8,991 results on '"Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)"'
Search Results
2. Microtubule remodelling as a driving force of axon guidance and pruning
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Coralie Fassier, Xavier Nicol, Melody Atkins, Institut du Fer à Moulin (IFM - Inserm U1270 - SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Nicol, Xavier
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Axon guidance ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,tubulin isotypes ,tubulin posttranslational modifications ,Cell Biology ,Axon pruning ,Microtubules ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,Microtubule-associated proteins ,Developmental Biology - Abstract
International audience; The establishment of neuronal connectivity relies on the microtubule (MT) cytoskeleton, which provides mechanical support, roads for axonal transport and mediates signalling events. Fine-tuned spatiotemporal regulation of MT functions by tubulin post-translational modifications and MT-associated proteins is critical for the coarse wiring and subsequent refinement of neuronal connectivity. The defective regulation of these processes causes a wide range of neurodevelopmental disorders associated with connectivity defects. This review focuses on recent studies unravelling how MT composition, post-translational modifications and associated proteins influence MT functions in axon guidance and/or pruning to build functional neuronal circuits. We here summarise experimental evidence supporting the key role of this network as a driving force for growth cone steering and branch-specific axon elimination. We further provide a global overview of the MT-interactors that tune developing axon behaviours, with a special emphasis on their emerging versatility in the regulation of MT dynamics/structure. Recent studies establishing the key and highly selective role of the tubulin code in the regulation of MT functions in axon pathfinding are also reported. Finally, our review highlights the emerging molecular links between these MT regulation processes and guidance signals that wire the nervous system.
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- 2023
3. Machine learning identifies a profile of inadequate responder to methotrexate in rheumatoid arthritis
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Julien Duquesne, Vincent Bouget, Paul Henry Cournède, Bruno Fautrel, Francis Guillemin, Pascal H P de Jong, Judith W Heutz, Marloes Verstappen, Annette H M van der Helm-van Mil, Xavier Mariette, Samuel Bitoun, Scienta Lab [Gif-sur-Yvette, France], Mathématiques et Informatique pour la Complexité et les Systèmes (MICS), CentraleSupélec-Université Paris-Saclay, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Leiden University Medical Center (LUMC), and Universiteit Leiden
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machine learning ,Rheumatology ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,[INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG] ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,treatment response ,biomarker ,Pharmacology (medical) ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,MTX ,RA - Abstract
Objectives Around 30% of patients with RA have an inadequate response to MTX. We aimed to use routine clinical and biological data to build machine learning models predicting EULAR inadequate response to MTX and to identify simple predictive biomarkers. Methods Models were trained on RA patients fulfilling the 2010 ACR/EULAR criteria from the ESPOIR and Leiden EAC cohorts to predict the EULAR response at 9 months (± 6 months). Several models were compared on the training set using the AUROC. The best model was evaluated on an external validation cohort (tREACH). The model's predictions were explained using Shapley values to extract a biomarker of inadequate response. Results We included 493 therapeutic sequences from ESPOIR, 239 from EAC and 138 from tREACH. The model selected DAS28, Lymphocytes, Creatininemia, Leucocytes, AST, ALT, swollen joint count and corticosteroid co-treatment as predictors. The model reached an AUROC of 0.72 [95% CI (0.63, 0.80)] on the external validation set, where 70% of patients were responders to MTX. Patients predicted as inadequate responders had only 38% [95% CI (20%, 58%)] chance to respond and using the algorithm to decide to initiate MTX would decrease inadequate-response rate from 30% to 23% [95% CI: (17%, 29%)]. A biomarker was identified in patients with moderate or high activity (DAS28 > 3.2): patients with a lymphocyte count superior to 2000 cells/mm3 are significantly less likely to respond. Conclusion Our study highlights the usefulness of machine learning in unveiling subgroups of inadequate responders to MTX to guide new therapeutic strategies. Further work is needed to validate this approach.
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- 2023
4. Impact of the gut microbiome on nicotine’s motivational effects and glial cells in the ventral tegmental area in male mice
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Alina Lakosa, Anaïs Rahimian, Flavio Tomasi, Fabio Marti, Lauren M. Reynolds, Léa Tochon, Vincent David, Anne Danckaert, Candice Canonne, Sylvana Tahraoui, Fabrice de Chaumont, Benoît Forget, Uwe Maskos, Morgane Besson, Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC), Institut Pasteur [Paris] (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire Plasticité du Cerveau Brain Plasticity (UMR 8249) (PdC), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Plateforme technologique Bioimagerie Photonique - Photonic BioImaging Technologic Platform, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), 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), This work was supported by the Institut Pasteur, Paris (GPF Microbes and Brain, project 'µBIOTADDICT'). UtechS PBI/C2RT is part of the France BioImaging infrastructure supported by the French National Research Agency (ANR-10-INSB-04-01, 'Investments for the future') and is supported by Conseil de la Region Ile-de-France (Domaine d’Intérêt Majeur DIM1HEALTH) and by Fondation Française pour la Recherche Médicale (Programme Grands Equipements)., and ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010)
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Pharmacology ,Psychiatry and Mental health ,[SDV]Life Sciences [q-bio] - Abstract
International audience; A link between gut dysbiosis and the pathogenesis of brain disorders has been identified. A role for gut bacteria in drug reward and addiction has been suggested but very few studies have investigated their impact on brain and behavioral responses to addictive drugs so far. In particular, their influence on nicotine’s addiction-like processes remains unknown. In addition, evidence shows that glial cells shape the neuronal activity of the mesolimbic system but their regulation, within this system, by the gut microbiome is not established. We demonstrate that a lack of gut microbiota in male mice potentiates the nicotine-induced activation of sub-regions of the mesolimbic system. We further show that gut microbiota depletion enhances the response to nicotine of dopaminergic neurons of the posterior ventral tegmental area (pVTA), and alters nicotine’s rewarding and aversive effects in an intra-VTA self-administration procedure. These effects were not associated with gross behavioral alterations and the nicotine withdrawal syndrome was not impacted. We further show that depletion of the gut microbiome modulates the glial cells of the mesolimbic system. Notably, it increases the number of astrocytes selectively in the pVTA, and the expression of postsynaptic density protein 95 in both VTA sub-regions, without altering the density of the astrocytic glutamatergic transporter GLT1. Finally, we identify several sub-populations of microglia in the VTA that differ between its anterior and posterior sub-parts, and show that they are re-organized in conditions of gut microbiota depletion. The present study paves the way for refining our understanding of the pathophysiology of nicotine addiction.
