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216 results on '"Bellec, A."'

1. Atlas of functional connectivity relationships across rare and common genetic variants, traits, and psychiatric conditions

Author: Sarah Lippé, Carrie E. Bearden, Kuldeep Kumar, Elise Douard, Thomas Rolland, Jean-Louis Martineau, David Shin, Marianne Bernadette van den Bree, Hanad Sharmarke, Clara Moreau, Pierre Orban, Annabelle Harvey, Aurélie Labbe, Pierre Bellec, Laura M. Schultz, Guillaume Huguet, David Edmund Johannes Linden, Petra Tamer, Paul M. Thompson, Sebastian Urchs, Sébastien Jacquemont, Laura Almasy, Nadine Younis, David C. Glahn, Ana I. Silva, Anne M. Maillard, Tomasz J. Nowakowski, Thomas Bourgeron, Khadije Jizi, Charles-Olivier Martin, Michael John Owen, Jeremy Hall, Institut Pasteur [Paris] (IP), 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], 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), Université de Montréal (UdeM), McGill University = Université McGill [Montréal, Canada], Children’s Hospital of Philadelphia (CHOP ), Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC), Cardiff University, Maastricht University [Maastricht], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of California [Los Angeles] (UCLA), University of Pennsylvania, Harvard Medical School [Boston] (HMS), Boston Children's Hospital, Keck School of Medicine [Los Angeles], University of Southern California (USC), 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). 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). The CHUV cohort was supported by the SNF (Maillard Anne, Project, PMPDP3 171331). 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., Institut Pasteur [Paris], Centre de recherche du CHU Sainte-Justine [Montreal], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), University of California [San Francisco] (UCSF), University of California, and University of Pennsylvania [Philadelphia]
Subjects: 0303 health sciences, medicine.medical_specialty, Multivariate analysis, Concordance, Functional connectivity, Brain morphometry, Cognition, Biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Pleiotropy, medicine, Copy-number variation, Psychiatry, Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Polygenicity and pleiotropy are key properties of the genomic architecture of psychiatric disorders. An optimistic interpretation of polygenicity is that genomic variants converge on a limited set of mechanisms at some level from genes to behavior. Alternatively, convergence may be minimal or absent.We took advantage of brain connectivity, measured by resting-state functional MRI (rs- fMRI), as well as rare and common genomic variants to understand the effects of polygenicity and pleiotropy on large-scale brain networks, a distal step from genes to behavior. We processed ten rs-fMRI datasets including 32,988 individuals, to examine connectome-wide effects of 16 copy number variants (CNVs), 10 polygenic scores, 6 cognitive and brain morphometry traits, and 4 idiopathic psychiatric conditions.Although effect sizes of CNVs on connectivity were correlated to cognition and number of genes, increasing polygenicity was associated with decreasing effect sizes on connectivity. Accordingly, the effect sizes of polygenic scores on connectivity were 6-fold lower compared to CNVs. Despite this heterogeneity of connectivity profiles, multivariate analysis identified convergence of genetic risks and psychiatric disorders on the thalamus and the somatomotor network. Based on spatial correlations with transcriptomic data, we hypothesize that excitatory thalamic neurons may be primary contributors to brain alteration profiles shared across genetic risks and conditions. Finally, pleiotropy measured by genetic and transcriptomic correlations between 38 pairs of conditions/traits showed significant concordance with connectomic correlations, suggesting a substantial causal genetic component for shared connectivity.Such findings open avenues to delineate general mechanisms - amenable to intervention - across conditions and genetic risks.One sentence summaryEffects of rare and common genomic variants on brain functional connectivity shed light on the impact of polygenicity and pleiotropy in psychiatry.
Published: 2021

2. Integration of the SMXL/D53 strigolactone signalling repressors in the model of shoot branching regulation in Pisum sativum

Author: Stephanie C. Kerr, Julie Saffar, Elizabeth A. Dun, Catherine Rameau, Jean-Paul Pillot, Suyash Bhimgonda Patil, Yannick Bellec, Christine A. Beveridge, Sylvie Citerne, Yasmine Ligerot, Alexandre de Saint Germain, and Grégoire Aubert
Subjects: 0106 biological sciences, Cytokinins, Mutant, Arabidopsis, Strigolactone, Plant Science, 01 natural sciences, Lactones, 03 medical and health sciences, chemistry.chemical_compound, Gene Expression Regulation, Plant, Loss of Function Mutation, Auxin, Gene expression, Genetics, Arabidopsis thaliana, Gene, Phylogeny, Plant Proteins, 030304 developmental biology, Feedback, Physiological, 2. Zero hunger, chemistry.chemical_classification, 0303 health sciences, Indoleacetic Acids, biology, Peas, food and beverages, Oryza, Cell Biology, Plants, Genetically Modified, biology.organism_classification, Cell biology, chemistry, Cytokinin, Co-Repressor Proteins, Heterocyclic Compounds, 3-Ring, Signal Transduction, 010606 plant biology & botany
Abstract: DWARF53 (D53) in rice (Oryza sativa) and its homologs in Arabidopsis (Arabidopsis thaliana), SUPPRESSOR OF MAX2-LIKE 6 (SMXL6), SMXL7 and SMXL8, are well established negative regulators of strigolactone signalling involved in shoot branching. Little is known of pea (Pisum sativum) homologs and whether D53 and related SMXLs are specific to strigolactone signalling pathways. Here, we identify two allelic pea mutants, dormant3 (dor3), and demonstrate through gene mapping and sequencing that DOR3 corresponds to a homolog of D53 and SMXL6/SMXL7, designated PsSMXL7. Phenotype analysis, gene expression, protein and hormone quantification assays were performed to determine the role of PsSMXL7 in bud outgrowth regulation and the role of PsSMXL7 and D53 in integrating strigolactone and cytokinin responses. Like D53 and related SMXLs, we show that PsSMXL7 is strigolactone degradable, and induces feedback upregulation of PsSMXL7 transcript. Here we reveal a system conserved in pea and rice, whereby CK also upregulates PsSMXL7/D53 transcripts, providing a clear mechanism for strigolactone and cytokinin cross-talk in the regulation of branching. Further deepening our understanding of the branching network in pea, we provide evidence that strigolactone acts via PsSMXL7 to modulate auxin content via PsAFB5, which itself regulates expression of strigolactone biosynthesis genes. We therefore show that PsSMXL7 is key to a triple hormone network involving an auxin-SL feedback mechanism and SL-CK crosstalk.
Published: 2021
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3. 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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4. Relationship Between Obesity and Ventilator-Associated Pneumonia

Author: Saad Nseir, Amélie Le Gouge, Olivier Pouly, Jean-Baptiste Lascarrou, Jean-Claude Lacherade, Jean-Paul Mira, Emmanuelle Mercier, Pierre-Louis Declercq, Michel Sirodot, Gaël Piton, François Tinturier, Elisabeth Coupez, Stéphane Gaudry, Michel Djibré, Didier Thevenin, Malika Balduyck, Jean Reignier, Hoang-Nam Bui, Olivier Gontier, Jean-Pierre Quenot, Carole Schwebel, Véronique Leray, Nathalie Rolin, Frédéric Bellec, Vincent Das, Antoine Roquilly, Laurent Brisard, Thierry Boulain, Nadia Anguel, Jérôme Devaquet, Virginie Maxime, Daniel Da Silva, Emmanuel Canet, Bertrand Guidet, Charles Grégoire, Frédéric Martino, Delphine Chatelier, Vlad Botoc, Guillaume Thiery, Christine Kummerlen, J-Etienne Herbrecht, Philippe Letocart, Pierre Asfar, Frederique Ganster, Richecoeur Jack, Argaud Laurent, Zerimech Farid, and Maboudou Patrice
Subjects: Pulmonary and Respiratory Medicine, Mechanical ventilation, medicine.medical_specialty, business.industry, Incidence (epidemiology), medicine.medical_treatment, Hazard ratio, Ventilator-associated pneumonia, Critical Care and Intensive Care Medicine, medicine.disease, Intensive care unit, Enteral administration, law.invention, 03 medical and health sciences, 0302 clinical medicine, Parenteral nutrition, 030228 respiratory system, Interquartile range, law, Internal medicine, medicine, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business
Abstract: Background Patients with obesity are at higher risk for community-acquired and nosocomial infections. However, no study has specifically evaluated the relationship between obesity and ventilator-associated pneumonia (VAP). Research Question Is obesity associated with an increased incidence of VAP? Study Design and Methods This study was a post hoc analysis of the Impact of Early Enteral vs Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA2) open-label, randomized controlled trial performed in 44 French ICUs. Adults receiving invasive mechanical ventilation and vasopressor support for shock and parenteral nutrition or enteral nutrition were included. Obesity was defined as BMI ≥ 30 kg/m2 at ICU admission. VAP diagnosis was adjudicated by an independent blinded committee, based on all available clinical, radiologic, and microbiologic data. Only first VAP episodes were taken into account. Incidence of VAP was analyzed by using the Fine and Gray model, with extubation and death as competing risks. Results A total of 699 (30%) of the 2,325 included patients had obesity; 224 first VAP episodes were diagnosed (60 and 164 in obese and nonobese groups, respectively). The incidence of VAP at day 28 was 8.6% vs 10.1% in the two groups (hazard ratio, 0.85; 95% CI 0.63-1.14; P = .26). After adjustment on sex, McCabe score, age, antiulcer treatment, and Sequential Organ Failure Assessment at randomization, the incidence of VAP remained nonsignificant between obese and nonobese patients (hazard ratio, 0.893; 95% CI, 0.66-1.2; P = .46). Although no significant difference was found in duration of mechanical ventilation and ICU length of stay, 90-day mortality was significantly lower in obese than in nonobese patients (272 of 692 [39.3%] patients vs 718 of 1,605 [44.7%]; P = .02). In a subgroup of patients (n = 123) with available pepsin and alpha-amylase measurements, no significant difference was found in rate of abundant microaspiration of gastric contents, or oropharyngeal secretions between obese and nonobese patients. Interpretation Our results suggest that obesity has no significant impact on the incidence of VAP.
Published: 2021
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5. 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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6. Cis-regulatory chromatin loops arise before TADs and gene activation, and are independent of cell fate during early Drosophila development

