trust 2016PG-BRI002 to PS and MC. Development of citation workflows is supported NSF 1448069 (to PS). DAA is being developed as a pilot project of the National Data Service, with additional funds to support storage and technology development, including NIH P41 GM103403 (NE-CAT) and 1S10RR028832 (HMS) and DOE DE-AC02-06CH11357, NIH 1U54EB020406-01, Big Data for Discovery Science Center, and NIST 60NANB15D077 (Globus Project), Department of Biological Chemistry and Molecular Pharmacology [Boston] ( DBCMP ), Harvard Medical School [Boston] ( HMS ), Laboratory of molecular and structural microbiology, Institut Pasteur Montevideo-Réseau International des Instituts Pasteur ( RIIP ), Shanghai Institutes for Biological Sciences ( Institute of Biochemistry and Cell Biology ), Chinese Academy of Sciences [Beijing] ( CAS ), Yale University, Faculty of Science, Utrecht University, University of Zürich [Zürich] ( UZH ), Institute of Biological Chemistry ( IBC Sinica ), Vanderbilt University of Nashville, University of California [San Diego] ( UC San Diego ), Massachusetts Institute of Technology ( MIT ), Department of Biological Chemistry and Molecular Pharmacology ( DBCMP ), National Heart, Lung, and Blood Institute [Bethesda] ( NHLBI ), Stanford University School of Medicine, Havard Medical School, University of Cambridge [UK] ( CAM ), University of Texas at Dallas [Richardson] ( UT Dallas ), Instituto de Biologia Molecular e Celular ( IBMC ), Institut de biologie structurale ( IBS - UMR 5075 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), University of Maryland Baltimore County [Baltimore] ( UMBC ), National Institute of Neurological Disorders and Stroke [Bethesda] ( NINDS ), National Institutes of Health [Bethesda] ( NIH ), The University of Texas Medical Branch ( UTMB ), Yale School of Medicine, University of California [San Francisco] ( UCSF ), Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemistry, Drennan, Catherine L., Schwartz, Thomas, Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), and Instituto de Investigação e Inovação em Saúde
Subjects: Data set, Data quality, General Physics and Astronomy, Experimental data, General Chemistry, Data grid, General Biochemistry, Genetics and Molecular Biology, Data science, Genetics, Paradigm shift, Data access, Data mining, Biology, The Internet
Abstract: The validation and analysis of X-ray crystallographic data is essential for reproducibility and the development of crystallographic methods. Here, the authors describe a repository for crystallographic datasets and demonstrate some of the ways it could serve the crystallographic community., Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis.
Published: 2016
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17. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells

Author: Sylvie Rival-Gervier, Bryan L. Roth, Cheryl H. Arrowsmith, Abdellah Allali-Hassani, Alena Siarheyeva, Xi Ping Huang, Dmitri Kireev, William P. Janzen, Jian Jin, Peter Brown, Aled M. Edwards, Arturas Petronis, Tim J. Wigle, Feng Liu, Viviane Labrie, Irene Chau, Peter A. DiMaggio, Thomas J. Mangano, Aiping Dong, Wolfram Tempel, Sun Chong Wang, Xin Chen, Gregory A. Wasney, Benjamin A. Garcia, Jacqueline L. Norris, Masoud Vedadi, Ashutosh Tripathy, Stephen V. Frye, Catherine Simpson, James Ellis, Dalia Barsyte-Lovejoy, Samantha G. Pattenden, Structural Genomics Consortium, University of Toronto, Division of Medicinal Chemistry and Natural Products, Center for Integrative Chemical Biology and Drug Discovery, Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), Krembil Family Epigenetic Laboratory, Centre of Addiction and Mental Health, Department of Chemistry, Princeton University, Division of Medical Chemistry and Natural Products, UNC Eshelman School of Pharmacy, Department of Biochemistry and Biophysics, UNC Macromolecular Interactions Facility, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Development and Stem Cell Biology Program, Hospital for Sick Children, Department of Molecular Genetics, Campbell Family Center Research Institute and Department of medical Biophysics, Ontaria Cancer Institute, Biologie du développement et reproduction (BDR), and Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)
Subjects: p53, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, Methyltransferase, g9a protéine, dna methylation, Biology, Article, Cell Line, micro rna, EHMT2, Small hairpin RNA, Mice, 03 medical and health sciences, Histone H3, 0302 clinical medicine, stem cells, chip chip, histone lysine n methyltransferase, Animals, Humans, Gene Silencing, Epigenetics, Enzyme Inhibitors, Molecular Biology, mouse, 030304 developmental biology, chromatin structure, complexes, 0303 health sciences, Reporter gene, Gene knockdown, Molecular Structure, glp protéine, unc0638, Histone-Lysine N-Methyltransferase, lysine 9 methylation, Cell Biology, Cell biology, Biochemistry, 030220 oncology & carcinogenesis, DNA methylation, Quinazolines, gene expression, cancer cells, methyltransferase, pluripotent stem cells, transcription, repression, epigenetic
Abstract: Erratum : Nat. Chem. Biol. 2011 7(9):648 2011 7(8): following 574 ; Protein lysine methyltransferases G9a and GLP modulate the transcriptional repression of a variety of genes via dimethylation of Lys9 on histone H3 (H3K9me2) as well as dimethylation of non-histone targets. Here we report the discovery of UNC0638, an inhibitor of G9a and GLP with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets. UNC0638 treatment of a variety of cell lines resulted in lower global H3K9me2 levels, equivalent to levels observed for small hairpin RNA knockdown of G9a and GLP with the functional potency of UNC0638 being well separated from its toxicity. UNC0638 markedly reduced the clonogenicity of MCF7 cells, reduced the abundance of H3K9me2 marks at promoters of known G9a-regulated endogenous genes and disproportionately affected several genomic loci encoding microRNAs. In mouse embryonic stem cells, UNC0638 reactivated G9a-silenced genes and a retroviral reporter gene in a concentration-dependent manner without promoting differentiation.
Published: 2011
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18. Neutrophil Gelatinase–Associated Lipocalin, a Novel Mineralocorticoid Biotarget, Mediates Vascular Profibrotic Effects of Mineralocorticoids

Author: Nicolette Farman, Faiez Zannad, Antoine Tarjus, Patrick Rossignol, Ernesto Martínez-Martínez, Tak W. Mak, Frederic Jaisser, Renaud Fay, Cristián A. Amador, Natalia López-Andrés, Celine Latouche, Soumaya El Moghrabi, Thorsten Berger, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-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), Fundación Miguel Servet, The Campbell Family Institute for Cancer Research, University Health Network, CIC-Nancy, Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: Male, Galectin 3, 030204 cardiovascular system & hematology, Lipocalin, Kidney, Nephrectomy, fibroblast, MESH: Hypertension, MESH: Recombinant Proteins, Mice, chemistry.chemical_compound, 0302 clinical medicine, Mineralocorticoid receptor, Fibrosis, MESH: Animals, MESH: Peptide Fragments, Aorta, Cells, Cultured, Oncogene Proteins, 0303 health sciences, MESH: Cytokines, Aldosterone, MESH: Hypertrophy, MESH: Lipocalin-2, MESH: Myocytes, Smooth Muscle, MESH: Aorta, MESH: Cardiomyopathy, Hypertrophic, Lipocalins, Recombinant Proteins, 3. Good health, medicine.anatomical_structure, Obesity, Abdominal, Hypertension, Knockout mouse, lipocalin 2, MESH: Fibrosis, Cytokines, Female, MESH: Lipocalins, MESH: Acute-Phase Proteins, Procollagen, MESH: Cells, Cultured, medicine.medical_specialty, MESH: Myocardium, MESH: Rats, medicine.drug_class, Myocytes, Smooth Muscle, collagen type I, MESH: Procollagen, Biology, Article, MESH: Obesity, Abdominal, 03 medical and health sciences, MESH: Oncogene Proteins, Lipocalin-2, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Proto-Oncogene Proteins, Internal medicine, Internal Medicine, medicine, Animals, Humans, Fibroblast, MESH: Mice, 030304 developmental biology, mineralocorticoid receptor, aldosterone, MESH: Humans, Myocardium, MESH: Aldosterone, Hypertrophy, MESH: Kidney, Cardiomyopathy, Hypertrophic, Fibroblasts, medicine.disease, Peptide Fragments, MESH: Galectin 3, MESH: Male, Rats, MESH: Nephrectomy, MESH: Proto-Oncogene Proteins, Endocrinology, chemistry, Mineralocorticoid, MESH: Fibroblasts, MESH: Female, Ex vivo, Acute-Phase Proteins
Abstract: International audience; Activation of the mineralocorticoid receptor has been shown to be deleterious in cardiovascular diseases (CVDs). We have recently shown that lipocalin 2 (Lcn2), or neutrophil gelatinase-associated lipocalin (NGAL), is a primary target of aldosterone/mineralocorticoid receptor in the cardiovascular system. Lcn2 is a circulating protein, which binds matrix metalloproteinase 9 and modulates its stability. We hypothesized that Lcn2 could be a mediator of aldosterone/mineralocorticoid receptor profibrotic effects in the cardiovascular system. Correlations between aldosterone and profibrotic markers, such as procollagen type I N-terminal peptide, were investigated in healthy subjects and subjects with abdominal obesity. The implication of Lcn2 in the mineralocorticoid pathway was studied using Lcn2 knockout mice subjected to a nephrectomy/aldosterone/salt (NAS) challenge for 4 weeks. In human subjects, NGAL/matrix metalloproteinase 9 was positively correlated with plasma aldosterone and fibrosis biomarkers. In mice, loss of Lcn2 prevented the NAS-induced increase of plasma procollagen type I N-terminal peptide, as well as the increase of collagen fibers deposition and collagen I expression in the coronary vessels and the aorta. The lack of Lcn2 also blunted the NAS-induced increase in systolic blood pressure. Ex vivo, treatment of human fibroblasts with recombinant Lcn2 induced the expression of collagen I and the profibrotic galectin-3 and cardiotrophin-1 molecules. Our results showed that Lcn2 plays a key role in aldosterone/mineralocorticoid receptor-mediated vascular fibrosis. The clinical data indicate that this may translate in human patients. Lcn2 is, therefore, a new biotarget in cardiovascular fibrosis induced by mineralocorticoid activation.
Published: 2015
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19. Cohort Profile: The Nicotine Dependence in Teens (NDIT) Study