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- 2023
5. Comparative outcomes of extracorporeal membrane oxygenation for COVID-19 delivered in experienced European centres during successive SARS-CoV-2 variant outbreaks (ECMO-SURGES): an international, multicentre, retrospective cohort study
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Matthieu Schmidt, David Hajage, Micha Landoll, Benjamin Pequignot, Elise Langouet, Matthieu Amalric, Armand Mekontso-Dessap, Luis Chiscano-Camon, Katy Surman, Dylan Finnerty, Patricia Santa-Teresa, Antonio Arcadipane, Pablo Millán, Roberto Roncon-Albuquerque, Aaron Blandino-Ortiz, Pablo Blanco-Schweizer, Pilar Ricart, Ricardo Gimeno-Costa, Carlos Luis Albacete, Philip Fortuna, Peter Schellongowski, Dieter Dauwe, Hadrien Winiszewski, Antoine Kimmoun, Bruno Levy, Greet Hermans, Giacomo Grasselli, Guillaume Lebreton, Christophe Guervilly, Gennaro Martucci, Christian Karagiannidis, Jordi Riera, Alain Combes, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), 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), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Universität Witten Herdecke, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Marseille, IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Vall d'Hebron University Hospital [Barcelona], Royal Papworth Hospital [Cambridge, UK] (RPH), Hospital General Universitario 'Gregorio Marañón' [Madrid], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Universidad Loyola Andalucía = Loyola University Andalucía, Hospital de São João [Porto], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Rio Hortega University Hospital (Hospital Universitario Río Hortega) [Valladolid, Spain] (RHUH), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Hospital Clínico Universitario Virgen de la Arrixaca = University Hospital Virgen de la Arrixaca [Murcia], Centro Hospitalar de Lisboa Central E.P.E, Medizinische Universität Wien = Medical University of Vienna, University Hospitals Leuven [Leuven], Service d'anesthésie et soins intensifs [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), and Vall d’Hebron Research Institute (VHIR)
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Pulmonary and Respiratory Medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases - Abstract
International audience
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- 2023
6. Association of atypical skin manifestations at the onset of systemic juvenile idiopathic arthritis with difficult-to-treat disease: A retrospective multicenter study
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Laurye-Anne Eveillard, Pierre Quartier, Naim Ouldali, Brigitte Bader-Meunier, Florence Aeschlimann, Claire Abasq, Claire Ballot, Pauline Bouric, Alexandra Desdoits, Cécile Dumaine, Caroline Galeotti, Véronique Hentgen, Alain Lefevre-Utile, Aurélie Chausset, Thomas Hubiche, Ingrid Kupfer-Bessaguet, Stéphanie Leclerq-Mercier, Stéphanie Mallet, Isabelle Melki, Etienne Merlin, Juliette Miquel, Maryam Piram, Deborah Talmud, Nicolas Garcelon, Caroline Vinit, Anne Welfringer, Emmanuelle Bourrat, Ulrich Meinzer, Hôpital Robert Debré Paris, Hôpital Robert Debré, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Jean Verdier [AP-HP], Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université Côte d'Azur (UCA), Centre Hospitalier Intercommunal de Cornouaille (CHIC), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Centre Hospitalier Régional d'Orléans (CHRO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
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[SDV]Life Sciences [q-bio] ,Humans ,Dermatology ,Arthritis, Juvenile ,Retrospective Studies - Abstract
International audience
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- 2022
7. Effective initial management of anastomotic leak in the maintenance of functional colorectal or coloanal anastomosis
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Alexandra Nassar, Alexandre Challine, Lauren O’Connell, Thibault Voron, Najim Chafaï, Clotilde Debove, Yann Parc, Jeremie H. Lefèvre, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), St Vincent's University Hospital, and Sorbonne Université (SU)
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Surgery ,[SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery ,General Medicine - Abstract
International audience; PurposeThe present study assessed the factors associated with the maintenance of a functional anastomosis in a large consecutive series of patients with anastomotic leakage (AL).MethodsAll consecutive patients presenting with AL after colorectal or coloanal anastomosis (2012–2019) were analyzed. The primary end point was a functional anastomosis without a stoma at 1 year.ResultsA total of 156 patients were included. AL was initially treated by antibiotics (38%), drainage (43%) or urgent surgery (19%). Initial treatment of AL was not adequate in 24.3%, and reintervention in the form of drainage or surgery was required. A total of 60.9% of patients had a functional anastomosis without a stoma 1 year after surgery. Factors associated with the risk of anastomotic failure at 1 year were diabetes (odds ratio [OR] = 4.24 [95% confidence interval {CI} 1.39–14.24] p = 0.014), neoadjuvant chemoradiotherapy (OR = 3.03 [95% CI 1.14–8.63] p = 0.03) and Grade B (OR = 6.49 [95% CI 2.23–21.74] p = 0.001) or C leak (OR = 35.35 [95% CI 9.36–168.21] p
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- 2022
8. CT-based diagnostic algorithm to identify bowel and/or mesenteric injury in patients with blunt abdominal trauma
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Alexandre Lansier, Camille Bourillon, Charles-André Cuénod, Emilia Ragot, Arnaud Follin, Sophie Hamada, Olivier Clément, Philippe Soyer, Anne-Sophie Jannot, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Groupe Hospitalier Diaconesses Croix Saint-Simon, Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)
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[SDV]Life Sciences [q-bio] ,Radiology, Nuclear Medicine and imaging ,General Medicine - Abstract
To develop a CT-based algorithm and evaluate its performance for the diagnosis of blunt bowel and/or mesenteric injury (BBMI) in patients with blunt abdominal trauma.This retrospective study included a training cohort of 79 patients (29 with BBMI and 50 patients with blunt abdominal trauma without BBMI) and a validation cohort of 37 patients (13 patients with BBMI and 24 patients with blunt abdominal trauma without BBMI). CT examinations were blindly analyzed by two independent radiologists. For each CT sign, the kappa value, sensitivity, specificity, and accuracy were calculated. A diagnostic algorithm was built using a recursive partitioning model on the training cohort, and its performances were assessed on the validation cohort.CT signs with kappa value0.6 were extraluminal gas, hemoperitoneum, no or moderate bowel wall enhancement, and solid organ injury. CT signs yielding best accuracies in the training cohort were extraluminal gas (98%; 95% CI: 91-100), bowel wall defect (97%; 95% CI: 91-100), irregularity of mesenteric vessels (97%; 95% CI: 90-99), and mesenteric vessel extravasation (97%; 95% CI: 90-99). Using a recursive partitioning model, a decision tree algorithm including extraluminal gas and no/moderate bowel wall enhancement was built, achieving 86% sensitivity (95% CI: 74-99) and 96% specificity (95% CI: 91-100) in the training cohort and 92% sensitivity (95% CI: 78-97) and 88% specificity (95% CI: 74-100) in the validation cohort for the diagnosis of BBMI.An effective diagnostic algorithm was built to identify BBMI in patients with blunt abdominal trauma using only extraluminal gas and no/moderate bowel wall enhancement on CT examination.• A CT diagnostic algorithm that included extraluminal gas and no/moderate bowel wall enhancement was built for the diagnosis of surgical blunt bowel and/or mesenteric injury. • A decision tree combining only two reproducible CT signs has high diagnostic performance for the diagnosis of surgical blunt bowel and/or mesenteric injury.
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- 2022
9. Sotrovimab to prevent severe COVID-19 in high-risk patients infected with Omicron BA.2
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Guillaume Martin-Blondel, Anne-Genevieve Marcelin, Cathia Soulié, Sofia Kaisaridi, Clovis Lusivika-Nzinga, Céline Dorival, Laura Nailler, Anaïs Boston, Cléa Melenotte, André Cabié, Christophe Choquet, François Coustillères, Jean-Philippe Martellosio, Géraldine Gaube, Albert Trinh-Duc, Anne-Marie Ronchetti, Valerie Pourcher, Marie Chauveau, Karine Lacombe, Nathan Peiffer-Smadja, Pierre Housset, Aurore Perrot, Gilles Pialoux, Aurélie Martin, Vincent Dubee, Mathilde Devaux, Jérôme Frey, Charles Cazanave, Roland Liblau, Fabrice Carrat, Youri Yordanov, Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANRS France Recherche Nord & sud Sida-hiv hépatites, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Accueil des Urgences (AGEN - SAU), Centre Hospitalier d'Agen, Centre Hospitalier Sud Francilien, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Hôtel-Dieu de Nantes, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Services de Maladies Infectieuses et Tropicales [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), CHR de Metz-Thionville, CHU Bordeaux [Bordeaux], Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service d'Allergologie et d'Immunologie [CHU Toulouse], Épidémiologie clinique des maladies virales chroniques [iPLesp] (CLEPIVIR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [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), Service d'Urgences Adultes [CHU Saint-Antoine], and Gestionnaire, Hal Sorbonne Université
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[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,Microbiology (medical) ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,Infectious Diseases ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,COVID-19 ,Humans ,Antibodies, Monoclonal, Humanized ,Antibodies, Neutralizing - Abstract
International audience; Before the Omicron era, the neutralizing antibody targeting the SARS-CoV2 Spike protein Sotrovimab has been shown to reduce the risk of COVID-19-related hospitalization in patients who are at high risk for progression (1, 2). We recently showed that early administration of Sotrovimab in Omicron-infected patients with very high-risk for progression was associated with a low rate of COVID-19-related hospitalization within one month after treatment administration (3%), and with no death (1). However, the dominance of the Omicron sublineage BA.2 led health agencies to suspend Sotrovimab emergency use authorizations because of its lower neutralizing ability in vitro compared to BA.1 sublineage (3, 4). Clinical efficiency of Sotrovimab to prevent COVID-19 related complications in high-risk patients with mild-to-moderate COVID-19 Omicron BA.2 remains unknown. Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients with mild-to-moderate COVID-19 who received 500 mg of Sotrovimab IV to prevent COVID-19-related complications.