Author: Mounia Lagha, Olivier Messina, Jean-Bernard Fiche, Markus Götz, Marcelo Nollmann, Ingolf Reim, Sergio Martín Espínola, Andrés M. Cardozo Gizzi, Maelle Bellec, Matthieu Dejean, and Christophe Houbron
Subjects: Regulation of gene expression, 0303 health sciences, Enhancer-Promoter loops, CIS-regulatory modules, Quantitative imaging, purl.org/becyt/ford/3.1 [https], Computational biology, Development, Biology, Cell fate determination, Gene regulation, Chromatin, 03 medical and health sciences, Multicellular organism, 0302 clinical medicine, Chromatin organization, Genetics, purl.org/becyt/ford/3 [https], Enhancer, Transcription factor, 030217 neurology & neurosurgery, 030304 developmental biology, Epigenomics, Cis-regulatory module
Abstract: Acquisition of cell fate is thought to rely on the specific interaction of remote cis-regulatory modules (CRMs), for example, enhancers and target promoters. However, the precise interplay between chromatin structure and gene expression is still unclear, particularly within multicellular developing organisms. In the present study, we employ Hi-M, a single-cell spatial genomics approach, to detect CRM–promoter looping interactions within topologically associating domains (TADs) during early Drosophila development. By comparing cis-regulatory loops in alternate cell types, we show that physical proximity does not necessarily instruct transcriptional states. Moreover, multi-way analyses reveal that multiple CRMs spatially coalesce to form hubs. Loops and CRM hubs are established early during development, before the emergence of TADs. Moreover, CRM hubs are formed, in part, via the action of the pioneer transcription factor Zelda and precede transcriptional activation. Our approach provides insight into the role of CRM–promoter interactions in defining transcriptional states, as well as distinct cell types. Fil: Espínola, Sergio Martín. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Université de Montpellier. Centre de Biologie Structurale; Francia Fil: Götz, Markus. Université de Montpellier. Centre de Biologie Structurale; Francia. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia Fil: Bellec, Maelle. Centre National de la Recherche Scientifique; Francia. Université de Montpellier. Institut de Génétique Moléculaire de Montpellier; Francia. Université de Montpellier. Centre de Biologie Structurale; Francia. Institut National de la Santé et de la Recherche Médicale; Francia Fil: Messina, Olivier. Centre National de la Recherche Scientifique; Francia. Université de Montpellier. Institut de Génétique Moléculaire de Montpellier; Francia. Université de Montpellier. Centre de Biologie Structurale; Francia. Institut National de la Santé et de la Recherche Médicale; Francia Fil: Fiche, Jean Bernard. Université de Montpellier. Centre de Biologie Structurale; Francia. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia Fil: Houbron, Christophe. Université de Montpellier. Centre de Biologie Structurale; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Centre National de la Recherche Scientifique; Francia Fil: Dejean, Matthieu. Centre National de la Recherche Scientifique; Francia. Université de Montpellier. Institut de Génétique Moléculaire de Montpellier; Francia Fil: Reim, Ingolf. Universitat Erlangen Nuremberg; Alemania Fil: Cardozo Gizzi, Andres Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional; Argentina Fil: Lagha, Mounia. Centre National de la Recherche Scientifique; Francia. Université de Montpellier. Institut de Génétique Moléculaire de Montpellier; Francia Fil: Nollmann, Marcelo. Centre National de la Recherche Scientifique; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Université de Montpellier. Centre de Biologie Structurale; Francia
Published: 2021
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7. 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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8. Unraveling reproducible dynamic states of individual brain functional parcellation

Author: Yu Zhang, Pierre Bellec, Max Mignotte, and Amal Boukhdhir
Subjects: Computer science, Stability (learning theory), Neurosciences. Biological psychiatry. Neuropsychiatry, computer.software_genre, 03 medical and health sciences, Functional brain, 0302 clinical medicine, Data-driven brain parcellation, Artificial Intelligence, Voxel, Time windows, Methods, Association (psychology), Within-subject reproducibility, Seed-based parcellation, 030304 developmental biology, 0303 health sciences, business.industry, Applied Mathematics, General Neuroscience, Subject specific, Spatial reproducibility, Between-subject reproducibility, Pattern recognition, Computer Science Applications, Dynamic states of parcellation, Artificial intelligence, High dimensionality, Functional organization, business, computer, 030217 neurology & neurosurgery, RC321-571
Abstract: Data-driven parcellations are widely used for exploring the functional organization of the brain, and also for reducing the high dimensionality of fMRI data. Despite the flurry of methods proposed in the literature, functional brain parcellations are not highly reproducible at the level of individual subjects, even with very long acquisitions. Some brain areas are also more difficult to parcellate than others, with association heteromodal cortices being the most challenging. An important limitation of classical parcellations is that they are static, that is, they neglect dynamic reconfigurations of brain networks. In this paper, we proposed a new method to identify dynamic states of parcellations, which we hypothesized would improve reproducibility over static parcellation approaches. For a series of seed voxels in the brain, we applied a cluster analysis to regroup short (3 min) time windows into “states” with highly similar seed parcels. We split individual time series of the Midnight scan club sample into two independent sets of 2.5 hr (test and retest). We found that average within-state parcellations, called stability maps, were highly reproducible (over 0.9 test-retest spatial correlation in many instances) and subject specific (fingerprinting accuracy over 70% on average) between test and retest. Consistent with our hypothesis, seeds in heteromodal cortices (posterior and anterior cingulate) showed a richer repertoire of states than unimodal (visual) cortex. Taken together, our results indicate that static functional parcellations are incorrectly averaging well-defined and distinct dynamic states of brain parcellations. This work calls to revisit previous methods based on static parcellations, which includes the majority of published network analyses of fMRI data. Our method may, thus, impact how researchers model the rich interactions between brain networks in health and disease., Author Summary Functional brain parcellation has been a very active topic of investigation for the past two decades, yet there is no evidence to date of reproducible results at the individual level—see for example Figure 2 in Gordon, Laumann, Gilmore, et al. (2017), with a Dice coefficient plateauing around 0.7 using 40 min or more of data. In this paper, we show that highly reproducible brain parcels can be observed using short (3 min) time windows. Different modes—or states—of reproducible parcellations can be observed in a single brain region, and these modes have only little overlap with each other. We carefully quantified these individual dynamic states of parcellation using the Midnight Brain Scan dataset, featuring 5 hr of functional MRI per subject. Our results indicate that static functional parcellation are incorrectly averaging well-defined and distinct dynamic states. This brings important caution for any work based on static atlases, which is the dominant approach currently in so-called network analysis of fMRI data.
Published: 2021

9. Influence of 'protective' symbionts throughout the different steps of an aphid–parasitoid interaction

Author: Yannick Outreman, Laura Bellec, Corentin Sochard, Jean-Christophe Simon, Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), 16-CE02-0014, ANR Hmicmac, and ANR-16-CE02-0014,Hmicmac,Co-adaptations hôtes-microbiote: mécanismes et conséquences(2016)
Subjects: 0106 biological sciences, 0301 basic medicine, Hamiltonella defensa, AcademicSubjects/SCI01320, Parasitism, Zoology, 010603 evolutionary biology, 01 natural sciences, Parasitoid, 03 medical and health sciences, Symbiosis, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Evolutionary dynamics, host–parasitoid interactions, Aphid, biology, Host (biology), fungi, AcademicSubjects/SCI01130, Acyrthosiphon pisum, food and beverages, protective symbioses, Articles, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Regiella insecticola, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, 030104 developmental biology, host-parasitoid interactions, Animal Science and Zoology, defensive behaviors, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Microbial associates are widespread in insects, some conferring a protection to their hosts against natural enemies like parasitoids. These protective symbionts may affect the infection success of the parasitoid by modifying behavioral defenses of their hosts, the development success of the parasitoid by conferring a resistance against it or by altering life-history traits of the emerging parasitoids. Here, we assessed the effects of different protective bacterial symbionts on the entire sequence of the host-parasitoid interaction (i.e., from parasitoid attack to offspring emergence) between the pea aphid, Acyrthosiphon pisum, and its main parasitoid, Aphidius ervi and their impacts on the life-history traits of the emerging parasitoids. To test whether symbiont-mediated phenotypes were general or specific to particular aphid–symbiont associations, we considered several aphid lineages, each harboring a different strain of either Hamiltonella defensa or Regiella insecticola, two protective symbionts commonly found in aphids. We found that symbiont species and strains had a weak effect on the ability of aphids to defend themselves against the parasitic wasps during the attack and a strong effect on aphid resistance against parasitoid development. While parasitism resistance was mainly determined by symbionts, their effects on host defensive behaviors varied largely from one aphid–symbiont association to another. Also, the symbiotic status of the aphid individuals had no impact on the attack rate of the parasitic wasps, the parasitoid emergence rate from parasitized aphids nor the life-history traits of the emerging parasitoids. Overall, no correlations between symbiont effects on the different stages of the host–parasitoid interaction was observed, suggesting no trade-offs or positive associations between symbiont-mediated phenotypes. Our study highlights the need to consider various sequences of the host-parasitoid interaction to better assess the outcomes of protective symbioses and understand the ecological and evolutionary dynamics of insect–symbiont associations.
Published: 2020
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10. Task-Induced Functional Connectivity of Picture Naming in Healthy Aging: The Impacts of Age and Task Complexity