Author: Jennifer O’Loughlin, Erika N Dugas, Jennifer Brunet, Joseph DiFranza, James C Engert, Andre Gervais, Katherine Gray-Donald, Igor Karp, Nancy C Low, Catherine Sabiston, Marie-Pierre Sylvestre, Rachel F Tyndale, Nathalie Auger, Belanger Mathieu, Barnett Tracie, Michael Chaiton, Meghan J Chenoweth, Evelyn Constantin, Gisèle Contreras, Lisa Kakinami, Aurelie Labbe, Katerina Maximova, Elizabeth McMillan, Erin K O’Loughlin, Roman Pabayo, Marie-Hélène Roy-Gagnon, Michèle Tremblay, Robert J Wellman, Andraeavan Hulst, Gilles Paradis, 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), School of Human Kinetics, University of Ottawa, University of Massachusetts System (UMASS), Agence de la Sante´ et des Services Sociaux, School of Dietetics and Human Nutrition, McGill University = Université McGill [Montréal, Canada], Department of Kinesiology and Physical Education, Department of Medecine [Montréal], Department of Psychiatry [Montréal], and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH)
Subjects: Male, Gerontology, Canada, medicine.medical_specialty, Passive smoking, Adolescent, Epidemiology, education, medicine.disease_cause, medicine, Humans, Prospective Studies, Psychiatry, Nicotine dependence, Prospective cohort study, Cohort Profiles, Schools, business.industry, 4. Education, Smoking, Tobacco Use Disorder, General Medicine, medicine.disease, Mental health, Obesity, Adolescent Behavior, Cohort, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Self Report, business, Graduation, Cohort study
Abstract: The Nicotine Dependence in Teens (NDIT) study is a prospective cohort investigation of 1294 students recruited in 1999–2000 from all grade 7 classes in a convenience sample of 10 high schools in Montreal, Canada. Its primary objectives were to study the natural course and determinants of cigarette smoking and nicotine dependence in novice smokers. The main source of data was self-report questionnaires administered in class at school every 3 months from grade 7 to grade 11 (1999–2005), for a total of 20 survey cycles during high school education. Questionnaires were also completed after graduation from high school in 2007–08 and 2011–12 (survey cycles 21 and 22, respectively) when participants were aged 20 and 24 years on average, respectively. In addition to its primary objectives, NDIT has embedded studies on obesity, blood pressure, physical activity, team sports, sedentary behaviour, diet, genetics, alcohol use, use of illicit drugs, second-hand smoke, gambling, sleep and mental health. Results to date are described in 58 publications, 20 manuscripts in preparation, 13 MSc and PhD theses and 111 conference presentations. Access to NDIT data is open to university-appointed or affiliated investigators and to masters, doctoral and postdoctoral students, through their primary supervisor ( www.nditstudy.ca ).
Published: 2014
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20. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters

Author: Marion Travert, Jean-Philippe Jais, Olivier A. Bernard, Tak W. Mak, Rob A. Cairns, Laurence Lamant, Thérèse Rousset, Marie Parrens, Lucile Couronné, François Lemonnier, Bettina Fabiani, Laurence de Leval, Philippe Gaulard, Christian Bastard, Olivier Tournillac, 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), Génétique des tumeurs (U985), Institut Gustave Roussy (IGR)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service informatique médicale et biostatistique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Thérapie ciblée combinatoire en Onco-Hématologie (EA3846), Université d'Auvergne - Clermont-Ferrand I (UdA), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire d'anatomie cytologie pathologiques, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Campbell Family Institute for Breast Cancer Research, University Health Network, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pathologie Clinique, Université de Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This study was supported in part by grants from INCa (Institut National du Cancer), ARC (Association pour la Recherche contre le Cancer), Ligue Nationale Contre le Cancer (équipe labelisée), PHRC (Programme Hospitalier de Recherche Clinique), FRM (Fondation pour la Recherche Médicale, équipe labellisée) and the Cancer Plan research Programme (Belgium, LdL). FL was a M2 student, granted from ARC and MT, a post-doctorant granted by FRM., 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 ), Génétique des tumeurs ( U985 ), Institut Gustave Roussy ( IGR ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Université Toulouse III - Paul Sabatier ( UPS ), Thérapie ciblée combinatoire en Onco-Hématologie ( EA3846 ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Service d'anatomie et cytologie pathologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lausanne ( UNIL ) -Centre Hospitalier Universitaire Vaudois [Lausanne] ( CHUV ) -Institut Universitaire de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lausanne = University of Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Guellaen, Georges, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]
Subjects: Male, Myeloid, MESH : Recurrence, MESH : Aged, Chromosomal translocation, MESH : T-Lymphocytes, Helper-Inducer, Biochemistry, 0302 clinical medicine, International Prognostic Index, Recurrence, MESH : Female, MESH: Aged, 0303 health sciences, Not Otherwise Specified, Hematology, T-Lymphocytes, Helper-Inducer, MESH: Lymphoma, T-Cell, Peripheral, 3. Good health, DNA-Binding Proteins, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH : Proto-Oncogene Proteins, Female, MESH : DNA-Binding Proteins, MESH : Mutation, Angioimmunoblastic T-cell lymphoma, MESH: Mutation, T cell, MESH : Male, Immunology, Dioxygenases, 03 medical and health sciences, Proto-Oncogene Proteins, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, Clinical significance, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: T-Lymphocytes, Helper-Inducer, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Aged, MESH: Humans, business.industry, MESH : Lymphoma, T-Cell, Peripheral, MESH : Humans, Lymphoma, T-Cell, Peripheral, Cell Biology, medicine.disease, MESH: Male, Lymphoma, MESH: Recurrence, MESH: Proto-Oncogene Proteins, Mutation, business, MESH: Female, MESH: DNA-Binding Proteins
Abstract: Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (TFH) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed TFH markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival.
Published: 2012
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21. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma.: IDH2 mutations in AITL

Author: Cairns, Rob, Iqbal, Javeed, Lemonnier, François, Kucuk, Can, de Leval, Laurence, Jais, Jean-Philippe, Parrens, Marie, Martin, Antoine, Xerri, Luc, Brousset, Pierre, Chan, Li Chong, Chan, Wing-Chung, Gaulard, Philippe, Mak, Tak, Campbell Family Institute for Breast Cancer Research, University Health Network, Department of Pathology and Microbiology, University of Nebraska Medical Center, University of Nebraska System-University of Nebraska System, 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), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Pathologie Clinique, Université de Lausanne = University of Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Service informatique médicale et biostatistique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Anatomie et de Cytologie Pathologiques [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Département de biopathologie, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Department of Pathology, The University of Hong Kong (HKU), This work is supported by the CIHR, The Canadian Cancer Society, The Terry Fox Foundation, and the Leukemia and Lymphoma Society (TWM), INCa (Institut National du Cancer), PHRC (Programme Hospitalier de Recherche Clinique) and FRM (Fondation pour la Recherche Médicale) (PG), The Institut Universitaire de France and the CITTIL program (PB), the Cancer Plan research Programme (Belgium) (LdL), NCI grant (5U01/CA114778), NIH grant (U01/CA84967), lymphoma SPORE grant P50CA13641-02, and Eppley Core Grant (W-CC and JI)., and Guellaen, Georges
Subjects: [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract: International audience; Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) occur in most grade 2 and 3 gliomas, secondary glioblastomas, and a subset of acute myelogenous leukemias but have not been detected in other tumor types. The mutations occur at specific arginine residues and result in the acquisition of a novel enzymatic activity that converts 2-oxoglutarate to D-2-hydroxyglutarate. This study reports IDH1 and IDH2 genotyping results from a set of lymphomas, which included a large set of peripheral T-cell lymphomas. IDH2 mutations were identified in approximately 20% of angioimmunoblastic T-cell lymphomas (AITLs), but not in other peripheral T-cell lymphoma entities. These results were confirmed in an independent set of AITL patients, where the IDH2 mutation rate was approximately 45%. This is the second common genetic lesion identified in AITL after TET2 and extends the number of neoplastic diseases where IDH1 and IDH2 mutations may play a role.
Published: 2012
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22. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. : IDH2 mutations in AITL

Author: Tak W. Mak, Luc Xerri, Jean-Philippe Jais, Li Chong Chan, Javeed Iqbal, Marie Parrens, Laurence de Leval, Antoine Martin, Wing C. Chan, François Lemonnier, Philippe Gaulard, Can Küçük, Pierre Brousset, Rob A. Cairns, Campbell Family Institute for Breast Cancer Research, University Health Network, Department of Pathology and Microbiology, University of Nebraska Medical Center, University of Nebraska System-University of Nebraska System, 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), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Pathologie Clinique, Université de Lausanne = University of Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Service informatique médicale et biostatistique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Anatomie et de Cytologie Pathologiques [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Département de biopathologie, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Department of Pathology, The University of Hong Kong (HKU), This work is supported by the CIHR, The Canadian Cancer Society, The Terry Fox Foundation, and the Leukemia and Lymphoma Society (TWM), INCa (Institut National du Cancer), PHRC (Programme Hospitalier de Recherche Clinique) and FRM (Fondation pour la Recherche Médicale) (PG), The Institut Universitaire de France and the CITTIL program (PB), the Cancer Plan research Programme (Belgium) (LdL), NCI grant (5U01/CA114778), NIH grant (U01/CA84967), lymphoma SPORE grant P50CA13641-02, and Eppley Core Grant (W-CC and JI)., 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université de Lausanne ( UNIL ) -Centre Hospitalier Universitaire Vaudois [Lausanne] ( CHUV ) -Institut Universitaire de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre de Recherche en Cancérologie de Toulouse ( CRCT ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], The University of Hong Kong ( HKU ), Université de Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne-Université Paris 13 (UP13)
Subjects: Male, Mutation rate, Angioimmunoblastic T-cell lymphoma, IDH1, Genotype, Immunology, Kaplan-Meier Estimate, Biology, medicine.disease_cause, Lymphoma, T-Cell, Biochemistry, IDH2, 03 medical and health sciences, 0302 clinical medicine, Lymphoma, T-Cell, Peripheral - enzymology - genetics - pathology, Gene Frequency, Mutation Rate, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Isocitrate Dehydrogenase - genetics, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Aged, 0303 health sciences, Mutation, Lymphoid Neoplasia, Lymphoma, T-Cell, Peripheral, Cell Biology, Hematology, medicine.disease, Prognosis, Isocitrate Dehydrogenase, 3. Good health, Lymphoma, Lymphoma, T-Cell - enzymology - genetics - pathology, Isocitrate dehydrogenase, 030220 oncology & carcinogenesis, Immunoblastic Lymphadenopathy, Cancer research, Female, Immunoblastic Lymphadenopathy - enzymology - genetics - pathology
Abstract: Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) occur in most grade 2 and 3 gliomas, secondary glioblastomas, and a subset of acute myelogenous leukemias but have not been detected in other tumor types. The mutations occur at specific arginine residues and result in the acquisition of a novel enzymatic activity that converts 2-oxoglutarate to D-2-hydroxyglutarate. This study reports IDH1 and IDH2 genotyping results from a set of lymphomas, which included a large set of peripheral T-cell lymphomas. IDH2 mutations were identified in approximately 20% of angioimmunoblastic T-cell lymphomas (AITLs), but not in other peripheral T-cell lymphoma entities. These results were confirmed in an independent set of AITL patients, where the IDH2 mutation rate was approximately 45%. This is the second common genetic lesion identified in AITL after TET2 and extends the number of neoplastic diseases where IDH1 and IDH2 mutations may play a role., link_to_OA_fulltext
Published: 2012
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23. Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release via growth hormone-induced ERK hyperactivation, which contributes to short stature