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- 2022
10. Ethical Aspects of Artificial Intelligence in Radiation Oncology
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Lucien, Lahmi, Marie-France, Mamzer, Anita, Burgun, Catherine, Durdux, Jean-Emmanuel, Bibault, Institut Curie [Paris], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Service d'informatique médicale, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
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Cancer Research ,[INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG] ,Oncology ,Artificial Intelligence ,Radiation Oncology ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Humans ,Radiology, Nuclear Medicine and imaging ,Delivery of Health Care ,Workflow ,[INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI] - Abstract
International audience; Radiation oncology is a field that heavily relies on new technology. Data science and artificial intelligence will have an important role in the entire radiotherapy workflow. A new paradigm of routine healthcare data reuse to automate treatments and provide decision support is emerging. This review will discuss the ethical aspects of the use of artificial intelligence (AI) in radiation oncology. More specifically, the review will discuss the evolution of work through the ages, as well as the impact AI will have on it. We will then explain why AI opens a new technical era for the field and we will conclude on the challenges in the years to come.
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- 2022
11. Immune landscape after allo-HSCT: TIGIT- and CD161-expressing CD4 T cells are associated with subsequent leukemia relapse
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Viviane Gournay, Nicolas Vallet, Vivien Peux, Kristi Vera, Jennifer Bordenave, Marion Lambert, Aurélien Corneau, David Michonneau, Régis Peffault de Latour, Sophie Caillat-Zucman, Gérard Socié, Mathieu F. Chevalier, BRUNEL, Nadège, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
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CD4-Positive T-Lymphocytes ,[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Immunology ,Hematopoietic Stem Cell Transplantation ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Cell Biology ,Hematology ,Ligands ,Biochemistry ,Leukemia, Myeloid, Acute ,Cross-Sectional Studies ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,Recurrence ,[SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology ,Humans ,Transplantation, Homologous ,Blood Commentary ,Receptors, Immunologic - Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective treatment for selected patients with acute myeloid leukemia (AML) and relies on a “graft-versus-leukemia” effect (GVL) where donor T lymphocytes mediate control of malignant cell growth. However, relapse remains the major cause of death after allo-HSCT. In various malignancies, several immunoregulatory mechanisms have been shown to restrain antitumor immunity, including ligand-mediated engagement of inhibitory receptors (IRs) on effector cells, and induction of immunosuppressive cell subsets, such as regulatory T cells (Tregs) or myeloid-derived suppressor cells (MDSCs). Relapse after HSCT remains a major therapeutic challenge, but immunoregulatory mechanisms involved in restraining the GVL effect must be better deciphered in humans. We used mass cytometry to comprehensively characterize circulating leukocytes in 2 cohorts of patients after allo-HSCT. We first longitudinally assessed various immunoregulatory parameters highlighting specific trends, such as opposite dynamics between MDSCs and Tregs. More generally, the immune landscape was stable from months 3 to 6, whereas many variations occurred from months 6 to 12 after HSCT. Comparison with healthy individuals revealed that profound alterations in the immune equilibrium persisted 1 year after HSCT. Importantly, we found that high levels of TIGIT and CD161 expression on CD4 T cells at month 3 after HSCT were distinct features significantly associated with subsequent AML relapse in a second cross-sectional cohort. Altogether, these data provide global insights into the reconstitution of the immunoregulatory landscape after HSCT and highlight non-canonical IRs associated with relapse, which could open the path to new prognostic tools or therapeutic targets to restore subverted anti-AML immunity.
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- 2022
12. Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels
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Erin Rooney Riggs, Taylor I. Bingaman, Carrie-Ann Barry, Andrea Behlmann, Krista Bluske, Bret Bostwick, Alison Bright, Chun-An Chen, Amanda R. Clause, Avinash V. Dharmadhikari, Mythily Ganapathi, Claudia Gonzaga-Jauregui, Andrew R. Grant, Madeline Y. Hughes, Se Rin Kim, Amanda Krause, Jun Liao, Aimé Lumaka, Michelle Mah, Caitlin M. Maloney, Shruthi Mohan, Ikeoluwa A. Osei-Owusu, Emma Reble, Olivia Rennie, Juliann M. Savatt, Hermela Shimelis, Rebecca K. Siegert, Tam P. Sneddon, Courtney Thaxton, Kelly A. Toner, Kien Trung Tran, Ryan Webb, Emma H. Wilcox, Jiani Yin, Xinming Zhuo, Masa Znidarsic, Christa Lese Martin, Catalina Betancur, Jacob A.S. Vorstman, David T. Miller, Christian P. Schaaf, Geisinger Autism & Developmental Medicine Institute [Danville, PA, USA] (ADMI), Drexel University, Invitae Corporation, Illumina, Baylor College of Medicine (BCM), Baylor University, Natera [San Carlos, CA, USA], Children’s Hospital Los Angeles [Los Angeles], Keck School of Medicine [Los Angeles], University of Southern California (USC), Columbia University Irving Medical Center (CUIMC), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], New York Medical College (NYMC), University of Illinois [Chicago] (UIC), University of Illinois System, National Human Genome Research Institute (NHGRI), University of the Witwatersrand [Johannesburg] (WITS), Université de Liège, Trillium Health Partners - Mississauga Hospital [Mississauga, ON, Canada] (THP-MH), University of Washington [Seattle], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), St. Michael's Hospital, The Hospital for sick children [Toronto] (SickKids), Garvan Institute of medical research, Warren Alpert Medical School of Brown University, University of California [Los Angeles] (UCLA), University of California (UC), The Jackson Laboratory [Bar Harbor] (JAX), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Heidelberg University Hospital [Heidelberg], This work was supported by the National Human Genome Research Institute of the National Institutes of Health under award number U24HG006834., and Betancur, Catalina
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ClinGen ,MESH: Humans ,Autism Spectrum Disorder ,Autism ,MESH: Autism Spectrum Disorder* / genetics ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,MESH: Autism Spectrum Disorder* / diagnosis ,MESH: Intellectual Disability* / diagnosis ,MESH: Intellectual Disability* / genetics ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Neurodevelopmental Disorders ,Intellectual Disability ,MESH: Autistic Disorder* / genetics ,MESH: Autistic Disorder* / diagnosis ,Humans ,Autistic Disorder ,MESH: Neurodevelopmental Disorders* / genetics ,Genetics (clinical) ,Gene–disease validity - Abstract
International audience; Purpose: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not.Methods: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship.Results: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants.Conclusion: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs.