Author: Julien Jarret, Pierre Bellec, Simona Maria Brambati, Yves Joanette, Perrine Ferré, and Université de Montréal. Faculté des arts et des sciences. Département de psychologie
Subjects: Functional connectivity, fMRI, 05 social sciences, Picture naming, Cognition, Task-induced functional connectivity, 050105 experimental psychology, Task (project management), 03 medical and health sciences, Healthy aging, 0302 clinical medicine, 0501 psychology and cognitive sciences, Psychology, 030217 neurology & neurosurgery, Language, Cognitive psychology
Abstract: The topological organization of the brain, governed by the capacity of brain regions to synchronize their activity, allows for cost-effective performance during everyday cognitive activity. Functional connectivity is an fMRI method deemed task-specific and demand-dependent. Although the brain undergoes significant changes during healthy aging, conceptual knowledge and word-production accuracy are generally preserved. The exploration of task-induced functional connectivity patterns during active picture naming may thus provide additional information about healthy functional cerebral mechanisms that are specifically adapted to the cognitive activity at hand. The goal of this study is to assess and describe age-related differences in functional connectivity during an overt picture-naming task, as well as to compare age-related differences under complex task demand, defined by lexical frequency. Results suggest both age-specific and task-specific mechanisms. In the context of preserved behavioral performance in a picture-naming task, older adults show a complex array of differences in functional connectivity architecture, including both increases and decreases. In brief, there is increased segregation and specialization of regions that are classically assigned to naming processes. Results also expand on previous word-production studies and suggest that motor regions are particularly subject to age-related differences. This study also provides the first indication that intrinsic task demand, as manipulated by lexical frequency, interacts little with the relationship between age and functional connectivity. Together, these findings confirm the value of task-induced functional connectivity analysis in revealing the brain organization that subserves task performance during healthy aging.
Published: 2020
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11. 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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12. Noninvasive ventilation vs. high-flow nasal cannula oxygen for preoxygenation before intubation in patients with obesity: a post hoc analysis of a randomized controlled trial

Author: Rodriguez, Maeva, Ragot, Stéphanie, Coudroy, Rémi, Quenot, Jean-Pierre, Vignon, Philippe, Forel, Jean-Marie, Demoule, Alexandre, Mira, Jean-Paul, Ricard, Jean-Damien, Nseir, Saad, Colin, Gwenhael, Pons, Bertrand, Danin, Pierre-Eric, Devaquet, Jérome, Prat, Gwenael, Merdji, Hamid, Petitpas, Franck, Vivier, Emmanuel, Mekontso-Dessap, Armand, Nay, Mai-Anh, Asfar, Pierre, Dellamonica, Jean, Argaud, Laurent, Ehrmann, Stephan, Fartoukh, Muriel, Girault, Christophe, Robert, René, Thille, Arnaud, Frat, Jean-Pierre, Chatellier, Delphine, Boissier, Florence, Veinstein, Anne, Dahyot-Fizelier, Claire, Dargent, Auguste, Large, Audrey, Begot, Emmanuelle, Mancia, Claire, Decavele, Maxence, Dres, Martin, Lehingue, Samuel, Papazian, Laurent, Paul, Marine, Marin, Nathalie, Le Meur, Matthieu, Laissy, Mohammed, Rouzé, Anahita, Henry-Lagarrigue, Matthieu, Yehia, Aihem, Martino, Frédéric, Cerf, Charles, Bailly, Pierre, Helms, Julie, Putegnat, Jean Baptiste, Razazi, Keyvan, Boulain, Thierry, Cabasson, Séverin, Wallet, Florent, Klouche, Kada, Bellec, Frédéric, Service de Médecine Intensive Réanimation [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_treatment, Respiratory failure, Critical Care and Intensive Care Medicine, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Hypoxemia, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, High-flow oxygen, law, Preoxygenation, Post-hoc analysis, medicine, Intubation, 030212 general & internal medicine, Obesity, Respiratory system, 2. Zero hunger, business.industry, RC86-88.9, Research, Medical emergencies. Critical care. Intensive care. First aid, 3. Good health, Intubation procedure, 030228 respiratory system, Anesthesia, Non-invasive ventilation, medicine.symptom, business, Nasal cannula
Abstract: Background Critically ill patients with obesity may have an increased risk of difficult intubation and subsequent severe hypoxemia. We hypothesized that pre-oxygenation with noninvasive ventilation before intubation as compared with high-flow nasal cannula oxygen may decrease the risk of severe hypoxemia in patients with obesity. Methods Post hoc subgroup analysis of critically ill patients with obesity (body mass index ≥ 30 kg·m−2) from a multicenter randomized controlled trial comparing preoxygenation with noninvasive ventilation and high-flow nasal oxygen before intubation of patients with acute hypoxemic respiratory failure (PaO2/FiO2 Results Among the 313 patients included in the original trial, 91 (29%) had obesity with a mean body mass index of 35 ± 5 kg·m−2. Patients with obesity were more likely to experience an episode of severe hypoxemia during intubation procedure than patients without obesity: 34% (31/91) vs. 22% (49/222); difference, 12%; 95% CI 1 to 23%; P = 0.03. Among patients with obesity, 40 received preoxygenation with noninvasive ventilation and 51 with high-flow nasal oxygen. Severe hypoxemia occurred in 15 patients (37%) with noninvasive ventilation and 16 patients (31%) with high-flow nasal oxygen (difference, 6%; 95% CI − 13 to 25%; P = 0.54). The lowest pulse oximetry values during intubation procedure were 87% [interquartile range, 77–93] with noninvasive ventilation and 86% [78–92] with high-flow nasal oxygen (P = 0.98). After multivariable analysis, factors independently associated with severe hypoxemia in patients with obesity were intubation difficulty scale > 5 points and respiratory primary failure as reason for admission. Conclusions Patients with obesity and acute hypoxemic respiratory failure had an increased risk of severe hypoxemia during intubation procedure as compared to patients without obesity. However, preoxygenation with noninvasive ventilation may not reduce this risk compared with high-flow nasal oxygen. Trial registration Clinical trial number: NCT02668458 (http://www.clinicaltrials.gov)
Published: 2021
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13. 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, 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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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14. 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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15. The control of transcriptional memory by stable mitotic bookmarking

Author: Mounia Lagha, Melissa M. Harrison, George Hunt, Jeremy Dufourt, Antonio Trullo, Maelle Bellec, Cyril Favard, Jean-Christophe Andrau, Ovidiu Radulescu, Mattias Mannervik, Hélène Lenden-Hasse, Marissa M Gaskill, Marie Lamarque, Heloïse Faure-Gautron, Amal Zine El Aabidine, Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: [SDV]Life Sciences [q-bio], General Physics and Astronomy, Mitosis, General Biochemistry, Genetics and Molecular Biology, Histones, 03 medical and health sciences, Gene expression, Animals, Transcription factor, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, Bookmarking, 030302 biochemistry & molecular biology, Acetylation, General Chemistry, Chromatin, Cell biology, Histone, Mitotic exit, biology.protein, Maternal to zygotic transition, Drosophila, Transcription Factors
Abstract: To maintain cellular identities during development, gene expression profiles must be faithfully propagated through cell generations. The reestablishment of gene expression patterns upon mitotic exit is thought to be mediated, in part, by mitotic bookmarking by transcription factors (TF). However, the mechanisms and functions of TF mitotic bookmarking during early embryogenesis remain poorly understood. In this study, taking advantage of the naturally synchronized mitoses of Drosophila early embryos, we provide evidence that the pioneer-like transcription factor GAF acts as stable mitotic bookmarker during zygotic genome activation. We report that GAF remains associated to a large fraction of its interphase targets including at cis-regulatory sequences of key developmental genes, with both active and repressive chromatin signatures. GAF mitotic targets are globally accessible during mitosis and are bookmarked via histone acetylation (H4K8ac). By monitoring the kinetics of transcriptional activation in living embryos, we provide evidence that GAF binding establishes competence for rapid activation upon mitotic exit.
Published: 2021

16. Bazooka/Par3 cooperates with Sanpodo for the assembly of Notch clusters following asymmetric division of Drosophila sensory organ precursor cells

Author: Elise Houssin, Karen Bellec, Roland Le Borgne, Mathieu Pinot, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), University of Glasgow, ANR-16-CE13-004-01, Agence Nationale de la Recherche, Equipe Labellis&#x00E9, e, Ligue Contre le Cancer, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and ANR-16-CE13-0004,CYTOSIGN,Polarité épithéliale et signalisation au cours de la cytodiérèse des cellules animales(2016)
Subjects: animal structures, Cell division, QH301-705.5, Science, [SDV]Life Sciences [q-bio], Notch signaling pathway, Cell fate determination, Biology, asymmetric cell division, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, developmental biology, 0302 clinical medicine, cell biology, Asymmetric cell division, polarity, Biology (General), 030304 developmental biology, 0303 health sciences, General Immunology and Microbiology, D. melanogaster, General Neuroscience, General Medicine, Par3, Cell biology, Ubiquitin ligase, Signalling, biology.protein, Notch signalling, Medicine, epithelium, Developmental biology, 030217 neurology & neurosurgery, Cytokinesis
Abstract: In multiple cell lineages, Delta-Notch signalling regulates cell fate decisions owing to unidirectional signalling between daughter cells. In Drosophila pupal sensory organ lineage, Notch regulates the intra-lineage pIIa/pIIb fate decision at cytokinesis. Notch and Delta that localise apically and basally at the pIIa-pIIb interface are expressed at low levels and their residence time at the plasma membrane is in the order of minutes. How Delta can effectively interact with Notch to trigger signalling from a large plasma membrane area remains poorly understood. Here, we report that the signalling interface possesses a unique apico-basal polarity with Par3/Bazooka localising in the form of nano-clusters at the apical and basal level. Notch is preferentially targeted to the pIIa-pIIb interface, where it co-clusters with Bazooka and its cofactor Sanpodo. Clusters whose assembly relies on Bazooka and Sanpodo activities are also positive for Neuralized, the E3 ligase required for Delta activity. We propose that the nano-clusters act as snap buttons at the new pIIa-pIIb interface to allow efficient intra-lineage signalling.
Published: 2021
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17. 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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18. The Consortium for the early identification of Alzheimer's disease–Quebec (CIMA‐Q)