Author: Mylène Tajan, Marianne Mus, Thomas Edouard, Karine Tréguer, Jean-Pierre Salles, Alexandra Montagner, Armelle Yart, Patrick Raynal, Toshiyuki Araki, M. Tauber, Philippe Valet, Audrey De Rocca Serra-Nédélec, Marie Dance, Benjamin G. Neel, Tréguer, Karine, Tajana, Mylène, Yart, Armelle, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Endocrinologie, Maladies Osseuses, Génétique et Gynécologie Médicale, Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Campbell Family Cancer Research Institute, University of Toronto-Ontario Cancer Institute, Laboratoire de biologie moléculaire eucaryote (LBME), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Mécanismes des cardiopathies et résistance hormonale dans le Noonan et syndrome apparentés (M2CHRNRS), Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Ontario Cancer Institute, Melanie H. Cobb, Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse - Jean Jaurès (UT2J), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and ProdInra, Archive Ouverte
Subjects: MAPK/ERK pathway, TYROSINE-PHOSPHATASE SHP2, medicine.medical_treatment, [SDV]Life Sciences [q-bio], MESH: Insulin-Like Growth Factor I, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein tyrosine phosphatase, growth hormone insensitivity, MESH: Animals, Newborn, MESH: Janus Kinase 2, [SHS]Humanities and Social Sciences, Mice, Phosphatidylinositol 3-Kinases, Insulin-like growth factor, 0302 clinical medicine, HEIGHT, STAT5 Transcription Factor, MESH: Animals, Insulin-Like Growth Factor I, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, MESH: Biometry, MESH: Extracellular Signal-Regulated MAP Kinases, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Multidisciplinary, Noonan Syndrome, ACTIVATED PROTEIN-KINASE, MOUSE MODEL, DEFECTS, Biological Sciences, [SDV] Life Sciences [q-bio], MESH: Noonan Syndrome, Signal transduction, medicine.symptom, signaling, MESH: Protein Tyrosine Phosphatase, Non-Receptor Type 11, MESH: ras Proteins, medicine.medical_specialty, MESH: Enzyme Activation, Biometry, MESH: Mutation, MESH: Rats, 030209 endocrinology & metabolism, SIGNALING PATHWAYS, PTPN11 SHP2, MUTATIONS, DELETION, MALFORMATIONS, Biology, Short stature, MESH: Mitogen-Activated Protein Kinase Kinases, MESH: Phosphoproteins, 03 medical and health sciences, Internal medicine, medicine, Animals, MESH: Mice, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Mitogen-Activated Protein Kinase Kinases, Binding Sites, MESH: Phosphorylation, MESH: Proto-Oncogene Proteins c-akt, Growth factor, MESH: STAT5 Transcription Factor, Janus Kinase 2, Phosphoproteins, medicine.disease, Rats, Enzyme Activation, PTPN11, Endocrinology, Animals, Newborn, MESH: Binding Sites, MESH: Phosphatidylinositol 3-Kinases, Growth Hormone, MESH: Growth Hormone, Mutation, ras Proteins, Noonan syndrome, Proto-Oncogene Proteins c-akt
Abstract: Noonan syndrome (NS), a genetic disease caused in half of cases by activating mutations of the tyrosine phosphatase SHP2 ( PTPN11 ), is characterized by congenital cardiopathies, facial dysmorphic features, and short stature. How mutated SHP2 induces growth retardation remains poorly understood. We report here that early postnatal growth delay is associated with low levels of insulin-like growth factor 1 (IGF-1) in a mouse model of NS expressing the D61G mutant of SHP2. Conversely, inhibition of SHP2 expression in growth hormone (GH)-responsive cell lines results in increased IGF-1 release upon GH stimulation. SHP2-deficient cells display decreased ERK1/2 phosphorylation and rat sarcoma (RAS) activation in response to GH, whereas expression of NS-associated SHP2 mutants results in ERK1/2 hyperactivation in vitro and in vivo. RAS/ERK1/2 inhibition in SHP2-deficient cells correlates with impaired dephosphorylation of the adaptor Grb2-associated binder-1 (GAB1) on its RAS GTPase-activating protein (RASGAP) binding sites and is rescued by interfering with RASGAP recruitment or function. We demonstrate that inhibition of ERK1/2 activation results in an increase of IGF-1 levels in vitro and in vivo, which is associated with significant growth improvement in NS mice. In conclusion, NS-causing SHP2 mutants inhibit GH-induced IGF-1 release through RAS/ERK1/2 hyperactivation, a mechanism that could contribute to growth retardation. This finding suggests that, in addition to its previously shown beneficial effect on NS-linked cardiac and craniofacial defects, RAS/ERK1/2 modulation could also alleviate the short stature phenotype in NS caused by PTPN11 mutations.
Published: 2012
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24. A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence

Author: Colleen Simpson, Yali Xuan, Natalie Naranjo Galloni, Giles C. Warner, Jonathan C. Irish, Patricia P Reis, Nilva K. Cervigne, Bayardo Perez-Ordonez, David P. Goldstein, Melania Pintilie, Levi Waldron, Suzanne Kamel-Reid, Antti Mäkitie, Patrick Gullane, Ralph W. Gilbert, Igor Jurisica, Dale Brown, Korva-, nenä- ja kurkkutautien klinikka, Ontario Canc Inst, Campbell Family Inst Canc Res, Univ Hlth Network, Universidade Estadual Paulista (Unesp), Univ Toronto, Hosp Calderon Guardia, Worcester Royal Hosp, and Univ Helsinki
Subjects: Oncology, Cancer Research, MATRIX METALLOPROTEINASES, 0302 clinical medicine, Surgical oncology, Cluster Analysis, PROTOONCOGENE EIF4E, Mouth neoplasm, 0303 health sciences, MOLECULAR MARKER, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, oral squamous cell carcinoma, 030220 oncology & carcinogenesis, Meta-analysis, Cohort, Carcinoma, Squamous Cell, Mouth Neoplasms, SQUAMOUS-CELL CARCINOMA, Research Article, medicine.medical_specialty, global gene expression profiling, recurrence, education, 3122 Cancers, lcsh:RC254-282, surgical resection margins, DIFFERENTIALLY EXPRESSED GENES, 03 medical and health sciences, Internal medicine, NECK-CANCER PATIENTS, medicine, Carcinoma, Biomarkers, Tumor, Genetics, RESECTION MARGINS, Humans, prognostic signature, HEAD, 030304 developmental biology, LYMPH-NODE METASTASES, Proportional hazards model, business.industry, Gene Expression Profiling, Computational Biology, medicine.disease, Microarray Analysis, Log-rank test, Gene expression profiling, stomatognathic diseases, PROGNOSTIC-FACTOR, Neoplasm Recurrence, Local, business
Abstract: Made available in DSpace on 2013-08-28T14:13:42Z (GMT). No. of bitstreams: 1 WOS000296103700001.pdf: 2457858 bytes, checksum: 545eea3e75bd038470734a9d7ca294e8 (MD5) Made available in DSpace on 2013-09-30T18:16:23Z (GMT). No. of bitstreams: 2 WOS000296103700001.pdf: 2457858 bytes, checksum: 545eea3e75bd038470734a9d7ca294e8 (MD5) WOS000296103700001.pdf.txt: 50065 bytes, checksum: 434c3e90a02c2cdef30a6b0d3b9ba71e (MD5) Previous issue date: 2011-10-11 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:32:43Z No. of bitstreams: 2 WOS000296103700001.pdf: 2457858 bytes, checksum: 545eea3e75bd038470734a9d7ca294e8 (MD5) WOS000296103700001.pdf.txt: 50065 bytes, checksum: 434c3e90a02c2cdef30a6b0d3b9ba71e (MD5) Made available in DSpace on 2014-05-20T13:32:43Z (GMT). No. of bitstreams: 2 WOS000296103700001.pdf: 2457858 bytes, checksum: 545eea3e75bd038470734a9d7ca294e8 (MD5) WOS000296103700001.pdf.txt: 50065 bytes, checksum: 434c3e90a02c2cdef30a6b0d3b9ba71e (MD5) Previous issue date: 2011-10-11 Ontario Institute for Cancer Research (OICR) Galloway Fund Canada Research Chair Program Canada Foundation for Innovation Ontario Research Fund IBM Ontario Ministry of Health and Long Term Care (MOHLTC) Canadian Institutes of Health Research (CIHR) Background: Oral Squamous Cell Carcinoma (OSCC) is a major cause of cancer death worldwide, which is mainly due to recurrence leading to treatment failure and patient death. Histological status of surgical margins is a currently available assessment for recurrence risk in OSCC; however histological status does not predict recurrence, even in patients with histologically negative margins. Therefore, molecular analysis of histologically normal resection margins and the corresponding OSCC may aid in identifying a gene signature predictive of recurrence.Methods: We used a meta-analysis of 199 samples (OSCCs and normal oral tissues) from five public microarray datasets, in addition to our microarray analysis of 96 OSCCs and histologically normal margins from 24 patients, to train a gene signature for recurrence. Validation was performed by quantitative real-time PCR using 136 samples from an independent cohort of 30 patients.Results: We identified 138 significantly over-expressed genes (> 2-fold, false discovery rate of 0.01) in OSCC. By penalized likelihood Cox regression, we identified a 4-gene signature with prognostic value for recurrence in our training set. This signature comprised the invasion-related genes MMP1, COL4A1, P4HA2, and THBS2. Overexpression of this 4-gene signature in histologically normal margins was associated with recurrence in our training cohort (p = 0.0003, logrank test) and in our independent validation cohort (p = 0.04, HR = 6.8, logrank test).Conclusion: Gene expression alterations occur in histologically normal margins in OSCC. Over-expression of the 4-gene signature in histologically normal surgical margins was validated and highly predictive of recurrence in an independent patient cohort. Our findings may be applied to develop a molecular test, which would be clinically useful to help predict which patients are at a higher risk of local recurrence. Ontario Canc Inst, Toronto, on M4X 1K9, Canada Campbell Family Inst Canc Res, Toronto, ON, Canada Univ Hlth Network, Div Appl Mol Oncol, Princess Margaret Hosp, Toronto, ON, Canada São Paulo State Univ UNESP, Dept Surg & Orthoped, Fac Med, Botucatu, SP, Brazil Univ Hlth Network, Dept Pathol, Toronto Gen Hosp, Ontario Canc Inst, Toronto, ON, Canada Univ Hlth Network, Dept Biostat, Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON, Canada Univ Toronto, Dalla Lana Sch Publ Hlth Sci, Toronto, ON, Canada Hosp Calderon Guardia, Dept Otolaryngol, San Jose, Costa Rica Worcester Royal Hosp, Dept Otolaryngol Head & Neck Surg, Worcester, MA USA Univ Helsinki, Cent Hosp, Dept Otolaryngol Head & Neck Surg, Helsinki, Finland Univ Hlth Network, Ontario Canc Inst, Princess Margaret Hosp, Dept Otolaryngol Surg Oncol, Toronto, ON, Canada Univ Toronto, Dept Comp Sci, Toronto, ON, Canada Univ Toronto, Dept Lab Med & Pathobiol, Toronto, on M5S 1A1, Canada Univ Toronto, Dept Med Biophys, Toronto, on M5S 1A1, Canada São Paulo State Univ UNESP, Dept Surg & Orthoped, Fac Med, Botucatu, SP, Brazil CFI: 12301 CFI: 203383 Ontario Research Fund: GL2-01-030 CIHR: 202370
Published: 2011