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- 2022
13. Diversity of the nucleic acid forms of circulating HBV in chronically infected patients and its impact on viral cycle
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Jules Sotty, Pierre Bablon, Bouchra Lekbaby, Jérémy Augustin, Morgane Girier-Dufournier, Lucas Langlois, Céline Dorival, Fabrice Carrat, Stanislas Pol, Hélène Fontaine, Nazim Sarica, Christine Neuveut, Chantal Housset, Dina Kremdsorf, Aurélie Schnuriger, Patrick Soussan, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Henri Mondor, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [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), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service de Virologie [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de virologie [Hôpital Tenon], CHU Tenon [AP-HP], and Gestionnaire, Hal Sorbonne Université
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Hepatitis B virus ,Hepatology ,[SDV]Life Sciences [q-bio] ,HBV pregenomic RNA ,Viral circulating forms ,Virus Replication ,Hepatitis B ,Chronic infection ,[SDV] Life Sciences [q-bio] ,Hepatitis B, Chronic ,Viral genome diversity ,Nucleic Acids ,DNA, Viral ,HBV ,Humans ,RNA ,RNA, Viral ,Prospective Studies ,Viral cycle ,Viral hepatitis ,Liver disease ,Alternative splicing ,Chronic hepatitis - Abstract
International audience; Background: Besides the prototypical hepatitis B virus (HBV) infectious particle, which contains a full-length double-stranded DNA (flDNA), additional circulating virus-like particles, which carry pregenomic RNA (pgRNA), spliced1RNA (sp1RNA) or spliced-derived DNA (defDNA) forms have been described. We aimed to determine the level of these four circulating forms in patients and to evaluate their impact on viral lifecycle.Methods: Chronic HBV untreated patients (n = 162), included in the HEPATHER cohort, were investigated. Pangenomic qPCRs were set up to quantify the four circulating forms of HBV nucleic acids (HBVnaf). In vitro infection assays were performed to address the impact of HBVnaf.Results: Hierarchical clustering individualized two clusters of HBVnaf diversity among patients: (1) cluster 1 (C1) showing a predominance of flDNA; (2) cluster 2 (C2) showing various proportions of the different forms. HBeAg-positive chronic hepatitis phase and higher viral load (7.0 ± 6.4 vs 6.6 ± 6.2 Log10 copies/ml; p < 0.001) characterized C2 compared to C1 patients. Among the different HBVnaf, pgRNA was more prevalent in C1 patients with high vs low HBV viral load (22.1% ± 2.5% vs 4.1% ± 1.8% of HBVnaf, p < 0.0001) but remained highly prevalent in C2 patients, whatever the level of replication. C2 patients samples used in infection assays showed that: (1) HBVnaf secretion was independent of the viral strain; (2) the viral cycle efficiency differed according to the proportion of HBVnaf in the inoculum, independently of cccDNA formation. Inoculum enrichment before infection suggests that pgRNA-containing particles drive this impact on viral replication.Conclusion: Besides the critical role of HBV replication in circulating HBVnaf diversity, our data highlight an impact of this diversity on the dynamics of viral cycle.Clinical trial registration: Patients were included from a prospective multicenter French national cohort (ANRS CO22 HEPATHER, NCT01953458).
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- 2022
14. Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial
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Thomas Schmitz, Muriel Doret-Dion, Loic Sentilhes, Olivier Parant, Olivier Claris, Laurent Renesme, Julie Abbal, Aude Girault, Héloïse Torchin, Marie Houllier, Nolwenn Le Saché, Alexandre J Vivanti, Daniele De Luca, Norbert Winer, Cyril Flamant, Claire Thuillier, Pascal Boileau, Julie Blanc, Véronique Brevaut, Pierre-Emmanuel Bouet, Géraldine Gascoin, Gaël Beucher, Valérie Datin-Dorriere, Stéphane Bounan, Pascal Bolot, Christophe Poncelet, Corinne Alberti, Moreno Ursino, Camille Aupiais, Olivier Baud, Philippe Boize, Charles Garabédian, Florence Flamein, Maela Le Lous, Alain Beuchée, Jean Gondry, Pierre Tourneux, Perrine Coste-Mazeau, Antoine Bedu, Denis Gallot, Karen Coste, Céline Chauleur, Hugues Patural, Gilles Kayem, Delphine Mitanchez, Hélène Heckenroth, Farid Boubred, Jeanne Sibiude, Luc Desfrère, Caroline Bohec, Thierry Mansir, Antoine Koch, Pierre Kuhn, Nadia Tillouche, Fabrice Lapeyre, Franck Perrotin, Géraldine Favrais, Edouard Lecarpentier, Xaxier Durrmeyer, Véronique Equy, Thierry Debillon, Luc Rigonnot, Stéphanie Lefoulgoc, Claudia Brie, Anne-Sophie Pagès, Romy Rayssiguier, Gilles Cambonie, Corinne Cudeville, Doriane Madeleneau, Olivier Morel, Jean-Michel Hascoet, Vincent Letouzey, Massimo Di Maio, Laurent J. Salomon, Alexandre Lapillonne, Hôpital Robert Debré, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), AP-HP - Hôpital Antoine Béclère [Clamart], Service de Pédiatrie et Réanimations néonatales [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), CHI Poissy-Saint-Germain, Physiologie et physiopathologie endocriniennes (PHYSENDO), École Nationale Supérieure de Formation de l'Enseignement Agricole de Toulouse-Auzeville (ENSFEA), Education, Formation, Travail, Savoirs (EFTS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-École Nationale Supérieure de Formation de l'Enseignement Agricole de Toulouse-Auzeville (ENSFEA), Hôpital Nord [CHU - APHM], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], Hôpital Robert Debré Paris, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Centre d'Investigation Clinique 1426 (CIC 1426), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
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Respiratory Distress Syndrome, Newborn ,Double-Blind Method ,Pregnancy ,[SDV]Life Sciences [q-bio] ,Infant, Newborn ,Humans ,Premature Birth ,Female ,Infant, Premature, Diseases ,General Medicine ,Betamethasone - Abstract
International audience; BackgroundAntenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome.MethodsWe designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks’ gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076.FindingsBetween Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI –0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI –0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3–4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia.InterpretationBecause non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction.
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- 2022
15. TAXN: Translate Align Extract Normalize, a multilingual extraction tool for clinical texts
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Neuraz, Antoine, Lerner, Ivan, Birot, Olivier, Arias, Camila, Han, Larry, Bonzel, Clara, Cai, Tianxi, Huynh, Kim, Coulet, Adrien, Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Harvard Medical School [Boston] (HMS), and International Medical Informatics Association (IMIA)
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[INFO.INFO-TT]Computer Science [cs]/Document and Text Processing ,Natural language processing ,Implementation ,Named Entity Recognition ,Term normalization ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Several studies have shown that about 80% of the medical information in an electronic health record is only available through unstructured data. Resources such as medical terminologies in languages other than English are limited and restrain the NLP tools. We propose here to leverage English based resources in other languages using a combination of translation, word alignment, entity extraction and term normalization (TAXN). We implement this extraction pipeline in an opensource library called "medkit". We demonstrate the interest of this approach through a specific use-case: enriching a phenotypic dictionary for post-acute sequelae in COVID-19 (PASC). TAXN proved to be efficient to propose new synonyms of UMLS terms using a corpus of 70 articles in French with 356 terms enriched with at least one validated new synonym. This study was based on freely available deeplearning models.
