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1. Brain functional connectivity mirrors genetic pleiotropy in psychiatric conditions.

Author: Moreau, Clara, Kumar, Kuldeep, Harvey, Annabelle, Huguet, Guillaume, Urchs, Sebastian, Schultz, Laura, Sharmarke, Hanad, Jizi, Khadije, Martin, Charles-Olivier, Younis, Nadine, Tamer, Petra, Martineau, Jean-Louis, Orban, Pierre, Silva, Ana, Hall, Jeremy, van den Bree, Marianne, Owen, Michael, Linden, David, Lippé, Sarah, Almasy, Laura, Glahn, David, Thompson, Paul, Bourgeron, Thomas, Bellec, Pierre, Jacquemont, Sebastien, and Bearden, Carrie
Subjects: autism spectrum disorder, copy-number variant, functional connectivity, pleiotropy, psychiatry, Humans, Genetic Pleiotropy, Magnetic Resonance Imaging, Mental Disorders, Brain, Connectome
Abstract: Pleiotropy occurs when a genetic variant influences more than one trait. This is a key property of the genomic architecture of psychiatric disorders and has been observed for rare and common genomic variants. It is reasonable to hypothesize that the microscale genetic overlap (pleiotropy) across psychiatric conditions and cognitive traits may lead to similar overlaps at the macroscale brain level such as large-scale brain functional networks. We took advantage of brain connectivity, measured by resting-state functional MRI to measure the effects of pleiotropy on large-scale brain networks, a putative step from genes to behaviour. We processed nine resting-state functional MRI datasets including 32 726 individuals and computed connectome-wide profiles of seven neuropsychiatric copy-number-variants, five polygenic scores, neuroticism and fluid intelligence as well as four idiopathic psychiatric conditions. Nine out of 19 pairs of conditions and traits showed significant functional connectivity correlations (rFunctional connectivity), which could be explained by previously published levels of genomic (rGenetic) and transcriptomic (rTranscriptomic) correlations with moderate to high concordance: rGenetic-rFunctional connectivity = 0.71 [0.40-0.87] and rTranscriptomic-rFunctional connectivity = 0.83 [0.52; 0.94]. Extending this analysis to functional connectivity profiles associated with rare and common genetic risk showed that 30 out of 136 pairs of connectivity profiles were correlated above chance. These similarities between genetic risks and psychiatric disorders at the connectivity level were mainly driven by the overconnectivity of the thalamus and the somatomotor networks. Our findings suggest a substantial genetic component for shared connectivity profiles across conditions and traits, opening avenues to delineate general mechanisms-amenable to intervention-across psychiatric conditions and genetic risks.
Published: 2023

2. Genetic Heterogeneity Shapes Brain Connectivity in Psychiatry.

Author: Moreau, Clara, Harvey, Annabelle, Kumar, Kuldeep, Huguet, Guillaume, Urchs, Sebastian, Douard, Elise, Schultz, Laura, Sharmarke, Hanad, Jizi, Khadije, Martin, Charles-Olivier, Younis, Nadine, Tamer, Petra, Rolland, Thomas, Martineau, Jean-Louis, Orban, Pierre, Silva, Ana, Hall, Jeremy, van den Bree, Marianne, Owen, Michael, Linden, David, Labbe, Aurelie, Lippé, Sarah, Almasy, Laura, Glahn, David, Thompson, Paul, Bourgeron, Thomas, Bellec, Pierre, Jacquemont, Sebastien, and Bearden, Carrie
Subjects: Autism spectrum disorder, Copy number variant, Functional connectivity, Genetic heterogeneity, Polygenic score, Transdiagnostic approach, Humans, Genetic Heterogeneity, Genetic Predisposition to Disease, Multifactorial Inheritance, Brain, DNA Copy Number Variations, Psychiatry, Genome-Wide Association Study
Abstract: BACKGROUND: Polygenicity and genetic heterogeneity pose great challenges for studying psychiatric conditions. Genetically informed approaches have been implemented in neuroimaging studies to address this issue. However, the effects on functional connectivity of rare and common genetic risks for psychiatric disorders are largely unknown. Our objectives were to estimate and compare the effect sizes on brain connectivity of psychiatric genomic risk factors with various levels of complexity: oligogenic copy number variants (CNVs), multigenic CNVs, and polygenic risk scores (PRSs) as well as idiopathic psychiatric conditions and traits. METHODS: Resting-state functional magnetic resonance imaging data were processed using the same pipeline across 9 datasets. Twenty-nine connectome-wide association studies were performed to characterize the effects of 15 CNVs (1003 carriers), 7 PRSs, 4 idiopathic psychiatric conditions (1022 individuals with autism, schizophrenia, bipolar conditions, or attention-deficit/hyperactivity disorder), and 2 traits (31,424 unaffected control subjects). RESULTS: Effect sizes on connectivity were largest for psychiatric CNVs (estimates: 0.2-0.65 z score), followed by psychiatric conditions (0.15-0.42), neuroticism and fluid intelligence (0.02-0.03), and PRSs (0.01-0.02). Effect sizes of CNVs on connectivity were correlated to their effects on cognition and risk for disease (r = 0.9, p = 5.93 × 10-6). However, effect sizes of CNVs adjusted for the number of genes significantly decreased from small oligogenic to large multigenic CNVs (r = -0.88, p = 8.78 × 10-6). PRSs had disproportionately low effect sizes on connectivity compared with CNVs conferring similar risk for disease. CONCLUSIONS: Heterogeneity and polygenicity affect our ability to detect brain connectivity alterations underlying psychiatric manifestations.
Published: 2023

3. Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia.

Author: Moreau, Clara A, Urchs, Sebastian GW, Kuldeep, Kumar, Orban, Pierre, Schramm, Catherine, Dumas, Guillaume, Labbe, Aurélie, Huguet, Guillaume, Douard, Elise, Quirion, Pierre-Olivier, Lin, Amy, Kushan, Leila, Grot, Stephanie, Luck, David, Mendrek, Adrianna, Potvin, Stephane, Stip, Emmanuel, Bourgeron, Thomas, Evans, Alan C, Bearden, Carrie E, Bellec, Pierre, and Jacquemont, Sebastien
Subjects: Brain, Humans, Magnetic Resonance Imaging, Cohort Studies, Cognition, Attention Deficit Disorder with Hyperactivity, Schizophrenia, Gene Duplication, Gene Deletion, Mutation, Adolescent, Adult, Child, Child, Preschool, Female, Male, Young Adult, DNA Copy Number Variations, Autism Spectrum Disorder, Preschool
Abstract: 16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.
Published: 2020

4. Genetic Heterogeneity Shapes Brain Connectivity in Psychiatry

Author: Clara A. Moreau, Annabelle Harvey, Kuldeep Kumar, Guillaume Huguet, Sebastian G.W. Urchs, Elise A. Douard, Laura M. Schultz, Hanad Sharmarke, Khadije Jizi, Charles-Olivier Martin, Nadine Younis, Petra Tamer, Thomas Rolland, Jean-Louis Martineau, Pierre Orban, Ana Isabel Silva, Jeremy Hall, Marianne B.M. van den Bree, Michael J. Owen, David E.J. Linden, Aurelie Labbe, Sarah Lippé, Carrie E. Bearden, Laura Almasy, David C. Glahn, Paul M. Thompson, Thomas Bourgeron, Pierre Bellec, Sebastien Jacquemont, RS: MHeNs - R2 - Mental Health, Psychiatry 1, RS: MHeNs School for Mental Health and Neuroscience, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, School for Mental Health & Neuroscience, RS: MHeNs - R3 - Neuroscience, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Children’s Hospital of Philadelphia (CHOP ), Centre de Recherche de l’Institut Universitaire en Santé Mentale de Montréal (CRIUSMM), Université de Montréal (UdeM), Cardiff University, Maastricht University [Maastricht], HEC Montréal (HEC Montréal), Semel Institute for Neuroscience and Human Behavior [Los Angeles, Ca], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of Pennsylvania, Harvard Medical School [Boston] (HMS), Boston Children's Hospital, Centre de recherche de l'Institut universitaire de gériatrie de Montreal (CRIUGM), and This research was supported by Compute Canada (ID 3037 and gsf-624), the Brain Canada Multi investigator research initiative (MIRI), Canada First Research Excellence Fund, Institute of Data Valorization, Healthy Brain Healthy Lives (Dr. Jacquemont). Dr. Jacquemont is a recipient of a Canada Research Chair in neurodevelopmental disorders, and a chair from the Jeanne et Jean Louis Levesque Foundation. This work was supported by a grant from the Brain Canada Multi-Investigator initiative (Dr. Jacquemont) and a grant from The Canadian Institutes of Health Research (CIHR 400528, Dr. Jacquemont). Clara Moreau and Thomas Bourgeron are supported by AIMS-2-TRIALS - which received support from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394. The Cardiff CNV cohort was supported by the Wellcome Trust Strategic Award 'DEFINE' and the National Centre for Mental Health with funds from Health and Care Research Wales (code 100202/Z/12/Z). Data from the UCLA cohort provided by Dr. Bearden (participants with 22q11.2 deletions or duplications and controls) was supported through grants from the NIH (U54EB020403), NIMH (R01MH085953, R01MH100900, 1U01MH119736, R21MH116473 ), and the Simons Foundation (SFARI Explorer Award). Finally, data from another study were obtained through the OpenFMRI project (http://openfmri.org) from the Consortium for Neuropsychiatric Phenomics (CNP), which was supported by NIH Roadmap for Medical Research grants UL1-DE019580, RL1MH083268, RL1MH083269, RL1DA024853, RL1MH083270, RL1LM009833, PL1MH083271, and PL1NS062410. Dr P. Bellec is a fellow ('Chercheur boursier Junior 2') of the 'Fonds de recherche du Québec - Santé', Data preprocessing and analyses were supported in part by the Courtois foundation (Dr Bellec). This work was supported by Simons Foundation Grant Nos. SFARI219193 and SFARI274424. We thank all of the families at the participating Simons Variation in Individuals Project (VIP) sites, as well as the Simons VIP Consortium. We appreciate obtaining access to imaging and phenotypic data on SFARI Base. Approved researchers can obtain the Simons VIP population dataset described in this study by applying at https://base.sfari.org. We are grateful to all families who participated in the 16p11.2 European Consortium. Dr. P. Thompson was funded in part by the U.S. NIH grants R01MH116147, P41EB015922, R01MH111671, and U01 AG068057. Ms. Petra Tamer received the Canadian Institute of Health Research (CIHR) Scholarship.
Subjects: Psychiatry, Multifactorial Inheritance, DNA Copy Number Variations, Brain, Copy number variant, Functional connectivity, Genetic Heterogeneity, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Humans, Genetic Predisposition to Disease, Polygenic score transdiagnostic approach, Autism spectrum disorder, Biological Psychiatry, Genome-Wide Association Study
Abstract: BACKGROUND: Polygenicity and genetic heterogeneity pose great challenges for studying psychiatric conditions. Genetically informed approaches have been implemented in neuroimaging studies to address this issue. However, the effects on functional connectivity of rare and common genetic risks for psychiatric disorders are largely unknown. Our objectives were to estimate and compare the effect sizes on brain connectivity of psychiatric genomic risk factors with various levels of complexity: oligogenic copy number variants (CNVs), multigenic CNVs, and polygenic risk scores (PRSs) as well as idiopathic psychiatric conditions and traits.METHODS: Resting-state functional magnetic resonance imaging data were processed using the same pipeline across 9 datasets. Twenty-nine connectome-wide association studies were performed to characterize the effects of 15 CNVs (1003 carriers), 7 PRSs, 4 idiopathic psychiatric conditions (1022 individuals with autism, schizophrenia, bipolar conditions, or attention-deficit/hyperactivity disorder), and 2 traits (31,424 unaffected control subjects).RESULTS: Effect sizes on connectivity were largest for psychiatric CNVs (estimates: 0.2-0.65 z score), followed by psychiatric conditions (0.15-0.42), neuroticism and fluid intelligence (0.02-0.03), and PRSs (0.01-0.02). Effect sizes of CNVs on connectivity were correlated to their effects on cognition and risk for disease (r = 0.9, p = 5.93 × 10-6). However, effect sizes of CNVs adjusted for the number of genes significantly decreased from small oligogenic to large multigenic CNVs (r = -0.88, p = 8.78 × 10-6). PRSs had disproportionately low effect sizes on connectivity compared with CNVs conferring similar risk for disease.CONCLUSIONS: Heterogeneity and polygenicity affect our ability to detect brain connectivity alterations underlying psychiatric manifestations.
Published: 2023
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5. Predicting future cognitive decline from non-brain and multimodal brain imaging data in healthy and pathological aging

Author: Hebling Vieira, Bruno, Liem, Franziskus, Dadi, Kamalaker, Engemann, Denis A, Gramfort, Alexandre, Bellec, Pierre, Craddock, Richard Cameron, Damoiseaux, Jessica S, Steele, Christopher J, Yarkoni, Tal, Langer, Nicolas, Margulies, Daniel S, Varoquaux, Gael, Universität Zürich [Zürich] = University of Zurich (UZH), Modèles et inférence pour les données de Neuroimagerie (MIND), IFR49 - Neurospin - CEA, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université du Québec à Montréal = University of Québec in Montréal (UQAM), The University of Texas Medical Branch (UTMB), Wayne State University [Detroit], Concordia University [Montreal], The University of Texas Medical School at Houston, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), Méthodes computationnelles et mathématiques pour comprendre la société et la santé à partir de données (SODA), Inria Saclay - Ile de France, ANR-20-IADJ-0002,AI-cog,IA pour les sociétés touchées par le vieillissement: des concepts fondamentaux aux outils pratiques pour l'apprentissage cognitif facilité par l'IA(2020), University of Zurich, and Hebling Vieira, Bruno
Subjects: Aging, Neuroimaging, 2717 Geriatrics and Gerontology, [STAT.OT]Statistics [stat]/Other Statistics [stat.ML], 1309 Developmental Biology, 1302 Aging, Activities of Daily Living, Biomarker, Machine learning, Predictive modeling, Cross-validation, Open science, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Cognitive Dysfunction, Aged, Aged, 80 and over, [STAT.AP]Statistics [stat]/Applications [stat.AP], 10093 Institute of Psychology, General Neuroscience, Brain, 2800 General Neuroscience, Middle Aged, Magnetic Resonance Imaging, 2728 Neurology (clinical), Neurology (clinical), Geriatrics and Gerontology, 150 Psychology, Developmental Biology
Abstract: Previous literature has focused on predicting a diagnostic label from structural brain imaging. Since subtle changes in the brain precede a cognitive decline in healthy and pathological aging, our study predicts future decline as a continuous trajectory instead. Here, we tested whether baseline multimodal neuroimaging data improve the prediction of future cognitive decline in healthy and pathological aging. Nonbrain data (demographics, clinical, and neuropsychological scores), structural MRI, and functional connectivity data from OASIS-3 (N = 662; age = 46–96 years) were entered into cross-validated multitarget random forest models to predict future cognitive decline (measured by CDR and MMSE), on average 5.8 years into the future. The analysis was preregistered, and all analysis code is publicly available. Combining non-brain with structural data improved the continuous prediction of future cognitive decline (best test-set performance: R2 = 0.42). Cognitive performance, daily functioning, and subcortical volume drove the performance of our model. Including functional connectivity did not improve predictive accuracy. In the future, the prognosis of age-related cognitive decline may enable earlier and more effective individualized cognitive, pharmacological, and behavioral interventions., Neurobiology of Aging, 118, ISSN:0197-4580, ISSN:1558-1497
Published: 2022
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6. Discontinuous stereotactic body radiotherapy schedule increases overall survival in early-stage non-small cell lung cancer

Author: Jérôme Doyen, Joël Castelli, Enrique Chajon, F. Thillays, Hervé Lena, Pierre-Yves Bondiau, Stéphane Supiot, R. de Crevoisier, Charles Ricordel, Loig Vaugier, Line Claude, J. Bellec, and L. Duvergé
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Urology, Radiosurgery, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Humans, Medicine, Stage (cooking), Lung cancer, Neoplasm Staging, Retrospective Studies, Performance status, business.industry, Proportional hazards model, Hazard ratio, medicine.disease, Small Cell Lung Carcinoma, Confidence interval, Treatment Outcome, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Propensity score matching, T-stage, business
Abstract: The duration of stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) may affect patient outcomes. We aimed to determine the impact of a continuous versus discontinuous SBRT schedule on local control (LC) and overall survival (OS) in NSCLC patients.Consecutive NSCLC stage I patients (475) treated with SBRT in four centers were retrospectively analyzed. The delivered dose ranged from 48 to 75 Gy in 3-10 fractions. Based on the ratio between the treatment duration (TD) and number of fractions (n), patients were divided into two groups: continuous schedule (CS) (TD ≤ 1.6n; 239 patients) and discontinuous schedule (DS) (TD 1.6n; 236 patients). LC and OS were compared using Cox regression analyses after propensity score matching (216 pairs).The median follow-up period was 41 months. Multivariate analysis showed that the DS (hazard ratio (HR): 0.42; 95 % confidence interval (CI): 0.22-0.78) and number of fractions (HR: 1.24; 95 % CI: 1.07-1.43) were significantly associated with LC. The DS (HR: 0.67; 95 % CI: 0.51-0.89), age (HR: 1.02; 95 % CI: 1-1.03), WHO performance status (HR: 2.27; 95 % CI: 1.39-3.7), and T stage (HR: 1.4; 95 % CI: 1.03-1.87) were significantly associated with OS. The 3-year LC and OS were 92 % and 64 % and 81 % and 53 % for DS and CS treatments, respectively (p 0.01). Cox analysis confirmed that the discontinuous SBRT schedule significantly increased LC and OS.DS is associated with significantly improved LC and OS in early-stage NSCLC patients treated with SBRT.
Published: 2021
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7. Amyloid and Tau Pathology Associations With Personality Traits, Neuropsychiatric Symptoms, and Cognitive Lifestyle in the Preclinical Phases of Sporadic and Autosomal Dominant Alzheimer’s Disease