Author: Sylvie Belleville, Andréa C. LeBlanc, Marie‐Jeanne Kergoat, Frédéric Calon, Pierrette Gaudreau, Sébastien S. Hébert, Carol Hudon, Nicole Leclerc, Naguib Mechawar, Simon Duchesne, Serge Gauthier, Consortium for the Early Identification of Alzheimer's disease‐Quebec (CIMA‐Q), Pierre Bellec, Christian Bocti, Howard Chertkow, Louis Collins, Stephen Cunnane, Carol Hudon Marie‐Jeanne‐Kergoat, Natalie Philips, Jean‐Paul Soucy, Thien Thanh Dang Vu, Louis Verret, and Juan Manuel Villalpando
Subjects: Oncology, medicine.medical_specialty, Cryopreserved PBMNC, Disease, lcsh:Geriatrics, Peripheral blood mononuclear cell, lcsh:RC346-429, 03 medical and health sciences, 0302 clinical medicine, CIMA-Q, Neuroimaging, Internal medicine, Medicine, Dementia, Cognitive decline, CIMA‐Q, lcsh:Neurology. Diseases of the nervous system, Diagnostic Assessment & Prognosis, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, Consortium for the early identification of Alzheimer's disease-Quebec, business.industry, Lumbar puncture, Neuropsychology, Mild cognitive impairment, Biomarker, Alzheimer's disease, Early diagnosis, medicine.disease, 3. Good health, lcsh:RC952-954.6, Psychiatry and Mental health, Subjective cognitive decline, Biomarker (medicine), Neurology (clinical), Consortium for the early identification of Alzheimer's disease‐Quebec, business, 030217 neurology & neurosurgery, Clinical cohort
Abstract: Introduction The Consortium for the early identification of Alzheimer's disease–Quebec (CIMA-Q) created a research infrastructure to recruit, characterize, and track disease progression in individuals at risk of dementia. Methods CIMA-Q established standardized clinical, neuropsychological, neuroimaging, blood (plasma, serum, RNA, genomic DNA), cryopreserved peripheral blood mononuclear cells, and cerebrospinal fluid collection protocols. These data and biological materials are available to the research community. Results In phase 1, 115 persons with subjective cognitive decline, 88 with mild cognitive impairment, 31 with early probable Alzheimer's disease, and 56 older adults with no worries nor impairments received detailed clinical and cognitive evaluations as well as blood and peripheral blood mononuclear cells collections. Among them, 142 underwent magnetic resonance imaging, 29 a 18fluorodeoxyglucose positron emission tomography, and 60 a lumbar puncture. Discussion CIMA-Q provides procedures and resources to identify early biomarkers and novel therapeutic targets, and holds promise for detecting cognitive decline in Alzheimer's disease., Highlights • Well-ascertained cohort of 290 community-dwelling elderly individuals in Quebec. • Large number of individuals with subjective cognitive decline studied longitudinally. • Clinical, neuropsychology, neuroimaging, and biomaterials available for Alzheimer's disease studies.
Published: 2019
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19. 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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20. 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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21. 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

22. Imaging translation dynamics in live embryos reveals spatial heterogeneities

Author: Antonio Trullo, Maelle Bellec, Jeremy Dufourt, Matthieu Dejean, Sylvain de Rossi, Cyril Favard, Mounia Lagha, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Infectiologie de Montpellier (IRIM), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Dufourt, Jeremy
Subjects: Embryo, Nonmammalian, [SDV]Life Sciences [q-bio], Biology, 03 medical and health sciences, 0302 clinical medicine, Protein biosynthesis, Animals, RNA, Messenger, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Messenger RNA, Multidisciplinary, Dynamics (mechanics), RNA, Embryo, Translation (biology), Single Molecule Imaging, Cell biology, [SDV] Life Sciences [q-bio], Multicellular organism, Kinetics, Drosophila melanogaster, Protein Biosynthesis, 030217 neurology & neurosurgery
Abstract: Quantifying translation in space and time During development, precise control of gene expression establishes reproducible patterns, leading to the formation of organs at the right time and place. The emergence of developmental patterns has been primarily studied at the transcriptional level, but the fate of these transcripts has received little attention. Dufourt et al. used the SunTag labeling method to image the dynamics of translation of individual messenger RNA (mRNA) molecules in living fruit fly embryos. This work revealed “translation factories”—clusters of mRNA and translation machinery—and heterogeneities in the efficiency of translation between identical mRNAs. Science , abc3483, this issue p. 840
Published: 2021
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23. 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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24. Fourteen-day survival among older adults with severe infection with severe acute respiratory syndrome coronavirus 2 treated with corticosteroid: a cohort study

Author: Laure Gallay, Viet-Thi Tran, Elodie Perrodeau, Nicolas Vignier, Matthieu Mahevas, Francesca Bisio, Emmanuel Forestier, Francois-Xavier Lescure, François-Xavier Lescure, Thibaut Fraisse, Diane Sanderink, Bertrand Lioger, Camille Boutrou, Anne - Laure Destrem, Pascal Gicquel, Martin Martinot, Jérémie Pasquier, Jean Reuter, Helene Desmurs-Clavel, Nicolas Benech, Boris Bienvenu, Guillemette Frémont, François Goehringer, Guillaume Chapelet, Olivier Grossi, Didier Laureillard, Cyrille Gourjault, Alexandre Lahens, Célia Azoulay, Nicolas Carlier, Gianpiero Tebano, Jérôme Pacanowski, Simone Tunesi, Nadège Lemaire, Laurent Bellec, Firouze Bani-Sadr, Marie Pichenot, Kevin Alexandre, Laurie Masse, Olivier Robineau, Camille Thorey, Sophie Deriaz, Julien Saison, Marie Gousseff, Laura Goehrs, Fanny Pommeret, and Université de Paris, Centre de Recherche Epidémiologie et Statistiques (CRESS UMR 1153) (CRESS UMR 1153)
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], 030106 microbiology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Prednisone, Internal medicine, medicine, 030212 general & internal medicine, Adverse effect, ComputingMilieux_MISCELLANEOUS, business.industry, Hazard ratio, General Medicine, medicine.disease, 3. Good health, Pneumonia, Infectious Diseases, Relative risk, Corticosteroid, business, medicine.drug, Cohort study
Abstract: Objective To assess the effectiveness of corticosteroids among older adults with coronavirus disease 2019 (COVID-19) pneumonia requiring oxygen. Methods We used routine care data from 36 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids with at least 0.4 mg/kg/day equivalent prednisone (treatment group) versus standard of care (control group). Participants were adults aged 80 years or older with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or CT scan images typical of COVID-19 pneumonia, requiring oxygen ≥3 L/min, and with an inflammatory syndrome (C-reactive protein ≥40 mg/L). The primary outcome was overall survival at day 14. 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 267 patients included in the analysis, 98 were assigned to the treatment group. Their median age was 86 years (interquartile range 83–90 years) and 95% had a SARS-CoV-2 PCR-confirmed diagnosis. In total, 43/98 (43.9%) patients in the treatment group and 84/166 (50.6%) in the control group died before day 14 (weighted hazard ratio 0.67, 95% CI 0.46–0.99). The treatment and control groups did not differ significantly for the proportion of patients discharged to home/rehabilitation at day 14 (weighted relative risk 1.12, 95% CI 0.68–1.82). Twenty-two (16.7%) patients receiving corticosteroids developed adverse events, but only 11 (6.4%) from the control group. Conclusions Corticosteroids were associated with a significant increase in the overall survival at day 14 of patients aged 80 years and older hospitalized for severe COVID-19.
Published: 2021
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25. 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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26. 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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27. Bazooka/Par3 cooperates with Sanpodo for the assembly of Notch signaling clusters following asymmetric division of Drosophila sensory organ precursor cells

Author: E. Houssin, Karen Bellec, R. Le Borgne, Mathieu Pinot, Université Laval [Québec] (ULaval), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: 0303 health sciences, Polarity (international relations), Cell division, biology, [SDV]Life Sciences [q-bio], Cell, Notch signaling pathway, Cell fate determination, Ubiquitin ligase, Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Precursor cell, biology.protein, medicine, 030217 neurology & neurosurgery, Cytokinesis, 030304 developmental biology
Abstract: SummaryIn multiple cell lineages, Delta-Notch signaling regulates cell fate decisions owing to unidirectional signaling between daughter cells. InDrosophilapupal sensory organ lineage, Notch regulates pIIa/pIIb fate decision at cytokinesis. Notch and Delta that localize apically and basally at the pIIa-pIIb interface, are expressed at low levels and their residence time at the plasma membrane is in the order of the minute. How Delta can effectively interact with Notch to trigger signaling from a large plasma membrane remains poorly understood. Here, we report that the signaling interface possesses a unique apicobasal polarity with Par3/Bazooka localizing in the form of nano-clusters at the apical and basal level. Notch is preferentially targeted to the pIIa-pIIb interface where it co-clusters with Bazooka and the Notch cofactor Sanpodo. Clusters whose assembly relies on Bazooka and Sanpodo activities, are also positive for Neuralized, the E3 ligase required for Delta-activity. We propose that the nano-clusters act as snap buttons at the new pIIa-pIIb interface to allow efficient intra-lineage signaling.
Published: 2021