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- 2023
16. Comparison of the validity, perceived usefulness, and usability of I-MeDeSA and TEMAS, two tools to evaluate alert system usability
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Romaric Marcilly, Wu-Yi Zheng, Paul Quindroit, Sylvia Pelayo, Sarah Berdot, Bruno Charpiat, Jennifer Corny, Sylvain Drouot, Pauline Frery, Géraldine Leguelinel-Blache, Lisa Mondet, Arnaud Potier, Laurine Robert, Laurie Ferret, Melissa Baysari, CHU Lille, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Blackdog institute, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Bicêtre, CHR de Metz-Thionville, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier de Lunéville (GHEMM ), Centre hospitalier [Valenciennes, Nord], and The University of Sydney
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Clinical ,Usability ,[SCCO.PSYC]Cognitive science/Psychology ,Health Informatics ,Ergonomics ,[INFO.INFO-HC]Computer Science [cs]/Human-Computer Interaction [cs.HC] ,Assessment tool ,Decision support systems ,Human factors - Abstract
International audience; Objective: Two tools are currently available in the literature to evaluate the usability of medication alert systems, the instrument for evaluating human factors principles in medication-related decision support alerts (I-MeDeSA) and the tool for evaluating medication alerting systems (TEMAS). This study aimed to compare their convergent validity, perceived usability, usefulness, strengths, and weaknesses, as well as users' preferences.Method: To evaluate convergent validity, two experts mapped TEMAS' items against I-MeDeSA's items with respect to the usability dimensions they target. To assess perceived usability, usefulness, strengths, and weaknesses of both tools, staff with expertise in their medication alerting system were asked to use French versions of the TEMAS and I-MeDeSA. After the use of each tool, participants were asked to complete the System Usability Scale (SUS) and answer questions about the understandability and usefulness of each tool. Finally, participants were asked to name their preferred tool. Numeric scores were statistically compared. Free-text responses were analyzed using an inductive approach.Results: Forty-five participants from 10 hospitals took part in the study. In terms of convergent validity, I-MeDeSA focuses more on the usability of the graphical user interface while TEMAS considers a wider range of usability principles. Both tools have a fair level of perceived usability (I-MeDeSA' SUS score = 61.85 and TEMAS' SUS score = 62.87), but results highlight that revisions are necessary to both tools to improve their usability. Participants found TEMAS more useful than I-MeDeSA (t = -3.63, p =.005) and had a clear preference for TEMAS to identify problems in formative evaluation (39 of 45; 0.867, p
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- 2023
17. Transinteractome analysis reveals distinct niche requirements for isotype‐based plasma cell subsets in the bone marrow
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Bonaud, Amélie, Larraufie, Pierre, Khamyath, Mélanie, Szachnowski, Ugo, Flint, Shaun, Brunel‐meunier, Nadège, Delhommeau, François, Munier, Annie, Lönnberg, Tapio, Toffano‐nioche, Claire, Gautheret, Daniel, Balabanian, Karl, Espéli, Marion, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Inflammation, microbiome, immunosurveillance (MI2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cytométrie et Imagerie Saint-Antoine (CISA), Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, and The Wellcome Trust Sanger Institute [Cambridge]
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Transinteractome ,MESH: Plasma cell Bone marrow Niche Stromal cell Transinteractome ,[SDV]Life Sciences [q-bio] ,Niche ,Stromal cell ,Bone marrow ,Plasma cell - Abstract
International audience; Bone marrow (BM) long-lived plasma cells (PCs) are essential for long-term protection against infection, and their persistence within this organ relies on interactions with Cxcl12-expressing stromal cells that are still not clearly identified. Here, using single cell RNAseq and in silico transinteractome analyses, we identified Leptin receptor positive (LepR +) mesenchymal cells as the stromal cell subset most likely to interact with PCs within the BM. Moreover, we demonstrated that depending on the isotype they express, PCs may use different sets of integrins and adhesion molecules to interact with these stromal cells. Altogether, our results constitute an unprecedented characterization of PC subset stromal niches and open new avenues for the specific targeting of BM PCs based on their isotype.
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- 2023
18. Mathematical modeling of adipocyte size distributions: identifiability and parameter estimation from rat data
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Giacobbi, Anne-Sophie, Meyer, Leo, Ribot, Magali, Yvinec, Romain, Soula, Hedi, Audebert, Chloe, Mathematical Modeling in Biology [LCQB] (LCQB-MMB), Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Denis Poisson (IDP), Université d'Orléans (UO)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Dynamiques de populations multi-échelles pour des systèmes physiologiques (MUSCA), 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)-Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and ANR-20-CE45-0003,MATIDY,Modèles mathématiques de la dynamique du tissu adipeux(2020)
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adipocyte size distribution ,partial differential equation ,[SDV]Life Sciences [q-bio] ,[MATH]Mathematics [math] ,parameter estimation ,parameter identifiability - Abstract
International audience; Fat cells, called adipocytes, are designed to regulate energy homeostasis by storing energy in the form of lipids. Adipocyte size distribution is assumed to play a role in the development of obesity-related diseases. This population of cells that do not have a characteristic size, indeed a bimodal size distribution is observed in adipose tissue. We propose a model based on a partial differential equation to describe adipocyte size distribution. The model includes a description of the lipid fluxes and the cell size fluctuations and using a formulation of a stationary solution fast computation of bimodal distribution is achieved. We investigate the parameter identifiability and estimate parameter values with CMA-ES algorithm. We first validate the procedure on synthetic data, then we estimate parameter values with experimental data of 32 rats. We discuss the estimated parameter values and their variability within the population, as well as the relation between estimated values and their biological significance. Finally, a sensitivity analysis is performed to specify the influence of parameters on 1 cell size distribution and explain the differences between the model and the measurements. The proposed framework enables the characterization of adipocyte size distribution with four parameters and can be easily adapted to measurements of cell size distribution in different health conditions.
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- 2023
19. Congenital mirror movements are associated with defective polymerization of RAD51
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Trouillard, Oriane, Dupaigne, Pauline, Dunoyer, Margaux, Doulazmi, Mohamed, Herlin, Morten Krogh, Frismand, Solène, Riou, Audrey, Legros, Véronique, Chevreux, Guillaume, Veaute, Xavier, Busso, Didier, Fouquet, Coralie, Saint-Martin, Cécile, Méneret, Aurélie, Trembleau, Alain, Dusart, Isabelle, Dubacq, Caroline, Roze, Emmanuel, Développement et plasticité des réseaux neuronaux = Development and Plasticity of Neural Networks (NPS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Mouvement, Investigations, Thérapeutique. Mouvement normal et anormal : physiopathologie et thérapeutique expérimentale [ICM Paris] (Mov’It), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Maintenance des génomes, Microscopies Moléculaire et Bionanosciences, Centre National de la Recherche Scientifique-Université Paris Sud, Maintenance des génomes, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Departement of clinical genetics, Aarhus University Hospital, Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de neurologie [Rennes], Université de Rennes (UR), Université de Paris, CNRS, Institut Jacques Monod, Paris, France, Stabilité génétique, cellules souches et radiations (SGCSR (U_1274 / UMR_E_008)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Développement, évolution et plasticité du système nerveux (DEPSN), Centre National de la Recherche Scientifique (CNRS), This work was supported by the Fondation Desmarest, Merz-Pharma, Elivie, Orkyn, Djillali Mehri, CNRS, INSERM and Sorbonne Université. This work was also funded by grants from the Agence Nationale de la Recherche (ANR) (ANR-14-CE13-0004-01, ANR-18-CE16-0005-02), from the National Institute of Health NIDCD (R01-DC-017989, USA) and it was performed within the framework of LABEX LIFESENSES (ANR- 10-LABX-65) supported by French state funds managed by the ANR within the Investissements d’Avenir program (ANR-11-IDEX-0004-02)., ANR-18-CE16-0005,Momic,La décussation du faisceau corticospinal et la latéralisation du contrôle moteur : le paradigme des Mouvements Miroirs Congénitaux (MoMiC)(2018), ANR-14-CE13-0004,AxoDevo,Evolution du guidage axonal(2014), and ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011)
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[SDV]Life Sciences [q-bio] - Abstract
International audience; Background. Mirror movements are involuntary movements of one hand that mirror intentional movements of the other hand. Congenital mirror movements (CMM) is a rare genetic disorder with autosomal dominant inheritance, in which mirror movements are the main neurological manifestation. CMM is associated with an abnormal decussation of the corticospinal tract, a major motor tract for voluntary movements. RAD51 is known to play a key role in homologous recombination with a critical function in DNA repair. While RAD51 haploinsufficiency was first proposed to explain CMM, other mechanisms could be involved. Methods. We performed Sanger sequencing of RAD51 in five newly identified CMM families to identify new pathogenic variants. We further investigated the expression of wild-type and mutant RAD51 in the patients' lymphoblasts at mRNA and protein levels. We then characterized the functions of RAD51 altered by non-truncating variants using biochemical approaches. Results. The level of wild-type RAD51 protein was lower in all the CMM patients' cells compared with their non-carrier relatives. The reduction was less pronounced in asymptomatic carriers. In vitro, mutant RAD51 proteins showed loss-of-function for polymerization, DNA binding, and strand exchange activity. Conclusion. Our study demonstrates that RAD51 haploinsufficiency, including loss-offunction of non-truncating variants, results in CMM. The incomplete penetrance likely results from post-transcriptional compensation. Changes in RAD51 levels and/or polymerization properties could influence guidance of the corticospinal axons during development. Our findings open up new perspectives to understand the role of RAD51 in neurodevelopment.