25. Cancer classification using the Immunoscore: a worldwide task force

Author: Iris D. Nagtegaal, Paul Waring, Michael I. Nishimura, Richard Palmqvist, Carlo Bifulco, Yutaka Kawakami, Christian H. Ottensmeier, Alessandro Lugli, Christoph Huber, Réjean Lapointe, Lotfi Chouchane, Noriyuki Sato, Helen K. Angell, Scott Kopetz, Kyogo Itoh, Michele Maio, Yili Wang, Bernard A. Fox, Thomas F. Gajewski, Christine Lagorce, Franck Pagès, Cedrik M. Britten, Ena Wang, Giuseppe Masucci, Patricia Shaw, Frank A. Sinicrope, Jill O'Donnell-Tormey, Fabiana Tatangelo, Andreas Lundqvist, Heinz Zwierzina, James P. Allison, Toshihiko Torigoe, P. Patel, Inti Zlobec, Blaise Clarke, Martin Asslaber, Corrado D'Arrigo, Shoichi Hazama, Martin C. Mihm, Harpreet Singh-Jasuja, Luigi Laghi, Anne Berger, Jérôme Galon, Samir N. Khleif, Paolo Delrio, Shilin N. Shukla, Gerardo Botti, Hartmann Arndt, Francesco M. Marincola, Leif Håkansson, Paolo A. Ascierto, Robert E. Hawkins, Bradly G. Wouters, Sacha Gnjatic, Graham Pawelec, Fabio Grizzi, Fernando Vidal-Vanaclocha, Shuji Ogino, Sebastian Kreiter, Kiyotaka Okuno, Peter Gibbs, Magdalena Thurin, Giorgio Trinchieri, Pamela S. Ohashi, Radiotherapie, RS: GROW - School for Oncology and Reproduction, 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 ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance Publique-Hopitaux de Paris, Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Society for Immunotherapy of Cancer, Milwaukee, Infectious Disease and Immunogenetics Section (IDIS), Clinical Center and trans-NIH Center for Human Immunology (CHI), Cancer Diagnosis Program, National Cancer Institute ( NIH ), Oncology - Pathology - Anatomy, Institute of Pathology-University of Bern, Department of Pathology, Providence Portland Medical Center, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione G.Pascale', TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Weill Medical College of Cornell University [New York], Colorectal Surgery Department, Istituto Nazionale per lo Studio e la Cura dei Tumori, University of Erlangen, Institute of Pathology, Medical University Graz, Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Department of Oncology-Pathology, Karolinska Institutet [Stockholm], Harvard Medical School and Massachusetts General Hospital, Boston, CEU-San Pablo University School of Medicine and HM-Hospital of Madrid Scientific Foundation, Institute of Applied Molecular Medicine (IMMA), Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, University of Lund, Immatics Biotechnologies GmbH, Experimental Cancer Medicine Centre, University of Southampton Faculty of Medicine, Department Haematology and Oncology, Innsbruck Medical University [Austria] ( IMU ), Molecular Gastroenterology and Department of Gastroenterology, Istituto Clinico Humanitas [Milan] ( IRCCS Milan ), Humanitas University [Milan] ( Hunimed ) -Humanitas University [Milan] ( Hunimed ), Ontario Cancer Institute and Campbell Family Institute for Cancer Research, Princess Margaret Hospital, Departments of Laboratory Medicine, Pathobiology & Radiation Oncology, Division of Cellular Signaling, Institute for Advanced Medical Research, Department of Digestive Surgery and Surgical Oncology, Yamaguchi University [Yamaguchi], Department of Surgery, Kinki University, Cancer Research Institute, New York, Avicenne Hospital, Center for Medical Research, Eberhard Karls Universität Tübingen, Oncology Institute, Loyola University Medical Center ( LUMC ), School of Cancer and Imaging Sciences, University of Manchester [Manchester], Research Center, University Hospital, Department of Oncology-Pathology [Karolinska Institutet], Georgia Health Sciences University Cancer Center, Augusta University, Brigham and Women's Hospital [Boston], Department of Medical Oncology, Royal Melbourne Hospital, University of Melbourne, Sapporo Medical University School of Medicine, Department of Immunology and Immunotherapy, Kurume University School of Medicine, The Gujarat Cancer & Research Institute, Asarwa, Department of Medical Biosciences, Pathology, Pathology Department, Radboud University Medical Center [Nijmegen], Institute for Cancer Research, Center of Translational medicine, Department of Histopathology, Dorset County Hospital, MD Anderson Cancer Center, Houston, Mayo Clinic and Mayo College of Medicine, Rochester, Cancer Inflammation Program, Center for Cancer Research, Oncology and Hematology, University of Chicago, Medical Oncology and Innovative Therapies Unit, Fondazione Melanoma Onlus, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute-Robert W. Franz Cancer Center, Department of Molecular Microbiology and Immunology, Oregon Health and Science University, BMC, Ed., 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), Université Paris Descartes - Paris 5 (UPD5), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Harvard Medical School [Boston] (HMS), Memorial Sloane Kettering Cancer Center [New York], Lund University [Lund], Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed)-Humanitas University [Milan] (Hunimed), University of Toronto-University of Toronto, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Loyola University Medical Center (LUMC), 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), University System of Georgia (USG)-University System of Georgia (USG), Sapporo Medical University-Sapporo Medical University, Kurume University-Kurume University, Oregon Health and Science University [Portland] (OHSU), 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), Innsbruck Medical University [Austria] (IMU), and Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)
Subjects: Oncology, medicine.medical_specialty, Medicin och hälsovetenskap, Internationality, Colorectal cancer, Advisory Committees, lcsh:Medicine, Review, Medical and Health Sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Internal medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Tumor Microenvironment, medicine, Humans, Stage (cooking), Biomarker discovery, 030304 developmental biology, Medicine(all), 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Merkel cell carcinoma, business.industry, Biochemistry, Genetics and Molecular Biology(all), lcsh:R, Cancer, General Medicine, Classification, medicine.disease, Primary tumor, 3. Good health, Treatment Outcome, Tumor progression, 030220 oncology & carcinogenesis, Immunology, Biomarker (medicine), business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the 'Immunoscore' into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
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26. Human CYP2D6 varies across the estrous cycle in brains of transgenic mice altering drug response.

Author: Miksys S, McDonald C, Baghai Wadji F, Gonzalez FJ, and Tyndale RF
Subjects: Animals, Female, Humans, Mice, Harmine pharmacology, Propranolol pharmacology, Male, Liver metabolism, Liver drug effects, Cytochrome P-450 CYP2D6 Inhibitors pharmacology, Hypothermia chemically induced, Hypothermia metabolism, Mice, Transgenic, Cytochrome P-450 CYP2D6 metabolism, Cytochrome P-450 CYP2D6 genetics, Brain metabolism, Brain drug effects, Estrous Cycle drug effects
Abstract: Cytochrome P450 (CYP) 2Ds are drug metabolizing enzymes found in brain and liver which metabolize numerous centrally acting drugs. Inhibition and induction of CYP2D-mediated metabolism in rodent brain alters brain drug and metabolite concentrations and resulting drug response. In female rats, brain CYP2D metabolism varies across the estrous cycle and with exogenous estrogen, changing brain drug concentrations and response. In this study harmine-induced hypothermia was lower in humanized CYP2D6 transgenic female mice during estrus compared to diestrus. Pretreatment into the cerebral ventricles with propranolol, a selective irreversible inhibitor of human CYP2D6 in brain, increased hypothermia in estrus but not in diestrus. In vivo enzyme activity was higher in brains of transgenic mice in estrus compared to diestrus and was lower after pretreatment with inhibitor in estrus, but not in diestrus. Hepatic activity and plasma harmine concentrations were unaffected by either estrous phase or inhibition of brain CYP2D6. In wild-type female mice, harmine-induced hypothermia was unaffected by either estrous phase or inhibitor pretreatment. Male mice were used as positive controls, where pretreatment with inhibitor increased harmine-induced hypothermia in transgenic but not wild-type, mice. This study provides evidence for female hormone cycle-based regulation of drug metabolism by human CYP2D6 in brain and resulting drug response. This suggests that brain CYP2D6 metabolism may vary, for example, during the menstrual cycle, pregnancy, or menopause, or while taking oral contraceptives or hormone therapy. This variation could contribute to individual differences in response to centrally acting CYP2D6-substrate drugs by altering local brain drug and/or metabolite concentrations., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
Published: 2024
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27. Substance Use and Concurrent Disorders: Current Context and the Need for Treatment Integration.

Author: Hendershot CS and Foll BL
Abstract: Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Bernard Le Foll has obtained funding from Indivior for a clinical trial sponsored by Indivior. Bernard Le Foll has in-kind donations of placebo edibles from Indivia. Bernard Le Foll has obtained industry funding from Canopy Growth Corporation (through research grants handled by the Centre for Addiction and Mental Health and the University of Toronto). He has participated in a session of a National Advisory Board Meeting (Emerging Trends BUP-XR) for Indivior Canada and is part of the Steering Board for a clinical trial for Indivior. He has been a consultant for Shinogi and ThirdBridge. He got travel support to attend an event by Bioprojet. He is supported by CAMH, Waypoint Centre for Mental Health Care, a clinician-scientist award from the Department of Family and Community Medicine of the University of Toronto, and a Chair in Addiction Psychiatry from the Department of Psychiatry of the University of Toronto. Christian S. Hendershot reports research funding from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, the Canadian Institutes of Health Research, and the Pharmacotherapies for Alcohol and Substance Use Disorders Alliance; advisory board participation for Apollo Therapeutics; receipt of scientific consulting fees from Eli Lilly and Company, and protocol/data safety monitoring board membership and conference travel support from the National Institute on Drug Abuse. Christian S. Hendershot is supported by the Keck School of Medicine of the University of Southern California.
Published: 2024
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28. Correlates of Using Medically-Authorized Cannabis in a Large Cohort of People Living with HIV Who Use Cannabis.

Author: Coelho SG, Wardell JD, Kroch A, and Rueda S
Abstract: Many people living with HIV (PLWH) use cannabis to manage symptoms, but a large proportion do so without medical cannabis authorization and use cannabis obtained outside the medical stream. In jurisdictions where non-medical cannabis use is legal, PLWH who hold medical cannabis authorization may represent a unique subgroup; yet, research on the correlates of using medical cannabis (authorized by a healthcare provider) in the context of non-medical cannabis legalization is lacking. Thus, this study examined the cannabis- and health-related correlates of medical cannabis use among PLWH in Ontario, Canada, where non-medical cannabis is legal. PLWH (N = 868; 85.37% men, mean age 51.34 years [SD = 12.25]) who were enrolled in the Ontario HIV Treatment Network Cohort Study in 2022 and who reported past-year cannabis use completed an assessment of sociodemographic characteristics, HIV-related variables, cannabis and other substance use, and health-related quality of life. Relatively few participants (n = 122; 14.06%) reported any medical cannabis use, with most (n = 746; 85.94%) reporting exclusive use of non-medical cannabis. Logistic regression analyses showed that greater HIV symptom distress, poorer physical-health-related quality of life, more frequent cannabis use, and using smokeless forms of cannabis were each uniquely associated with increased likelihood of using medical cannabis relative to exclusively using non-medical cannabis. Results suggest that even in jurisdictions where non-medical cannabis is legal, a subset of PLWH continue to access cannabis through the medical stream, and these individuals report distinct patterns of cannabis use and poorer physical health. Findings may inform cannabis policy and clinical care for PLWH who use cannabis., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical Approval: This study was performed in line with the relevant principles of the Declaration of Helsinki. All study procedures were approved by the University of Toronto Human Subjects Review Committee (#23954) and the Centre for Addiction and Mental Health Research Ethics Board (CAMH REB#027/2021). Informed Consent: Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2024
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29. The Implementation of Integrated Youth Services in Canada: Planning and Costing of a Pan-Canadian Model: La mise en œuvre des services intégrés pour les jeunes au Canada : planification et établissement des coûts d'un modèle pancanadien.