28. 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

29. Clathrin adaptor AP-1 and Stratum act in parallel pathways to control Notch activation in Drosophila Sensory Organ Precursor Cells

Author: Mathieu Pinot, Karen Bellec, Roland Le Borgne, Isabelle Gicquel, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), ANR-16-CE13-0004 Cytosign, Agence Nationale pour La Recherche, Fondation pour la Recherche Médiclae (FRM) FDT, ANR-16-CE13-0004,CYTOSIGN,Polarité épithéliale et signalisation au cours de la cytodiérèse des cellules animales(2016), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio], Adaptor Protein Complex 1, Notch signaling pathway, Penetrance, Cell fate determination, Clathrin, 03 medical and health sciences, Precursor cell, Cell polarity, Asymmetric cell division, Animals, Drosophila Proteins, Guanine Nucleotide Exchange Factors, Cell Lineage, Molecular Biology, Notch signaling, 030304 developmental biology, Epithelial polarity, Cell Nucleus, 0303 health sciences, Receptors, Notch, biology, Chemistry, Stem Cells, 030302 biochemistry & molecular biology, Cell Polarity, Sense Organs, AP-1, Stratum, Cell biology, Midbody, Drosophila melanogaster, Phenotype, Gain of Function Mutation, biology.protein, Notch signalling, Cytokinesis, Intracellular, Intracellular trafficking, Research Article, Developmental Biology
Abstract: Drosophila sensory organ precursors divide asymmetrically to generate pIIa/pIIb cells, the identity of which relies on activation of Notch at cytokinesis. Although Notch is present apically and basally relative to the midbody at the pIIa-pIIb interface, the basal pool of Notch is reported to be the main contributor for Notch activation in the pIIa cell. Intra-lineage signalling requires appropriate apico-basal targeting of Notch, its ligand Delta and its trafficking partner Sanpodo. We have previously reported that AP-1 and Stratum regulate the trafficking of Notch and Sanpodo from the trans-Golgi network to the basolateral membrane. Loss of AP-1 or Stratum caused mild Notch gain-of-function phenotypes. Here, we report that their concomitant loss results in a penetrant Notch gain-of-function phenotype, indicating that they control parallel pathways. Although unequal partitioning of cell fate determinants and cell polarity were unaffected, we observed increased amounts of signalling-competent Notch as well as Delta and Sanpodo at the apical pIIa-pIIb interface, at the expense of the basal pool of Notch. We propose that AP-1 and Stratum operate in parallel pathways to localize Notch and control where receptor activation takes place., Summary: The Notch pathway activation relies on the correct localization of the Notch signalling actors. We report that AP-1 and Stratum ensure the basolateral targeting of Notch during asymmetric cell division.
Published: 2021
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30. Palliative care in hematopoietic stem-cell transplanted patients: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

Author: Valérie Coiteux, Alice Polomeni, Malika Ainaoui, Adeline Bellec, Chloé Prod’homme, Jacinthe Bonneau, Thomas Descamps, Amandine Charbonnier, Aurélie Berr, Murielle Goncalves, Agnès Ruscassie, Eva de Berranger, Marion Gire, Cécile Borel, Ibrahim Yakoub-Agha, HAL-SU, Gestionnaire, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pontchaillou [Rennes], Institut de Cancérologie de Strasbourg Europe (ICANS), CHU Amiens-Picardie, Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Cancer Research, medicine.medical_specialty, Palliative care, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Soins palliatifs, Medicine, Radiology, Nuclear Medicine and imaging, Gynecology, Hematopoietic cell transplantation, Multidisciplinary approach, Pluridisciplinarité, business.industry, Allogreffe, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, General Medicine, Allogreffe pédiatrique, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, business
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., L’allogreffe de cellules hématopoïétiques, seule perspective curative pour certaines hémopathies malignes, comporte des risques de morbi-mortalité importants. Les attentes des patients et de leurs proches vis-à-vis de la procédure, les incertitudes pronostiques, ainsi que l’existence de nouvelles possibilités thérapeutiques, engendrent un recours fréquent, onéreux aux soins intensifs. Si les médecins greffeurs maîtrisent parfaitement les soins actifs, leur connaissance en ce qui concerne les soins palliatifs est limitée, rendant l’accès à ces soins très restreint et souvent tardif. Favorisant une réflexion sur la proportionnalité des soins et sur la qualité de vie des patients, les soins palliatifs peuvent contribuer à la prise en charge des patients allogreffés et à l’accompagnement de leurs proches. Néanmoins, des obstacles à cette approche demeurent. Cet article a pour objectif de proposer des recommandations pour favoriser l’intégration de la démarche palliative au sein des unités d’allogreffe.
Published: 2021
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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. The Clathrin adaptor AP-1 and the Rab-stabilizing chaperone Stratum act in two parallel pathways to control the activation of the Notch pathway in Drosophila

Author: Isabelle Gicquel, Karen Bellec, Roland Le Borgne, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, biology, Chemistry, Notch signaling pathway, Clathrin, Cell biology, 03 medical and health sciences, Midbody, 0302 clinical medicine, Chaperone (protein), biology.protein, Rab, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030217 neurology & neurosurgery, Cytokinesis, Intracellular, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Epithelial polarity
Abstract: Drosophila sensory organ precursors divide asymmetrically to generate pIIa/pIIb cells whose identity relies on the differential activation of Notch during cytokinesis. While Notch is present apically and basally relative to the midbody at the pIIa-pIIb interface, only the basal pool of Notch is reported to contribute to Notch activation in the pIIa cell. Such proper intra-lineage signalling therefore requires appropriate apico-basal targeting of Notch, its ligand Delta and its trafficking partner Sanpodo. We previously reported that AP-1 and Stratum regulate the intracellular trafficking of Notch and Sanpodo from the trans-Golgi network to basolateral membrane. Loss of AP-1 or of Stratum caused mild Notch phenotype. Here, we report that the concomitant loss of AP-1 and Stratum result in the stabilization of the apical pool of Notch, Delta and Spdo, the loss of the basal pool of Notch at the pIIa-pIIb interface, and is associated with activation of Notch in the two SOP daughters. We propose that AP-1 and Stratum control two parallel pathways towards plasma membrane and that Notch intra-lineage signalling could also occur at the apical pIIa-pIIb interface.
Published: 2020

33. Cis-regulatory chromatin loops arise before TADs and gene activation, and are independent of cell fate during development

Author: Maelle Bellec, Christophe Houbron, Andrés M. Cardozo Gizzi, Jean-Bernard Fiche, Marcelo Nollmann, Markus Götz, Sergio Martín Espínola, Mounia Lagha, Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Regulation of gene expression, 0303 health sciences, Cell type, [SDV]Life Sciences [q-bio], Promoter, Computational biology, Biology, Cell fate determination, Chromatin, 03 medical and health sciences, Multicellular organism, 0302 clinical medicine, Enhancer, Transcription factor, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: During development, naïve cells gradually acquire distinct cell fates, through sophisticated mechanisms of precise spatio-temporal gene regulation. Acquisition of cell fate is thought to rely on the specific interaction of remotecis-regulatory modules (e.g. enhancers, silencers) (CRM) and target promoters. However, the precise interplay between chromatin structure and gene expression is still unclear, particularly in single cells within multicellular developing organisms. Here we employ Hi-M, a single-cell spatial genomics approach, to systematically detect CRM-promoter looping interactions within topological associating domains (TADs) duringDrosophiladevelopment. By comparingcis-regulatory loops in alternate cell types, we show that physical proximity does not necessarily instruct transcriptional states. Moreover, multi-way analyses revealed the existence of local interactions between multiple remote CRMs to form hubs. We found that loops and CRM hubs are established early during development, prior to the emergence of TADs. Moreover, CRM hubs are formed via the action of the pioneer transcription factor Zelda and precede transcriptional activation. Our approach offers a new perspective on the role of CRM-promoter interactions in defining transcriptional activation and repression states, as well as distinct cell types.
Published: 2020

34. Imaging translation dynamics in live embryos reveals spatial heterogeneities

Author: Antonio Trullo, Maelle Bellec, Mounia Lagha, Sylvain de Rossi, Matthieu Dejean, Jeremy Dufourt, Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Regulation of gene expression, TRANSCRIPTION FACTOR TWIST, 0303 health sciences, Messenger RNA, [SDV]Life Sciences [q-bio], 030302 biochemistry & molecular biology, Translation (biology), Embryo, Biology, Cell biology, 03 medical and health sciences, Multicellular organism, Simultaneous visualization, Transcription (biology), 030304 developmental biology
Abstract: The translation of individual mRNA molecules is a key biological process, yet this multi-step process has never been imaged in living multicellular organisms. Here we deploy the recently developed Suntag method to visualize and quantify translation dynamics of single mRNAs in living Drosophila embryos. By focusing on the translation of the conserved major epithelial-mesenchymal transition (EMT)-inducing transcription factor Twist, we identified spatial heterogeneity in mRNA translation efficiency and reveal the existence of translation factories, where clustered mRNAs are co-translated preferentially at basal perinuclear regions. Simultaneous visualization of transcription and translation dynamics in a living multicellular organism opens exciting new avenues for understanding of gene regulation during development.
Published: 2020

35. Live‐imaging of revertant and therapeutically restored dystrophin in the Dmd EGFP‐mdx mouse model for Duchenne muscular dystrophy