Author: Alexa Pichet Binette, Étienne Vachon-Presseau, John Morris, Randall Bateman, Tammie Benzinger, D. Louis Collins, Judes Poirier, John C.S. Breitner, Sylvia Villeneuve, Ricardo Allegri, Fatima Amtashar, Randy Bateman, Sarah Berman, Courtney Bodge, Susan Brandon, William (Bill) Brooks, Jill Buck, Virginia Buckles, Sochenda Chea, Jasmeer Chhatwal, Patricio Chrem, Helena Chui, Jake Cinco, Jack Clifford, Carlos Cruchaga, Mirelle D‘Mello, Tamara Donahue, Jane Douglas, Noelia Edigo, Nilufer Erekin-Taner, Anne Fagan, Marty Farlow, Angela Farrar, Howard Feldman, Gigi Flynn, Nick Fox, Erin Franklin, Hisako Fujii, Cortaiga Gant, Samantha Gardener, Bernardino Ghetti, Alison Goate, Jill Goldman, Brian Gordon, Neill Graff-Radford, Julia Gray, Jenny Gurney, Jason Hassenstab, Mie Hirohara, David Holtzman, Russ Hornbeck, Siri Houeland DiBari, Takeshi Ikeuchi, Snezana Ikonomovic, Gina Jerome, Mathias Jucker, Celeste Karch, Kensaku Kasuga, Takeshi Kawarabayashi, William (Bill) Klunk, Robert Koeppe, Elke Kuder-Buletta, Christoph Laske, Jae-Hong Lee, Johannes Levin, Daniel Marcus, Ralph Martins, Neal Scott Mason, Colin Masters, Denise Maue-Dreyfus, Eric McDade, Lucy Montoya, Hiroshi Mori, Akem Nagamatsu, Katie Neimeyer, James Noble, Joanne Norton, Richard Perrin, Marc Raichle, John Ringman, Jee Hoon Roh, Stephen Salloway, Peter Schofield, Hiroyuki Shimada, Tomoyo Shiroto, Mikio Shoji, Wendy Sigurdson, Hamid Sohrabi, Paige Sparks, Kazushi Suzuki, Laura Swisher, Kevin Taddei, Jen Wang, Peter Wang, Mike Weiner, Mary Wolfsberger, Chengjie Xiong, Xiong Xu, Angela Tam, Anne Labonté, Anne-Marie Faubert, Axel Mathieu, Cécile Madjar, Charles Edouard Carrier, Christian Dansereau, Christina Kazazian, Claude Lepage, Cynthia Picard, David Maillet, Diane Michaud, Doris Couture, Doris Dea, Claudio Cuello, Alan Barkun, Alan Evans, Blandine Courcot, Christine Tardif, Clément Debacker, Clifford R. Jack, David Fontaine, David S. Knopman, Gerhard Maultaup, Jamie Near, Jeannie-Marie Leoutsakos, Jean-Robert Maltais, Jason Brandt, Jens Pruessner, John C. Morris, Laksanun Cheewakriengkrai, Lisa-Marie Münter, Louis Collins, Mallar Chakravarty, Mark A. Sager, Marina Dauar-Tedeschi, Mark Eisenberg, Natasha Rajah, Paul Aisen, Joanne Toussaint, Pedro Rosa-Neto, Pierre Bellec, Penelope Kostopoulos, Pierre Etienne, Pierre N. Tariot, Pierre Orban, Reisa A. Sperling, Rick Hoge, Ronald G. Thomas, Serge Gauthier, Suzanne Craft, Thomas J. Montine, Vasavan Nair, Véronique Bohbot, Vinod Venugopalan, Vladimir Fonov, Yasser Ituria-Medina, Zaven S. Khachaturian, Eduard Teigner, Elena Anthal, Elsa Yu, Fabiola Ferdinand, Galina Pogossova, Ginette Mayrand, Guerda Duclair, Guylaine Gagné, Holly Newbold-Fox, Illana Leppert, Isabelle Vallée, Jacob W. Vogel, Jennifer Tremblay-Mercier, Joanne Frenette, Josée Frappier, Justin Kat, Justin Miron, Karen Wan, Laura Mahar, Leopoldina Carmo, Louise Théroux, Mahsa Dadar, Marianne Dufour, Marie-Elyse Lafaille-Magnan, Melissa Appleby, Mélissa Savard, Miranda Tuwaig, Mirela Petkova, Pierre Rioux, Pierre-François Meyer, Rana El-Khoury, Renee Gordon, Renuka Giles, Samir Das, Seqian Wang, Shirin Tabrizi, Sulantha Mathotaarachchi, Sylvie Dubuc, Tanya Lee, Thomas Beaudry, Valérie Gervais, Véronique Pagé, Julie Gonneaud, Gülebru Ayranci, Tharick A. Pascoal, René Desautels, Fatiha Benbouhoud, Eunice Farah Saint-Fort, Sander C.J. Verfaillie, Sarah Farzin, Alyssa Salaciak, Stephanie Tullo, Etienne Vachon-Presseau, Leslie-Ann Daoust, Theresa Köbe, Nathan Spreng, Melissa McSweeney, Nathalie Nilsson, Morteza Pishnamazi, and Christophe Bedetti
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, tau Proteins, Disease, Article, 03 medical and health sciences, Cognition, 0302 clinical medicine, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Dementia, Big Five personality traits, Family history, Life Style, Biological Psychiatry, Aged, Amyloid beta-Peptides, Extraversion and introversion, business.industry, medicine.disease, Neuroticism, 3. Good health, 030104 developmental biology, Positron-Emission Tomography, Cohort, Alzheimer's disease, business, 030217 neurology & neurosurgery
Abstract: Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.
Published: 2021
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8. Clinical phenotype and outcomes of pneumococcal versus meningococcal purpura fulminans: a multicenter retrospective cohort study

Author: Fabrice Daviaud, Xavier Valette, Martin Cour, Matthieu Schmidt, Frédéric Pène, Bertrand Sauneuf, Damien Contou, Jean Dellamonica, Bruno Mégarbane, Alexandre Lautrette, Cédric Bruel, Jean-Marc Tadié, Gaëtan Plantefève, Antoine Marchalot, Gaetan Beduneau, Martial Tchir, Christian Brun-Buisson, Julien Grouille, Nicolas Terzi, Delphine Colling, Jérémie Lemarié, Samir Jaber, Jean-Pierre Quenot, Elodie Gelisse, Nicolas de Prost, Gabriel Preda, Nicolas Lerolle, Pascal Beuret, Claire Pichereau, Guillaume Schnell, Mathieu Jozwiak, François Barbier, Armand Mekontso Dessap, Sylvie Ricome, Yacine Tandjaoui, Nadège Demars, Sebastien Preau, Damien Roux, Frédéric Bellec, Amélie Bazire, Arnaud Galbois, Laurent Argaud, Emmanuel Guerot, Stephan Ehrmann, Romain Sonneville, Rémi Coudroy, Olivier Leroy, Pierre Kalfon, Sebastien Jochmans, Lara Zafrani, Vincent Das, Benjamin Zuber, Laurent Guérin, Etienne de Montmollin, Christophe Lenclud, Antoine Kimmoun, Alexandre Conia, Caroline Jannière, Pascal Blanc, Gwenhael Colin, Charlène Le Moal, Centre Hospitalier Victor Dupouy, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, HOPEFUL Study group: Laurent Argaud, François Barbier, Amélie Bazire, Gaëtan Béduneau, Frédéric Bellec, Pascal Beuret, Pascal Blanc, Cédric Bruel, Christian Brun-Buisson, Gwenhaël Colin, Delphine Colling, Alexandre Conia, Rémi Coudroy, Martin Cour, Damien Contou, Fabrice Daviaud, Vincent Das, Jean Dellamonica, Nadège Demars, Stephan Ehrmann, Arnaud Galbois, Elodie Gelisse, Julien Grouille, Laurent Guérin, Emmanuel Guérot, Samir Jaber, Caroline Jannière, Sébastien Jochmans, Mathieu Jozwiak, Pierre Kalfon, Antoine Kimmoun, Alexandre Lautrette, Jérémie Lemarié, Charlène Le Moal, Christophe Lenclud, Nicolas Lerolle, Olivier Leroy, Antoine Marchalot, Bruno Mégarbane, Armand Mekontso Dessap, Etienne de Montmollin, Frédéric Pène, Claire Pichereau, Gaëtan Plantefève, Sébastien Préau, Gabriel Preda, Nicolas de Prost, Jean-Pierre Quenot, Sylvie Ricome, Damien Roux, Bertrand Sauneuf, Matthieu Schmidt, Guillaume Schnell, Romain Sonneville, Jean-Marc Tadié, Yacine Tandjaoui, Martial Tchir, Nicolas Terzi, Xavier Valette, Lara Zafrani, Benjamin Zuber, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Henri Mondor, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Duchange, Nathalie
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Neisseria meningitidis, Critical Care and Intensive Care Medicine, medicine.disease_cause, Pneumococcal Infections, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Septic shock, Streptococcus pneumoniae, Research Letter, Medicine, Humans, Meningitis, Clinical phenotype, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Retrospective Studies, 0303 health sciences, Purpura fulminans, business.industry, RC86-88.9, 030208 emergency & critical care medicine, Retrospective cohort study, Medical emergencies. Critical care. Intensive care. First aid, medicine.disease, 3. Good health, Meningococcal Infections, [SDV] Life Sciences [q-bio], Phenotype, Treatment Outcome, business
Abstract: Auteurs : The HOPEFUL Study group; International audience; No abstract available
Published: 2021
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9. Impact of a qSOFA-based triage procedure on antibiotic timing in ED patients with sepsis: A prospective interventional study

Author: Julien Petit, Julien Passerieux, Olivier Maître, Charlotte Guérin, Clément Rozelle, Olivier Cordeau, Aline Cassonnet, Anne Malet, Thierry Boulain, François Barbier, Catherine Bellec, Victoria Carré, Cherki Elhadj, Nathalie Delorme, Pascal Ducroquet, Lida Ebrahim, Sylvain Gauffre, Olivier Giovannetti, Audrey Guérineau, Matthieu Lacroix, Maxence Leclerc, Rémi Leclerc, Florent Maillard, Olivier Maitre, Karim Mediouni, Nesrine Nabli, Camille Pelletier, Dan Popescu, Lavinia Stoican, Jacqueline Surville, and Edem Tsegan-Yawo
Subjects: Adult, Male, medicine.medical_specialty, Non-Randomized Controlled Trials as Topic, Organ Dysfunction Scores, medicine.drug_class, Antibiotics, Sensitivity and Specificity, Time-to-Treatment, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Clinical endpoint, Humans, In patient, Prospective Studies, Aged, Aged, 80 and over, business.industry, Septic shock, 030208 emergency & critical care medicine, General Medicine, Middle Aged, medicine.disease, Triage, Confidence interval, Anti-Bacterial Agents, Emergency Medicine, Female, Emergency Service, Hospital, business
Abstract: Background It has not been investigated whether the quick sepsis-related organ failure assessment score (qSOFA), a new bedside tool for early sepsis detection, may help accelerating antibiotic initiation in ED patients with sepsis. Methods In this prospective pre/post quasi-experimental single-ED study, patients admitted with a suspected bacterial infection were managed using standard triage procedures only (baseline) or in association with qSOFA (intervention, with prioritization of patients with a qSOFA ≥ 2). Results A total of 151/328 (46.0%) and 185/350 (52.8%) patients with definite bacterial infection met the criteria for sepsis in the baseline and intervention periods, respectively. The sensitivity and specificity of a qSOFA ≥ 2 for sepsis prediction were 17.3% (95% confidence interval [CI], 13.6%–21.7%) and 98.8% (95% CI, 97.0%–99.5%). Eleven (7.3%) and 28 (13.5%) patients with sepsis in the baseline and intervention periods received a first antibiotic dose within one hour following triage (primary endpoint, absolute difference 6.2%, 95% CI [−0.5%, 12.7%], P = 0.08). The proportions of patients with sepsis receiving a first antibiotic dose within three hours following triage (39.7% [50/151] versus 36.8% [68/185], absolute difference − 2.9%, 95% CI [−13.3%, 7.3%], P = 0.65), requiring ICU admission, or dying in the hospital were similar in both periods. The median ED occupation rate at triage was 104.3% (interquartile range [IQR], 80.4%–128.3%), with a median number of 157 ED visits per day (IQR, 147–169). Conclusions A qSOFA-based triage procedure does not improve antibiotic timing and outcomes in patients with sepsis admitted to a high-volume ED. The qSOFA value at triage was poorly sensitive for early sepsis detection. Trial registration ( ClinicalTrials.gov ): NCT03299894 .
Published: 2020
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10. Data-Driven Analyses of Longitudinal Hippocampal Imaging Trajectories: Discrimination and Biomarker Prediction of Change Classes

Author: Shannon M, Drouin, G Peggy, McFall, Olivier, Potvin, Pierre, Bellec, Mario, Masellis, Simon, Duchesne, and Roger A, Dixon
Subjects: Male, Alzheimer Disease, Humans, Female, Neuroimaging, Longitudinal Studies, Atrophy, Hippocampus, Biomarkers
Abstract: Hippocampal atrophy is a well-known biomarker of neurodegeneration, such as that observed in Alzheimer's disease (AD). Although distributions of hippocampal volume trajectories for asymptomatic individuals often reveal substantial heterogeneity, it is unclear whether interpretable trajectory classes can be objectively detected and used for prediction analyses.To detect and predict hippocampal trajectory classes in a computationally competitive context using established AD-related risk factors/biomarkers.We used biomarker/risk factor and longitudinal MRI data in asymptomatic adults from the AD Neuroimaging Initiative (n = 351; Mean = 75 years; 48.7% female). First, we applied latent class growth analyses to left (LHC) and right (RHC) hippocampal trajectory distributions to identify distinct classes. Second, using random forest analyses, we tested 38 multi-modal biomarkers/risk factors for their relative importance in discriminating the lower (potentially elevated atrophy risk) from the higher (potentially reduced risk) class.For both LHC and RHC trajectory distribution analyses, we observed three distinct trajectory classes. Three biomarkers/risk factors predicted membership in LHC and RHC lower classes: male sex, higher education, and lower plasma Aβ1-42. Four additional factors selectively predicted membership in the lower LHC class: lower plasma tau and Aβ1-40, higher depressive symptomology, and lower body mass index.Data-driven analyses of LHC and RHC trajectories detected three classes underlying the heterogeneous distributions. Machine learning analyses determined three common and four unique biomarkers/risk factors discriminating the higher and lower LHC/RHC classes. Our sequential analytic approach produced evidence that the dynamics of preclinical hippocampal trajectories can be predicted by AD-related biomarkers/risk factors from multiple modalities.
Published: 2022

11. Implementation of portable head CT imaging in patients with severe acute brain injury in a French ICU: a prospective before-after design pilot study

Author: Launey, Yoann, Mycinski, Clément, Eugène, François, Bellec, Elise, Serpolay, Hubert, Ferré, Jean-Christophe, Seguin, Philippe, and Gauvrit, Jean-Yves
Subjects: Intensive Care Units, Multidisciplinary, Brain Injuries, Humans, Pilot Projects, Prospective Studies, Tomography, X-Ray Computed
Abstract: Head-CT-scanning is a cornerstone procedure during the management of patients admitted for acute brain injury (ABI) in intensive care unit (ICU). But intrahospital transfer for these procedure is known to increase the rate of severe adverse events potentially worsening the brain injuries. Portable head-CT (pCTH) may facilitate pCTH performance in safer conditions for the patients avoiding transfer out of the ICU. To evaluate the safety and the time duration required to use a portable head CT (pCTH) scanner in the intensive care unit (ICU) in the French healthcare system in ICU patients admitted for acute brain injury, we prospectively included all ICU-patients admitted for severe ABI over a 2-year period following before–after design. As the main outcome, we compared the time required to perform a scan with pCTH to that with conventional head CT (cCTH) and reported adverse events and reactions. In total, forty-six patients were included and finally, 41 patients were analyzed (21 in the pCTH group and 20 in the cCTH group). The median (interquartile) time required to perform a scan with pCTH was 28 (23–48) minutes compared to 30 (25–36) minutes with cCTH (p = 0.825). The duration time required to perform a pCTH was similar to that with cCTH in an ICU of the French healthcare system without significant difference in adverse events reactions.
Published: 2022
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12. Cardiac radioablation for ventricular tachycardia: Which approach for incorporating cardiorespiratory motions into the planning target volume?

Author: Julien, Bellec, Louis, Rigal, Aurélien, Hervouin, Raphaël, Martins, Mathieu, Lederlin, Nicolas, Jaksic, Joël, Castelli, Karim, Benali, Renaud, de Crevoisier, Antoine, Simon, CRLCC Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), the French Federation of Cardiology (FFC)., Jonchère, Laurent, and CHU Saint-Etienne
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, Cardiac radioablation, Lung Neoplasms, Radiotherapy Planning, Computer-Assisted, Respiration, ITV, Biophysics, General Physics and Astronomy, Ventricular tachycardia, General Medicine, Motion, 4D CT, Tachycardia, Ventricular, cardiovascular system, Humans, Radiology, Nuclear Medicine and imaging, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Four-Dimensional Computed Tomography, Motion management
Abstract: International audience; PURPOSE: To evaluate different approaches for generating a cardiorespiratory ITV for cardiac radioablation. METHODS: Four patients with ventricular tachycardia were included in this study. For each patient, cardiac-gated and respiration-correlated 4D-CT scans were acquired. The cardiorespiratory ITV was defined using registrations of the cardiac and respiratory 4D-CT images. Five different approaches, which differed in the number of incorporated cardiac phases (1, 2, 10, or 1 with a fixed 3 mm margin (FM) expansion) and respiratory phases (2 or 10), were evaluated. For each approach, a VMAT treatment plan was simulated. Target coverage (TC) and spill were evaluated geometrically and dosimetrically for each approach. RESULTS: When employing one cardiac phase, the TC did not exceed 85%. Using the two extreme phases of the cardiac and respiratory cycles resulted in a geometric TC 89%, dosimetric TC > 92%) was only achieved when combining 10 respiratory phases with either 2 or 10 cardiac phases or a single cardiac phase with FM. The use of a single cardiac phase with FM combined with 10 respiratory phases lead to a mean geometric and dosimetric spill of 43% and 35%, respectively. CONCLUSION: For cardiac radioablation, the use of two extreme cardiac phases combined with 10 respiratory phases is a robust approach to generate a cardiorespiratory ITV. The use of a single cardiac phase with or without fixed margin expansion is not recommended based on this study.
Published: 2022
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13. Validation of Artificial Intelligence to Support the Automatic Coding of Patient Adverse Drug Reaction Reports, Using Nationwide Pharmacovigilance Data

Author: Guillaume L, Martin, Julien, Jouganous, Romain, Savidan, Axel, Bellec, Clément, Goehrs, Mehdi, Benkebil, Ghada, Miremont, Joëlle, Micallef, Francesco, Salvo, Antoine, Pariente, Louis, Létinier, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), 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), CHU Bordeaux [Bordeaux], Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Assistance Publique - Hôpitaux de Marseille (APHM), Agence Nationale de Sécurité du Médicament et des Produits de Santé, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pharmacology, Pharmacovigilance, COVID-19 Vaccines, Drug-Related Side Effects and Adverse Reactions, Artificial Intelligence, Adverse Drug Reaction Reporting Systems, COVID-19, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pharmacology (medical), Toxicology
Abstract: International audience; INTRODUCTION: Adverse drug reaction reports are usually manually assessed by pharmacovigilance experts to detect safety signals associated with drugs. With the recent extension of reporting to patients and the emergence of mass media-related sanitary crises, adverse drug reaction reports currently frequently overwhelm pharmacovigilance networks. Artificial intelligence could help support the work of pharmacovigilance experts during such crises, by automatically coding reports, allowing them to prioritise or accelerate their manual assessment. After a previous study showing first results, we developed and compared state-of-the-art machine learning models using a larger nationwide dataset, aiming to automatically pre-code patients' adverse drug reaction reports. OBJECTIVES: We aimed to determine the best artificial intelligence model identifying adverse drug reactions and assessing seriousness in patients reports from the French national pharmacovigilance web portal. METHODS: Reports coded by 27 Pharmacovigilance Centres between March 2017 and December 2020 were selected (n = 11,633). For each report, the Portable Document Format form containing free-text information filled by the patient, and the corresponding encodings of adverse event symptoms (in Medical Dictionary for Regulatory Activities Preferred Terms) and seriousness were obtained. This encoding by experts was used as the reference to train and evaluate models, which contained input data processing and machine-learning natural language processing to learn and predict encodings. We developed and compared different approaches for data processing and classifiers. Performance was evaluated using receiver operating characteristic area under the curve (AUC), F-measure, sensitivity, specificity and positive predictive value. We used data from 26 Pharmacovigilance Centres for training and internal validation. External validation was performed using data from the remaining Pharmacovigilance Centres during the same period. RESULTS: Internal validation: for adverse drug reaction identification, Term Frequency-Inverse Document Frequency (TF-IDF) + Light Gradient Boosted Machine (LGBM) achieved an AUC of 0.97 and an F-measure of 0.80. The Cross-lingual Language Model (XLM) [transformer] obtained an AUC of 0.97 and an F-measure of 0.78. For seriousness assessment, FastText + LGBM achieved an AUC of 0.85 and an F-measure of 0.63. CamemBERT (transformer) + Light Gradient Boosted Machine obtained an AUC of 0.84 and an F-measure of 0.63. External validation for both adverse drug reaction identification and seriousness assessment tasks yielded consistent and robust results. CONCLUSIONS: Our artificial intelligence models showed promising performance to automatically code patient adverse drug reaction reports, with very similar results across approaches. Our system has been deployed by national health authorities in France since January 2021 to facilitate pharmacovigilance of COVID-19 vaccines. Further studies will be needed to validate the performance of the tool in real-life settings.
Published: 2022
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14. Glyphosate-based herbicide exposure: effects on gill microbiota of rainbow trout (Oncorhynchus mykiss) and the aquatic bacterial ecosystem