Author: Henderson JL, de Oliveira C, and Mathias S
Abstract: Objective: The implementation of Integrated Youth Services (IYS) can help ensure that youth are adequately supported. The objective of this analysis was to provide a model for the planning and costing of IYS throughout Canada over a 15-year period., Methods: To estimate resource allocation for IYS, we determined the number of hubs and hub staffing requirements by service level and jurisdiction, backbone support and infrastructure requirements by jurisdiction. A needs-based analytic framework for planning was employed to estimate the number of hubs required. The optimal mix of hub staffing requirements was determined based on prior literature. The costs of running each hub were estimated using publicly available data and internal documents from existing IYS agencies. Finally, the cost of setting up IYS hubs, IYS virtual care and respective backbone support throughout Canada was estimated and projected over 15 years and the cost-savings of IYS were calculated., Results: At maturity, it was estimated that 399 hubs-188 small, 43 medium, 168 large-across Canada would be required to address youth mental health and substance use needs. The cost of implementing IYS initiatives across Canada would vary between $4,349,126 (for less populous jurisdictions) and $248,950,524 (for more populous jurisdictions), for a total annual cost of $676,633,388 (excluding costs of infrastructure). It was estimated that the implementation of IYS hubs would lead to cost-savings of $2.1 billion annually and have the potential to be cost-effective., Conclusion: The implementation of IYS hubs can provide good value for money, in the form of high client satisfaction, earlier supports with improved youth outcomes and decreased health care costs. Future work should address gaps in data availability on mental health and substance use-related needs of youth with neurodevelopmental disorders, youth experiencing homelessness, youth in congregate living and foster care, and Indigenous youth., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Published: 2024
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30. A Gender-Informed Smoking Cessation App for Women: Protocol for an Acceptability and Feasibility Study.

Author: Melamed OC, Mehra K, Panda R, Minian N, Veldhuizen S, Zawertailo L, Buckley L, Maslej M, Greaves L, Brabete AC, Rose J, Ratto M, and Selby P
Subjects: Humans, Female, Adult, Middle Aged, Patient Acceptance of Health Care psychology, Male, Smoking Cessation methods, Smoking Cessation psychology, Mobile Applications, Feasibility Studies
Abstract: Background: Tobacco smoking remains the leading preventable cause of death and disease among women. Quitting smoking offers numerous health benefits; however, women tend to have less success than men when attempting to quit. This discrepancy is partly due to sex- and gender-related factors, including the lower effectiveness of smoking cessation medication and the presence of unique motives for smoking and barriers to quitting among women. Despite the gendered nature of smoking, most smoking cessation apps are gender-neutral and fail to address women's specific needs., Objective: This study aims to test the acceptability and feasibility of a smartphone app that delivers gender-informed content to support women in quitting smoking., Methods: We co-developed a smoking cessation app specifically tailored for women, named My Change Plan-Women (MCP-W). This app builds upon our previous gender-neutral app, MCP, by retaining its content grounded in behavioral change techniques aimed at supporting tobacco reduction and cessation. This includes goal setting for quitting, identifying triggers to smoking, creating coping strategies, tracking cigarettes and cravings, and assessing financial savings from quitting smoking. The MCP-W app contains additional gender-informed content that acknowledges barriers to quitting, such as coping with stress, having smokers in one's social circle, and managing unpleasant emotions. This content is delivered through testimonials and animated videos. This study is a prospective, single-group, mixed methods investigation in which 30 women smokers will trial the app for a period of 28 days. Once participants provide informed consent, they will complete a baseline survey and download the app on their smartphones. After 28 days, participants will complete follow-up surveys. Acceptability will be assessed using the Theoretical Framework of Acceptability, which evaluates whether participants perceive the app as helpful in changing their smoking. The app will be deemed acceptable if the majority of participants rate it as such, and feasible if the majority of the participants use it for at least 7 days. Furthermore, after the 28-day trial period, participants will complete a semistructured interview regarding their experience with the app and suggestions for improvement., Results: Development of the MCP-W app was completed in September 2023. Participant recruitment for testing of the app commenced in February 2024 and was completed in July 2024. We will analyze the data upon completion of data collection from all 30 participants. We expect to share the results of this acceptability trial in the middle of 2025., Conclusions: Offering smoking cessation support tailored specifically to address the unique needs of women through a smartphone app represents a novel approach. This study will test whether women who smoke perceive this approach to be acceptable and feasible in their journey toward smoking cessation., International Registered Report Identifier (irrid): DERR1-10.2196/60677., (©Osnat C Melamed, Kamna Mehra, Roshni Panda, Nadia Minian, Scott Veldhuizen, Laurie Zawertailo, Leslie Buckley, Marta Maslej, Lorraine Greaves, Andreea C Brabete, Jonathan Rose, Matt Ratto, Peter Selby. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 10.12.2024.)
Published: 2024
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31. Real-World Treatment of Schizophrenia in Adults With a 22q11.2 Microdeletion: Traitement dans le monde réel de la schizophrénie chez des adultes atteints du syndrome de microdélétion 22q11.2.

Author: Van L, Heung T, Reyes NGD, Boot E, Chow EWC, Corral M, and Bassett AS
Abstract: Objective: One in every 4 individuals born with a 22q11.2 microdeletion will develop schizophrenia. Thirty years of clinical genetic testing capability have enabled detection of this major molecular susceptibility for psychotic illness. However, there is limited literature on the treatment of schizophrenia in individuals with a 22q11.2 microdeletion, particularly regarding the issue of treatment resistance., Methods: From a large, well-characterized adult cohort with a typical 22q11.2 microdeletion followed for up to 25 years at a specialty clinic, we studied all 107 adults (49 females, 45.8%) meeting the criteria for schizophrenia or schizoaffective disorder. We performed a comprehensive review of lifetime (1,801 patient-years) psychiatric records to determine treatments used and the prevalence of treatment-resistant schizophrenia (TRS). We used Clinical Global Impression-Improvement (CGI-I) scores to compare within-individual responses to clozapine and nonclozapine antipsychotics. For a subgroup with contemporary data ( n = 88, 82.2%), we examined antipsychotics and dosage at the last follow-up., Results: Lifetime treatments involved on average 4 different antipsychotic medications per individual. Sixty-three (58.9%) individuals met the study criteria for TRS, a significantly greater proportion than for a community-based comparison (42.9%; χ 2 = 10.38, df = 1, p < 0.01). The non-TRS group was enriched for individuals with genetic diagnosis before schizophrenia diagnosis. Within-person treatment response in TRS was significantly better for clozapine than for nonclozapine antipsychotics ( p < 0.0001). At the last follow-up, clozapine was the most common antipsychotic prescribed, followed by olanzapine, risperidone, and paliperidone. Total antipsychotic chlorpromazine equivalent dosages were in typical clinical ranges (median: 450 mg; interquartile range: 300, 750 mg)., Conclusion: The results for this large sample indicate that patients with 22q11.2 microdeletion have an increased propensity to treatment resistance. The findings provide evidence about how genetic diagnosis can inform clinical psychiatric management and could help reduce treatment delays. Further research is needed to shed light on the pathophysiology of antipsychotic response and on strategies to optimize outcomes., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Published: 2024
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32. Cognitive flexibility in autism: How task predictability and sex influence performances.

Author: Lacroix A, Torija E, Logemann A, Baciu M, Cserjesi R, Dutheil F, Gomot M, and Mermillod M
Abstract: While cognitive flexibility challenges are frequently reported in autistic individuals, inconsistencies in the findings prompt further investigation into the factors influencing this flexibility. We suggest that unique aspects of the predictive brain in autistic individuals might contribute to these challenges, potentially varying by sex. Our study aimed to test these hypotheses by examining cognitive flexibility under different predictability conditions in a sample including a similar number of males and females. We conducted an online study with 263 adults (127 with an autism diagnosis), where participants completed a flexibility task under varying levels of predictability (unpredictable, moderately predictable, and predictable). Our results indicate that as task predictability increases, performance improves; however, the response time gap between autistic and non-autistic individuals also widens. Moreover, we observe significant differences between autistic males and females, which differ from non-autistic individuals, highlighting the need to consider sex differences in research related to the cognition of autistic individuals. Overall, our findings contribute to a better understanding of cognitive flexibility and sex differences in autism in light of predictive brain theories and suggest avenues for further research., (© 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)
Published: 2024
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33. Structure-Guided Discovery of Subtype Selective SIRT6 Inhibitors with a β-Carboline Skeleton for the Treatment of Breast Cancer.

Author: Liang C, Wang S, Feng D, Wang S, Zheng C, Qu Y, Wang W, Ma Y, Li H, Yang H, Cao H, Hua H, Cheng M, and Li D
Abstract: SIRT6 promotes the progression of breast cancer by inducing drug resistance by reinforcing DNA damage repair mechanisms. This study utilized a combination of high-throughput virtual screening and FLUOR DE LYS assays. Hit 14 which features a novel β-carboline skeleton as a potent SIRT6 inhibitor was found. Subsequent structure-guided optimization led to the synthesis of 60 3,6,9-position modified derivatives based on the differences analysis of SIRTs family proteins. Of which, 10d inhibited the deacetylase activity of SIRT6, with an IC 50 of 5.81 μM and more than 27 times subtype selectivity. Phe64, Met157, and Ser56 were identified as the key residues. Moreover, 10d suppressed breast cancer cell proliferation, migration, invasion, and induced apoptosis in MCF-7 cells by disrupting the DNA damage repair pathway. Additionally, 10d demonstrated a safe and effective antibreast cancer effect in vivo , presenting a promising strategy for the treatment of breast cancer by targeting SIRT6.
Published: 2024
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34. Targeting socioeconomic inequity to reduce liver disease related to alcohol use.

Author: Probst C and Kilian C
Abstract: Competing Interests: We declare that we were supported to conduct the research referenced in this Comment by a grant from the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number R01AA028009 (paid through our institution). The content of this Comment is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Published: 2024
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35. Association of NTRK2 gene with suicidality: a meta-analysis.