Author: Adrien Morin, Amalia Stantzou, Olga Petrova, Tudor Manoliu, Markus Schuelke, Isabelle Richard, Helge Amthor, Mina V. Petkova, Corinne Laplace-Builhé, Luis Garcia, Franziska Seifert, Susanne Morales-Gonzalez, Jessica Bellec‐Dyevre, Aurélie Goyenvalle, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt-Universität zu Berlin, Institut Gustave Roussy (IGR), Laboratoire International Associé 'Biothérapies Appliquées aux Handicaps Neuromusculaires' (LIA BAHN), Centre Scientifique de Monaco, Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hôpital Raymond Poincaré [AP-HP], Association FranÃ§aise contre les Myopathies, AFM Deutsche Forschungsgemeinschaft, DFG: 369424301 CDFA‐06‐11 Deutsche Forschungsgemeinschaft, DFG Association FranÃ§aise contre les Myopathies, AFM Deutsche Forschungsgemeinschaft, DFG: 369424301 CDFA‐06‐11 Deutsche Forschungsgemeinschaft, DFG Association FranÃ§aise contre les Myopathies, AFM Association FranÃ§aise contre les Myopathies, AFM, We thank Synthena (Bern, Switzerland) for providing tcDNA and Thomas Bestetti for performing tcDNA injections. This work was supported by the Association Monegasque contre les Myopathies, the Action Benni&Co, the German research foundation (DFG, project number: 369424301), the Université Franco‐Allemande (CDFA‐06‐11) and the Association Française contre les Myopathies. We thank Dr. Jan Schmoranzer from the Charité AMBIO imaging facility for his help and Dr. Feng Zhang for the plasmid pX601‐AAV‐CMV::NLS‐SaCas9‐NLS‐3xHA‐bGHpA, U6::BsaI‐sgRNA. Open access funding enabled and organized by Projekt DEAL., This work was supported by the Association Monégasque contre les Myopathies, the Action Benni&Co, the German research foundation (DFG, project number: 369424301), the Université Franco‐Allemande (CDFA‐06‐11), and the Association Française contre les Myopathies., Université Humboldt de Berlin, CHU Raymond Poincaré, Richard, Isabelle, and Humboldt University Of Berlin
Subjects: 0301 basic medicine, musculoskeletal diseases, Duchenne muscular dystrophy, mdx mouse, congenital, hereditary, and neonatal diseases and abnormalities, tcDNA, Histology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV]Life Sciences [q-bio], Nonsense mutation, Biology, revertant muscle fibre, Pathology and Forensic Medicine, 03 medical and health sciences, Exon, 0302 clinical medicine, In vivo, Physiology (medical), medicine, CRISPR/Cas9, dystrophin-EGFP fusion protein, ComputingMilieux_MISCELLANEOUS, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, musculoskeletal system, mdx reporter mouse model, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, Neurology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, biology.protein, Neurology (clinical), Dystrophin, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, 030217 neurology & neurosurgery, Ex vivo, Intravital microscopy
Abstract: International audience; Background: Dmdmdx, harbouring the c.2983C>T nonsense mutation in Dmd exon 23, is a mouse model for Duchenne muscular dystrophy (DMD), frequently used to test therapies aimed at dystrophin restoration. Current translational research is methodologically hampered by the lack of a reporter mouse model, which would allow direct visualization of dystrophin expression as well as longitudinal in vivo studies. Methods: We generated a DmdEGFP-mdx reporter allele carrying in cis the mdx-23 mutation and a C-terminal EGFP-tag. This mouse model allows direct visualization of spontaneously and therapeutically restored dystrophin-EGFP fusion protein either after natural fibre reversion, or for example, after splice modulation using tricyclo-DNA to skip Dmd exon 23, or after gene editing using AAV-encoded CRISPR/Cas9 for Dmd exon 23 excision. Results: Intravital 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. Conclusion: Intravital imaging of DmdEGFP-mdx muscle permits novel experimental approaches such as the study of revertant and therapeutically restored dystrophin in vivo and ex vivo.
Published: 2020
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36. Minimal Consequences of CMAH and DBA/2 Backgrounds on a FKRP Deficient Model

Author: Isabelle Richard, Evelyne Gicquel, Jessica Bellec, William Lostal, Camille Vaubourg, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, and Richard, Isabelle
Subjects: 0301 basic medicine, mdx mouse, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Inflammation, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Mixed Function Oxygenases, genetic background, 03 medical and health sciences, Mice, 0302 clinical medicine, Fibrosis, medicine, gene modifiers, Animals, Pentosyltransferases, Muscular dystrophy, Gene, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Regeneration (biology), Binding protein, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Phenotype, Molecular biology, animal models, Disease Models, Animal, 030104 developmental biology, Neurology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Muscular Dystrophies, Limb-Girdle, Mice, Inbred mdx, muscular dystrophies, Neurology (clinical), medicine.symptom, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: Muscular dystrophies (MD) are a large group of genetic diseases characterized by a progressive loss of muscle. The Latent TGFβ Binding Protein 4 (LTBP4) in the DBA/2 background and the Cytidine Monophosphate-sialic Acid Hydroxylase (CMAH) proteins were previously identified as genetic modifiers in severe MD. Objective: We investigated whether these modifiers could also influence a mild phenotype such as the one observed in a mouse model of Limb-Girdle MD2I (LGMD2I). Methods: The FKRPL276I mouse model was backcrossed onto the DBA/2 background, and in separate experiments the Cmah gene was inactivated in FKRPL276I mice by crossing with a Cmah-/- mouse and selecting the double-mutants. The mdx mouse was used as control for these two genome modifications. Consequences at the histological level as well as quantification of expression level by RT-qPCR of genes relevant for muscular dystrophy were then performed. Results: We observed minimal to no effect of the DBA/2 background on the mild FKRPL276I mouse phenotype, while this same background was previously shown to increase inflammation and fibrosis in the mdx mouse. Similarly, the Cmah-/- deletion had no observable effect on the FKRPL276I mouse phenotype whereas it was seen to increase features of regeneration in mdx mice. Conclusions: These modifiers were not observed to impact the severity of the presentation of the mild FKRPL276I model. An interesting association of the CMAH modifier with the regeneration process in the mdx model was seen and sheds new light on the influence of this protein on the dystrophic phenotype.
Published: 2020
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37. Rhythms during the polar night: evidence of clock-gene oscillations in the Arctic scallop Chlamys islandica

Author: Damien Tran, Lionel Camus, Hector Andrade, Laure Bellec, Mickael Perrigault, Carl Ballantine, Environnements et Paléoenvironnements OCéaniques (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, Light, Circadian clock, Zoology, 010603 evolutionary biology, 01 natural sciences, bivalve, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Chlamys islandica, Circadian Clocks, arctic, clock genes, Animals, 030304 developmental biology, General Environmental Science, 0303 health sciences, Chronobiology, polar night, General Immunology and Microbiology, biology, Polar night, Arctic Regions, behavior, General Medicine, Darkness, biology.organism_classification, Circadian Rhythm, behaviour, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, CLOCK, Pectinidae, Light intensity, Arctic, 13. Climate action, marine chronobiology, [SDV.EE.BIO]Life Sciences [q-bio]/Ecology, environment/Bioclimatology, General Agricultural and Biological Sciences
Abstract: Arctic regions are highly impacted by climate change and are characterized by drastic seasonal changes in light intensity and duration with extended periods of permanent light or darkness. Organisms use cyclic variations in light to synchronize daily and seasonal biological rhythms to anticipate cyclic variations in the environment, to control phenology and to maintain fitness. In this study, we investigated the diel biological rhythms of the Arctic scallop, Chlamys islandica , during the autumnal equinox and polar night. Putative circadian clock genes and putative light perception genes were identified in the Arctic scallop. Clock gene expression oscillated in the three tissues studied (gills, muscle, mantle edge). The oscillation of some genes in some tissues shifted from daily to tidal periodicity between the equinox and polar night periods and was associated with valve behaviour. These results are the first evidence of the persistence of clock gene expression oscillations during the polar night and might suggest that functional clockwork could entrain rhythmic behaviours in polar environments.
Published: 2020
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38. 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

39. The general impact of haploinsufficiency on brain connectivity underlies the pleiotropic effect of neuropsychiatric CNVs

Author: Claudia Modenato, Amy Lin, Sarah Lippé, Carrie E. Bearden, Aurélie Labbe, David Edmund Johannes Linden, Marianne Bernadette van den Bree, Jean-Louis Martineau, Nadine Younis, Pierre Bellec, Petra Tamer, Sebastian Urchs, Hanad Sharmarke, Aia E. Jønch, Elise Douard, Khadije Jizi, Sandra Martin-Brevet, Clara Moreau, Jeremy Hall, Anne M. Maillard, Sébastien Jacquemont, Charles-Olivier Martin, Celia M. T. Greenwood, Guillaume Huguet, Pierre Orban, Kumar Kuldeep, Paul M. Thompson, Michael John Owen, and Ana I. Silva
Subjects: Genetics, 0303 health sciences, congenital, hereditary, and neonatal diseases and abnormalities, endocrine system diseases, Cognition, Biology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Autism spectrum disorder, Schizophrenia, Basal ganglia, mental disorders, medicine, Autism, Attention deficit hyperactivity disorder, Copy-number variation, Haploinsufficiency, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Large effect-size mutations such as copy number variants (CNVs) have the potential to provide key insights into the underlying biological mechanisms linking deleterious genetic variants to brain architecture and neuropsychiatric disorders. To date, the effect of CNVs on functional brain connectivity remains mostly unstudied, and findings are derived from analyses conducted one mutation at a time. The lack of systematic cross-CNV comparisons hinders our understanding of any potential general mechanisms linking CNVs to effects on brain organization. We performed connectome-wide analyses using resting-state functional MRI data from 436 carriers of neuropsychiatric CNVs at the 1q21.1, 15q11.2, 16p11.2, 22q11.2 loci, and 4 neutral-effect CNVs, 66 carriers of scarcer neuropsychiatric CNVs, 756 individuals with idiopathic autism spectrum disorder (ASD), schizophrenia, attention deficit hyperactivity disorder, and 5,377 controls. Neuropsychiatric CNVs showed global shifts of mean connectivity. The effect size of CNVs on relative connectivity (adjusted for the mean) was correlated with the known level of neuropsychiatric risk conferred by CNVs. We reported architecture similarities between individuals with idiopathic psychiatric conditions and high-risk neuropsychiatric-CNVs, predominantly in the thalamus, the posterior cingulate cortex, and the anterior insula. We identified a linear relationship between connectivity and intolerance to haploinsufficiency measured for all genes encompassed by CNVs across 18 loci. This profile involved the thalamus, the basal ganglia, somatomotor and frontoparietal networks and was correlated with lower general intelligence and higher autism severity scores. An exploratory factor analysis confirmed the contribution of these regions to three latent components shared across CNVs and neuropsychiatric disorders. We posit that deleting genes intolerant to haploinsufficiency reorganize connectivity along general dimensions irrespective of where deletions occur in the genome. This haploinsufficiency brain signature opens new avenues to understand polygenicity in psychiatric conditions and the pleiotropic effect of CNVs on cognition and risk for neuropsychiatric disorders.
Published: 2020
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40. Brainhack: Developing a culture of open, inclusive, community-driven neuroscience