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- 2023
20. Positionnement temporel indépendant des évènements : application à des textes cliniques en français
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Bannour, Nesrine, Tannier, Xavier, Rance, Bastien, Névéol, Aurélie, Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Sciences et Technologies des Langues (STL), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Nesrine Bannour a bénéficié d’un financement de l’ITMO Cancer Aviesan. Bastien Rance est soutenu par le programme SIRIC CARPEM., Servan, Christophe, and Vilnat, Anne
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étiquetage de séquences ,Extraction d'informations temporelles ,Texte clinique ,[INFO.INFO-CL]Computer Science [cs]/Computation and Language [cs.CL] - Abstract
International audience; L'extraction de relations temporelles consiste à identifier et classifier la relation entre deux mentions. Néanmoins, la définition des mentions temporelles dépend largement du type du texte et du domained'application. En particulier, le texte clinique est complexe car il décrit des évènements se produisant à des moments différents et contient des informations redondantes et diverses expressions temporellesspécifiques au domaine. Dans cet article, nous proposons une nouvelle représentation des relations temporelles, qui est indépendante du domaine et de l'objectif de la tâche d'extraction. Nous nousintéressons à extraire la relation entre chaque portion du texte et la date de création du document. Nous formulons l'extraction de relations temporelles comme une tâche d'étiquetage de séquences.Une macro F-mesure de 0,8 est obtenue par un modèle neuronal entraîné sur des textes cliniques, écrits en français. Nous évaluons notre représentation temporelle par le positionnement temporel desévènements de toxicité des chimiothérapies.
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- 2023
21. Mitochondria Transfer from Mesenchymal Stem Cells Confers Chemoresistance to Glioblastoma Stem Cells through Metabolic Rewiring
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Jean Nakhle, Khattar Khattar, Tülin Özkan, Adel Boughlita, Daouda Abba Moussa, Amelie Darlix, Frédérique Lorcy, Valérie RIGAU, Luc BAUCHET, Sabine Gerbal-Chaloin, Martine Daujat-Chavanieu, Floriant Bellvert, Laurent Turchi, Thierry Virolle, Jean-Philippe Hugnot, Nicolas Buisine, Mireille Galloni, Valerie Dardalhon, Anne-Marie Rodriguez, Marie-Luce Vignais, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Geroscience and rejuvenation research center (RESTORE), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Ankara University School of Medicine [Turkey], Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM), Hôpital Gui de Chauliac [CHU Montpellier], Neurochirurgie [Hôpital Gui de Chauliac], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul FluxoMet (TBI-MetaToul), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Physiologie moléculaire et adaptation (PhyMA), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), Institut de recherche en biothérapie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Neuroradiologie [Hôpital Gui de Chauliac], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
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[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology - Abstract
International audience; Glioblastomas (GBM) are heterogeneous tumors with high metabolic plasticity. Their poor prognosis is linked to the presence of glioblastoma stem cells (GSC), which support resistance to therapy, notably to temozolomide (TMZ). Mesenchymal stem cells (MSC) recruitment to GBM contributes to GSC chemoresistance, by mechanisms still poorly understood. Here, we provide evidence that MSCs transfer mitochondria to GSCs through tunneling nanotubes, which enhances GSCs resistance to TMZ. More precisely, our metabolomics analyses reveal that MSC mitochondria induce GSCs metabolic reprograming, with a nutrient shift from glucose to glutamine, a rewiring of the tricarboxylic acid cycle from glutaminolysis to reductive carboxylation and increase in orotate turnover as well as in pyrimidine and purine synthesis. Metabolomics analysis of GBM patient tissues at relapse after TMZ treatment documents increased concentrations of AMP, CMP, GMP, and UMP nucleotides and thus corroborate our in vitro analyses. Finally, we provide a mechanism whereby mitochondrial transfer from MSCs to GSCs contributes to GBM resistance to TMZ therapy, by demonstrating that inhibition of orotate production by Brequinar (BRQ) restores TMZ sensitivity in GSCs with acquired mitochondria. Altogether, these results identify a mechanism for GBM resistance to TMZ and reveal a metabolic dependency of chemoresistant GBM following the acquisition of exogenous mitochondria, which opens therapeutic perspectives based on synthetic lethality between TMZ and BRQ.Significance: Mitochondria acquired from MSCs enhance the chemoresistance of GBMs. The discovery that they also generate metabolic vulnerability in GSCs paves the way for novel therapeutic approaches.
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- 2023
22. Successful treatment of JAK1 associated inflammatory disease
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Fayand, Antoine, Hentgen, Véronique, Posseme, Céline, Lacout, Carole, Picard, Capucine, Moguelet, Philippe, Cescato, Margaux, Sbeih, Nabiha, Moreau, Thomas R.J., Zhu, Yixiang Yj., Charuel, Jean-Luc, Corneau, Aurélien, Deibener-Kaminsky, Joelle, Dupuy, Stéphanie, Fusaro, Mathieu, Hoareau, Benedicte, Hovnanian, Alain, Langlois, Vincent, Le Corre, Laurent, Maciel, Thiago, Miskinyte, Snaigune, Miyara, Makoto, Moulinet, Thomas, Perret, Magali, Schuhmacher, Marie Hélène, Rignault-Bricard, Rachel, Viel, Sébastien, Vinit, Angélique, Soria, Angèle, Duffy, Darragh, Launay, Jean-Marie, Callebert, Jacques, Herbeuval, Jean Philippe, Rodero, Mathieu P, Georgin-Lavialle, Sophie, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Groupe de Pathologie Infectieuse Pédiatrique [Paris] (GPIP), Société Française de Pédiatrie (SFP), Centre Hospitalier de Versailles André Mignot (CHV), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), CHU Trousseau [APHP], Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Pitié-Salpêtrière [AP-HP], Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Biomedtech Facilities (UMS 2009 / US36), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Groupe Hospitalier du Havre Hôpital Jacques Monod (MONTIVILLIERS) (GHH), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Emile Durkheim [Epinal] (CH Epinal / CHED), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, and Hôpital Lariboisière-Fernand-Widal [APHP]
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JAK 1 ,JAK inhibitors ,atopic dermatitis ,inborn errors of immunity ,[SDV]Life Sciences [q-bio] ,allergy - Abstract
International audience; Background: Gain of function (GOF) variants of JAK1 drive a rare immune dysregulation syndrome associated with atopic dermatitis, allergy and eosinophilia.Objectives: To describe the clinical and immunological characteristics associated with a new GOF variant of JAK1 and report the therapeutic efficacy of JAK inhibition.Methods: We identified a family affected by JAK1 associated autoinflammatory disease and performed clinical assessment and immunological monitoring on 9 patients. JAK1 signalling was studied by flow and mass cytometry in patients' cells at basal state, or after immune stimulation. A molecular disease signature in the blood was studied at the transcriptomic level. Patients were treated with one of two JAK inhibitors; either baricitinib or upadacitinib. Clinical, cellular, and molecular response were evaluated over a 2-year period.Results: Affected individuals displayed a syndromic disease with prominent allergy including atopic dermatitis, ichthyosis, arthralgia, chronic diarrhoea, disseminated calcifying fibrous tumours and elevated whole blood histamine levels. A variant of JAK1 localized in the pseudokinase domain was identified in all 9 affected tested patients. Hyper-phosphorylation of STAT3 was found in 5 out of 6 patients tested. Treatment of patients' cells with baricitinib controlled most of the atypical hyper-phosphorylation of STAT3. Administration of baricitinib to patients led to rapid improvement of the disease in all adults and was associated with reduction of systemic inflammation.Conclusions: Patients with this new JAK1 GOF pathogenic variant displayed very high levels of blood histamine and showed a variable combination of atopy with articular and gastrointestinal manifestations as well as calcifying fibrous tumours. The disease, that appears to be linked to STAT3 hyper-activation, was well controlled under treatment by JAK inhibitors in adult patients.