Author: Ye W, Zhang RS, Hosang GM, Fabbri C, King N, Strauss J, Jones I, Jones L, Breen G, Kennedy JL, Vincent JB, and Zai CC
Subjects: Humans, Alleles, Brain-Derived Neurotrophic Factor genetics, Genetic Association Studies methods, Genotype, Haplotypes genetics, Membrane Glycoproteins genetics, Suicidal Ideation, Suicide psychology, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide genetics, Receptor, trkB genetics
Abstract: Background: Previous studies have shown that genes in brain development pathways may have important roles in affecting risk of suicidal behaviors, with our previous meta-analysis supporting a role of the brain-derived neurotrophic factor (BDNF) gene. NTRK2 is a gene that encodes the neurotrophic receptor tyrosine kinase 2, which is a receptor for BDNF. In the current study, we aim to examine the potential association between NTRK2 single nucleotide polymorphism (SNPs) and suicidal ideation/behaviors., Methods: We first conducted a literature search using keywords like 'NTRK2', 'TRKB', and 'suicid*' to identify papers on NTRK2 SNPs and suicidal ideation/behaviors. In addition, we have individual-level genotype data for all the identified SNPs in literature search. We used the R meta package to perform meta-analyses on both the genotype count and the allele count data. Moreover, we performed meta-analyses on specific haplotypes within each haplotype block., Main Results: Following our literature search and meta-analyses on 20 NTRK2 SNPs across up to 8467 samples, we found three SNPs, rs10868235 [N = 5,318, odds ratio (OR) = 1.34, P = 0.02], rs1867283 (N = 5,134, OR = 0.73, P = 0.04), and rs1147198 (N = 5,132, OR = 1.36, P = 0.03) to be nominally associated with suicidal attempts. Those three findings, however, did not survive multiple-testing corrections. Also, none of the haplotype blocks showed significant involvement in suicidality., Conclusion: Our results suggest that the NTRK2 gene may not have a major role in suicidality. Future efforts, however, should explore gene-gene interaction and pathway analyses., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2024
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36. Commentary on Andreacchi et al.: Policy responses to shifting epidemiological trends in alcohol use in Canada.

Author: Kilian C and Probst C
Published: 2024
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37. Human-fecal microbiota transplantation in relation to gut microbiome signatures in animal models for schizophrenia: A scoping review.

Author: Singh R, Panganiban K, Au E, Ravikumar R, Pereira S, Prevot TD, Mueller DJ, Remington G, Agarwal SM, Verdu EF, Bercik P, De Palma G, and Hahn MK
Subjects: Animals, Humans, Mice, Fecal Microbiota Transplantation, Schizophrenia therapy, Schizophrenia metabolism, Gastrointestinal Microbiome physiology, Disease Models, Animal
Abstract: More recently, attention has turned to the putative role of gut microbiome (GMB) in pathogenesis, symptomatology, treatment response and/or resistance in schizophrenia (SCZ). It is foreseeable that fecal microbiota transplantation (FMT) from SCZ patients (SCZ-FMT) to germ-free mice could represent a suitable experimental framework for a better understanding of the relationship between GMB and SCZ. Thus, we set out to identify literature (i) characterizing the GMB in animal models of SCZ, and (ii) employing SCZ-FMT into rodents to model SCZ in relation to behavioral and molecular phenotypes. Five studies examining animal models of SCZ suggest distinct GMB composition compared to respective control groups, which was correlated with SCZ-like behavioral phenotypes. Four additional studies investigated SCZ-FMT into rodents in relation to behavioral phenotypes, including spontaneous hyperlocomotion, social deficits, exaggerated startle response, and cognitive impairments, resembling those observed in SCZ patients. Mice receiving SCZ-FMT showed altered neurochemical and metabolic pathways in the brain. Animal models of SCZ have shown altered GMB composition, whereas reported behavioral and neurochemical alterations following FMT from patients into rodents suggest early face and construct validity for SCZ-FMT animal models. However, the predictive validity of these models remains to be validated., Competing Interests: Declaration of Competing Interest MKH has received Alkermes consultant fees., (Copyright © 2024 Elsevier B.V. All rights reserved.)
Published: 2024
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38. Sex-dependent association study of complement C4 gene with treatment-resistant schizophrenia and hospitalization frequency.

Author: Teymouri K, Ebrahimi M, Chen CC, Sriretnakumar V, Mohiuddin AG, Tiwari AK, Pouget JG, Zai CC, and Kennedy JL
Subjects: Humans, Male, Female, Adult, Middle Aged, Retrospective Studies, Psychotic Disorders genetics, Sex Factors, Schizophrenia genetics, DNA Copy Number Variations, Complement C4a genetics, Hospitalization statistics & numerical data, Complement C4 genetics, Schizophrenia, Treatment-Resistant genetics
Abstract: The complement component 4 (C4) gene, codes for two isotypes, C4A and C4B, and can exist in long or short forms (C4L and C4S). The C4AL variant has been associated with elevated schizophrenia (SCZ) risk. Here, we investigated the relationship between C4 variation and clinical outcomes in SCZ. N = 434 adults with SCZ or schizoaffective disorder were included in this retrospective study. A three-step genotyping workflow was performed to determine C4 copy number variants. These variants were tested for association with clinical outcome measures, including treatment-resistant SCZ (TRS), number of hospitalizations (NOH), and symptom severity (PANSS). Sex and ancestry stratified analyses were performed. We observed a marginally significant association between C4S and TRS in males only, and a negative association between C4S and NOH in the total sample. C4AS had negative association with NOH in males and non-Europeans. Lastly, C4A copy numbers and C4A predicted brain expression showed negative association with NOH in males only. Our study provides further support for sex-specific effect of C4 on SCZ clinical outcomes, and also suggests that C4S and C4AS might have a protective effect against increased severity. C4 could potentially serve as a genetic biomarker in the future, however, more research is required., Competing Interests: Declaration of competing interest JLK is a member of the Scientific Advisory Board of Myriad Neuroscience (paid). JLK, AKT, JGP, and CCZ are authors on several patents relating to pharmacogenetic tests for psychiatric medications. JLK and CCZ are authors on a patent on genetic biomarkers of suicide risk. The remaining authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Published: 2024
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39. Health service utilization, substance use treatment response, and death in patients with opioid use disorder and comorbid hepatitis C findings from prospective cohort study with administrative database linkage.

Author: Dennis BB, Babe G, Gayowsky A, Rosic T, Rodrigues M, Bach P, Perez R, de Oliveira C, Samet J, Weaver V, Young S, Dionne J, Ahmed A, Kim D, Thabane L, and Samaan Z
Subjects: Humans, Female, Male, Adult, Prospective Studies, Ontario epidemiology, Middle Aged, Databases, Factual, Opiate Substitution Treatment, Patient Acceptance of Health Care statistics & numerical data, Drug Overdose mortality, Drug Overdose epidemiology, Analgesics, Opioid therapeutic use, Opioid-Related Disorders epidemiology, Opioid-Related Disorders mortality, Hepatitis C drug therapy, Hepatitis C epidemiology, Hepatitis C mortality, Comorbidity
Abstract: Background: Among patients with opioid use disorder (OUD), high rates of overdose and death have been reported in subgroups with Hepatitis C Virus (HCV). Evidence on the comorbid effect of HCV on clinical and substance use trajectories has been limited by small sample sizes, short follow-up, and heavy reliance on administrative data which lacks granularity on important prognostic factors. Additionally, few studies include populations on substance use treatment., Aim: To establish the impact of HCV exposure (antibody positivity) on health care utilization patterns, substance use treatment response, and death in a cohort of patients with OUD on opioid agonist therapy (OAT)., Methods: This multi-center prospective cohort study recruited adult patients with OUD on OAT from 57 substance use treatment centers in Ontario, Canada. The study collected substance use outcomes, and classified patients with ≥50 % positive opioid urine screens over one year of follow-up as having poor treatment response. Additional data obtained via linkage with ICES administrative databases evaluated the relationship between HCV status, healthcare service utilization, and death over 3 years of follow-up. Multiple logistic regression models established the adjusted impact of HCV on various outcomes., Results: Among recruited participants (n = 3430), 44.10 % were female with a mean age of 38.64 years (Standard deviation: 10.96). HCV was prevalent in 10.6 % of the cohort (n = 365). Methadone was used most often (83.9 %, n = 2876), followed by sublingual buprenorphine (16.2 %, n = 554). Over the three-year follow-up, 5.3 % of patients died (n = 181). Unadjusted results reveal rates of hospitalization (all-cause, mental-health related, critical care) and emergency department visits (mental health-related), were significantly higher among HCV patients. Associations diminished in adjusted models. Active injection drug use exhibited the highest predictive risk for all outcomes., Conclusion: A high degree of acute physical and mental illness and its resulting health service utilization burden is concentrated among patients with OUD and comorbid HCV. Future research should explore the role for targeted interventions and how best to implement integrated healthcare models to better address the complex health needs of HCV populations who inject drugs., Competing Interests: Declaration of competing interest None. The authors have no declarations of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)
Published: 2024
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40. Mood regulation in euthymic patients with a history of antidepressant-induced mania.

Author: Halabi R, Yusuff K, Park C, DeShaw A, Gonzalez-Torres C, Husain MI, O'Donovan C, Alda M, Mulsant BH, and Ortiz A
Subjects: Humans, Female, Male, Adult, Middle Aged, Anxiety drug therapy, Psychiatric Status Rating Scales, Antidepressive Agents therapeutic use, Antidepressive Agents adverse effects, Mania drug therapy, Mania chemically induced, Affect drug effects, Bipolar Disorder drug therapy
Abstract: Introduction: The use of antidepressants in bipolar disorder (BD) remains contentious, in part due to the risk of antidepressant-induced mania (AIM). However, there is no information on the architecture of mood regulation in patients who have experienced AIM. We compared the architecture of mood regulation in euthymic patients with and without a history of AIM., Methods: Eighty-four euthymic participants were included. Participants rated their mood, anxiety and energy levels daily using an electronic (e-) visual analog scale, for a mean (SD) of 280.8(151.4) days. We analyzed their multivariate time series by computing each variable's auto-correlation, inter-variable cross-correlation, and composite multiscale entropy of mood, anxiety, and energy. Then, we compared the data features of participants with a history of AIM and those without AIM, using analysis of covariance, controlling for age, sex, and current treatment., Results: Based on 18,103 daily observations, participants with AIM showed significantly stronger day-to-day auto-correlation and cross-correlation for mood, anxiety, and energy than those without AIM. The highest cross-correlation in participants with AIM was between mood and energy within the same day (median (IQR), 0.58 (0.27)). The strongest negative cross-correlation in participants with AIM was between mood and anxiety series within the same day (median (IQR), -0.52 (0.34))., Conclusion: Patients with a history of AIM have a different underlying mood architecture compared to those without AIM. Their mood, anxiety and energy stay the same from day-to-day; and their anxiety is negatively correlated with their mood., (© 2024 The Author(s). Bipolar Disorders published by John Wiley & Sons Ltd.)
Published: 2024
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41. "Like the Wild West": Health care provider perspectives on impacts of recreational cannabis legalization on patients and providers at a tertiary psychiatric hospital in Ontario, Canada.