Author: Laure Bellec, Jessy Le Du-Carré, Fabrice Almeras, Lucile Durand, Marie-Anne Cambon-Bonavita, Morgane Danion, and Thierry Morin
Subjects: Gills, Mammals, Ecology, Bacteria, co-occurrence network, Herbicides, Microbiota, Glycine, microbiome, gill, dysbiosis, chronic exposition, Applied Microbiology and Biotechnology, Microbiology, Gastrointestinal Microbiome, glyphosate, Oncorhynchus mykiss, RNA, Ribosomal, 16S, Animals, Humans
Abstract: The herbicide glyphosate has been widely used in the past 40 years, under the assumption that side effects were minimal. In recent years, its impact on microbial compositions and potential indirect effects on plant, animal and human health have been strongly suspected. Glyphosate and co-formulates have been detected in various water sources, but our understanding of their potential effects on aquatic animals is still in its infancy compared with mammals. In this study, we investigated the effect of chronic exposure to an environmentally relevant concentration of glyphosate on bacterial communities of rainbow trout (Oncorhynchus mykiss). Gills, gut contents and gut epithelia were then analyzed by metabarcoding targeting the 16S rRNA gene. Our results revealed that rainbow trout has its own bacterial communities that differ from their surrounding habitats and possess microbiomes specific to these three compartments. The glyphosate-based herbicide treatment significantly affected the gill microbiome, with a decrease in diversity. Glyphosate treatments disrupted microbial taxonomic composition and some bacteria seem to be sensitive to this environmental pollutant. Lastly, co-occurrence networks showed that microbial interactions in gills tended to decrease with chemical exposure. These results demonstrate that glyphosate could affect microbiota associated with aquaculture fish.
Published: 2022

15. Beyond advertising: New infrastructures for publishing integrated research objects

Author: Elizabeth DuPre, Chris Holdgraf, Agah Karakuzu, Loïc Tetrel, Pierre Bellec, Nikola Stikov, and Jean-Baptiste Poline
Subjects: Computer and Information Sciences, Atmospheric Science, Science and Technology Workforce, Biomedical Research, Science Policy, QH301-705.5, Social Sciences, Research and Analysis Methods, Careers in Research, Cellular and Molecular Neuroscience, Meteorology, Sociology, Advertising, Clouds, Genetics, Humans, Computer Networks, Biology (General), Molecular Biology, Ecology, Evolution, Behavior and Systematics, Data Curation, Scientific Publishing, Data Management, Publishing, Marketing, Internet, Ecology, Computational Biology, Research Assessment, Cloud Computing, Computing Methods, Communications, Professions, Computational Theory and Mathematics, Modeling and Simulation, Perspective, People and Places, Earth Sciences, Scientists, Population Groupings
Published: 2022

16. Correlation between radiation dose and myocardial remodeling after stereotactic radiation therapy for ventricular tachycardia: First assessment of dose-effect relationship in human

Author: Karim Benali, Louis Rigal, Antoine Simon, Julien Bellec, Pierre Jaïs, Tsukasa Kamakura, Clifford G. Robinson, Phillip Cuculich, Renaud De Crevoisier, Raphaël P. Martins, Jonchère, Laurent, CHU Saint-Etienne, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), CHU Bordeaux [Bordeaux], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), CHU Pontchaillou [Rennes], and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Anti-arrhythmic effects, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Myocardium, Radiation dose, Cardiac SBRT, Arrhythmias, Cardiac, Ventricular tachycardia, Arrhythmias, Radiation Dosage, Radiosurgery, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Radiation therapy, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Tachycardia, Ventricular, Humans, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, Anti-Arrhythmia Agents, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2022
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17. Nanoprecipitation of Biocompatible Poly(malic acid) Derivative, Its Ability to Encapsulate a Molecular Photothermal Agent and Photothermal Properties of the Resulting Nanoparticles

Author: Marian Gabriela Vargas Guerrero, Jean-Baptiste Pluta, Nathalie Bellec, Sandrine Cammas-Marion, Franck Camerel, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CNRS, University of Rennes 1 and 'Ligue contre le cancer CD 35, 45, 85' are gratefully acknowledged for their financial support., Jonchère, Laurent, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Photothermal Therapy, Polymers, poly(benzyl malate), Malates, metal-bis(dithiolene), Pharmaceutical Science, Organic chemistry, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Article, Analytical Chemistry, nanoprecipitation, photothermal, QD241-441, Drug Discovery, [CHIM] Chemical Sciences, Humans, [CHIM]Chemical Sciences, biocompatible nanoparticles, Physical and Theoretical Chemistry, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Chemistry (miscellaneous), Molecular Medicine, Nanoparticles, 0210 nano-technology
Abstract: International audience; Biocompatible nanoparticles (NPs) of hydrophobic poly(benzyl malate) (PMLABe) were prepared by nanoprecipitation. The influence of nanoprecipitation parameters (initial PMLABe, addition rate, organic solvent/water ratio and stirring speed) were studied to optimize the resulting formulations in terms of hydrodynamic diameter (Dh) and dispersity (PDI). PMLABe NPs with a Dh of 160 nm and a PDI of 0.11 were isolated using the optimized nanoprecipitation conditions. A hydrophobic near infra-red (NIR) photothermally active nickel-bis(dithiolene) complex (Ni8C12) was then encapsulated into PMLABe NPs using the optimized nanoprecipitation conditions. The size and encapsulation efficiency of the NPs were measured, revealing that up to 50 weight percent (wt%) of Ni8C12 complex can efficiently be encapsulated with a slight increase in Dh of the corresponding Ni8C12-loaded NPs. Moreover, we have shown that NP encapsulating Ni8C12 were stable under storage conditions (4 °C) for at least 10 days. Finally, the photothermal properties of Ni8C12-loaded NPs were evaluated and a high photothermal efficiency (62.7 ± 6.0%) waswas measured with NPs incorporating 10 wt% of the Ni8C12 complex.
Published: 2021
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18. Evolution Over Time of Ventilatory Management and Outcome of Patients With Neurologic Disease

Author: Tejerina E. E., Pelosi P., Robba C., Penuelas O., Muriel A., Barrios D., Frutos-Vivar F., Raymondos K., Du B., Thille A. W., Rios F., Gonzalez M., Del-Sorbo L., Marin M. D. C., Valle Pinheiro B., Soares M. A., Nin N., Maggiore S. M., Bersten A., Amin P., Cakar N., Young Suh G., Abroug F., Jibaja M., Matamis D., Ali Zeggwagh A., Sutherasan Y., Anzueto A., Esteban A, Fernando Ríos, Damian Violi, Marisol Rodríguez-Goñi, Roger Lamoglie, Fernando Villarejo, Norberto Tiribelli, Santiago Ilutovich, Matías Brizuela, Mariana Monllau, Fernando Saldarini, Silvina Borello, Alberto Marino, Mauricio Vinzio, Karina Bonasegla, Julián Hernández, María Belén Yapur, María Eugenia González, Sebastián E Mare, Judith Sagardía, Marco Bezzi, Cecilia Pereyra, Julian Strati, Daniel Vargas, Claudia Diaz, Pablo Gómez, Marcelo Palavecino, Graciela Elizabeth, Aguilera García, M Eugenia, Luis Pablo Cardonnet, Lisandro Betttini, Hernán Nuñez, Lucas Vallejo, Fernando Fernández, Jorge Arroyo, Daniel Duarte, Gerardo Filippa, Cayetano Galetti, Hernan Nunia, Fernando Lambert, Elisa Estenssoro, Marina Busico, Javier Horacio Álvarez, Alejandro Raimondi, Gustavo Badariotti, Martín Lugaro, Fernando Lipovestky, Alan Javier Zazu, Hugo Capponcelli, Patricia Vogl, Cristina Orlandi, Alejandro Gómez, Gustavo Jannello, Alejandro Risso, Leticia Rapetti, Guillermo Chiappero, Juan Domingo Fernández, Rodrigo E Gómez-Paz, Marcos Juan Zec, Pascual Valdez, Jorgelina Guyon, Ariel Chena, Sergio Lasdica, Martin Deheza, Schimdt Alejandra, Francisco Criado, Norma Beatriz Márquez, Pablo Desmery, José Luis Scapellato, Gonzalo Javier Ríos, Cristian Casabella, Jasmin Board, Andrew Davies, Andrew Bersten, Elisha Matheson, Amy Waters, John Santamaria, Jennifer Holmes, Cartan Costello, Manoj K Saxena, John Myburgh, Ellen Kinkel, Forbes McGain, Claire Cattigan, Allison Bone, Ian Seppelt, Leonie Weisbrodt, Cheryl Cuzner, Christopher MacIsaac, Deborah Barge, Tania Caf, Cameron Knott, Graeme Duke, Imogen Mitchell, Helen Rodgers, Rachel Whyte, Elisha Fulton, Alistair Nichol, Hergen Buscher, Priya Nair, Claire Reynolds, Simon J G Hockley, Ian Moore, Katherine Davidson, David Milliss, Raju Pusapati, Helen Wong, Jason Fletcher, Julie Smith, Paul Goldrick, Dianne Stephens, Jane Thomas, Anders Aneman, Sutrisno Gunawan, Tom Cowlam, George Lukas, Rick McAllister, Minka Springham, Joanne Sutton, Jeff Presneill, Tony Sutherland, Dianne Hill, Howard Connor, Jenny Dennett, Tim Coles, Freddy Sandy, Sando Chavarria, Marcelo Choque, Ronald Pairumani, Juan Guerra, Marco Antônio Soares Reis, José Carlos Versiani, Eduardo Fonseca Sad, Maria Aparecida Braga, Dinalva Aparecida Gomes, Fernando Antônio Botoni, Maurício Meireles Góes, Frederico Costa Val Barros, Rogério de Castro Pereira, Hugo Urbano, Valéria de Carvalho Magela, Aline Camile Yehia, Bruno Bonaccorsi Fernandino, Marco Antônio Ribeiro Leão, Rovílson Lara, Rubens Altair Amaral de Pádua, Janine Dias Alves, Aloísio Marques do Nascimento, Bruno do Valle Pinheiro, Carlos Alberto Studart Gomes, Marcelo Alcântara Holanda, Frederico Rodrigues Anselmo, Niall Ferguson, Neill Adhikari, Robert Fowler, Cheromi Sittambalam, Mehar-Un-Nisa Raja, Nicole Marinoff, Lauralyn McIntryre, Shawna Reddie, Laura Jones, Irene Watpool, Jeffrey Singh, Madison Dennis, Andrea Matte, Marc Lipkus, Ryan Albert, Andrew Steel, Emily Stern, Michael Miletin, Antonio Raso, Robyn Klages, Jan Friedrich, Orla Smith, Laura Wilson, Deborah Cook, Mark Bailey, Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, Samer Haj-Bakri, Dietrich Henzler, Lisa Julien, Luis Soto-Román, Juan Carlos Maurelia, César Antonio Maquilon, Luis Soto-Germani, Bin Du, Yan Kang, Bo Wang, Fachun Zhou, Fang Xu, Haibo Qiu, Yi Yang, Qingyuan Zhan, Bing Sun, Zhenjie Hu, Bin Yu, Xi Zhu, Yu Bai, Gang Li, Yi Li, Geng Zhang, Jianbiao Meng, Xiaobo Huang, Hong Pu, Daxing Yu, Chuanyun Qian, Wei Zhang, Yongjie Yin, Debiao Song, Yunxuan Yue, Zhengxuan Lv, Chengmin Yu, Qunmei Yao, Xue Wang, Yuan Xu, Wei He, Mian Chen, Zhihua Hu, Dongpo Jiang, Jian Huang, Wei Yu, Juanxian Gu, Yangong Chao, Zhixiang Li, Zhicheng Zhang, Wanxia Li, Zhenyang He, Jianguo Li, Chang Liu, Tiehe Qin, Shouhong Wang, Feng Li, Jun Jin, Jianhong Fu, Hongyang Xu, Hongyuan Lin, Jianying Guo, Yalin Liu, Jinghua Wang, Maoqin Li, Jiaqiong Li, Lei Chen, Qing Song, Liang Pan, Xianyao Wan, Jiuzhi Zhang, Weihai Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria Curro', Mirko Belliato, Chiara Verga, Marta Ferrari, Erika Mannelli, Valerio Mangani, Giorgio Tulli, Francesca Frigieri, Armando Pedulla', Monica Rocco, Giorgia Citterio, Di Russo, Gaetano Perchiazzi, Loredana Pitagora, Antonio Pesenti, Michela Bombino, Davide Chiumello, Federica Tallarini, Serena Azzari, Antonina Pigna, Ivano Aprile, Marco Adversi, Antonio Corcione, Marianna Esposito, Annunziata Mattei, Vito Marco Ranieri, Rosario Urbino, Ilaria Maria Mastromauro, Antonino Giarratano, Maurizio Raineri Santi, Ambrogio Sansone, Younsuck Koh, Moo Suk Park, Je Hyeong Kim, Kyung Chan Kim, Hye Sook Choi, Yun Seong Kim, Jin Hwa Lee, Myung-Goo Lee, Won-Yeon Lee, Jin Young An, Gee Young Suh, Ki-Suck Jung, Asisclo J Villagómez Ortiz, César Cruz Lozano, Zalatiel Maycotte Luna, José Francisco López Baca, José Elizalde, Guillermo Cueto Robledo, Mario Alonso Treviño Salinas, Ricardo Martinez Zubieta, Claudia Olvera-Guzman, Marco Montes De Oca, Silvio A Ñamendys-Silva, José Salvador Martínez Cano, Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, 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Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, Christopher Spradley, Dimple Tejwani, Sindhaghatta Venkatram, Gilda Diaz-Fuentes, Amber Monson, Anthony Saleh, Madhav Gudi, George Liziamma, Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, Crissie Despirito, Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, Steven Y Chang, Brian Sherman, Rosanna Del Giudice, John Oropell, Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, Matthew Kirchner, Erwin J Oei, Sebastian Circo, Nelson Medina, Mohammed Al-Jagbeer, V J Cardenas Jr, Smyth Smith, Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, Travis Parry, Craig A Piquette, Kerry Canady, Rahul Nanchal, Dana K Soetaert, Maria Del Mar Torres-Perez, Carlos Robles-Arias, William Rodriguez-Cintron, Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, Erin Braden, Geneva Tatem, Javier Hurtado, Alberto Deicas, Daniel Weiss, Marta Beron, Román Garrido, Cristina Santos, Mario Cancela, Raúl Lombardi, Pedro Alzugaray, Jorge Gerez, Silvia Mareque, Graciela Franca, Oscar Cluzet, Edgardo Nuñez, Julio Pontet, Sergio Cáceres, Elias Caragna, Alberto Soler, Frank Torres, Gastón Pittini, Gabriel D Empaire, Stevens Salva, Fernando Pérez, Clara Pacheco, Zoraida Parra, Ingrid Von der Osten, Luis Williams, José Salinas, Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, Nghuyen Ba Tuan, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Arts Assistenten IC (9), Intensive Care, MUMC+: MA Medische Staf IC (9), Tejerina E.E., Pelosi P., Robba C., Penuelas O., Muriel A., Barrios D., Frutos-Vivar F., Raymondos K., Du B., Thille A.W., Rios F., Gonzalez M., Del-Sorbo L., Marin M.D.C., Valle Pinheiro B., Soares M.A., Nin N., Maggiore S.M., Bersten A., Amin P., Cakar N., Young Suh G., Abroug F., Jibaja M., Matamis D., Ali Zeggwagh A., Sutherasan Y., Anzueto A., Esteban A, and Fernando Ríos, Damian Violi, Marisol Rodríguez-Goñi, Roger Lamoglie, Fernando Villarejo, Norberto Tiribelli, Santiago Ilutovich, Matías Brizuela, Mariana Monllau, Fernando Saldarini, Silvina Borello, Alberto Marino, Norberto Tiribelli, Mauricio Vinzio, Karina Bonasegla, Julián Hernández, María Belén Yapur, María Eugenia González, Sebastián E Mare, Judith Sagardía, Marco Bezzi, Cecilia Pereyra, Julian Strati, Daniel Vargas, Claudia Diaz, Pablo Gómez, Marcelo Palavecino, Graciela Elizabeth, Aguilera García, M Eugenia, Luis Pablo Cardonnet, Lisandro Betttini, Hernán Nuñez, Lucas Vallejo, Fernando Fernández, Jorge Arroyo, Daniel Duarte, Gerardo Filippa, Cayetano Galetti, Hernan Nunia, Fernando Lambert, Elisa Estenssoro, Marina Busico, Fernando Villarejo, Javier Horacio Álvarez, Alejandro Raimondi, Gustavo Badariotti, Martín Lugaro, Fernando Lipovestky, Alan Javier Zazu, Hugo Capponcelli, Patricia Vogl, Cristina Orlandi, Alejandro Gómez, Gustavo Jannello, Alejandro Risso, Leticia Rapetti, Guillermo Chiappero, Juan Domingo Fernández, Rodrigo E Gómez-Paz, Marcos Juan Zec, Pascual Valdez, Jorgelina 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Friedrich, Orla Smith, Laura Wilson, Deborah Cook, Mark Bailey, Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, Samer Haj-Bakri, Dietrich Henzler, Lisa Julien, Luis Soto-Román, Juan Carlos Maurelia, César Antonio Maquilon, Luis Soto-Germani, Bin Du, Yan Kang, Bo Wang, Fachun Zhou, Fang Xu, Haibo Qiu, Yi Yang, Qingyuan Zhan, Bing Sun, Zhenjie Hu, Bin Yu, Xi Zhu, Yu Bai, Gang Li, Yi Li, Geng Zhang, Jianbiao Meng, Xiaobo Huang, Hong Pu, Bin Du, Daxing Yu, Chuanyun Qian, Wei Zhang, Yongjie Yin, Debiao Song, Yunxuan Yue, Zhengxuan Lv, Chengmin Yu, Qunmei Yao, Xue Wang, Yuan Xu, Wei He, Mian Chen, Zhihua Hu, Dongpo Jiang, Jian Huang, Wei Yu, Juanxian Gu, Yangong Chao, Zhixiang Li, Zhicheng Zhang, Wanxia Li, Zhenyang He, Jianguo Li, Chang Liu, Tiehe Qin, Shouhong Wang, Feng Li, Jun Jin, Jianhong Fu, Hongyang Xu, Hongyuan Lin, Jianying Guo, Yalin Liu, Jinghua Wang, Maoqin Li, Jiaqiong Li, Lei Chen, Qing Song, Liang Pan, Xianyao Wan, Jiuzhi Zhang, Weihai Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria Curro', Mirko Belliato, Chiara Verga, Marta Ferrari, Erika Mannelli, Valerio Mangani, Giorgio Tulli, Francesca Frigieri, Armando Pedulla', Monica Rocco, Giorgia Citterio, Di Russo, Gaetano Perchiazzi, Loredana Pitagora, Antonio Pesenti, Michela Bombino, Davide Chiumello, Federica Tallarini, Serena Azzari, Antonina Pigna, Ivano Aprile, Marco Adversi, Antonio Corcione, Marianna Esposito, Annunziata Mattei, Vito Marco Ranieri, Rosario Urbino, Ilaria Maria Mastromauro, Antonino Giarratano, Maurizio Raineri Santi, Ambrogio Sansone, Younsuck Koh, Moo Suk Park, Je Hyeong Kim, Kyung Chan Kim, Hye Sook Choi, Yun Seong Kim, Jin Hwa Lee, Myung-Goo Lee, Won-Yeon Lee, Jin Young An, Gee Young Suh, Ki-Suck Jung, Asisclo J Villagómez Ortiz, César Cruz Lozano, Zalatiel Maycotte Luna, José Francisco López Baca, José Elizalde, Guillermo Cueto Robledo, Mario Alonso Treviño Salinas, Ricardo Martinez Zubieta, Claudia Olvera-Guzman, Marco Montes De Oca, Silvio A Ñamendys-Silva, José Salvador Martínez Cano, Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Jasmin Board, Andrew Davies, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, Vicente Arraez, Mar Gobernado, Susana Moradillo, Carolina Gímenez-Esparza, Teresa Sánchez de Dios, Carlos Marian Crespo, Cecilia Hermosa, Federico Gordo, Genis Carrasco, María Ángeles Alonso, Alejandro Algora, Raúl de Pablo, Sofía García, Ana Carolina Caballero, José María Montón, Teresa Mut, Eva Manteiga, Alejandro de la Serna, Ana Esther Trujillo, Rafael Blancas, Inmaculada Vallverdú, José Manuel Serrano, Miquel Ferrer, Juan Diego Jiménez, Carlos Gallego, Dolores Vila, Luis Marina, Valentín Parra, Juan Ramón Cortés, Chen Chin-Ming, Ai-Chin Cheng, Fekri Abroug, Besbes Mohamed, Imed Chouchene, Mounir Bouaziz, Stambouli Neji, Islem Ouanes, Ayed Samia, Nahit Cakar, Ismail Kati, Ali Aydım Altunkan, Remzi Iscimen, Zafer Dogan, Bilge Çetin, Tayfun Adanir, Sabriye Guvenc, Unase Büyükkoçak, Antonio Anzueto, Ashley Ellis, Gary Kinasewitz, Allan Walkey, Phil Alkana, Gregory A Schmidt, Susan Gillen, Kathleen Lilli, Jennifer Twombley, Denice Wells, Larry Welder, Alejandro Arroliga, Alfredo Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, Christopher Spradley, Dimple Tejwani, Sindhaghatta Venkatram, Gilda Diaz-Fuentes, Amber Monson, Anthony Saleh, Madhav Gudi, George Liziamma, Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, Crissie Despirito, Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, Steven Y Chang, Brian Sherman, Rosanna Del Giudice, John Oropell, Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, Matthew Kirchner, Ashley Ellis, Gary Kinasewitz, Erwin J Oei, Sebastian Circo, Nelson Medina, Mohammed Al-Jagbeer, V J Cardenas Jr, Smyth Smith, Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, Travis Parry, Craig A Piquette, Kerry Canady, Rahul Nanchal, Dana K Soetaert, Maria Del Mar Torres-Perez, Carlos Robles-Arias, William Rodriguez-Cintron, Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, Erin Braden, Geneva Tatem, Javier Hurtado, Alberto Deicas, Daniel Weiss, Marta Beron, Román Garrido, Cristina Santos, Mario Cancela, Raúl Lombardi, Pedro Alzugaray, Jorge Gerez, Silvia Mareque, Graciela Franca, Oscar Cluzet, Edgardo Nuñez, Julio Pontet, Sergio Cáceres, Elias Caragna, Alberto Soler, Frank Torres, Gastón Pittini, Gabriel D Empaire, Stevens Salva, Fernando Pérez, Clara Pacheco, Zoraida Parra, Ingrid Von der Osten, Luis Williams, José Salinas, Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, Nghuyen Ba Tuan
Subjects: Male, medicine.medical_treatment, pulmonary complications, RESPIRATORY-DISTRESS-SYNDROME, Critical Care and Intensive Care Medicine, CASE-FATALITY, 0302 clinical medicine, Risk Factors, Brain Injuries, Traumatic, Multicenter Studies as Topic, Hospital Mortality, Prospective Studies, Simplified Acute Physiology Score, Stroke, POPULATION, Age Factors, ANEURYSMAL SUBARACHNOID HEMORRHAGE, Middle Aged, Hemorrhagic Stroke, Intensive Care Units, Observational Studies as Topic, Anesthesia, Breathing, Female, medicine.symptom, Ventilator Weaning, Cohort study, Adult, TRAUMATIC BRAIN-INJURY, Pressure support ventilation, mechanical ventilation, prognosis factors, ACUTE LUNG INJURY, 03 medical and health sciences, medicine, Humans, Aged, Ischemic Stroke, Mechanical ventilation, Noninvasive Ventilation, business.industry, MORTALITY, neurologic patients, Organ dysfunction, 030208 emergency & critical care medicine, Length of Stay, medicine.disease, TRENDS, Respiration, Artificial, 030228 respiratory system, Etiology, NEUROCRITICAL CARE, Nervous System Diseases, Tracheotomy, business
Abstract: OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.
Published: 2021
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19. Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia

Author: Carrie E. Bearden, Guillaume Dumas, Aurélie Labbe, Pierre-Olivier Quirion, Stéphane Potvin, Thomas Bourgeron, Clara Moreau, Emmanuel Stip, Kumar Kuldeep, Guillaume Huguet, Amy Lin, Sebastian Urchs, Pierre Bellec, Stéphanie Grot, Alan C. Evans, Catherine Schramm, Sébastien Jacquemont, David Luck, Leila Kushan, Adrianna Mendrek, Pierre Orban, Elise Douard, Université de Montréal (UdeM), Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), McGill University = Université McGill [Montréal, Canada], Centre de Recherche de l’Institut Universitaire en Santé Mentale de Montréal (CRIUSMM), Jewish General Hospital, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), HEC Montréal (HEC Montréal), Semel Institute for Neuroscience and Human Behavior [Los Angeles, Ca], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Bishop’s University [Sherbrooke, Canada], United Arab Emirates University (UAEU), This research was supported by Calcul Quebec and Compute Canada, the Brain Canada Multi investigator research initiative (MIRI), funds from the Institute of Data Valorization (IVADO). S.J. is a recipient of a Canada Research Chair in neurodevelopmental disorders, and a chair from the Jeanne et Jean Louis Levesque Foundation. C.S. is supported by a fellowship from the Institute for Data Valorization. Kuldeep Kumar is supported by The Institute of Data Valorization (IVADO) Postdoctoral Fellowship program, through the Canada First Research Excellence Fund. This work was supported by a grant from the Brain Canada Multi-Investigator initiative (S.J.) and a grant from The Canadian Institutes of Health Research (S.J.). Dr P. Bellec is a fellow ('Chercheur boursier Junior 2') of the 'Fonds de recherche du Québec—Santé', Data preprocessing and analyses were supported in part by the Courtois foundation (P.B.)., Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), and University of California-University of California
Subjects: 0301 basic medicine, Male, Autism Spectrum Disorder, Autism, General Physics and Astronomy, MESH: Cognition, MESH: Magnetic Resonance Imaging, Cohort Studies, 0302 clinical medicine, Cognition, Gene Duplication, MESH: Child, 2.1 Biological and endogenous factors, Copy-number variation, Aetiology, Child, lcsh:Science, MESH: Cohort Studies, Pediatric, MESH: Autism Spectrum Disorder, Multidisciplinary, Developmental disorders, MESH: Gene Duplication, Brain, Autism spectrum disorders, Serious Mental Illness, Magnetic Resonance Imaging, Mental Health, Autism spectrum disorder, Schizophrenia, MESH: Young Adult, Child, Preschool, Attention Deficit Disorder (ADD), Female, MESH: DNA Copy Number Variations, Adult, Pediatric Research Initiative, MESH: Mutation, Adolescent, DNA Copy Number Variations, Intellectual and Developmental Disabilities (IDD), Science, Thalamus, MESH: Attention Deficit Disorder with Hyperactivity, Biology, Affect (psychology), behavioral disciplines and activities, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Young Adult, MESH: Brain, Clinical Research, Behavioral and Social Science, mental disorders, Genetics, medicine, Humans, Preschool, MESH: Adolescent, MESH: Humans, [SCCO.NEUR]Cognitive science/Neuroscience, Human Genome, MESH: Child, Preschool, Neurosciences, MESH: Adult, General Chemistry, medicine.disease, MESH: Male, MESH: Schizophrenia, Brain Disorders, 030104 developmental biology, Attention Deficit Disorder with Hyperactivity, MESH: Gene Deletion, Mutation, lcsh:Q, Neuroscience, Insula, MESH: Female, 030217 neurology & neurosurgery, Gene Deletion
Abstract: 16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms., The impact of neurodevelopmental mutations on functional brain connectivity is poorly understood. Here the authors identify thalamo-sensorimotor dysconnectivity dimensions shared across 16p11.2 and 22q11.2 copy number variants, autism and schizophrenia, but not ADHD.
Published: 2020
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20. Deep learning models of cognitive processes constrained by human brain connectomes

Author: Nicolas Farrugia, Yu Zhang, and Pierre Bellec
Subjects: Computer science, Brain activity and meditation, Health Informatics, Machine learning, computer.software_genre, Cognition, Deep Learning, medicine, Connectome, Humans, Radiology, Nuclear Medicine and imaging, Human Connectome Project, Radiological and Ultrasound Technology, business.industry, Deep learning, Brain, Human brain, Isolated brain, Computer Graphics and Computer-Aided Design, Magnetic Resonance Imaging, medicine.anatomical_structure, Graph (abstract data type), Computer Vision and Pattern Recognition, Artificial intelligence, Neural Networks, Computer, business, computer
Abstract: Decoding cognitive processes from recordings of brain activity has been an active topic in neuroscience research for decades. Traditional decoding studies focused on pattern classification in specific regions of interest and averaging brain activity over many trials. Recently, brain decoding with graph neural networks has been shown to scale at fine temporal resolution and on the full brain, achieving state-of-the-art performance on the human connectome project benchmark. The reason behind this success is likely the strong inductive connectome prior that enables the integration of distributed patterns of brain activity. Yet, the nature of such inductive bias is still poorly understood. In this work, we investigate the impact of the inclusion of multiple path lengths (through high-order graph convolution), the homogeneity of brain parcels (graph nodes), and the type of interactions (graph edges). We evaluate the decoding models on a large population of 1200 participants, under 21 different experimental conditions, acquired from the Human Connectome Project database. Our findings reveal that the optimal choice for large-scale cognitive decoding is to propagate neural dynamics within empirical functional connectomes and integrate brain dynamics using high-order graph convolutions. In this setting, the model exhibits high decoding accuracy and robustness against adversarial attacks on the graph architecture, including randomization in functional connectomes and lesions in targeted brain regions and networks. The trained model relies on biologically meaningful features for the prediction of cognitive states and generates task-specific graph representations resembling task-evoked activation maps. These results demonstrate that a full-brain integrative model is critical for the large-scale brain decoding. Our study establishes principles of how to effectively leverage human connectome constraints in deep graph neural networks, providing new avenues to study the neural substrates of human cognition at scale.
Published: 2021

21. Cardiac stereotactic ablative radiotherapy for refractory ventricular arrhythmias: A radical alternative? A narrative review of rationale and cardiological aspects

Author: Karim Benali, Antoine Da Costa, Louis Rigal, Renaud de Crevoisier, Vincent Galand, Raphaël P. Martins, Nefissa Hammache, Antoine Simon, N. Jaksic, J. Bellec, Pierre Caille, CHU Saint-Etienne, Centre Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CRLCC Eugène Marquis (CRLCC), CHU Pontchaillou [Rennes], Jonchère, Laurent, 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), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: medicine.medical_specialty, cardiac radioablation, medicine.medical_treatment, Catheter ablation, 030204 cardiovascular system & hematology, Radiosurgery, 03 medical and health sciences, cardiac SBRT, 0302 clinical medicine, Refractory, Ablative case, catheter ablation, medicine, Humans, Radiology, Nuclear Medicine and imaging, 030212 general & internal medicine, cardiovascular diseases, Cardiac disorders, Intensive care medicine, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Radiological and Ultrasound Technology, business.industry, ventricular arrhythmias, Arrhythmias, Cardiac, Heart, refractory ventricular tachycardia, 3. Good health, Radiation therapy, cardiovascular system, Narrative review, [SDV.IB]Life Sciences [q-bio]/Bioengineering, business, cardiac sterteotactic radiotherapy
Abstract: International audience; Ventricular arrhythmias are serious life-threatening cardiac disorders. Despite many technological improvements, a non-negligible number of patients present refractory ventricular tachycardias, resistant to a catheter ablation procedure, placing these patients in a therapeutic impasse. Recently, a cardiac stereotactic radioablative technique has been developed to treat patients with refractory ventricular arrhythmias, as a bail out strategy. This new therapeutic option historically brings together two fields of expertise unknown to each other, pointing out the necessity of an optimal partnership between cardiologists and radiation oncologists. As described in this narrative review, the understanding of cardiological aspects of the technique for radiation oncologists and treatment technical aspects comprehension for cardiologists represent a major challenge for the application and the future development of this promising treatment.
Published: 2021
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22. Structural and functional multi-platform MRI series of a single human volunteer over more than fifteen years

Author: Pierre Bellec, Arnaud Boré, Isabelle Chouinard, Christian Beaulieu, Maxime Descoteaux, Olivier Potvin, Jean-Christophe Houde, Farnaz Farokhian, AmanPreet Badhwar, Louis Dieumegarde, Pascal Tétreault, and Simon Duchesne
Subjects: Statistics and Probability, Data records, Adult, medicine.medical_specialty, Aging, Data Descriptor, Time Factors, Computer science, Brain imaging, Library and Information Sciences, 030218 nuclear medicine & medical imaging, Education, 03 medical and health sciences, 0302 clinical medicine, Magnetic resonance imaging, Neuroimaging, medicine, Humans, Medical physics, lcsh:Science, Multi platform, Volunteer, Data collection, Resting state fMRI, Middle Aged, Healthy Volunteers, 3. Good health, Computer Science Applications, Metadata, Time course, lcsh:Q, Statistics, Probability and Uncertainty, 030217 neurology & neurosurgery, Information Systems, Neuroscience
Abstract: We present MRI data from a single human volunteer consisting in over 599 multi-contrast MR images (T1-weighted, T2-weighted, proton density, fluid-attenuated inversion recovery, T2* gradient-echo, diffusion, susceptibility-weighted, arterial-spin labelled, and resting state BOLD functional connectivity imaging) acquired in over 73 sessions on 36 different scanners (13 models, three manufacturers) over the course of 15+ years (cf. Data records). Data included planned data collection acquired within the Consortium pour l’identification précoce de la maladie Alzheimer - Québec (CIMA-Q) and Canadian Consortium on Neurodegeneration in Aging (CCNA) studies, as well as opportunistic data collection from various protocols. These multiple within- and between-centre scans over a substantial time course of a single, cognitively healthy volunteer can be useful to answer a number of methodological questions of interest to the community., Measurement(s)brainTechnology Type(s)magnetic resonance imagingSample Characteristic - OrganismHomo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.9925037
Published: 2019
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23. Dissecting autism and schizophrenia through neuroimaging genomics

Author: Clara Moreau, Armin Raznahan, Sébastien Jacquemont, M. Mallar Chakravarty, Pierre Bellec, Paul M. Thompson, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Montréal (UdeM), Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), National Institute of Mental Health (NIMH), Centre de recherche de l'Institut universitaire de gériatrie de Montreal (CRIUGM), Douglas Mental Health University Institute, McGill University = Université McGill [Montréal, Canada], Laboratory of Neuro Imaging [Los Angeles] (LONI), University of California [Los Angeles] (UCLA), University of California-University of California, This research was supported by the Brain Canada Multi investigator research initiative (MIRI), funds from the Institute of Data Valorization (IVADO). S.J. is supported by the Canadian Institute of Health Research CIHR_400528 and the The Institute of Data Valorization (IVADO) through the Canada First Research Excellence Fund, Healthy Brains for Healthy Lives through the Canada First Research Excellence Fund. P.B. is a fellow (‘Chercheur boursier Junior 2’) of the ‘Fonds de recherche du Québec—Santé’., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and University of California (UC)-University of California (UC)
Subjects: 0301 basic medicine, Autism Spectrum Disorder, autism, Genomics, Disease, Biology, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, medicine, Humans, Copy-number variation, MESH: Neuroimaging, Medical diagnosis, Review Articles, MESH: Autism Spectrum Disorder, neuroimaging, MESH: Humans, AcademicSubjects/SCI01870, MESH: Genomics, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, MESH: Schizophrenia, schizophrenia, 030104 developmental biology, Autism spectrum disorder, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Autism, AcademicSubjects/MED00310, Neurology (clinical), Neuroscience, 030217 neurology & neurosurgery, copy number variants
Abstract: Neuroimaging genomic studies of autism spectrum disorder and schizophrenia have mainly adopted a ‘top-down’ approach, beginning with the behavioural diagnosis, and moving down to intermediate brain phenotypes and underlying genetic factors. Advances in imaging and genomics have been successfully applied to increasingly large case-control studies. As opposed to diagnostic-first approaches, the bottom-up strategy begins at the level of molecular factors enabling the study of mechanisms related to biological risk, irrespective of diagnoses or clinical manifestations. The latter strategy has emerged from questions raised by top-down studies: why are mutations and brain phenotypes over-represented in individuals with a psychiatric diagnosis? Are they related to core symptoms of the disease or to comorbidities? Why are mutations and brain phenotypes associated with several psychiatric diagnoses? Do they impact a single dimension contributing to all diagnoses? In this review, we aimed at summarizing imaging genomic findings in autism and schizophrenia as well as neuropsychiatric variants associated with these conditions. Top-down studies of autism and schizophrenia identified patterns of neuroimaging alterations with small effect-sizes and an extreme polygenic architecture. Genomic variants and neuroimaging patterns are shared across diagnostic categories suggesting pleiotropic mechanisms at the molecular and brain network levels. Although the field is gaining traction; characterizing increasingly reproducible results, it is unlikely that top-down approaches alone will be able to disentangle mechanisms involved in autism or schizophrenia. In stark contrast with top-down approaches, bottom-up studies showed that the effect-sizes of high-risk neuropsychiatric mutations are equally large for neuroimaging and behavioural traits. Low specificity has been perplexing with studies showing that broad classes of genomic variants affect a similar range of behavioural and cognitive dimensions, which may be consistent with the highly polygenic architecture of psychiatric conditions. The surprisingly discordant effect sizes observed between genetic and diagnostic first approaches underscore the necessity to decompose the heterogeneity hindering case-control studies in idiopathic conditions. We propose a systematic investigation across a broad spectrum of neuropsychiatric variants to identify putative latent dimensions underlying idiopathic conditions. Gene expression data on temporal, spatial and cell type organization in the brain have also considerable potential for parsing the mechanisms contributing to these dimensions’ phenotypes. While large neuroimaging genomic datasets are now available in unselected populations, there is an urgent need for data on individuals with a range of psychiatric symptoms and high-risk genomic variants. Such efforts together with more standardized methods will improve mechanistically informed predictive modelling for diagnosis and clinical outcomes., Moreau et al. review advances and roadblocks in neuroimaging genomic studies of autism and schizophrenia. They propose combining diagnosis-first (‘top-down’) and gene-first (‘bottom-up’) strategies to parse out the contribution of genes and biological processes to dimensions involved in these psychiatric conditions.
Published: 2021
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24. Integrons, a predictive biomarker for antibiotic resistance in acute sepsis: the IRIS study

Author: Emmanuelle Mercier, Elie Guichard, Delphine Chainier, Olivier Barraud, Marie-Cécile Ploy, Bruno Giraudeau, Armelle Mathonnet, Loïc Chimot, Arnaud Desachy, Bruno François, Frédéric Bellec, Jean-Pierre Frat, D. Postil, and Jean-Claude Lacherade
Subjects: Microbiology (medical), Adult, medicine.medical_specialty, medicine.drug_class, Urinary system, Antibiotics, Cephalosporin, Urine, Integrons, Sepsis, Antibiotic resistance, Internal medicine, medicine, Humans, Pharmacology (medical), Predictive biomarker, Pharmacology, biology, business.industry, Drug Resistance, Microbial, medicine.disease, biology.organism_classification, Anti-Bacterial Agents, Infectious Diseases, Cross-Sectional Studies, business, Bacteria, Biomarkers
Abstract: Background Considering the increase in MDR Gram-negative bacteria (GNB), the choice of empirical antibiotic therapy is challenging. In parallel, use of broad-spectrum antibiotics should be avoided to decrease antibiotic selection pressure. Accordingly, clinicians need rapid diagnostic tools to narrow antibiotic therapy. Class 1–3 integrons, identified by intI1–3 genes, are genetic elements that play a major role in antibiotic resistance in GNB. Objectives The objective of the IRIS study was to evaluate the negative and positive predictive values (NPVs and PPVs, respectively) of intI1–3 as markers of antibiotic resistance. Methods The IRIS study was an observational cross-sectional multicentre study that enrolled adult subjects with suspected urinary tract or intra-abdominal infections. intI1–3 were detected directly from routinely collected biological samples (blood, urine or intra-abdominal fluid) using real-time PCR. A patient was considered ‘MDR positive’ if at least one GNB, expressing acquired resistance to at least two antibiotic families among β-lactams, aminoglycosides, fluoroquinolones and/or co-trimoxazole, was isolated from at least one biological sample. Results Over a 2 year period, 513 subjects were enrolled and 409 had GNB documentation, mostly Enterobacterales. intI1 and/or intI2 were detected in 31.8% of patients and 24.4% of patients were considered ‘MDR positive’. The NPV of intI1 and/or intI2 as a marker of acquired antibiotic resistances was estimated at 92.8% (89.1%–95.5%). The NPVs for first-line antibiotics were all above 92%, notably >96% for resistance to third-generation cephalosporins. Conclusions The IRIS study strongly suggests that the absence of intI1 and intI2 in biological samples from patients with GNB-related infections is predictive of the absence of acquired resistances.
Published: 2021