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- 2023
23. Evaluating the Portability of Rheumatoid Arthritis Phenotyping Algorithms: case study on French EHRs
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Fabacher, Thibaut, Sauleau, Erik-André, Leclerc, Noémie, Bergier, Hugo, Gottenberg, Jacques-Eric, Coulet, Adrien, Névéol, Aurélie, Groupe Méthodes en Recherche Clinique [Strasbourg] (GMRC), Nouvel Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, I-Cube Research, Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), CHU Strasbourg, Sciences et Technologies des Langues (STL), Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
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Phenotyping ,Rheumatoid Arthritis ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,[INFO]Computer Science [cs] ,Natural Language Processing - Abstract
International audience; Previous work has successfully used machine learning and natural language processing for the phenotyping of Rheumatoid Arthritis (RA) patients in hospitals within the United States and France. Our goal is to evaluate the adaptability of RA phenotyping algorithms to a new hospital, both at the patient and encounter levels. Two algorithms are adapted and evaluated with a newly developed RA gold standard corpus, including annotations at the encounter level. The adapted algorithms offer comparably good performance for patient-level phenotyping on the new corpus (F1 0.68 to 0.82), but lower performance for encounter-level (F1 0.54). Regarding adaptation feasibility and cost, the first algorithm incurred a heavier adaptation burden because it required manual feature engineering. However, it is less computationally intensive than the second, semi-supervised, algorithm.
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- 2023
24. Prognostic impact of cytoreductive surgery conducted with primary intent, versus cytoreductive surgery after neoadjuvant chemotherapy, in the management of patients with advanced epithelial ovarian cancers: a multicentre, propensity score‐matched study from the <scp>FRANCOGYN</scp> group
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Henri Wohrer, Meriem Koual, Enrica Bentivegna, Louise Benoit, Marie Metairie, Pierre‐Adrien Bolze, Yohan Kerbage, Emilie Raimond, Cherif Akladios, Xavier Carcopino, Geoffroy Canlorbe, Jennifer Uzan, Vincent Lavoue, Camille Mimoun, Cyrille Huchon, Martin Koskas, Hélène Costaz, François Margueritte, Yohann Dabi, Cyril Touboul, Sofiane Bendifallah, Lobna Ouldamer, Nicolas Delanoy, Huyen‐Thu Nguyen‐Xuan, Anne‐Sophie Bats, Henri Azaïs, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Cancer Research and Personalized Medicine - CARPEM [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and None
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epithelial ovarian cancer ,interval cytoreductive surgery ,Obstetrics and Gynecology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,primary cytoreductive surgery ,propensity score ,neoadjuvant chemotherapy - Abstract
International audience; Objective: To compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score.Design: We conducted a propensity score-matched cohort study, using data from the FRANCOGYN cohort.Setting: Retrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer.Sample: Patients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS.Methods: The propensity score was designed using pre-therapeutic variables associated with both treatment allocation and overall survival (OS).Main outcome measures: The primary outcome was OS. Secondary outcomes included recurrence-free survival (RFS), quality of CRS and other variables related to surgical morbidity.Results: A total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group.Conclusions: Analysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.
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- 2023
25. ß-D-Glucan Assay in the Cerebrospinal Fluid for the Diagnosis of non-cryptococcal Fungal Infection of the Central Nervous System: A Retrospective Multicentric Analysis and a Comprehensive Review of the Literature
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Jeanne Bigot, Jordan Leroy, Taieb Chouaki, Laurence Cholley, Naïke Bigé, Marie-Dominique Tabone, Eolia Brissot, Sophie Thorez, Julien Maizel, Hervé Dupont, Boualem Sendid, Christophe Hennequin, Juliette Guitard, Mucoviscidose: physiopathologie et phénogénomique [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), and Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF)
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Microbiology (medical) ,Cerebrospinal fluid ,Infectious Diseases ,diagnosis ,galactomannan ,mannan ,BDGlucan ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Background Except for cryptococcosis, fungal infection of the central nervous system (FI-CNS) is a rare but severe complication. Clinical and radiological signs are non-specific, and the value of conventional mycological diagnosis is very low. This study aimed to assess the value of β1,3-D-glucan (BDG) detection in the cerebrospinal fluid (CSF) of non-neonatal non-cryptococcosis patients. Methods Cases associated with BDG assay in the CSF performed in 3 French University Hospitals over 5 years were included. Clinical, radiological, and mycological results were used to classify the episodes as proven/highly probable, probable, excluded, and unclassified FI-CNS. Sensitivity and specificity were compared to that calculated from an exhaustive review of the literature. Results In total, 228 episodes consisting of 4, 7, 177, and 40 proven/highly probable, probable, excluded, and unclassified FI-CNS, respectively, were analysed. The sensitivity of BDG assay in CSF to diagnose proven/highly probable/probable FI-CNS ranged from 72.7% [95% confidence interval {CI}: 43.4%‒90.2%] to 100% [95% CI: 51%‒100%] in our study and was 82% in the literature. For the first time, specificity could be calculated over a large panel of pertinent controls and was found at 81.8% [95% CI: 75.3%‒86.8%]. Bacterial neurologic infections were associated with several false positive results Conclusions Despite its sub-optimal performance, BDG assay in the CSF should be added to the diagnostic armamentarium for FI-CNS.
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- 2023
26. How to Improve Cancer Patients ENrollment in Clinical Trials From rEal-Life Databases Using the Observational Medical Outcomes Partnership Oncology Extension: Results of the PENELOPE Initiative in Urologic Cancers
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Emmanuelle Kempf, Morgan Vaterkowski, Damien Leprovost, Nicolas Griffon, David Ouagne, Stéphane Breant, Patricia Serre, Alexandre Mouchet, Bastien Rance, Gilles Chatellier, Ali Bellamine, Marie Frank, Julien Guerin, Xavier Tannier, Alain Livartowski, Martin Hilka, Christel Daniel, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), and Institut Curie [Paris]
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[INFO]Computer Science [cs] ,General Medicine - Abstract
PURPOSE To compare the computability of Observational Medical Outcomes Partnership (OMOP)–based queries related to prescreening of patients using two versions of the OMOP common data model (CDM; v5.3 and v5.4) and to assess the performance of the Greater Paris University Hospital (APHP) prescreening tool. MATERIALS AND METHODS We identified the prescreening information items being relevant for prescreening of patients with cancer. We randomly selected 15 academic and industry-sponsored urology phase I-IV clinical trials (CTs) launched at APHP between 2016 and 2021. The computability of the related prescreening criteria (PC) was defined by their translation rate in OMOP-compliant queries and by their execution rate on the APHP clinical data warehouse (CDW) containing data of 205,977 patients with cancer. The overall performance of the prescreening tool was assessed by the rate of true- and false-positive cases of three randomly selected CTs. RESULTS We defined a list of 15 minimal information items being relevant for patients' prescreening. We identified 83 PC of the 534 eligibility criteria from the 15 CTs. We translated 33 and 62 PC in queries on the basis of OMOP CDM v5.3 and v5.4, respectively (translation rates of 40% and 75%, respectively). Of the 33 PC translated in the v5.3 of the OMOP CDM, 19 could be executed on the APHP CDW (execution rate of 58%). Of 83 PC, the computability rate on the APHP CDW reached 23%. On the basis of three CTs, we identified 17, 32, and 63 patients as being potentially eligible for inclusion in those CTs, resulting in positive predictive values of 53%, 41%, and 21%, respectively. CONCLUSION We showed that PC could be formalized according to the OMOP CDM and that the oncology extension increased their translation rate through better representation of cancer natural history.