Author: Wiese JL, Watson TM, Bozinoff N, Rush B, Stergiopoulos V, Le Foll B, and Rueda S
Subjects: Humans, Ontario epidemiology, Health Personnel psychology, Female, Male, Medical Marijuana therapeutic use, Legislation, Drug, Adult, Tertiary Care Centers, Attitude of Health Personnel, Middle Aged, Cannabis, Hospitals, Psychiatric, Qualitative Research
Abstract: Introduction: Legalization has increased cannabis availability in Canada. Research shows complex relationships between cannabis use and mental health, and a need for health care providers to engage with patients about cannabis use. Providers have noted gaps in knowledge and research on the medical effects of cannabis as barriers to service delivery. It is unclear how providers and patients in mental health care settings have been impacted by legalization., Methods: From June 1 to July 2, 2021, we conducted a qualitative study involving semi-structured interviews with 20 health care providers in a range of roles (e.g., physicians, pharmacists, nurses) within a psychiatric hospital setting. Participants responded to open-ended questions with follow-up probes on various topics related to cannabis legalization. Topics included impacts on patient mental and physical health, clinical impacts, education and training, legal cannabis retail system and the medical cannabis access system., Results: Thematic analysis identified several themes in the data. Participants reported that legalization has had some positive impacts relating to clinical care and cannabis safety. They also expressed concerns with increased rates of cannabis use, risks to mental health and ongoing challenges engaging with patients about cannabis. Participants made recommendations for medical educators and regulators (e.g., updated curriculums, clinical guidelines), the mental health care sector (e.g., implementation of standardized screening), government (e.g., public health campaigns, safe use guidelines), the medical cannabis access system (e.g., increased regulation, research), and the legal cannabis system (e.g., zoning changes, point-of-sale information)., Conclusions: This study begins to address the paucity of data on impacts of legalization from mental health service delivery settings. Findings show that although legalization has had some positive impacts, there are ongoing patient concerns and unmet provider needs. More research is needed to understand the experiences of providers delivering care to populations experiencing mental health and/or substance use concerns who use cannabis in the post-legalization era., Competing Interests: Declaration of competing interest Dr. Bernard Le Foll has obtained funding from Pfizer Inc. (GRAND Awards, including salary support) for investigator-initiated projects. Dr. Le Foll has obtained funding from Indivior for a clinical trial sponsored by Indivior. Dr. Le Foll has in-kind donations of cannabis products from Aurora Cannabis Enterprises Inc. and study medication donations from Pfizer Inc. (varenicline for smoking cessation) and Bioprojet Pharma. He was also provided a coil for a Transcranial magnetic stimulation (TMS) study from Brainsway. Dr. Le Foll has obtained industry funding from Canopy Growth Corporation (through research grants handled by the Centre for Addiction and Mental Health and the University of Toronto), Bioprojet Pharma, Alcohol Countermeasure Systems (ACS), Alkermes and Universal Ibogaine. Lastly, Dr. Le Foll has received in kind donations of nabiximols from GW Pharmaceuticals for past studies funded by CIHR and NIH. He has participated in a session of a National Advisory Board Meeting (Emerging Trends BUP-XR) for Indivior Canada and is part of Steering Board for a clinical trial for Indivior. He has been consultant for Shinogi. He is supported by the Centre for Addiction and Mental Health, Waypoint Centre for Mental Health Care, a clinician-scientist award from the department of Family and Community Medicine of the University of Toronto, and a Chair in Addiction Psychiatry from the department of Psychiatry of University of Toronto. Other authors' declarations of interest: none., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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42. Pleiotropic effects on Sarcopenia subphenotypes point to potential molecular markers for the disease.

Author: Fonseca ID, Fabbri LE, Moraes L, Coelho DB, Dos Santos FC, and Rosse I
Subjects: Humans, Aged, Male, Female, Walking Speed genetics, Biomarkers, Polymorphism, Single Nucleotide, Sarcopenia genetics, Genome-Wide Association Study, Muscle Strength genetics, Phenotype, Genetic Pleiotropy
Abstract: Sarcopenia is a progressive age-related muscle disease characterized by low muscle strength, quantity and quality, and low physical performance. The clinical overlap between these subphenotypes (reduction in muscle strength, quantity and quality, and physical performance) was evidenced, but the genetic overlap is still poorly investigated. Herein, we investigated whether there is a genetic overlap amongst sarcopenia subphenotypes in the search for more effective molecular markers for this disease. For that, a Bioinformatics approach was used to identify and characterize pleiotropic effects at the genome, loci and gene levels using Genome-wide association study results. As a result, a high genetic correlation was identified between gait speed and muscle strength (rG=0.5358, p=3.39 × 10 -8 ). Using a Pleiotropy-informed conditional and conjunctional false discovery rate method we identified two pleiotropic loci for muscle strength and gait speed, one of them was nearby the gene PHACTR1. Moreover, 11 pleiotropic loci and 25 genes were identified for muscle mass and muscle strength. Lastly, using a gene-based GWAS approach three candidate genes were identified in the overlap of the three Sarcopenia subphenotypes: FTO, RPS10 and CALCR. The current study provides evidence of genetic overlap and pleiotropy among sarcopenia subphenotypes and highlights novel candidate genes and molecular markers associated with the risk of sarcopenia., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)
Published: 2024
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43. Comparative Effectiveness of Buprenorphine/Naloxone and Methadone on Methamphetamine/Amphetamine Use Among People with Opioid Use Disorder in Canada.

Author: Langlois J, Fairbairn N, Jutras-Aswad D, Le Foll B, Ahamad K, Lim R, and Socías ME
Abstract: Background: It has been suggested that opioid agonist therapy (OAT) may have a secondary benefit of reducing methamphetamine/amphetamine use. However, current evidence is limited and conflicting, and little is known on the impacts of different OATs on methamphetamine/amphetamine use. The aim of this study was to examine the comparative effectiveness of buprenorphine/naloxone and methadone on methamphetamine/amphetamine use among individuals with opioid use disorder (OUD) initiating OAT in Canada., Methods: Data for this study were derived from a 24-week pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care among OUD. Generalized linear mixed models were used to evaluate the independent effect of treatment (ie, methadone or buprenorphine/naloxone) and time in treatment (ie, week 2 through 24, continuous) on methamphetamine/amphetamine use (measured by urine drug test and self-report using Timeline Follow-Back)., Results: The sample included 210 participants that initiated OAT, of which 130 (61.9%) were using methamphetamine/amphetamine at baseline. In multivariable analysis, neither treatment nor time in treatment were significantly associated with the odds of methamphetamine/amphetamine use (adjusted odds ratio [AOR] = 0.61, 95% confidence interval [CI] = 0.34-1.08, P = .092; and AOR = 0.73, CI = 0.40-1.28, P = .283, respectively). No interaction between treatment and time in treatment was observed for methamphetamine/amphetamine use ( P = .367)., Conclusion: Methamphetamine/amphetamine use was common among this sample of people with OUD initiating OAT in Canada. Over the 24-week study period, buprenorphine/naloxone and methadone were not associated with a quantifiable change in methamphetamine/amphetamine use among this sample population. The observation of less methamphetamine/amphetamine use in the buprenorphine/naloxone arm warrants further research., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DJA receives study material from Tetra Bio-Pharma and Cardiol Therapeutics for trials funded by public funding bodies. BLF has received funding from Pfizer (Global Research Awards in Nicotine Dependence Program, including salary support) for investigator-initiated projects and from Indivior (for a clinical trial sponsored by Indivior), and he has received industry funding from Canopy Growth Corporation (through research grants handled by the Centre for Addiction and Mental Health and the University of Toronto), Bioprojet Pharma, Alcohol Countermeasure Systems, Alkermes, and Universal Ibogaine; he has received in-kind donations of cannabis products from Aurora Cannabis Enterprises, Inc and study medication donations from Pfizer (varenicline for smoking cessation) and Bioprojet Pharma; he was provided a coil for a transcranial magnetic stimulation study from Brainsway; he has received in-kind donations of nabiximols from GW Pharmaceuticals for past studies funded by CIHR and NIH; he has participated in a session of a National Advisory Board Meeting (Emerging Trends BUP-XR) for Indivior Canada and is part of Steering Board for a clinical trial for Indivior; and he has served as a consultant for Shinogi. MES has received partial support from Indivior’s investigator-initiated study program for work outside of this study. All other authors have no conflicting interests to declare.
Published: 2024
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44. Psychometric properties of the Taiwan version of Emotion Dysregulation Inventory in Autism Spectrum Disorder.

Author: Kuo CY, Liu CH, Huang YC, Liang SH, Lin HY, and Ni HC
Abstract: Background: While the Emotion Dysregulation Inventory (EDI) for autistic people has been validated in many Western countries, its psychometric properties have remained unclear in East Asia., Methods: We translated the EDI into traditional Chinese and evaluated its psychometric properties among autistic children and youth in Taiwan. We enrolled 200 participants (182 male/18 female) aged 7-30 years from five clinical trials and conducted secondary analyses, assessing internal consistency reliability, confirmatory factor analysis, and convergent validity., Results: Our results showed that the Taiwan version of the EDI had strong internal consistency (Cronbach's alpha are 0.978 and 0.864 for each factor). Confirmatory factor analysis demonstrated acceptable fit of two-factors structure. The Taiwan version of EDI showed good convergent validity with established measurements including the Aberrant Behavior Checklist-Irritability subscale and Child Behavior Checklist-Dysregulation Profile., Conclusion: Our findings support the Taiwan version of EDI is a reliable and potentially valid instrument for assessing emotion dysregulation in autistic children and youth in Taiwan., Competing Interests: Declaration of conflicting interest None of the authors have conflict of biomedical and nonfinancial interests related to this work., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)
Published: 2024
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45. Metabolic Dysfunction and Alcohol-related Liver Disease (MetALD): Position statement by an expert panel on alcohol-related liver disease.

Author: Arab JP, Díaz LA, Rehm J, Im G, Arrese M, Kamath PS, Lucey MR, Mellinger J, Thiele M, Thursz M, Bataller R, Burton R, Chokshi S, Francque SM, Krag A, Lackner C, Lee BP, Liangpunsakul S, MacClain C, Mandrekar P, Mitchell MC, Morgan MY, Morgan TR, Pose E, Shah VH, Shawcross D, Sheron N, Singal AK, Stefanescu H, Terrault N, Trépo E, Moreno C, Louvet A, and Mathurin P
Abstract: This position statement explores the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.e., phosphatidylethanol), use of validated questionnaires (i.e. AUDIT-C), and collateral information from friends and relatives could help facilitate differentiation between alcohol-related liver disease (ALD) per se and liver disease with both metabolic and alcohol-related components (MetALD). Heavy alcohol use can contribute to cardiometabolic risk factors such as high blood pressure, hypertriglyceridemia, and hyperglycemia. As a result, caution should be exercised in the application of only one metabolic dysfunction criterion to diagnose MASLD, as suggested in the 2023 nomenclature document, particularly in individuals exceeding weekly alcohol use thresholds of 140 grams for women and 210 grams for men. This is particularly important in those individuals with isolated high blood pressure, hypertriglyceridemia, or hyperglycemia, where the disease process may be driven by alcohol itself. Additionally, metabolic dysfunction and alcohol use should be reassessed over time, especially after periods of changes in risk factor exposure. This approach could ensure a more accurate prognosis and effective management of SLD addressing both metabolic and alcohol-related factors., Competing Interests: Declaration of Competing Interest Jessica Mellinger: Consulting fees from GSK., (Copyright © 2024 European Association for the Study of the Liver. All rights reserved.)
Published: 2024
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46. Willingness of population health survey participants to provide personal health information and biological samples.