Author: Selim Melvin Atay, Iska Moxon-Emre, Anders Eklund, Paula P. Brooks, Nandita Vijayakumar, Anibal Sólon Heinsfeld, Jean-Baptiste Poline, Yaroslav O. Halchenko, David Meunier, Daniela M. Hohmann, Martin Szinte, Arshitha Basavaraj, Andrija Štajduhar, Link Tejavibulya, Michael Dayan, Anisha Keshavan, Chao Jiang, Felix Hoffstaedter, Michael P. Milham, Davide Momi, Hua Xie, Ai Wern Chung, Georg Langs, Hao-Ting Wang, Xenia Kobeleva, Robert Oostenveld, Thomas G. Close, Lena Dorfschmidt, Jesse A. Brown, Serge Koudoro, J.P. Manzano-Patron, Isil P. Bilgin, Shreyas Fadnavis, Sylvain Takerkart, R. Cameron Craddock, Stephan Heunis, Scott Peltier, Kathryn Berluti, Hayli Spence, Pablo F. Damasceno, David H. O’Connor, Eleftherios Garyfallidis, Eugene P. Duff, Rudolph Pienaar, Nicolas Traut, AmanPreet Badhwar, Ali R. Khan, Marissa Laws, Abigail S. Greene, Richard A. I. Bethlehem, Angela R. Laird, Krista DeStasio, Ina Thome, Camille Maumet, Alexandru D. Iordan, P. Christiaan Klink, Damion V. Demeter, John A. Onofrey, Cassandra D. Gould van Praag, Jakub Vohryzek, Suzanne T. Witt, Aysha Motala, Valerie Hayot-Sasson, Geetika Gupta, Alexandre Rosa Franco, John W. VanMeter, Michel Thiebaut de Schotten, James M. Shine, Lucina Q. Uddin, Thomas S. Hartmann, Guillaume Flandin, Clara Moreau, Tomislav Lipic, Claire Bradley, Fernando A. Barrios, Daniel S. Margulies, R. Austin Benn, Sofie Van Den Bossche, Lydia Riedl, Xihe Xie, Christopher R. Madan, Roberto Toro, Viviana Siless, Fabrizio De Vico Fallani, Nikoloz Sirmpilatze, Emily Olafson, Anqi Qiu, Theresa W. Cheng, Valentina Borghesani, Sidhant Chopra, Claire Cury, Giorgio Marinato, Horea-Ioan Ioanas, Giorgia Cona, Michael Joseph, Angela Tam, Mathias Scharinger, Daniel A. Handwerker, Katherine L. Bottenhorn, Sina Mansour L, Kathryn L. Mills, Christopher J. Markiewicz, Elizabeth Levitis, Cyril Pernet, Stephanie J. Forkel, Agah Karakuzu, Edwina R Orchard, Sarah L. Dziura, Saige Rutherford, Kamalaker Dadi, Enrico Glerean, Desiree Lussier, Davide Poggiali, Molly Simmonite, Jason Kai, Jessica Flannery, Ting Xu, Jon Haitz Legarreta, Nasim Anousheh, Marco Bedini, Tristan Glatard, Thomas E. Nichols, Joscelin Rocha-Hidalgo, Erin W. Dickie, Dipankar Bachar, Malin Sandström, Xi-Nian Zuo, Pedro Pinheiro-Chagas, Laura C. Rice, Jakša Vukojević, Javier Gonzalez-Castillo, José C. García Alanis, Lorenzo Pasquini, Yu-Fang Yang, Matteo Mancini, Deena Shariq, Chao-Gan Yan, Laura Tomaz da Silva, César Caballero-Gaudes, Yasmine Bassil, Aurina Arnatkeviciute, Dustin Scheinost, Satrajit S. Ghosh, Gaël Varoquaux, Etienne Combrisson, Bramsh Qamar Chandio, Kelly Garner, Tiago Quendera, Patrick Friedrich, Shawn A. Rhoads, Roxane Licandro, Elizabeth DuPre, Aki Nikolaidis, Simon Schwab, Stephanie Noble, Guillaume Auzias, Daniel J. Lurie, Mahboobeh Parsapoor, Eneko Uruñuela, Andrew Doyle, Peer Herholz, Saampras Ganesan, Vincent Koppelmans, Corey Horien, Samir Das, Junaid S. Merchant, Siyuan Gao, Matheus Marcon, Nathalia Bianchini Esper, B.T. Thomas Yeo, Katja Heuer, Caroline O’Brien, Micaela Y. Chan, Sook-Lei Liew, Lindsay D. Oliver, Kirstie Whitaker, Christoph Vogelbacher, Dylan M. Nielson, Krisanne Litinas, Dorien C. Huijser, Pierre Bellec, R. Todd Constable, David N. Kennedy, Julia Sprenger, Lea-Theresa Mais, Oscar Esteban, Patrick J. Park, Patrick Callahan, Christopher R. Nolan, Johanna Bayer, Guillaume Dumas, Elise Bannier, Elizabeth A. McDevitt, Ariel Rokem, Samuel A. Nastase, Olivia W. Stanley, Ruggero Basanisi, Daniele Marinazzo, Gregory Kiar, Lisa Novello, Samuel Guay, John C. Flournoy, Stefano Moia, Kendra Oudyk, Fang-Cheng Yeh, Gustav Nilsonne, Thomas B. Shaw, Steve Wideman, Saskia Bollmann, Steffen Bollmann, Julia M. Huntenburg, Augusto Buchweitz, Matteo Visconti di Oleggio Castello, Dimitra Maoutsa, Lucy B. Whitmore, Catherine Alice Hahn, Antonino Vallesi, Remi Gau, Felipe Meneguzzi, Université Catholique de Louvain = Catholic University of Louvain (UCL), Yale University [New Haven], Max Planck Institute for Human Cognitive and Brain Sciences [Leipzig] (IMPNSC), Max-Planck-Gesellschaft, Florida International University [Miami] (FIU), University of Reading (UOR), University of Würzburg, Champalimaud Centre for the Unknown [Lisbon], University of Melbourne, University of Cambridge [UK] (CAM), Georgetown University [Washington] (GU), Philipps Universität Marburg = Philipps University of Marburg, Université de Montréal (UdeM), University College of London [London] (UCL), University of Sussex, Universiteit Gent = Ghent University (UGENT), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Université de Sherbrooke (UdeS), Middle East Technical University [Ankara] (METU), McGill University = Université McGill [Montréal, Canada], 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, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Universiteit Leiden, Karolinska Institutet [Stockholm], Princeton University, Universität Zürich [Zürich] = University of Zurich (UZH), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), University medical center and campus biotech Geneva, Emory University [Atlanta, GA], Cardiff University's Brain Research Imaging Centre [Cardiff] (CUBRIC), School of Psychology [Cardiff University], Cardiff University-Cardiff University, The University of Sydney, Weill Cornell Medicine [Cornell University], Cornell University [New York], Università degli Studi di Padova = University of Padua (Unipd), Jülich Research Centre, University of Texas at Austin [Austin], Institut Pasteur [Paris] (IP), Centre de Recherche Interdisciplinaire / Center for Research and Interdisciplinarity [Paris, France] (CRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Basque Center on Cognition Brain and Language [Gipuzkoa, Espagne] (BCBL), Linköping University (LIU), University of Queensland [Brisbane], University of New South Wales [Sydney] (UNSW), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), University of Maryland [College Park], University of Maryland System, University of Washington [Seattle], Harvard Medical School [Boston] (HMS), Child Mind Institute, University of Western Ontario (UWO), Indiana University [Bloomington], Indiana University System, Monash university, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Neuroimagerie: méthodes et applications (Empenn), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), National Institute of Mental Health (NIMH), Università degli Studi di Trento (UNITN), Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (CNIC), Instituto de Salud Carlos III [Madrid] (ISC), Queensland University of Technology [Brisbane] (QUT), University of California [San Francisco] (UC San Francisco), University of California (UC), Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), University of Texas at Dallas [Richardson] (UT Dallas), University of Oregon [Eugene], Monash University [Melbourne], Boston Children's Hospital, Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Neuroimagerie: méthodes et applications (EMPENN), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAL, IMAGE ET LANGAGE (IRISA-D6), Chinese Academy of Sciences [Beijing] (CAS), Beijing Normal University (BNU), This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 867458 awarded to Julia M. Huntenburg, from ANR-19-DATA-0025 NeuroWebLab for Katja Heuer, Roberto Toro, and Nicholas Traut, and from NIH K00MH122372 for Stephanie Noble., Brainhack Community: Nasim Anousheh, Aurina Arnatkeviciute, Guillaume Auzias, Dipankar Bachar, Elise Bannier, Ruggero Basanisi, Arshitha Basavaraj, Marco Bedini, Pierre Bellec, R Austin Benn, Kathryn Berluti, Steffen Bollmann, Saskia Bollmann, Claire Bradley, Jesse Brown, Augusto Buchweitz, Patrick Callahan, Micaela Y Chan, Bramsh Q Chandio, Theresa Cheng, Sidhant Chopra, Ai Wern Chung, Thomas G Close, Etienne Combrisson, Giorgia Cona, R Todd Constable, Claire Cury, Kamalaker Dadi, Pablo F Damasceno, Samir Das, Fabrizio De Vico Fallani, Krista DeStasio, Erin W Dickie, Lena Dorfschmidt, Eugene P Duff, Elizabeth DuPre, Sarah Dziura, Nathalia B Esper, Oscar Esteban, Shreyas Fadnavis, Guillaume Flandin, Jessica E Flannery, John Flournoy, Stephanie J Forkel, Alexandre R Franco, Saampras Ganesan, Siyuan Gao, José C García Alanis, Eleftherios Garyfallidis, Tristan Glatard, Enrico Glerean, Javier Gonzalez-Castillo, Cassandra D Gould van Praag, Abigail S Greene, Geetika Gupta, Catherine Alice Hahn, Yaroslav O Halchenko, Daniel Handwerker, Thomas S Hartmann, Valérie Hayot-Sasson, Stephan Heunis, Felix Hoffstaedter, Daniela M Hohmann, Corey Horien, Horea-Ioan Ioanas, Alexandru Iordan, Chao Jiang, Michael Joseph, Jason Kai, Agah Karakuzu, David N Kennedy, Anisha Keshavan, Ali R Khan, Gregory Kiar, P Christiaan Klink, Vincent Koppelmans, Serge Koudoro, Angela R Laird, Georg Langs, Marissa Laws, Roxane Licandro, Sook-Lei Liew, Tomislav Lipic, Krisanne Litinas, Daniel J Lurie, Désirée Lussier, Christopher R Madan, Lea-Theresa Mais, Sina Mansour L, J P Manzano-Patron, Dimitra Maoutsa, Matheus Marcon, Daniel S Margulies, Giorgio Marinato, Daniele Marinazzo, Christopher J Markiewicz, Camille Maumet, Felipe Meneguzzi, David Meunier, Michael P Milham, Kathryn L Mills, Davide Momi, Clara A Moreau, Aysha Motala, Iska Moxon-Emre, Thomas E Nichols, Dylan M Nielson, Gustav Nilsonne, Lisa Novello, Caroline O'Brien, Emily Olafson, Lindsay D Oliver, John A Onofrey, Edwina R Orchard, Kendra Oudyk, Patrick J Park, Mahboobeh Parsapoor, Lorenzo Pasquini, Scott Peltier, Cyril R Pernet, Rudolph Pienaar, Pedro Pinheiro-Chagas, Jean-Baptiste Poline, Anqi Qiu, Tiago Quendera, Laura C Rice, Joscelin Rocha-Hidalgo, Saige Rutherford, Mathias Scharinger, Dustin Scheinost, Deena Shariq, Thomas B Shaw, Viviana Siless, Molly Simmonite, Nikoloz Sirmpilatze, Hayli Spence, Julia Sprenger, Andrija Stajduhar, Martin Szinte, Sylvain Takerkart, Angela Tam, Link Tejavibulya, Michel Thiebaut de Schotten, Ina Thome, Laura Tomaz da Silva, Nicolas Traut, Lucina Q Uddin, Antonino Vallesi, John W VanMeter, Nandita Vijayakumar, Matteo Visconti di Oleggio Castello, Jakub Vohryzek, Jakša Vukojević, Kirstie Jane Whitaker, Lucy Whitmore, Steve Wideman, Suzanne T Witt, Hua Xie, Ting Xu, Chao-Gan Yan, Fang-Cheng Yeh, B T Thomas Yeo, Xi-Nian Zuo, ANR-19-DATA-0025,NeuroWebLab,Un laboratoire de neuroscience collectif: Au delà de FAIR(2019), European Project: 867458,LC-FMR, Maumet, Camille, Un laboratoire de neuroscience collectif: Au delà de FAIR - - NeuroWebLab2019 - ANR-19-DATA-0025 - DONNEES - VALID, Brainhack: Developing a culture of open, inclusive, community-driven neuroscience - LC-FMR - 867458 - INCOMING, Leiden University, Weill Cornell Medicine [New York], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Universiteit Gent = Ghent University [Belgium] (UGENT), University Hospital Bonn, Sherbrooke Connectivity Imaging Lab [Sherbrooke] (SCIL), Département d'informatique [Sherbrooke] (UdeS), Faculté des sciences [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS)-Université de Sherbrooke (UdeS)-Faculté des sciences [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS)-Université de Sherbrooke (UdeS), Videos and Images Theory and Analytics Laboratory (VITAL), 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)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Erasmus University Rotterdam, Origami (Origami), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Université Lumière - Lyon 2 (UL2), Princeton Neuroscience Institute [Princeton], Human Neuroscience Platform, Brighton and Sussex Medical School (BSMS), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Institute of Neuroscience and Medicine [Jülich] (INM-1), Département de Neuroscience - Department of Neuroscience, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Queensland Brain Institute, Universidad Nacional Autónoma de México (UNAM), Radboud university [Nijmegen], McGovern Institute for Brain Research [Cambridge], Massachusetts Institute of Technology (MIT), The Brainhack Community - https://pubmed.ncbi.nlm.nih.gov/33932337, Philipps University of Marburg, University of the Basque Country [Bizkaia] (UPV/EHU), Universita degli Studi di Padova, Philipps Universität Marburg, Institut Pasteur [Paris], Empenn, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), University of California [San Francisco] (UCSF), University of California, Geochemistry, and University of Padova [Padova, Italy]
Subjects: 0301 basic medicine, Open science, Community building, Best practice, Neuroscience(all), Brainhack, Article, neuroscience, 03 medical and health sciences, 0302 clinical medicine, best practices, collaboration, community building, hackathon, inclusivity, open science, reproducibility, training, Congresses as Topic, Neurosciences, Practice Guidelines as Topic, Communication, Internet, Research community, Medical Bioscience, Psychology, ddc:610, Sociology, Brainhack Community, Training, Neurology & Neurosurgery, Scientific progress, organization & administration [Neurosciences], General Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Medicinsk biovetenskap, 030104 developmental biology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cognitive Sciences, Engineering ethics, 030217 neurology & neurosurgery
Abstract: Available online 30 April 2021. Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress. The present manuscript is part of a growing community effort to collate Brainhack-related insights and expertise into a Jupyter Book (http://brainhack.org/brainhack_jupyter_book/) that will serve as a centralized set of resources for the community; we acknowledge all the individuals who contributed and will make ongoing contributions to these resources. A pre-print version of the present manuscript is available as part of the Jupyter Book. Moreover, we would like to acknowledge all Brainhack organizers, supporters, presenters, and participants for their contribution to growing and maintaining this community. The benefits described in this manuscript would not be possible without them. We also thank all institutions, labs, and organizations who have helped this community grow, meet in stimulating environments, and add an excellent educational resource pool and agenda. With an expanding community, Brainhack’s support network keeps growing, and we thank all labs and individual researchers for their dedication and expertise offered to this community (see http://brainhack.org/brainhack_jupyter_book/acknowledgments.html for a full list of individual acknowledgments; an updated list will be maintained in the Jupyter Book). Grants and funding bodies: This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 867458 awarded to Julia M. Huntenburg; from ANR-19-DATA-0025 NeuroWebLab for Katja Heuer, Roberto Toro, and Nicholas Traut; and from NIH K00MH122372 for Stephanie Noble. The Brainhack Community member list and contributions of the different authors are detailed at http://brainhack.org/brainhack_jupyter_book/contributors.html. Our crediting system is described here: http://brainhack.org/brainhack_jupyter_book/neuroview_authorship-agreement.html.
Published: 2021
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41. 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