25. RAL GTPases mediate EGFR-driven intestinal stem cell proliferation and tumourigenesis

Author: Owen J. Sansom, Jim C. Norman, Emma Sandilands, Máté Nászai, Julia B. Cordero, Joel Johansson, Yachuan Yu, Álvaro Román-Fernández, Andrew D. Campbell, David M. Bryant, and Karen Bellec
Subjects: 0301 basic medicine, MAPK/ERK pathway, Lung Neoplasms, Mouse, GTPase, EGFR signalling, Animals, Genetically Modified, 0302 clinical medicine, Drosophila Proteins, ral proteins, Intestinal Mucosa, Biology (General), Tissue homeostasis, Cancer Biology, D. melanogaster, General Neuroscience, intestinal regeneration, Wnt signaling pathway, General Medicine, drosophila, Stem Cells and Regenerative Medicine, RALA, Endocytosis, Cell biology, ErbB Receptors, Cell Transformation, Neoplastic, Drosophila melanogaster, 030220 oncology & carcinogenesis, tumourigenesis, Medicine, Female, Stem cell, Mitogen-Activated Protein Kinases, Research Article, Human, Signal Transduction, animal structures, QH301-705.5, Science, Breast Neoplasms, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, stem cells, Cell Line, Tumor, Animals, Humans, Progenitor cell, Mammary Glands, Human, Receptors, Invertebrate Peptide, Cell Proliferation, Monomeric GTP-Binding Proteins, Hyperplasia, General Immunology and Microbiology, Regeneration (biology), Mice, Inbred C57BL, 030104 developmental biology, ral GTP-Binding Proteins
Abstract: RAS-like (RAL) GTPases function in Wnt signalling-dependent intestinal stem cell proliferation and regeneration. Whether RAL proteins work as canonical RAS effectors in the intestine and the mechanisms of how they contribute to tumourigenesis remain unclear. Here, we show that RAL GTPases are necessary and sufficient to activate EGFR/MAPK signalling in the intestine, via induction of EGFR internalisation. Knocking downDrosophila RalAfrom intestinal stem and progenitor cells leads to increased levels of plasma membrane-associated EGFR and decreased MAPK pathway activation. Importantly, in addition to influencing stem cell proliferation during damage-induced intestinal regeneration, this role of RAL GTPases impacts on EGFR-dependent tumourigenic growth in the intestine and in human mammary epithelium. However, the effect of oncogenic RAS in the intestine is independent from RAL function. Altogether, our results reveal previously unrecognised cellular and molecular contexts where RAL GTPases become essential mediators of adult tissue homeostasis and malignant transformation.
Published: 2021

26. Functional annotation of human cognitive states using deep graph convolution

Author: Yu Zhang, Bertrand Thirion, Loïc Tetrel, Pierre Bellec, Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Department of Psychology , Université de Montréal Centre de recherche de l’Institut universitaire de gériatrie de Montréal, Centre de recherche de l'Institut universitaire de gériatrie de Montreal (CRIUGM), Université de Montréal (UdeM), Modelling brain structure, function and variability based on high-field MRI data (PARIETAL), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-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)-Inria Saclay - Ile de France, and Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)
Subjects: Elementary cognitive task, Computer science, Brain activity and meditation, Cognitive Neuroscience, Graph convolutional network, Neurosciences. Biological psychiatry. Neuropsychiatry, Convolutional neural network, 050105 experimental psychology, 03 medical and health sciences, Cognition, 0302 clinical medicine, Connectome, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, 0501 psychology and cognitive sciences, Set (psychology), Human Connectome Project, business.industry, Deep learning, fMRI, 05 social sciences, Brain decoding, Brain, Pattern recognition, Human brain, Magnetic Resonance Imaging, medicine.anatomical_structure, Cognitive states, Neurology, Graph (abstract data type), Artificial intelligence, Nerve Net, business, 030217 neurology & neurosurgery, Brain dynamics, RC321-571, MRI
Abstract: A key goal in neuroscience is to understand brain mechanisms of cognitive functions. An emerging approach is “brain decoding”, which consists of inferring a set of experimental conditions performed by a participant, using pattern classification of brain activity. Few works so far have attempted to train a brain decoding model that would generalize across many different cognitive tasks drawn from multiple cognitive domains. To tackle this problem, we proposed a domain-general brain decoder that automatically learns the spatiotemporal dynamics of brain response within a short time window using a deep learning approach. By leveraging our prior knowledge on network organization of human brain cognition, we constructed deep graph convolutional neural networks to annotate cognitive states by first mapping the task-evoked fMRI response onto a brain graph, propagating brain dynamics among interconnected brain regions and functional networks, and generating state-specific representations of recorded brain activity. We evaluated the decoding model on a large population of 1200 participants, under 21 different experimental conditions spanning 6 different cognitive domains, acquired from the Human Connectome Project task-fMRI database. Using a 10s window of fMRI response, the 21 cognitive states were identified with a test accuracy of 89% (chance level 4.8%). Performance remained good when using a 6s window (82%). It was even feasible to decode cognitive states from a single fMRI volume (720ms), with the performance following the shape of the hemodynamic response. Moreover, a saliency map analysis demonstrated that the high decoding performance was driven by the response of biologically meaningful brain regions. Together, we provide an automated tool to annotate human brain activity with fine temporal resolution and fine cognitive granularity. Our model shows potential applications as a reference model for domain adaptation, possibly making contributions in a variety of domains, including neurological and psychiatric disorders.
Published: 2021
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27. Corticosteroids in patients hospitalized for COVID-19 pneumonia who require oxygen: observational comparative study using routine care data

Author: Viet-Thi Tran, Matthieu Mahévas, Firouze Bani-Sadr, Olivier Robineau, Thomas Perpoint, Elodie Perrodeau, Laure Gallay, Philippe Ravaud, François Goehringer, François-Xavier Lescure, Sophie Ismaël, Cédric Laouénan, Jennifer Soulier, Oriane Puéchal, Eric D’Ortenzio, Yazdan Yazdanpanah, Laurence Maulin, Stéphanie Martinez, Diane Sanderink, Pascale Fialaire, Séverine Ansart, Lucas Perez, Anne - Laure Destrem, Chloé Moulin, Pascal Gicquel, Frédéric Rivière, Martin Martinot, Mahsa Mohseni Zadeh, Tomasz Chroboczek, Thibaut Challan Belval, Lionel Piroth, Thibault Sixt, Florian Moretto, André Cabié, Jérémie Pasquier, Ornella Cabras, Marine Morrier, Jean Reuter, Thomas Henin, Pierre Braquet, Helene Desmurs-Clavel, Arnaud Hot, Boris Bienvenu, Belkacem Asselate, Nicolas Vignier, Steve Nguala, Sylvain Diamantis, Guillemette Frémont, Pierre Louis Nivose, Mathilde Thiébaut, Benjamin Lefevre, Hélène Auge, Paul le Turnier, Naila Benkalfate, Olivier Grossi, Samuel Pineau, Elisa Demonchy, Julie Merindol, Claire Durand, Nathalie Tieulié, Viviane Queyrel, Didier Laureillard, Paul Loubet, Ségolène Greffe, Nathalie Dournon, Youssouf Mohamed Kassim, Cyrille Gourjault, Alexandre Lahens, Paul Legendre, Caroline Morbieu, Matthieu Mahevas, Giovanna Melica, Jean-Daniel Levièvre, Frédéric Schlemmer, Simone Tunesi, Claire Leblanc, Anne Bourgarit-Durand, Alexandre Bleibtreu, Gianpiero Tebano, Jérôme Pacanowski, Jean-Benoit Zabbe, Mathilde Devaux, Laurent Bellec, Marine Gosset-Woimant, Céleste Lambert, Maxime Hentzien, Amélie Servettaz, Kevin Alexandre, Manuel Etienne, Romain Leguillon, Marion Dollat, Rémi Lefrancois, Anne Pouvaret, Yvon Ruch, Yannick Dieudonné, Guillaume Martin-Blondel, Xavier Boumaza, Margaux Lafaurie, Macha Tetart, Adrien Lemaignen, Nicole Ferreira-Maldent, Amélie Duréault, Marie Gousseff, Claire Chantepie, Francesca Bisio, Fanny Pommeret, Emeline Colomba Blamble, and Claire Ara Somohano
Subjects: 0301 basic medicine, Adult, Male, Microbiology (medical), medicine.medical_specialty, Adolescent, medicine.medical_treatment, Therapeutic evaluation, 030106 microbiology, Population, Severity of Illness Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Prednisone, Adrenal Cortex Hormones, Internal medicine, Observational study, Severity of illness, Medicine, Intubation, Corticosteroids, Humans, 030212 general & internal medicine, education, Aged, Mechanical ventilation, Aged, 80 and over, education.field_of_study, business.industry, Mortality rate, Hazard ratio, Oxygen Inhalation Therapy, COVID-19, General Medicine, Middle Aged, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Pneumonia, C-Reactive Protein, Infectious Diseases, Original Article, Female, business, medicine.drug
Abstract: OBJECTIVE: To assess the effectiveness of corticosteroids on outcomes of patients with COVID-19 pneumonia requiring oxygen without mechanical ventilation. METHODS: We used routine care data from 51 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids at 0.8 mg/kg/day eq. prednisone (CTC group) versus standard of care (no-CTC group) among adults 18 to 80 years old with confirmed COVID-19 pneumonia requiring oxygen without mechanical ventilation. The primary outcome was intubation or death by day 28. In our main analysis, characteristics of patients at baseline (i.e., time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. RESULTS: Among the 891 patients included in the analysis, 203 were assigned to the CTC group. Use of corticosteroids was not significantly associated with risk of intubation or death by day 28 (weighted hazard ratio [wHR] 0.92, 95% CI 0.61 to 1.39) or cumulative death rate (wHR 1.03, 95% CI 0.54 to 1.98). However, use of corticosteroids was associated with reduced risk of intubation or death by day 28 in the prespecified subgroups of patients requiring oxygen ≥ 3 L/min (wHR 0.50, 95% CI 0.30 to 0.85) or C-reactive protein level ≥ 100 mg/L (wHR 0.44, 95%CI 0.23 to 0.85). Number of hyperglycaemia events was higher for patients with than without corticosteroids, but number of infections was similar. CONCLUSIONS: We found no association between the use of corticosteroids and intubation or death in the broad population of patients 18 to 80 years old with COVID-19 hospitalized in non-intensive care unit settings. However, the treatment was associated with reduced risk of intubation or death for patients with ≥ 3 L/min oxygen or C-reactive protein level ≥ 100 mg/L at baseline. Further research need to confirm the right timing of corticosteroids for patients with COVID-19 requiring oxygen only.
Published: 2021
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28. Unravelling the Neural Basis of Spatial Delusions After Stroke

Author: Thiebaut De Schotten, Michel, Noble, Stephanie, Heuer, Katja, Bottenhorn, Katherine, Bilgin, Isil, Yang, Yu-Fang, Huntenburg, Julia, Bayer, Johanna M.M., Bethlehem, Richard A.I., Rhoads, Shawn, Vogelbacher, Christoph, Borghesani, Valentina, Levitis, Elizabeth, Wang, Hao-Ting, Van Den Bossche, Sofie, Kobeleva, Xenia, Legarreta, Jon Haitz, Guay, Samuel, Atay, Selim Melvin, Varoquaux, Gael, Huijser, Dorien, Sandström, Malin, Herholz, Peer, Nastase, Samuel, Badhwar, AmanPreet, Dumas, Guillaume, Schwab, Simon, Moia, Stefano, Dayan, Michael, Bassil, Yasmine, Brooks, Paula, Mancini, Matteo, Shine, James, O’Connor, David, Xie, Xihe, Poggiali, Davide, Friedrich, Patrick, Heinsfeld, Anibal, Riedl, Lydia, Toro, Roberto, Caballero-Gaudes, César, Eklund, Anders, Garner, Kelly, Nolan, Christopher, Demeter, Damion, Barrios, Fernando, Merchant, Junaid, McDevitt, Elizabeth, Oostenveld, Robert, Craddock, R. Cameron, Rokem, Ariel, Doyle, Andrew, Ghosh, Satrajit, Nikolaidis, Aki, Stanley, Olivia, Uruñuela, Eneko, Anousheh, Nasim, Arnatkeviciute, Aurina, Auzias, Guillaume, Bachar, Dipankar, Bannier, Elise, Basanisi, Ruggero, Basavaraj, Arshitha, Bedini, Marco, Bellec, Pierre, Benn, R. Austin, Berluti, Kathryn, Bollmann, Steffen, Bollmann, Saskia, Bradley, Claire, Brown, Jesse, Buchweitz, Augusto, Callahan, Patrick, Chan, Micaela, Chandio, Bramsh, Cheng, Theresa, Chopra, Sidhant, Chung, Ai Wern, Close, Thomas, Combrisson, Etienne, Cona, Giorgia, Constable, R. Todd, Cury, Claire, Dadi, Kamalaker, Damasceno, Pablo, Das, Samir, De Vico Fallani, Fabrizio, DeStasio, Krista, Dickie, Erin, Dorfschmidt, Lena, Duff, Eugene, Dupre, Elizabeth, Dziura, Sarah, Esper, Nathalia, Esteban, Oscar, Fadnavis, Shreyas, Flandin, Guillaume, Flannery, Jessica, Flournoy, John, Franco, Alexandre, Ganesan, Saampras, Gao, Siyuan, García Alanis, José, Garyfallidis, Eleftherios, Glatard, Tristan, Glerean, Enrico, Gonzalez-Castillo, Javier, Gould van Praag, Cassandra, Greene, Abigail, Gupta, Geetika, Hahn, Catherine Alice, Halchenko, Yaroslav, Handwerker, Daniel, Hartmann, Thomas, Hayot-Sasson, Valérie, Heunis, Stephan, Hoffstaedter, Felix, Hohmann, Daniela, Horien, Corey, Ioanas, Horea-Ioan, Iordan, Alexandru, Jiang, Chao, Joseph, Michael, Kai, Jason, Karakuzu, Agah, KENNEDY, David, Keshavan, Anisha, Khan, Ali, Kiar, Gregory, Klink, P. Christiaan, Koppelmans, Vincent, Koudoro, Serge, Laird, Angela, Langs, Georg, Laws, Marissa, Licandro, Roxane, Liew, Sook-Lei, Lipic, Tomislav, Litinas, Krisanne, Lurie, Daniel, Lussier, Désirée, Madan, Christopher, Mais, Lea-Theresa, Mansour L, Sina, Manzano-Patron, J.P., Maoutsa, Dimitra, Marcon, Matheus, Margulies, Daniel, Marinato, Giorgio, Marinazzo, Daniele, Markiewicz, Christopher, Meneguzzi, Felipe, Meunier, David, Milham, Michael, Mills, Kathryn, Momi, Davide, Moreau, Clara, Motala, Aysha, Moxon-Emre, Iska, Nichols, Thomas, Nielson, Dylan, Nilsonne, Gustav, Novello, Lisa, O’Brien, Caroline, Olafson, Emily, Oliver, Lindsay, Onofrey, John, Orchard, Edwina, Oudyk, Kendra, Park, Patrick, Parsapoor, Mahboobeh, Pasquini, Lorenzo, Peltier, Scott, Pernet, Cyril, Pienaar, Rudolph, Pinheiro-Chagas, Pedro, Poline, Jean-Baptiste, Qiu, Anqi, Quendera, Tiago, Rice, Laura, Rocha-Hidalgo, Joscelin, Rutherford, Saige, Scharinger, Mathias, Scheinost, Dustin, Shariq, Deena, Shaw, Thomas, Siless, Viviana, Simmonite, Molly, Sirmpilatze, Nikoloz, Spence, Hayli, Sprenger, Julia, Stajduhar, Andrija, Szinte, Martin, Takerkart, Sylvain, Tam, Angela, Tejavibulya, Link, Thome, Ina, Tomaz da Silva, Laura, Traut, Nicolas, Uddin, Lucina, Vallesi, Antonino, VanMeter, John, Vijayakumar, Nandita, di Oleggio Castello, Matteo Visconti, Vohryzek, Jakub, Vukojević, Jakša, Whitaker, Kirstie Jane, Whitmore, Lucy, Wideman, Steve, Witt, Suzanne, Xie, Hua, Xu, Ting, Yan, Chao-Gan, Yeh, Fang-Cheng, Yeo, B.T. Thomas, Zuo, Xi-Nian, Alves, Pedro, Fonseca, Ana, Silva, Daniela, Andrade, Matilde, Pinho‐e‐Melo, Teresa, Martins, Isabel, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), and Repositório da Universidade de Lisboa
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Support Vector Machine, Reduplicative paramnesia, Audiology, Logistic regression, Delusions, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Neuroimaging, Image Interpretation, Computer-Assisted, medicine, Humans, Functional disconnection, Prospective Studies, Stroke, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Brain Mapping, business.industry, Anosognosia, Confounding, 16. Peace & justice, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, Neurology, Case-Control Studies, Female, Neurology (clinical), Disconnection, business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery
Abstract: © 2021 American Neurological Association, Objective: Knowing explicitly where we are is an interpretation of our spatial representations. Reduplicative paramnesia is a disrupting syndrome in which patients present a firm belief of spatial mislocation. Here, we studied the largest sample of patients with delusional misidentifications of space (i.e. reduplicative paramnesia) after stroke to shed light on their neurobiology. Methods: In a prospective, cumulative, case-control study, we screened 400 patients with acute right-hemispheric stroke. We included 64 cases and 233 controls. First, lesions were delimited and normalized. Then, we computed structural and functional disconnection maps using methods of lesion-track and network-mapping. The maps were compared, controlling for confounders. Second, we built a multivariate logistic model including clinical, behavioural and neuroimaging data. Finally, we performed a nested cross-validation of the model with a support-vector machine analysis. Results: The most frequent misidentification subtype was confabulatory mislocation (56%), followed by place reduplication (19%) and chimeric assimilation (13%). Our results indicate that structural disconnection is the strongest predictor of the syndrome and included two distinct streams, connecting right fronto-thalamic and right occipito-temporal structures. In the multivariate model, the independent predictors of reduplicative paramnesia were the structural disconnection map, lesion sparing of right dorsal fronto-parietal regions, age and anosognosia. Good discrimination accuracy was demonstrated (area under the curve = 0.80[0.75-0.85]). Interpretation: Our results localize the anatomical circuits that may have a role in the abnormal spatial-emotional binding and in the defective updating of spatial representations underlying reduplicative paramnesia. This novel data may contribute to better understand the pathophysiology of delusional syndromes after stroke., The authors acknowledge our colleagues from the Department of Neurology and from the Language Research Laboratory for their contribution to patient screening. This work received funding from “PRÉMIO JOÃO LOBO ANTUNES” – SCML (grant to P.N.A.), from “Bolsa de Investigação em Doenças Vasculares Cerebrais 2017”–SPAVC (grant to P.N.A.) and from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 818521 to M.T.S.).“Data were provided in part bythe Human Connectome Project, WU-Minn Consortium(Principal Investigators: David Van Essen and KamilUgurbil; 1U54 MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University.
Published: 2021
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29. Assessment of emergency physicians' performance in identifying shockable rhythm in out-of-hospital cardiac arrest: an observational simulation study