Author: Jaswal H, Ialomiteanu A, Hamilton H, Rehm J, Wells S, and Shield KD
Subjects: Humans, Male, Female, Adult, Middle Aged, Young Adult, Adolescent, Saliva chemistry, Health Records, Personal, Aged, Health Surveys
Abstract: Background: Biological sample collection and data linkage can expand the utility of population health surveys. The present study investigates factors associated with population health survey respondents' willingness to provide biological samples and personal health information., Methods: Using data from the 2019 Centre for Addiction and Mental Health (CAMH) Monitor survey (n = 2,827), we examined participants' willingness to provide blood samples, saliva samples, probabilistic linkage, and direct linkage with personal health information. Associations of willingness to provide such information with socio-demographic, substance use, and mental health details were also examined. Question order effects were tested using a randomized trial., Results: The proportion of respondents willing to provide blood samples, saliva samples, probabilistic linkage, and direct linkage with personal health information were 19.9%, 36.2%, 82.1%, and 17%, respectively. Willingness significantly varied by age, race, employment, non-medical prescription opioid use (past year), cocaine use (lifetime), and psychological distress. Significant question order effects were observed. Respondents were more likely to be willing to provide a saliva sample when this question was asked first compared to first being asked for direct data linkage. Similarly, respondents were more likely to be willing to allow for probabilistic data linkage when this question was asked first compared to first being asked for a saliva sample., Conclusion: A lack of willingness to provide biological samples or permit data linkage may lead to representivity issues in studies which rely on such information. The presence of question order effects suggests that the willingness of respondents can be increased through strategic ordering of survey structures., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval for use of data from the 2019 CAMH Monitor study was granted by the CAMH Research Ethics Board. All participants provided informed consent before participating in the CAMH Monitor study. Consent for publication: Consent to publish data from the survey was asked of all participants. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
Published: 2024
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47. Assessing plasticity in the primary sensory cortex and its relation with atypical tactile reactivity in autism: A TMS-EEG protocol.

Author: Kariminezhad S, Zomorrodi R, Zrenner C, Blumberger DM, Ameis SH, Lin HY, Lai MC, Rajji TK, Lunsky Y, Sanches M, and Desarkar P
Subjects: Humans, Adult, Male, Female, Young Adult, Adolescent, Double-Blind Method, Touch physiology, Transcranial Magnetic Stimulation methods, Autistic Disorder physiopathology, Autistic Disorder therapy, Neuronal Plasticity physiology, Electroencephalography methods, Somatosensory Cortex physiopathology
Abstract: Background: Atypical sensory reactivity is a cardinal presentation in autism. Within the tactile domain, atypical tactile reactivity (TR) is common, it emerges early, persists into adulthood, and impedes social interaction and daily functioning. Hence, atypical TR is a key target for biological intervention to improve outcomes. Brain mechanisms informing biological interventions for atypical TR remains elusive. We previously reported hyper-plasticity in the motor cortex in autistic adults and found that repetitive transcranial magnetic stimulation (rTMS), designed to strengthen inhibitory processes in the brain, reduced hyper-plasticity. Whether the primary sensory cortex (S1) is characterized by hyper-plasticity, which may underlie atypical TR in autism is unknown., Objectives: We aim to test whether hyper-plasticity in the S1 underlies atypical TR in autism, and investigate if a single session of rTMS can safely reduce hyper-plasticity in S1 in autistic adults., Method: Plasticity will be assessed in the left S1 with integrated paired associative stimulation and electroencephalography (PAS-EEG) paradigm in 32 autistic adults and 32 age-, sex-, and intelligence quotient-matched controls. Autistic participants will be further randomized (double-blind, 1:1) to receive a single-session of either sham or active 20 Hz bilateral rTMS over the S1 and the plasticity will be re-assessed over the left S1 on the same day., Conclusions: Atypical TR has been identified as one of the top clinical research priorities that can influence outcome in autistic population. The study findings can be highly valuable to further elucidate the mechanism underlying atypical TR, which in turn can help with developing a mechanism-driven intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kariminezhad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2024
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48. The impact of an integrated alcohol policy: The example of Lithuania.

Author: Rehm J, Lange S, Miščikienė L, and Jiang H
Abstract: Introduction: Although integrated alcohol policies, characterised by being consistent, structurally connected and interdependent, are considered to be best practices, very few evaluations of such policies exist. We evaluated the impact of two phases of integrated alcohol policies implemented in Lithuania in 2008/2009 and 2017/2018 on adult (15+ years of age) alcohol per capita consumption., Methods: Alcohol per capita consumption was the main outcome, based on national data from Statistics Lithuania. Time-series analyses using generalised additive mixed models were used, and unrecorded consumption trends were examined. A sensitivity analysis was conducted with data from the World Health Organization., Results: The two phases of integrated alcohol policies were associated with average reductions in adult alcohol per capita consumption of almost 1 litre (-0.88 L; 95% confidence interval -1.43; -0.34). Sensitivity analyses with comparable international data on Lithuania yielded similar results., Discussion and Conclusions: Integrated alcohol policies had a substantial effect on the average level of consumption. However, the effect of major single policies for Lithuania and other Baltic countries has been estimated to be of about the same magnitude. We conclude that in order to be successful, integrated alcohol policies should include at least one major effective population-based policy., (© 2024 The Author(s). Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)
Published: 2024
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49. Adult Phenotype of CHD2 -Associated Disorders.

Author: Rong M, Zulfiqar Ali Q, Aledo-Serrano A, Bayat A, Devinsky O, Qaiser F, Chandran I, Ali A, Fasano A, Bassett AS, and Andrade DM
Abstract: Background and Objectives: Pathogenic CHD2 variants are associated with neurodevelopmental disorders and developmental and epileptic encephalopathy. While pediatric CHD2 phenotypes have been readily explored, adult phenotypes are not well understood. We aimed to investigate the phenotypic spectrum of adult patients with CHD2 variants., Methods: Patients 18 years or older with likely pathogenic or pathogenic (LP/P) CHD2 variants were included. We used standardized tools to evaluate current seizures, medication use, sleep, gastrointestinal symptoms, pain response, gait, social communication disorder, and adaptive behavioral skills of patients., Results: In this prospective study, 14 unrelated adult patients (age range: 18-45 years, median: 21 years) with LP/P CHD2 variants were described. Eleven novel variants were identified. No genotype-phenotype correlations were identified. 79% of adults still have ongoing seizures. Photosensitivity was present in 64% of adult patients. Autism spectrum disorder was diagnosed in 71% of patients. Only 29% were able to read and understand material at a sixth-grade level or higher. Behavioral issues were reported in 100% of adult patients, and 71% had internalizing features, such as anxiety. Self-injurious behaviors were present in 50%. Only 43% could ambulate independently. Additional characteristics included reflux (36%), constipation (71%), and abnormal pain responsiveness (43%). 1 patient presented with nonepileptic breath-holding spells leading to cyanosis. No patient could perform all basic activities of daily living independently, all the time. Higher seizure severity was associated with worse nonseizure outcomes ( p = 0.04)., Discussion: Most adults with CHD2 continue to have seizures, and seizure severity is associated with worse comorbidities such as maladaptive behaviors, gait, gastrointestinal, sleep, and abnormal pain responsiveness. Longevity has not been systematically studied in this group of patients. Here we describe a group of adult patients (up to 45 years of age) and the natural history of this condition. These data may provide prognostic insights for families of pediatric patients and help identify key points to be addressed in future precision trials for patients with CHD2 variants., Competing Interests: M. Rong received an unrestricted education grant from Biocodex. Q. Zulfiqar Ali reports no disclosures relevant to the manuscript. A. Aledo‐Serrano received educational, scientific and consulting fees from UCB, Biocodex, Eisai, Angelini, Jazz pharma. A. Bayat reports no disclosures relevant to the manuscript. O. Devinsky receives grant support from NINDS, NIMH, MURI, CDC and NSF. He has equity and/or compensation from the following companies: Ajna Biosciences, Tilray, Receptor Life Sciences, Hitch Biosciences, Tevard Biosciences, Regel Biosciences, Script Biosciences, Actio Biosciences, Empatica, SilverSpike, and California Cannabis Enterprises. He has received consulting fees from Zogenix, Ultragenyx, BridgeBio, GeneMedicine and Marinus. He holds patents for the use of cannabidiol in treating neurologic disorders which are owned by GW Pharmaceuticals for which he waived financial interests. He holds other patents in molecular biology. He is the managing partner of the PhiFund Ventures. F. Qaiser, I. Chandran, A. Ali, A. Fasano, and A.S. Bassett report no disclosures relevant to the manuscript. D.M. Andrade receives grant support from Ontario Brain Institute, McLaughlin Foundation, UHN Foundation, Dravet Syndrome Foundation, SYNGAP1 Research Fund. She also received consulting fees from UCB, Biocodex, Paladin, Jazz, Stoke, and Eisai. Finally, she receives royalties from UpToDate. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Published: 2024
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50. Polygenic score analyses on antidepressant response in late-life depression, results from the IRL-GRey study.

Author: Elsheikh SSM, Marshe VS, Men X, Islam F, Gonçalves VF, Paré G, Felsky D, Kennedy JL, Mulsant BH, Reynolds CF 3rd, Lenze EJ, and Müller DJ
Subjects: Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Depressive Disorder, Treatment-Resistant drug therapy, Depressive Disorder, Treatment-Resistant genetics, Treatment Outcome, Antidepressive Agents therapeutic use, Depressive Disorder, Major drug therapy, Depressive Disorder, Major genetics, Multifactorial Inheritance genetics, Venlafaxine Hydrochloride therapeutic use
Abstract: Late-life depression (LLD) is often accompanied by medical comorbidities such as psychiatric disorders and cardiovascular diseases, posing challenges to antidepressant treatment. Recent studies highlighted significant associations between treatment-resistant depression (TRD) and polygenic risk score (PRS) for attention deficit hyperactivity disorder (ADHD) in adults as well as a negative association between antidepressant symptom improvement with both schizophrenia and bipolar. Here, we sought to validate these findings with symptom remission in LLD. We analyzed the Incomplete Response in Late Life Depression: Getting to Remission (IRL-GRey) sample consisting of adults aged 60+ with major depression (N = 342) treated with venlafaxine for 12 weeks. We constructed PRSs for ADHD, depression, schizophrenia, bipolar disorder, neuroticism, general intelligence, antidepressant symptom remission and antidepressant percentage symptom improvement using summary statistics from the Psychiatric Genomics Consortium and the GWAS Catalog. Logistic regression was used to test the association of PRSs with venlafaxine symptom remission and percentage symptom improvement, co-varying for the genomic principal components, age, sex and depressive symptoms severity at baseline. We found a nominal (i.e., p value ≤ 0.05) association between symptom remission and both PRS for ADHD and (OR = 1.36 [1.07, 1.73], p = 0.011) and PRS for bipolar disorder (OR = 0.75 [0.58, 0.97], p = 0.031), as well as between percentage symptom improvement and PRS for general intelligence (beta = 6.81 (SE = 3.122), p = 0.03). However, the ADHD association was in the opposite direction as expected, and both associations did not survive multiple testing corrections. Altogether, these findings suggest that previous findings regarding ADHD PRS and antidepressant response (measured with various outcomes) do not replicate in older adults., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Published: 2024
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