42. 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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43. Bases référentielles de la radiothérapie en conditions stéréotaxiques pour les tumeurs ou métastases bronchopulmonaires, hépatiques, prostatiques, des voies aérodigestives supérieures, cérébrales et osseuses

Author: Vincent Marchesi, Sébastien Thureau, Georges Noël, C. Jenny, Delphine Antoni, Isabelle Barillot, F. Mornex, Thomas Lacornerie, Julian Biau, Stéphane Supiot, Albert Lisbona, P. Giraud, and J. Bellec
Subjects: 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Radiology, Nuclear Medicine and imaging, 030218 nuclear medicine & medical imaging
Abstract: Resume La radiotherapie en conditions stereotaxiques s’est largement developpee ces dernieres annees. De nombreux resultats ont ete publies sur de multiples localisations. Afin de clarifier les evidences parmi toutes les publications, une revue des recommandations disponibles a ete redigee pour les tumeurs malignes bronchopulmonaires, hepatiques, prostatiques, des voies aerodigestives superieures et pour les metastases osseuses et cerebrales. Ces donnees pourront etre utiles pour une standardisation des traitements et une amelioration de la qualite de ceux-ci. Ils peuvent etre aussi un guide utile pour les centres internationaux.
Published: 2018
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44. 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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45. 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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46. 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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47. 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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48. 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

49. 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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50. 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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