Author: Clément, Derkenne, Daniel, Jost, Florian, Roquet, Pascal, Corpet, Benoit, Frattini, Romain, Kedzierewicz, Guillaume, Bellec, Benjamin, Rajon, Marianne, Fernandez, Thomas, Loeb, Emmanuel, Pierantoni, Antoine, Lamblin, and Bertrand, Prunet
Subjects: Emergency Medical Services, Physicians, Ventricular Fibrillation, Emergency Medicine, Electric Countershock, Humans, Arrhythmias, Cardiac, Shock, General Medicine, Critical Care and Intensive Care Medicine, Cardiopulmonary Resuscitation, Out-of-Hospital Cardiac Arrest, Defibrillators
Abstract: BackgroundEmergency physicians can use a manual or an automated defibrillator to provide defibrillation of patients who had out-of-hospital cardiac arrest (OHCA). Performance of emergency physicians in identifying shockable rhythm with a manual defibrillator has been poorly explored whereas that of automated defibrillators is well known (sensitivity 0.91–1.00, specificity 0.96–0.99). We conducted this study to estimate the sensitivity/specificity and speed of shock/no-shock decision-making by prehospital emergency physicians for shockable or non-shockable rhythm, and their preference for manual versus automated defibrillation.MethodsWe developed a web application that simulates a manual defibrillator (https://simul-shock.firebaseapp.com/). In 2019, all (262) emergency physicians of six French emergency medical services were invited to participate in a study in which 60 ECG rhythms from real OHCA recordings were successively presented to the physicians for determination of whether they would or would not administer a shock. Time to decision was recorded. Answers were compared with a gold standard (concordant answers of three experts). We report sensitivity for shockable rhythms (decision to shock) and specificity for non-shockable rhythms (decision not to shock). Physicians were also asked whether they preferred manual or automated defibrillation.ResultsAmong 215 respondents, we were able to analyse results for 190 physicians. 57% of emergency physicians preferred manual defibrillation. Median (IQR) sensitivity for a shock delivery for shockable rhythm was 0.91 (0.81–1.00); median specificity for no-shock delivery for non-shockable rhythms was 0.91 (0.80–0.96). More precisely, sensitivities for shock delivery for ventricular tachycardia (VT) and coarse ventricular fibrillation (VF) were both 1.0 (1.0–1.0); sensitivity for fine VF was 0.6 (0.2–1). Specificity for not shocking a pulseless electrical activity (PEA) was 0.83 (0.72–0.86), and for asystole, specificity was 0.93 (0.86–1). Median speed of decision-making (in seconds) were: VT 2.0 (1.6–2.7), coarse VF 2.1 (1.7–2.9), asystole 2.4 (1.8–3.5), PEA 2.8 (2.0–4.2) and fine VF 2.8 (2.1–4.3).ConclusionsGlobal sensitivity and specificity were comparable with published automated external defibrillator studies. Shockable rhythms with the best clinical prognoses (VT and coarse VF) were very rapidly recognised with very good sensitivity. The decision-making for fine VF or asystole and PEA was less accurate.
Published: 2021

30. Cerebral functional networks during sleep in young and older individuals

Author: Pierre Maquet, Véronique Daneault, Nadia Gosselin, Jonathan P. Godbout, Julie Carrier, Philippe Pouliot, Christian Dansereau, Philip Dickinson, Julien Doyon, Pierre Orban, Gilles Vandewalle, Pierre Bellec, Jean-Marc Lina, and Nicolas Martin
Subjects: 0301 basic medicine, Adult, Male, Aging, Science, Thalamus, Electroencephalography, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Neuroplasticity, Basal ganglia, Medicine, Humans, Disengagement theory, Wakefulness, Aged, Multidisciplinary, medicine.diagnostic_test, business.industry, Neural ageing, Middle Aged, Sleep in non-human animals, 030104 developmental biology, Female, Sleep Stages, Circadian rhythms and sleep, Nerve Net, business, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery
Abstract: Even though sleep modification is a hallmark of the aging process, age-related changes in functional connectivity using functional Magnetic Resonance Imaging (fMRI) during sleep, remain unknown. Here, we combined electroencephalography and fMRI to examine functional connectivity differences between wakefulness and light sleep stages (N1 and N2 stages) in 16 young (23.1 ± 3.3y; 7 women), and 14 older individuals (59.6 ± 5.7y; 8 women). Results revealed extended, distributed (inter-between) and local (intra-within) decreases in network connectivity during sleep both in young and older individuals. However, compared to the young participants, older individuals showed lower decreases in connectivity or even increases in connectivity between thalamus/basal ganglia and several cerebral regions as well as between frontal regions of various networks. These findings reflect a reduced ability of the older brain to disconnect during sleep that may impede optimal disengagement for loss of responsiveness, enhanced lighter and fragmented sleep, and contribute to age effects on sleep-dependent brain plasticity.
Published: 2021

31. Open science datasets from PREVENT-AD, a longitudinal cohort of pre-symptomatic Alzheimer’s disease

Author: Alan C. Evans, Sylvia Villeneuve, Marie-Elyse Lafaille-Magnan, Jean-Baptiste Poline, Yasser Iturria-Medina, Stephanie O.M. Dyke, Pedro Rosa-Neto, Justin Kat, Pierre Etienne, Samir Das, Judes Poirier, M. Natasha Rajah, Pierre Bellec, Jennifer Tremblay-Mercier, D. Louis Collins, Cécile Madjar, Jordana Remz, Véronique D. Bohbot, Alexa Pichet Binette, John C.S. Breitner, Jeannie Marie S. Leoutsakos, Serge Gauthier, Christine L. Tardif, M. Mallar Chakravarty, and Richard D. Hoge
Subjects: Gerontology, Canada, Open science, Cognitive Neuroscience, Computer applications to medicine. Medical informatics, R858-859.7, tau Proteins, Neuroimaging, Disease, 050105 experimental psychology, Pre-symptomatic Alzheimer Disease, 03 medical and health sciences, 0302 clinical medicine, Open Science, Alzheimer Disease, Humans, Medicine, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Longitudinal cohort, RC346-429, Observational cohort, Retrospective Studies, Amyloid beta-Peptides, business.industry, 05 social sciences, Regular Article, Cognition, Middle Aged, Longitudinal imaging, medicine.disease, Cerebrospinal Fluid proteins, Neurology, Cohort, Neurology (clinical), Neurology. Diseases of the nervous system, Alzheimer's disease, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: Highlights • PREVENT-AD is openly releasing datasets to the neuroscience community. • PREVENT-AD is a longitudinal study of older adults at-risk of Alzheimer disease. • Data include imaging, genetics, fluid biochemistry, neurosensory, cognition and more. • Data collection methods and data sharing plans for open science are described., To move Alzheimer Disease (AD) research forward it is essential to collect data from large cohorts, but also make such data available to the global research community. We describe the creation of an open science dataset from the PREVENT-AD (PResymptomatic EValuation of Experimental or Novel Treatments for AD) cohort, composed of cognitively unimpaired older individuals with a parental or multiple-sibling history of AD. From 2011 to 2017, 386 participants were enrolled (mean age 63 years old ± 5) for sustained investigation among whom 349 have retrospectively agreed to share their data openly. Repositories are findable through the unified interface of the Canadian Open Neuroscience Platform and contain up to five years of longitudinal imaging data, cerebral fluid biochemistry, neurosensory capacities, cognitive, genetic, and medical information. Imaging data can be accessed openly at https://openpreventad.loris.ca while most of the other information, sensitive by nature, is accessible by qualified researchers at https://registeredpreventad.loris.ca. In addition to being a living resource for continued data acquisition, PREVENT-AD offers opportunities to facilitate understanding of AD pathogenesis.
Published: 2021

32. [Palliative care in hematopoietic stem-cell transplanted patients: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]

Author: Alice, Polomeni, Chloé, Prod'homme, Malika, Ainaoui, Adeline, Bellec, Aurélie, Berr, Jacinthe, Bonneau, Amandine, Charbonnier, Valérie, Coiteux, Eva, de Berranger, Thomas, Descamps, Marion, Gire, Murielle, Goncalves, Agnès, Ruscassié, Ibrahim, Yakoub-Agha, and Cécile, Borel
Subjects: Terminal Care, Clinical Deterioration, Attitude of Health Personnel, Interprofessional Relations, Clinical Decision-Making, Palliative Care, Hematopoietic Stem Cell Transplantation, Allografts, Prognosis, Bacterial Proteins, Glucosyltransferases, Health Care Surveys, Hematologic Neoplasms, Quality of Life, Humans, Interdisciplinary Communication, Advance Directives, Child, Qualitative Research, Societies, Medical
Abstract: Allogeneic hematopoietic cell transplantation (allo-HCT), the only curative therapy for numerous hematological malignancies, carries a significant risk of morbidity and mortality. The patients and families' expectations regarding the procedure, the prognosis uncertainties, as well as the existence of potential new therapeutic possibilities, lead to frequent use of intensive care. Even though the transplant physicians are highly skilled in acute care, their knowledge of palliative approach is limited, making the use of palliative care insufficient and often late. By promoting reflection on the proportionality of care and the patients' quality of life, palliative care may contribute to the allo-HCT patients management. Nevertheless, obstacles to this approach remain. The objective of this work is to propose recommendations to promote the implementation of palliative care into transplant units.
Published: 2020

33. Field output factors for small fields: A large multicentre study

Author: S. Dufreneix, Laure Vieillevigne, J. Bellec, and S. Josset
Subjects: Field (physics), Aperture, Biophysics, General Physics and Astronomy, Radiosurgery, Linear particle accelerator, Standard deviation, 030218 nuclear medicine & medical imaging, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Statistics, Dosimetry, Humans, Radiology, Nuclear Medicine and imaging, Radiometry, Mathematics, Photons, Detector, Collimator, General Medicine, 030220 oncology & carcinogenesis, Code of practice, Particle Accelerators, Monte Carlo Method
Abstract: Purpose The determination of output factors in small field dosimetry is a crucial point, especially when implementing stereotactic radiotherapy (SRT). Herein, a working group of the French medical physicist society (SFPM) was created to collect small field output factors. The objective was to gather and disseminate information on small field output factors based on different detectors for various clinical SRT equipment and measurement configurations. Method Participants were surveyed for information about their SRT equipment, including the type of linear particle accelerator (linac), collimator settings, measurement conditions for the output factors and the detectors used. Participants had to report both the ratio of detector readings and the correction factors applied as described in the IAEA TRS-483 code of practice for nominal field sizes smaller or equal to 3 cm. Mean field output factors and their associated standard deviations were calculated when data from at least 3 linacs were available. Results 23 centres were enrolled in the project. Standard deviations of the mean field output factors were systematically smaller than 1.5% for field sizes larger or equal to 1 cm and reached 5% for the smallest field size (0.5 cm). Deviations with published data were smaller than 2% except for the 0.5 cm circular fixed aperture collimator of the CyberKnife where it reached 3.5%. Conclusion These field output factor values obtained via a large multicentre study can be considered as an external cross verification for any radiotherapy centre starting a SRT program and should help minimize systematic errors when determining small field output factors.
Published: 2020

34. Functional connectivity subtypes associate robustly with ASD diagnosis

Author: Sebastian GW Urchs, Angela Tam, Pierre Orban, Clara Moreau, Yassine Benhajali, Hien Duy Nguyen, Alan C Evans, and Pierre Bellec
Subjects: General Immunology and Microbiology, Neurodevelopmental Disorders, General Neuroscience, Humans, Brain, Cluster Analysis, General Medicine, Autistic Disorder, General Biochemistry, Genetics and Molecular Biology, Research Personnel
Abstract: Our understanding of the changes in functional brain organization in autism is hampered by the extensive heterogeneity that characterizes this neurodevelopmental disorder. Data driven clustering offers a straightforward way to decompose autism heterogeneity into subtypes of connectivity and promises an unbiased framework to investigate behavioral symptoms and causative genetic factors. Yet, the robustness and generalizability of functional connectivity subtypes is unknown. Here, we show that a simple hierarchical cluster analysis can robustly relate a given individual and brain network to a connectivity subtype, but that continuous assignments are more robust than discrete ones. We also found that functional connectivity subtypes are moderately associated with the clinical diagnosis of autism, and these associations generalize to independent replication data. We explored systematically 18 different brain networks as we expected them to associate with different behavioral profiles as well as different key regions. Contrary to this prediction, autism functional connectivity subtypes converged on a common topography across different networks, consistent with a compression of the primary gradient of functional brain organization, as previously reported in the literature. Our results support the use of data driven clustering as a reliable data dimensionality reduction technique, where any given dimension only associates moderately with clinical manifestations.
Published: 2020

35. Supervised machine learning quality control for magnetic resonance artifacts in neonatal data sets

Author: Yang Ding, Gregory A. Lodygensky, Sabrina Suffren, and Pierre Bellec
Subjects: Male, Quality Control, Computer science, Stability (learning theory), Datasets as Topic, brain imaging, Machine learning, computer.software_genre, 050105 experimental psychology, Cross-validation, neonatal, 03 medical and health sciences, 0302 clinical medicine, open source, T2w, Image Interpretation, Computer-Assisted, motion detection, Image Processing, Computer-Assisted, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, AdaBoost, Research Articles, Radiological and Ultrasound Technology, business.industry, 05 social sciences, Infant, Newborn, Motion detection, Gold standard (test), Magnetic Resonance Imaging, Neurology, Undersampling, Data quality, Female, Neurology (clinical), Artificial intelligence, Noise (video), Supervised Machine Learning, Anatomy, business, Artifacts, computer, 030217 neurology & neurosurgery, Research Article, Canadian Neonatal Brain Platform
Abstract: Quality control (QC) of brain magnetic resonance images (MRI) is an important process requiring a significant amount of manual inspection. Major artifacts, such as severe subject motion, are easy to identify to naïve observers but lack automated identification tools. Clinical trials involving motion‐prone neonates typically pool data to obtain sufficient power, and automated quality control protocols are especially important to safeguard data quality. Current study tested an open source method to detect major artifacts among 2D neonatal MRI via supervised machine learning. A total of 1,020 two‐dimensional transverse T2‐weighted MRI images of preterm newborns were examined and classified as either QC Pass or QC Fail. Then 70 features across focus, texture, noise, and natural scene statistics categories were extracted from each image. Several different classifiers were trained and their performance was compared with subjective rating as the gold standard. We repeated the rating process again to examine the stability of the rating and classification. When tested via 10‐fold cross validation, the random undersampling and adaboost ensemble (RUSBoost) method achieved the best overall performance for QC Fail images with 85% positive predictive value along with 75% sensitivity. Similar classification performance was observed in the analyses of the repeated subjective rating. Current results served as a proof of concept for predicting images that fail quality control using no‐reference objective image features. We also highlighted the importance of evaluating results beyond mere accuracy as a performance measure for machine learning in imbalanced group settings due to larger proportion of QC Pass quality images.
Published: 2018

36. Data‐driven approaches for tau‐PET imaging biomarkers in Alzheimer's disease

Author: Alan C. Evans, Christian Dansereau, Wiesje M. van der Flier, Michael Schöll, Yasser Iturria-Medina, Niklas Mattsson, Sylvia Villeneuve, Olof Strandberg, Pierre Bellec, Oskar Hansson, Jacob W. Vogel, Rik Ossenkoppele, Philip Scheltens, Neurology, Amsterdam Neuroscience - Neurodegeneration, APH - Personalized Medicine, APH - Methodology, and Epidemiology and Data Science
Subjects: Male, Datasets as Topic, Neuroimaging, tau Proteins, Feature selection, 050105 experimental psychology, Pattern Recognition, Automated, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, mental disorders, Cluster Analysis, Humans, Medicine, Dementia, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Cluster analysis, Episodic memory, Research Articles, Aged, Aged, 80 and over, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, 05 social sciences, Cognition, medicine.disease, Cognitive test, Neurology, Positron emission tomography, Positron-Emission Tomography, Female, Neurology (clinical), Anatomy, business, Cartography, 030217 neurology & neurosurgery, Carbolines
Abstract: Previous positron emission tomography (PET) studies have quantified filamentous tau pathology using regions‐of‐interest (ROIs) based on observations of the topographical distribution of neurofibrillary tangles in post‐mortem tissue. However, such approaches may not take full advantage of information contained in neuroimaging data. The present study employs an unsupervised data‐driven method to identify spatial patterns of tau‐PET distribution, and to compare these patterns to previously published “pathology‐driven” ROIs. Tau‐PET patterns were identified from a discovery sample comprised of 123 normal controls and patients with mild cognitive impairment or Alzheimer's disease (AD) dementia from the Swedish BioFINDER cohort, who underwent [(18)F]AV1451 PET scanning. Associations with cognition were tested in a separate sample of 90 individuals from ADNI. BioFINDER [(18)F]AV1451 images were entered into a robust voxelwise stable clustering algorithm, which resulted in five clusters. Mean [(18)F]AV1451 uptake in the data‐driven clusters, and in 35 previously published pathology‐driven ROIs, was extracted from ADNI [(18)F]AV1451 scans. We performed linear models comparing [(18)F]AV1451 signal across all 40 ROIs to tests of global cognition and episodic memory, adjusting for age, sex, and education. Two data‐driven ROIs consistently demonstrated the strongest or near‐strongest effect sizes across all cognitive tests. Inputting all regions plus demographics into a feature selection routine resulted in selection of two ROIs (one data‐driven, one pathology‐driven) and education, which together explained 28% of the variance of a global cognitive composite score. Our findings suggest that [(18)F]AV1451‐PET data naturally clusters into spatial patterns that are biologically meaningful and that may offer advantages as clinical tools.
Published: 2018
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37. The Canadian Dementia Imaging Protocol: Harmonizing National Cohorts

Author: Christopher J.M. Scott, Vladimir S. Fonov, Cheryl R. McCreary, Joel Ramirez, Pierre Bellec, Maxime Descoteaux, Simon Duchesne, April Khademi, Isabelle Chouinard, Sandra E. Black, Richard D. Hoge, D. Louis Collins, Robert Bartha, Eric E. Smith, Olivier Potvin, and Stephen C. Strother
Subjects: Quality Control, Aging, Canada, Quality Assurance, Health Care, Siemens, Signal-To-Noise Ratio, resting state functional MRI, Imaging phantom, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Alzheimer Disease, Humans, magnetic resonance imaging, Medicine, Dementia, Radiology, Nuclear Medicine and imaging, Prospective Studies, standardization, neuroimaging, Resting state fMRI, medicine.diagnostic_test, Phantoms, Imaging, business.industry, Brain, Reproducibility of Results, Neurodegenerative Diseases, Magnetic resonance imaging, diffusion tensor imaging, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Linear Models, Medical Biophysics, business, Nuclear medicine, Quality assurance, Algorithms, morphometry, Diffusion MRI
Abstract: © 2018 International Society for Magnetic Resonance in Medicine Background: Harmonized protocols to collect imaging data must be devised, employed, and maintained in multicentric studies to reduce interscanner variability in subsequent analyses. Purpose: To present a standardized protocol for multicentric research on dementia linked to neurodegeneration in aging, harmonized on all three major vendor platforms. The protocol includes a common procedure for qualification, quality control, and quality assurance and feasibility in large-scale studies. Study Type: Prospective. Subjects: The study involved a geometric phantom, a single individual volunteer, and 143 cognitively healthy, mild cognitively impaired, and Alzheimer's disease participants in a large-scale, multicentric study. Field Strength/Sequences: MRI was perform with 3T scanners (GE, Philips, Siemens) and included 3D T 1 w, PD/T 2 w, T *2 , T 2 w-FLAIR, diffusion, and BOLD resting state acquisitions. Assessment: Measures included signal- and contrast-to-noise ratios (SNR and CNR, respectively), total brain volumes, and total scan time. Statistical Tests: SNR, CNR, and scan time were compared between scanner vendors using analysis of variance (ANOVA) and Tukey tests, while brain volumes were tested using linear mixed models. Results: Geometric phantom T 1 w SNR was significantly (P < 0.001) higher in Philips (mean: 71.4) than Siemens (29.5), while no significant difference was observed between vendors for T 2 w (32.0 and 37.2, respectively, P = 0.243). Single individual volunteer T 1 w CNR was higher in subcortical regions for Siemens (P < 0.001), while Philips had higher cortical CNR (P = 0.044). No significant difference in brain volumes was observed between vendors (P = 0.310/0.582/0.055). The average scan time was 41.0 minutes (SD: 2.8) and was not significantly different between sites (P = 0.071) and cognitive groups (P = 0.853). Data Conclusion: The harmonized Canadian Dementia Imaging Protocol suits the needs of studies that need to ensure quality MRI data acquisition for the measurement of brain changes across adulthood, due to aging, neurodegeneration, and other etiologies. A detailed description, exam cards, and operators' manual are freely available at the following site: www.cdip-pcid.ca. Level of Evidence: 2. Technical Efficacy: Stage 2. J. Magn. Reson. Imaging 2019;49:456–465.
Published: 2018
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38. Optimized radiotherapy to improve clinical outcomes for locally advanced lung cancer

Author: Bertrand De Latour, Joël Castelli, Ulrike Schick, Romain Corre, N. Jaksic, Charles Ricordel, Renaud de Crevoisier, Enrique Chajon, J. Bellec, and Hervé Lena
Subjects: Male, lcsh:Medical physics. Medical radiology. Nuclear medicine, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, lcsh:R895-920, Acceleration, Urology, NSCLC, lcsh:RC254-282, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Esophagus, Carcinoma, Non-Small-Cell Lung, Positron Emission Tomography Computed Tomography, medicine, Esophagitis, Humans, Radiology, Nuclear Medicine and imaging, IMRT, Lung cancer, Radiation Injuries, Lung, Pneumonitis, Aged, Retrospective Studies, Chemotherapy, SMART, Radiotherapy, business.industry, Research, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Quality Improvement, Confidence interval, Radiation therapy, Radiation Pneumonitis, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Concomitant, Toxicity, Female, Radiation Dose Hypofractionation, Radiotherapy, Intensity-Modulated, business
Abstract: Background We aimed to evaluate the toxicity, loco-regional control (LRC) and overall survival (OS) associated with accelerated intensity-modulated radiotherapy (IMRT) for locally advanced lung cancer. Methods Seventy-three patients were consecutively treated with IMRT from November 2011 to August 2016. A total dose of 66 Gy was delivered using two different schedules of radiotherapy: simultaneous modulated accelerated radiotherapy (SMART) (30 × 2.2 Gy, across 6 weeks) with or without chemotherapy, or moderate hypofractionated radiotherapy (HRT) (24 × 2.75 Gy, across 4 weeks) in patients unfit to receive concomitant chemotherapy. Data on esophageal and pulmonary toxicities, LRC and OS were prospectively collected. Results The median follow-up duration was 44 months. Severe pneumonitis and esophagitis (grade 3–4) were observed in 7% and 1% of patients respectively, with only one case of grade 4 (pneumonitis). Overall, the 1-year and 2-year LRCs were 76% [95 confidence interval (CI)%: 66–87%] and 62% [95 CI%: 49–77%] respectively. The 1 and 2-year OS rates were 72% [95% CI: 63–83%] and 54% [95 CI%: 43–68%] respectively. None parameters were correlated with LRC or OS. In particular, no difference was observed between patients treated with SMART and H-RT (p = 0.26 and 0.6 respectively), with a 1-year LRC of 74% [95 CI%: 62–86%] for SMART and 91% [95 CI%: 74–100%] for H-RT. No significant differences were observed in the toxicity rates associated with each of the RT schedules. Conclusions Accelerated IMRT for locally advanced lung cancer is associated with low toxicities and high LRC. Moderate hypofractionated RT, by decreasing the total treatment time, may be promising in improving clinical outcomes.
Published: 2018
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39. Consumption and exposure assessment to sunscreen products: A key point for safety assessment

Author: Sandrine Rakotomalala, Alain-Claude Roudot, Sonia Guillou, Murièle Bellec, Pierre-Jacques Ferret, A.S. Ficheux, Marie-Pierre Gomez-Berrada, and Dominique De Javel
Subjects: Adult, Male, Adolescent, Toxicology, 03 medical and health sciences, Key point, 0404 agricultural biotechnology, 0302 clinical medicine, Environmental health, Humans, Medicine, Child, Probability, Exposure assessment, Consumption (economics), business.industry, 04 agricultural and veterinary sciences, General Medicine, 040401 food science, Child, Preschool, 030220 oncology & carcinogenesis, Female, France, business, Sunscreening Agents, Food Science
Published: 2018
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40. Detecting stable individual differences in the functional organization of the human basal ganglia

Author: Francisco X. Castellanos, Manuel Garcia-Garcia, Michael P. Milham, Pierre Bellec, Brian Cheung, R. Cameron Craddock, and Aki Nikolaidis
Subjects: Adult, Male, 0301 basic medicine, Current (mathematics), Cognitive Neuroscience, Individuality, Stability (probability), Article, Basal Ganglia, Developmental psychology, Young Adult, 03 medical and health sciences, Consistency (database systems), 0302 clinical medicine, Similarity (network science), Basal ganglia, Humans, Cluster analysis, Reliability (statistics), Brain Mapping, business.industry, Cognition, Pattern recognition, Middle Aged, Magnetic Resonance Imaging, 030104 developmental biology, Neurology, Female, Artificial intelligence, Psychology, business, 030217 neurology & neurosurgery
Abstract: Moving from group level to individual level functional parcellation maps is a critical step for developing a rich understanding of the links between individual variation in functional network architecture and cognitive and clinical phenotypes. Still, the identification of functional units in the brain based on intrinsic functional connectivity and its dynamic variations between and within subjects remains challenging. Recently, the bootstrap analysis of stable clusters (BASC) framework was developed to quantify the stability of functional brain networks both across and within subjects. This multi-level approach utilizes bootstrap resampling for both individual and group-level clustering to delineate functional units based on their consistency across and within subjects, while providing a measure of their stability. Here, we optimized the BASC framework for functional parcellation of the basal ganglia by investigating a variety of clustering algorithms and similarity measures. Reproducibility and test-retest reliability were computed to validate this analytic framework as a tool to describe inter-individual differences in the stability of functional networks. The functional parcellation revealed by stable clusters replicated previous divisions found in the basal ganglia based on intrinsic functional connectivity. While we found moderate to high reproducibility, test-retest reliability was high at the boundaries of the functional units as well as within their cores. This is interesting because the boundaries between functional networks have been shown to explain most individual phenotypic variability. The current study provides evidence for the consistency of the parcellation of the basal ganglia, and provides the first group level parcellation built from individual-level cluster solutions. These novel results demonstrate the utility of BASC for quantifying inter-individual differences in the functional organization of brain regions, and encourage usage in future studies.
Published: 2018
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41. Brain properties predict proximity to symptom onset in sporadic Alzheimer’s disease

Author: Etienne Vachon-Presseau, Angela Tam, Alexa Pichet Binette, Pierre Orban, Melissa Savard, Sylvia Villeneuve, Renaud La Joie, John C.S. Breitner, Cynthia Picard, Pierre Bellec, Jacob W. Vogel, and Judes Poirier
Subjects: 0301 basic medicine, Male, Pediatrics, medicine.medical_specialty, Neuroimaging, Disease, Brain mapping, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Apolipoproteins E, Alzheimer Disease, Image Processing, Computer-Assisted, Medicine, Dementia, Humans, Cognitive Dysfunction, Age of Onset, structural MRI, Aged, Aged, 80 and over, Brain Mapping, medicine.diagnostic_test, Resting state fMRI, business.industry, biomarkers, Brain, Original Articles, Middle Aged, medicine.disease, Magnetic Resonance Imaging, MCI, 030104 developmental biology, machine learning, Cohort, Disease Progression, functional MRI, Female, Neurology (clinical), Age of onset, business, Functional magnetic resonance imaging, Cognition Disorders, 030217 neurology & neurosurgery
Abstract: Estimated years to symptom onset (EYO) is a measurement developed to track disease progression in patients with genetic Alzheimer’s disease. Vogel et al. apply this concept to individuals with a parental history of sporadic Alzheimer’s disease. A neuroimaging-based model successfully predicts EYO and years to clinical conversion in unseen data. See Tijms and Visser (doi:10.1093/brain/awy113) for a scientific commentary on this article., See Tijms and Visser (doi:10.1093/brain/awy113) for a scientific commentary on this article. Alzheimer’s disease is preceded by a lengthy ‘preclinical’ stage spanning many years, during which subtle brain changes occur in the absence of overt cognitive symptoms. Predicting when the onset of disease symptoms will occur is an unsolved challenge in individuals with sporadic Alzheimer’s disease. In individuals with autosomal dominant genetic Alzheimer’s disease, the age of symptom onset is similar across generations, allowing the prediction of individual onset times with some accuracy. We extend this concept to persons with a parental history of sporadic Alzheimer’s disease to test whether an individual’s symptom onset age can be informed by the onset age of their affected parent, and whether this estimated onset age can be predicted using only MRI. Structural and functional MRIs were acquired from 255 ageing cognitively healthy subjects with a parental history of sporadic Alzheimer’s disease from the PREVENT-AD cohort. Years to estimated symptom onset was calculated as participant age minus age of parental symptom onset. Grey matter volume was extracted from T1-weighted images and whole-brain resting state functional connectivity was evaluated using degree count. Both modalities were summarized using a 444-region cortical-subcortical atlas. The entire sample was divided into training (n = 138) and testing (n = 68) sets. Within the training set, individuals closer to or beyond their parent’s symptom onset demonstrated reduced grey matter volume and altered functional connectivity, specifically in regions known to be vulnerable in Alzheimer’s disease. Machine learning was used to identify a weighted set of imaging features trained to predict years to estimated symptom onset. This feature set alone significantly predicted years to estimated symptom onset in the unseen testing data. This model, using only neuroimaging features, significantly outperformed a similar model instead trained with cognitive, genetic, imaging and demographic features used in a traditional clinical setting. We next tested if these brain properties could be generalized to predict time to clinical progression in a subgroup of 26 individuals from the Alzheimer’s Disease Neuroimaging Initiative, who eventually converted either to mild cognitive impairment or to Alzheimer’s dementia. The feature set trained on years to estimated symptom onset in the PREVENT-AD predicted variance in time to clinical conversion in this separate longitudinal dataset. Adjusting for participant age did not impact any of the results. These findings demonstrate that years to estimated symptom onset or similar measures can be predicted from brain features and may help estimate presymptomatic disease progression in at-risk individuals.
Published: 2018

42. Non-invasive ventilation versus high-flow nasal cannula oxygen therapy with apnoeic oxygenation for preoxygenation before intubation of patients with acute hypoxaemic respiratory failure: a randomised, multicentre, open-label trial

Author: Jean-Pierre Frat, Jean-Damien Ricard, Jean-Pierre Quenot, Nicolas Pichon, Alexandre Demoule, Jean-Marie Forel, Jean-Paul Mira, Rémi Coudroy, Guillaume Berquier, Benoit Voisin, Gwenhaël Colin, Bertrand Pons, Pierre Eric Danin, Jérome Devaquet, Gwenael Prat, Raphaël Clere-Jehl, Franck Petitpas, Emmanuel Vivier, Keyvan Razazi, Mai-Anh Nay, Vincent Souday, Jean Dellamonica, Laurent Argaud, Stephan Ehrmann, Aude Gibelin, Christophe Girault, Pascal Andreu, Philippe Vignon, Laurence Dangers, Stéphanie Ragot, Arnaud W Thille, Delphine Chatellier, Florence Boissier, Anne Veinstein, René Robert, Céline Deletage-Métreau, Morgane Olivry, Claire Dahyot-Fizelier, Auguste Dargent, Audrey Large, Emmanuelle Begot, Claire Mancia, Maxence Decavele, Martin Dres, Samuel Lehingue, Laurent Papazian, Marine Paul, Nathalie Marin, Matthieu Le Meur, Mohammed Laissy, Anaita Rouzé, Saad Nseir, Matthieu Henry-Lagarrigue, Aihem Yehia, Frédéric Martino, Charles Cerf, Pierre Bailly, Julie Helms, Jean Baptiste Putegnat, Armand Mekontso-Dessap, Thierry Boulain, Pierre Asfar, Séverin Cabasson, Florent Wallet, Kada Klouche, Frédéric Bellec, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction Générale de l'Organisation des Soins (DGOS)-Université de Bourgogne (UB), Hôpital Dupuytren [CHU Limoges], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Charles Foix [AP-HP], Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), GHU AP-HP Centre Université de Paris, Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre Hospitalier Universitaire de Nice (CHU Nice), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Hôpital Foch [Suresnes], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Nouvel Hôpital Civil de Strasbourg, Université de Strasbourg (UNISTRA), Les Hôpitaux Universitaires de Strasbourg (HUS), Centre hospitalier Saint Joseph - Saint Luc [Lyon], CHU Henri Mondor, 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), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot [CHU - HCL], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de Recherche sur le Handicap Ventilatoire (GRHV), Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-CHU Rouen, Normandie Université (NU), CHU Rouen, Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Delphine Chatellier, Florence Boissier, Anne Veinstein, René Robert, Céline Deletage-Métreau, Morgane Olivry, Claire Dahyot-Fizelier, Auguste Dargent, Audrey Large, Emmanuelle Begot, Claire Mancia, Maxence Decavele, Martin Dres, Samuel Lehingue, Laurent Papazian, Marine Paul, Nathalie Marin, Matthieu Le Meur, Mohammed Laissy, Anaita Rouzé, Saad Nseir, Matthieu Henry-Lagarrigue, Aihem Yehia, Frédéric Martino, Charles Cerf, Pierre Bailly, Julie Helms, Jean Baptiste Putegnat, Armand Mekontso-Dessap, Thierry Boulain, Pierre Asfar, Séverin Cabasson, Florent Wallet, Kada Klouche, Frédéric Bellec, Delphine Chatellier, Florence Boissier, Anne Veinstein, René Robert, Céline Deletage-Métreau, Morgane Olivry, Maxence Decavele, Martin Dres, Samuel Lehingue, Laurent Papazian, Matthieu Le Meur, Mohammed Laissy, Anaita Rouzé, Saad Nseir, Matthieu Henry-Lagarrigue, Aihem Yehia, Charles Cerf, Armand Mekontso-Dessap, Thierry Boulain, Pierre Asfar, CCSD, Accord Elsevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Réanimation, Hôpital Jean Bernard, CHU de Poitiers, Poitiers, France, Equipe LIPNESS (LNC - U1231) (LIPNESS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Coordination des Prélèvements d’Organes et de Tissus (CHPOT), CHU Limoges, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire pluridisciplinaire de recherche en ingénierie des systèmes, mécanique et énergétique (PRISME), Université d'Orléans (UO)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Réanimation Médicale [Strasbourg], Institut universitaire des systèmes thermiques industriels (IUSTI), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médicale [Hôpital de l’Archet], Centre Hospitalier Universitaire de Nice (CHU de Nice)-Hôpital de l'Archet, Service de Réanimation Médicale, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France, parent, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Limoges, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Laboratoire de Génétique Chromosomique et Moléculaire [CHU Dijon], 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and CHU Henri Mondor [Créteil]
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Nose, medicine.disease_cause, Catheterization, 03 medical and health sciences, 0302 clinical medicine, Fraction of inspired oxygen, Intensive care, Oxygen therapy, medicine, Intubation, Intratracheal, Intubation, Humans, Oximetry, Hypoxia, Noninvasive Ventilation, medicine.diagnostic_test, business.industry, Tracheal intubation, Oxygen Inhalation Therapy, 030208 emergency & critical care medicine, Middle Aged, Respiration, Artificial, 3. Good health, [SDV] Life Sciences [q-bio], Pulse oximetry, 030228 respiratory system, Respiratory failure, Anesthesia, Acute Disease, Female, business, Respiratory Insufficiency, Nasal cannula
Abstract: International audience; BACKGROUND: Non-invasive ventilation has never been compared with high-flow oxygen to determine whether it reduces the risk of severe hypoxaemia during intubation. We aimed to determine if preoxygenation with non-invasive ventilation was more efficient than high-flow oxygen in reducing the risk of severe hypoxaemia during intubation. METHODS: The FLORALI-2 multicentre, open-label trial was done in 28 intensive care units in France. Adult patients undergoing tracheal intubation for acute hypoxaemic respiratory failure (a partial pressure of arterial oxygen [PaO2] to fraction of inspired oxygen [FiO2] ratio of \textless/=300 mm Hg) were randomly assigned (1:1; block size, four participants) to non-invasive ventilation or high-flow oxygen during preoxygenation, with stratification by PaO2/FiO2 ratio (\textless/=200 mm Hg vs \textgreater200 mm Hg). Key exclusion criteria were intubation for cardiac arrest, altered consciousness (defined as a Glasgow coma score of less than eight points), other contraindications to non-invasive ventilation (recent laryngeal, oesophageal, or gastric surgery, and substantial facial fractures), pulse oximetry not available, pregnant or breastfeeding women, and refusal to participate. The primary outcome was the occurrence of severe hypoxaemia (pulse oximetry \textless80%) during the procedure, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02668458. FINDINGS: Between April 15, 2016, and Jan 8, 2017, 2079 patients were intubated in the 28 participating units, and 322 were enrolled. We excluded five patients with no recorded data, two who withdrew consent or were under legal protection, one who was not intubated, and one who had a cardiac arrest. Of the 313 patients included in the intention-to-treat analysis, 142 were assigned to non-invasive ventilation and 171 to high-flow oxygen therapy. Severe hypoxaemia occurred in 33 (23%) of 142 patients after preoxygenation with non-invasive ventilation and 47 (27%) of 171 with high-flow oxygen (absolute difference -4.2%, 95% CI -13.7 to 5.5; p=0.39). In the 242 patients with moderate-to-severe hypoxaemia (PaO2/FiO2 \textless/=200 mm Hg), severe hypoxaemia occurred less frequently after preoxygenation with non-invasive ventilation than with high-flow oxygen (28 [24%] of 117 patients vs 44 [35%] of 125; adjusted odds ratio 0.56, 0.32 to 0.99, p=0.0459). Serious adverse events did not differ between treatment groups, with the most common immediate complications being systolic arterial hypotension (70 [49%] patients in the non-invasive ventilation group vs 86 [50%] patients in the high-flow oxygen group) and chest infiltrate on x-ray (28 [20%] vs 33 [19%]), and the most common late complications being death at day 28 (53 [37%] vs 58 [34%]) and ventilator-associated pneumonia during ICU stay (31 [22%] vs 35 [20%]). INTERPRETATION: In patients with acute hypoxaemic respiratory failure, preoxygenation with non-invasive ventilation or high-flow oxygen therapy did not change the risk of severe hypoxaemia. Future research should explore the effect of preoxygenation method in patients with moderate-to-severe hypoxaemia at baseline. FUNDING: French Ministry of Health.
Published: 2019
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43. Changes in structural network are associated with cortical demyelination in early multiple sclerosis

Author: Gabriel Mangeat, Constantina A. Treaba, Elena Herranz, Julien Cohen-Adad, Céline Louapre, Pierre Bellec, Jacob A. Sloane, Tobias Granberg, Russell Ouellette, Atef Badji, Caterina Mainero, and Nikola Stikov
Subjects: Adult, Male, Multiple Sclerosis, Biology, Article, 030218 nuclear medicine & medical imaging, White matter, Correlation, Disability Evaluation, 03 medical and health sciences, Myelin, 0302 clinical medicine, Connectome, Image Processing, Computer-Assisted, medicine, Humans, Radiology, Nuclear Medicine and imaging, Cerebral Cortex, Analysis of Variance, Radiological and Ultrasound Technology, medicine.diagnostic_test, Multiple sclerosis, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, Cerebral cortex, Case-Control Studies, Female, Neurology (clinical), Analysis of variance, Nerve Net, Anatomy, Neuroscience, 030217 neurology & neurosurgery, Demyelinating Diseases
Abstract: The aim of this study was to investigate the interplay between structural connectivity and cortical demyelination in early multiple sclerosis. About 27 multiple sclerosis patients and 18 age-matched controls underwent two MRI scanning sessions. The first was done at 7T and involved acquiring quantitative T1 and T2 * high-resolution maps to estimate cortical myelination. The second was done on a Connectom scanner and consisted of acquiring high angular resolution diffusion-weighted images to compute white matter structural connectivity metrics: strength, clustering and local efficiency. To further investigate the interplay between structural connectivity and cortical demyelination, patients were divided into four groups according to disease-duration: 0-1 year, 1-2 years, 2-3 years, and >3 years. ANOVA and Spearman's correlations were used to highlight relations between metrics. ANOVA detected a significant effect between disease duration and both cortical myelin (p = 2 × 10-8 ) and connectivity metrics (p < 10-4 ). We observed significant cortical myelin loss in the shorter disease-duration cohorts (0-1 year, p = .0015), and an increase in connectivity in the longer disease-duration cohort (2-3 years, strength: p = .01, local efficiency: p = .002, clustering: p = .001). Moreover, significant covariations between myelin estimation and white matter connectivity metrics were observed: Spearman's Rho correlation coefficients of 0.52 (p = .0003), 0.55 (p = .0001), and 0.53 (p = .0001) for strength, local efficiency, and clustering, respectively. An association between cortical myelin loss and changes in white matter connectivity in early multiple sclerosis was detected. These changes in network organization might be the result of compensatory mechanisms in response to the ongoing cortical diffuse damage in the early stages of multiple sclerosis.
Published: 2018
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44. Multisite generalizability of schizophrenia diagnosis classification based on functional brain connectivity

Author: Pierre Orban, Violaine Mongeau-Pérusse, Charles-Édouard Giguère, Hien D. Nguyen, Pierre Bellec, Christian Dansereau, Emmanuel Stip, Adrianna Mendrek, and Laurence Desbois
Subjects: Adult, Male, 0301 basic medicine, Computer science, Machine learning, computer.software_genre, Generalization, Psychological, Developmental psychology, Machine Learning, Young Adult, 03 medical and health sciences, Functional brain, 0302 clinical medicine, Image Processing, Computer-Assisted, Humans, Generalizability theory, Biological Psychiatry, 030304 developmental biology, 0303 health sciences, business.industry, Brain, Cognition, Magnetic Resonance Imaging, Oxygen, Psychiatry and Mental health, 030104 developmental biology, Case-Control Studies, Schizophrenia, Female, Schizophrenic Psychology, Diagnosis Classification, Artificial intelligence, Psychology, business, Classifier (UML), computer, 030217 neurology & neurosurgery
Abstract: Our objective was to assess the generalizability, across sites and cognitive contexts, of schizophrenia classification based on functional brain connectivity. We tested different training-test scenarios combining fMRI data from 191 schizophrenia patients and 191 matched healthy controls obtained at 6 scanning sites and under different task conditions. Diagnosis classification accuracy generalized well to a novel site and cognitive context provided data from multiple sites were used for classifier training. By contrast, lower classification accuracy was achieved when data from a single distinct site was used for training. These findings indicate that it is beneficial to use multisite data to train fMRI-based classifiers intended for large-scale use in the clinical realm.
Published: 2018
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45. Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2)

Author: Jean Reignier, Julie Boisramé-Helms, Laurent Brisard, Jean-Baptiste Lascarrou, Ali Ait Hssain, Nadia Anguel, Laurent Argaud, Karim Asehnoune, Pierre Asfar, Frédéric Bellec, Vlad Botoc, Anne Bretagnol, Hoang-Nam Bui, Emmanuel Canet, Daniel Da Silva, Michael Darmon, Vincent Das, Jérôme Devaquet, Michel Djibre, Frédérique Ganster, Maité Garrouste-Orgeas, Stéphane Gaudry, Olivier Gontier, Claude Guérin, Bertrand Guidet, Christophe Guitton, Jean-Etienne Herbrecht, Jean-Claude Lacherade, Philippe Letocart, Frédéric Martino, Virginie Maxime, Emmanuelle Mercier, Jean-Paul Mira, Saad Nseir, Gael Piton, Jean-Pierre Quenot, Jack Richecoeur, Jean-Philippe Rigaud, René Robert, Nathalie Rolin, Carole Schwebel, Michel Sirodot, François Tinturier, Didier Thévenin, Bruno Giraudeau, Amélie Le Gouge, Hervé Dupont, Marc Pierrot, François Beloncle, Danièle Combaux, Romain Mercier, Hadrien Winiszewski, Gilles Capellier, Gilles Hilbert, Didier Gruson, Pierre Kalfon, Bertrand Souweine, Elizabeth Coupez, Jean-Damien Ricard, Jonathan Messika, François Bougerol, Pierre-Louis Declercq, Auguste Dargent, Audrey Large, Djillali Annane, Bernard Clair, Agnès Bonadona, Rebecca Hamidfar, Christian Richard, Mathieu Henry-Lagarrigue, Ahiem Yehia Yehia, Johanna Temime, Stephanie Barrailler, Raphaël Favory, Erika Parmentier-Decrucq, Mercé Jourdain, Loredana Baboi, Marie Simon, Thomas Baudry, Mehran Monchi, Jérôme Roustan, Patrick Bardou, Alice Cottereau, Philippe Guiot, Noelle Brule, Mickael Landais, Antoine Roquilly, Thierry Boulain, Dalila Benzekri, Benoit Champigneulle, Jalel Tahiri, Gabriel Preda, Benoit Misset, Virginie Lemiale, Lara Zafrani, Muriel Fartoukh, Guillaume Thiéry, Delphine Chatellier, Rémi Coudroy, Renaud Chouquer, Samuel Gay, Christine Brasse, Arnaud Delahaye, Luis Ferreira, Régine Vermesch, Stéphanie Chevalier, Charlotte Quentin, Quentin Maestraggi, Francis Schneider, Ferhat Meziani, Charles Cerf, Grégoire Trebbia, Charlotte Salmon-Gandonnière, Laetitia Bodet-Contentin, Service d'anesthésie et réanimation chirurgicale [Nantes], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Réanimation Médicale [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Stress vasculaire et tissulaire en transplantation : microparticules et environnement, Université de Strasbourg (UNISTRA), Service de réanimation médicale [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Groupement Hospitalier - Hôpital Edouard Herriot, Service de Réanimation Médicale, Hospices Civils de Lyon (HCL), Service de médecine intensive - réanimation et médecine hyperbare [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de réanimation et de surveillance continue [CH Mautauban], Centre hospitalier de Montauban, Service de réanimation (CH Saint-Malo), Centre hospitalier de Saint-Malo, Service de Réanimation Polyvalente - CHR d’Orleans, Service de Réanimation Médicale [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Service d’anesthésie-réanimation [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), réanimation et soins continus [CH Saint-Denis], Centre Hospitalier de Saint-Denis [Ile-de-France], Service des Urgences et de Réanimation Médicale (Urg - SAINT ETIENNE), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de réanimation polyvalente [Hôpital Foch, Suresnes], Hôpital Foch [Suresnes], Service de Réanimation et USC Médico-Chirurgicale = Médecine intensive réanimation [CHU Tenon], CHU Tenon [AP-HP], Service de réanimation chirurgicale [Centre Hospitalier Emile Muller, Mulhouse], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), 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), Unité de Soins Intensifs [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Le Mans (CH Le Mans), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service de réanimation (CH La Roche-sur-Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Réanimation, Hôpital Jean Bernard, CHU de Poitiers, Poitiers, France, Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation Médicale, CHU Gabriel Montpied, CHU de Clermont-Ferrand, France, AP-HP Hôpital Saint-Louis, Service de réanimation et USC médico-chirurgicale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-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 Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Radiopharmaceutiques biocliniques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CIC Tours, Hôpital Bretonneau-Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation et USC Médico-Chirurgicale [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-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), Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Strasbourg ( UNISTRA ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Hospices Civils de Lyon ( HCL ), CHU Angers, CH Saint-Denis, Service des Urgences et de Réanimation Médicale ( Urg - SAINT ETIENNE ), Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Centre Hospitalier Emile Muller [Mulhouse] ( CH E.Muller Mulhouse ), Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ) -Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ), Infection, Antimicrobiens, Modélisation, Evolution ( IAME ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Le Mans, Biomatériaux et Bioingénierie, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Matériaux et nanosciences d'Alsace, Université de Strasbourg ( UNISTRA ) -Université de Haute-Alsace (UHA) Mulhouse - Colmar ( Université de Haute-Alsace (UHA) ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ) -Université de Haute-Alsace (UHA) Mulhouse - Colmar ( Université de Haute-Alsace (UHA) ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Bretonneau-Université de Tours-CHRU Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and CHRU Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Adult, Male, Parenteral Nutrition, Pediatrics, medicine.medical_specialty, Time Factors, Critical Care, Secondary infection, Enteral feeding, Clinical nutrition, Enteral administration, law.invention, 03 medical and health sciences, Enteral Nutrition, 0302 clinical medicine, Randomized controlled trial, law, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Humans, Vasoconstrictor Agents, Medicine, Cumulative incidence, Hospital Mortality, 030212 general & internal medicine, Nutritional support, Aged, Acute critical illness, business.industry, Malnutrition, Hazard ratio, Shock, 030208 emergency & critical care medicine, General Medicine, Length of Stay, Middle Aged, Interim analysis, Respiration, Artificial, The enteral route, 3. Good health, Treatment Outcome, Parenteral nutrition, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BackgroundWhether the route of early feeding affects outcomes of patients with severe critical illnesses is controversial. We hypothesised that outcomes were better with early first-line enteral nutrition than with early first-line parenteral nutrition.MethodsIn this randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2 trial) done at 44 French intensive-care units (ICUs), adults (18 years or older) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned (1:1) to either parenteral nutrition or enteral nutrition, both targeting normocaloric goals (20–25 kcal/kg per day), within 24 h after intubation. Randomisation was stratified by centre using permutation blocks of variable sizes. Given that route of nutrition cannot be masked, blinding of the physicians and nurses was not feasible. Patients receiving parenteral nutrition could be switched to enteral nutrition after at least 72 h in the event of shock resolution (no vasopressor support for 24 consecutive hours and arterial lactate
Published: 2018
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46. Application of calibrated fMRI in Alzheimer's disease

Author: Sylvie Belleville, Serge Gauthier, Douglas L. Arnold, Oury Monchi, Marie-Jeanne Kergoat, Isabelle Lajoie, Felipe B. Tancredi, Julien Doyon, Howard Chertkow, Richard D. Hoge, Pierre Bellec, Yan Deschaintre, Scott Nugent, Clément Debacker, Kenneth S. Dyson, Christian Bocti, and AmanPreet Badhwar
Subjects: Male, Cognitive Neuroscience, BOLD calibration constant, Precuneus, Grey matter, lcsh:Computer applications to medicine. Medical informatics, lcsh:RC346-429, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Functional neuroimaging, Alzheimer Disease, medicine, Dementia, Humans, Radiology, Nuclear Medicine and imaging, Cerebrovascular reactivity, lcsh:Neurology. Diseases of the nervous system, Aged, Aged, 80 and over, medicine.diagnostic_test, Functional Neuroimaging, Magnetic resonance imaging, Regular Article, Alzheimer's disease, Cerebral blood flow, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Oxygen, medicine.anatomical_structure, Neurology, Calibrated fMRI, Cerebrovascular Circulation, Calibration, lcsh:R858-859.7, Oxidative metabolism, Female, Spin Labels, Neurology (clinical), Oxygen extraction fraction, Occipital lobe, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: Calibrated fMRI based on arterial spin-labeling (ASL) and blood oxygen-dependent contrast (BOLD), combined with periods of hypercapnia and hyperoxia, can provide information on cerebrovascular reactivity (CVR), resting blood flow (CBF), oxygen extraction fraction (OEF), and resting oxidative metabolism (CMRO2). Vascular and metabolic integrity are believed to be affected in Alzheimer's disease (AD), thus, the use of calibrated fMRI in AD may help understand the disease and monitor therapeutic responses in future clinical trials. In the present work, we applied a calibrated fMRI approach referred to as Quantitative O2 (QUO2) in a cohort of probable AD dementia and age-matched control participants. The resulting CBF, OEF and CMRO2 values fell within the range from previous studies using positron emission tomography (PET) with 15O labeling. Moreover, the typical parietotemporal pattern of hypoperfusion and hypometabolism in AD was observed, especially in the precuneus, a particularly vulnerable region. We detected no deficit in frontal CBF, nor in whole grey matter CVR, which supports the hypothesis that the effects observed were associated specifically with AD rather than generalized vascular disease. Some key pitfalls affecting both ASL and BOLD methods were encountered, such as prolonged arterial transit times (particularly in the occipital lobe), the presence of susceptibility artifacts obscuring medial temporal regions, and the challenges associated with the hypercapnic manipulation in AD patients and elderly participants. The present results are encouraging and demonstrate the promise of calibrated fMRI measurements as potential biomarkers in AD. Although CMRO2 can be imaged with 15O PET, the QUO2 method uses more widely available imaging infrastructure, avoids exposure to ionizing radiation, and integrates with other MRI-based measures of brain structure and function., Highlights • An advanced calibrated fMRI method is employed to explore brain physiology in AD. • A pattern of hypoperfusion and hypometabolism was observed as in PET studies. • The method provides several potential biomarkers of interest in AD. • The technique may help by providing new insights into the pathophysiology of AD.
Published: 2017

47. Statistical power and prediction accuracy in multisite resting-state fMRI connectivity

Author: Christian Dansereau, Pierre Orban, Emilio Merlo Pich, Pierre Bellec, Celine Risterucci, Douglas L. Arnold, and Yassine Benhajali
Subjects: Adult, Male, FOS: Computer and information sciences, Support Vector Machine, Adolescent, Computer science, Rest, Cognitive Neuroscience, Models, Neurological, Machine Learning (stat.ML), Quantitative Biology - Quantitative Methods, Statistical power, 030218 nuclear medicine & medical imaging, Computational Engineering, Finance, and Science (cs.CE), Functional networks, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Statistics - Machine Learning, Neural Pathways, Statistics, Image Processing, Computer-Assisted, medicine, Humans, Multicenter Studies as Topic, Computer Science - Computational Engineering, Finance, and Science, Quantitative Methods (q-bio.QM), Brain Mapping, Resting state fMRI, medicine.diagnostic_test, Brain, Middle Aged, Magnetic Resonance Imaging, Neurology, Sample size determination, FOS: Biological sciences, Female, Functional magnetic resonance imaging, Monte Carlo Method, 030217 neurology & neurosurgery
Abstract: Connectivity studies using resting-state functional magnetic resonance imaging are increasingly pooling data acquired at multiple sites. While this may allow investigators to speed up recruitment or increase sample size, multisite studies also potentially introduce systematic biases in connectivity measures across sites. In this work, we measure the inter-site effect in connectivity and its impact on our ability to detect individual and group differences. Our study was based on real, as opposed to simulated, multisite fMRI datasets collected in N=345 young, healthy subjects across 8 scanning sites with 3T scanners and heterogeneous scanning protocols, drawn from the 1000 functional connectome project. We first empirically show that typical functional networks were reliably found at the group level in all sites, and that the amplitude of the inter-site effects was small to moderate, with a Cohen's effect size below 0.5 on average across brain connections. We then implemented a series of Monte-Carlo simulations, based on real data, to evaluate the impact of the multisite effects on detection power in statistical tests comparing two groups (with and without the effect) using a general linear model, as well as on the prediction of group labels with a support-vector machine. As a reference, we also implemented the same simulations with fMRI data collected at a single site using an identical sample size. Simulations revealed that using data from heterogeneous sites only slightly decreased our ability to detect changes compared to a monosite study with the GLM, and had a greater impact on prediction accuracy. However, the deleterious effect of multisite data pooling tended to decrease as the total sample size increased, to a point where differences between monosite and multisite simulations were small with N=120 subjects. Taken together, our results support the feasibility of multisite studies in rs-fMRI provided the sample size is large enough.
Published: 2017
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48. ITV versus mid-ventilation for treatment planning in lung SBRT: a comparison of target coverage and PTV adequacy by using in-treatment 4D cone beam CT

Author: Joël Castelli, Caroline Lafond, Enrique Chajon, J. Bellec, F. Arab-Ceschia, Centre Eugène Marquis (CRLCC), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: lcsh:Medical physics. Medical radiology. Nuclear medicine, Lung Neoplasms, medicine.medical_treatment, lcsh:R895-920, ITV, Planning target volume, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Radiosurgery, lcsh:RC254-282, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 030218 nuclear medicine & medical imaging, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Stereotactic body radiation therapy (SBRT), 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Radiology, Nuclear Medicine and imaging, Four-Dimensional Computed Tomography, Planning strategy, Radiation treatment planning, Image guidance, Cone beam ct, Lung, business.industry, Radiotherapy Planning, Computer-Assisted, Research, Mid-ventilation, Cone-Beam Computed Tomography, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Radiation therapy, Geometric uncertainties, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Breathing, Respiratory motions, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Radiotherapy, Intensity-Modulated, Lung cancer, Nuclear medicine, business, Stereotactic body radiotherapy, 4D-CBCT
Abstract: Background The internal target volume (ITV) approach and the mid-ventilation (MidV) concept are the two main respiratory motion-management strategies under free breathing. The purpose of this work was to compare the actual in-treatment target coverage during volumetric modulated arctherapy (VMAT) delivered through both ITV-based and MidV-based planning target volume (PTV) and to provide knowledge in choosing the optimal PTV for stereotactic body radiotherapy (SBRT) for lung lesions. Methods and materials Thirty-two lung cancer patients treated by a VMAT technique were included in the study. For each fraction, the mean time-weighted position of the target was localized by using a 4-dimensional cone-beam CT (4D-CBCT)-based image guidance procedure. The respiratory-correlated location of the gross tumor volume (GTV) during treatment delivery was determined for each fraction by using in-treatment 4D-CBCT images acquired concurrently with VMAT delivery (4D-CBCTin-treat). The GTV was delineated from each of the ten respiratory phase-sorted 4D-CBCTin-treat datasets for each fraction. We defined target coverage as the average percentage of the GTV included within the PTV during the patient’s breathing cycle averaged over the treatment course. Target coverage and PTVs were reported for a MidV-based PTV (PTVMidV) using dose-probabilistic margins and three ITV-based PTVs using isotropic margins of 5 mm (PTVITV + 5mm), 4 mm (PTVITV + 4mm) and 3 mm (PTVITV + 3mm). The in-treatment baseline displacements and target motion amplitudes were reported to evaluate the impact of both parameters on target coverage. Results Overall, 100 4D-CBCTin-treat images were analyzed. The mean target coverage was 98.6, 99.6, 98.9 and 97.2% for PTVMidV, PTVITV + 5mm, PTVITV + 4mm and PTVITV + 3mm, respectively. All the PTV margins led to a target coverage per treatment higher than 95% in at least 90% of the evaluated cases. Compared to PTVITV + 5mm, PTVMidV, PTVITV + 4mm and PTVITV + 3mm had mean PTV reductions of 16, 19 and 33%, respectively. Conclusion When implementing VMAT with 4D-CBCT-based image guidance, an ITV-based approach with a tighter margin than the commonly used 5 mm margin remains an alternative to the MidV-based approach for reducing healthy tissue exposure in lung SBRT. Compared to PTVMidV, PTVITV + 3mm significantly reduced the PTV while still maintaining an adequate in-treatment target coverage.
Published: 2020
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49. Live-imaging of revertant and therapeutically restored dystrophin in the Dmd

Author: M V, Petkova, A, Stantzou, A, Morin, O, Petrova, S, Morales-Gonzalez, F, Seifert, J, Bellec-Dyevre, T, Manoliu, A, Goyenvalle, L, Garcia, I, Richard, C, Laplace-Builhé, M, Schuelke, and H, Amthor
Subjects: Gene Editing, Mice, Transgenic, Exons, Genetic Therapy, Retina, Dystrophin, Muscular Dystrophy, Duchenne, Mice, Sarcolemma, Mice, Inbred mdx, Animals, Humans, CRISPR-Cas Systems, Alleles
Abstract: DmdWe generated a DmdIntravital microscopy in anaesthetized mice allowed live-imaging of sarcolemmal dystrophin-EGFP fusion protein of revertant fibres as well as following therapeutic restoration. Dystrophin-EGFP-fluorescence persisted ex vivo, allowing live-imaging of revertant and therapeutically restored dystrophin in isolated fibres ex vivo. Expression of the shorter dystrophin-EGFP isoforms Dp71 in the brain, Dp260 in the retina, and Dp116 in the peripheral nerve remained unabated by the mdx-23 mutation.Intravital imaging of Dmd
Published: 2019

50. Intestinal Availability and Metabolic Effects of Dietary

Author: Dominique, Hermier, Annaïg, Lan, Frédérique, Tellier, Anne, Blais, Marta Grauso, Culetto, Véronique, Mathé, Yannick, Bellec, Lionel, Gissot, Philippe, Schmidely, and Jean-Denis, Faure
Subjects: Male, Metabolic Syndrome, Mice, Inbred C57BL, Mice, Sphingolipids, Plant Extracts, Animals, Humans, Camellia, Intestinal Mucosa, Diet, High-Fat, Animal Feed
Abstract: Sphingolipids appear as a promising class of components susceptible to prevent the onset of the metabolic syndrome (MetS). Gut availability and effects of
Published: 2019

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