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- 2023
27. Using dichotomized survival data to construct a prior distribution for a Bayesian seamless Phase II/III clinical trial
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Benjamin Duputel, Nigel Stallard, François Montestruc, Sarah Zohar, Moreno Ursino, Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Warwick Medical School, University of Warwick [Coventry], eXYSTAT [Malakoff], and Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138))
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Statistics and Probability ,[STAT]Statistics [stat] ,Health Information Management ,Epidemiology ,[SDV]Life Sciences [q-bio] - Abstract
Master protocol designs allow for simultaneous comparison of multiple treatments or disease subgroups. Master protocols can also be designed as seamless studies, in which two or more clinical phases are considered within the same trial. They can be divided into two categories: operationally seamless, in which the two phases are separated into two independent studies, and inferentially seamless, in which the interim analysis is considered an adaptation of the study. Bayesian designs are scarcely studied. Our aim is to propose and compare Bayesian operationally seamless Phase II/III designs using a binary endpoint for the first stage and a time-to-event endpoint for the second stage. At the end of Phase II, arm selection is based on posterior (futility) and predictive (selection) probabilities. The results of the first phase are then incorporated into prior distributions of a time-to-event model. Simulation studies showed that Bayesian operationally seamless designs can approach the inferentially seamless counterpart, allowing for an increasing simulated power with respect to the operationally frequentist design.
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- 2023
28. Strategies for recognizing pneumonia look-alikes
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David Drummond, Alice Hadchouel, Arnaud Petit, Naziha Khen-Dunlop, Cécile Lozach, Christophe Delacourt, Laureline Berteloot, Université Paris Cité (UPCité), Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de chirurgie et urologie pédiatrique [CHU-Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Service de radiologie pédiatrique [CHU Necker]
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Community-Acquired Infections ,Diagnosis, Differential ,Radiography ,Pediatrics, Perinatology and Child Health ,Humans ,Pneumonia ,Pneumonia, Pneumococcal ,Child ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Anti-Bacterial Agents - Abstract
Community-acquired pneumonia is a common diagnosis in children. Among the many children whose symptoms and/or chest X-ray is consistent with community-acquired pneumonia, it can be difficult to distinguish the rare cases of differential diagnoses that require specific management. The aim of this educational article is to provide clinicians with a series of questions to ask themselves in order to detect a possible differential diagnosis of pneumonia in children. The value of this approach is illustrated by 13 real clinical cases in which a child was misdiagnosed as having lobar pneumonia. What is Known: • When a lobar pneumonia is diagnosed, an appropriate antibiotic treatment leads to the resolution of the clinical signs in most cases. • However, several diseases can be look-alikes for pneumonia and mislead the practitioner. What is New: • This article provides a new approach to identify differential diagnoses of pneumonia in children. • It is illustrated by 13 real-life situations of children misdiagnosed as having pneumonia.
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- 2022
29. 150-cm Versus 200-cm Biliopancreatic Limb One-Anastomosis Gastric Bypass: Propensity Score–Matched Analysis
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Thibaud Bertrand, Claire Rives-Lange, Anne-Sophie Jannot, Clement Baratte, Flore de Castelbajac, Estelle Lu, Sylvia Krivan, Maud Le Gall, Claire Carette, Sebastien Czernichow, Jean-Marc Chevallier, Tigran Poghosyan, Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), GHU AP-HP Centre Université de Paris, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 'IASO' General Hospital of Athens, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
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Nutrition and Dietetics ,[SDV]Life Sciences [q-bio] ,Endocrinology, Diabetes and Metabolism ,Surgery - Abstract
International audience; BackgroundIt has been suggested that shortening the length of the biliopancreatic limb (BPL) to 150 cm in one anastomosis gastric bypass (OAGB) would reduce nutritional complication rates without impairing weight loss outcomes. The aim of this study is to compare patients who underwent OAGB with a 200-cm BPL (OAGB-200) to patients with OAGB with a 150-cm BPL (OAGB-150) in terms of weight loss and late morbidity.MethodsThis is a monocentric retrospective matched cohort study including patients with a body mass index between 35 and 50 kg/m2 who underwent an OAGB-150 or an OAGB-200. Patients were matched 1:1 based on age, sex, and body mass index, prior to bariatric surgery.ResultsIn total, 784 patients who underwent OAGB were included (OAGB-150 n = 392 and OAGB-200 (n = 392). There was no significant difference in terms of early morbidity. Regarding late morbidity in patients with an OAGB-150, significantly lower rates for marginal ulcer (OR = 0.4, CI 95% [0.2; 0.8], p = 0.006), incisional hernia (OR = 0.5, CI 95% [0.3; 1], p = 0.041), and bowel obstruction (OR = 0.3, CI 95% [0.1; 0.9], p = 0.039) were reported. Likewise, regarding late nutritional deficiencies, post-OAGB-150, a significantly lower number of patients with hypoalbuminemia (OR = 0.3, CI 95% [0.2; 0.7], p = 0.006), low vitamin B9 (OR = 0.5, CI 95% [0.2; 1], p = 0.044), and low ferritin (OR = 0.5, CI 95% [0.3; 0.8], p = 0.005) were observed. There was no significant difference in the percentage of excess BMI loss at 1, 2, 3, 4, and 5 years.ConclusionCompared to OAGB-200 in patients with BMI ≤ 50 kg/m2, OAGB-150 results in fewer nutritional deficiency rates long term, without impairing weight loss.
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- 2022
30. Phenotypic Heterogeneity of Fulminant COVID-19--Related Myocarditis in Adults
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Petra Barhoum, Marc Pineton de Chambrun, Karim Dorgham, Mathieu Kerneis, Sonia Burrel, Paul Quentric, Christophe Parizot, Juliette Chommeloux, Nicolas Bréchot, Quentin Moyon, Guillaume Lebreton, Samia Boussouar, Matthieu Schmidt, Hans Yssel, Lucie Lefevre, Makoto Miyara, Jean-Luc Charuel, Stéphane Marot, Anne-Geneviève Marcelin, Charles-Edouard Luyt, Pascal Leprince, Zahir Amoura, Gilles Montalescot, Alban Redheuil, Alain Combes, Guy Gorochov, Guillaume Hékimian, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut E3M [CHU Pitié-Salpêtrière], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Dorgham, Karim
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[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,Adult ,Male ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,Adolescent ,SARS-CoV-2 ,COVID-19 ,Stroke Volume ,Middle Aged ,Systemic Inflammatory Response Syndrome ,Ventricular Function, Left ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Myocarditis ,Young Adult ,Phenotype ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Humans ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Female ,Cardiology and Cardiovascular Medicine ,Autoantibodies ,Retrospective Studies - Abstract
International audience; Background: Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19–related myocarditis.Objectives: This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19–related myocarditis fulfilling MIS-A criteria (MIS-A+) or not (MIS-A−).Methods: A monocentric retrospective analysis of consecutive fulminant COVID-19–related myocarditis in a 26-bed intensive care unit (ICU).Results: Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19–related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A− patients compared with MIS-A+ patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A− patients (31% vs 4%). MIS-A+ had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A− had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A− patients (54%) but in none of the MIS-A+ patients.Conclusion: MIS-A+ and MIS-A− fulminant COVID-19–related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients’ management and further understanding of their pathophysiology
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- 2022
31. A Liaison Brought to Light: Cerebellum-Hippocampus, Partners for Spatial Cognition
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Laure Rondi-Reig, Anne-Lise Paradis, Mehdi Fallahnezhad, Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), The National Agency for Research ANR-17-CE16-0019-03 (SynPredict), and ANR-18-CE16-0010-02 (RewInhib) supported LRR and MF. ANR-17-CE37-0015-02 (Navi-GPS) and SATT Lutech supported LRR and ALP., ANR-17-CE37-0015,NaviGPS,la Navigation au delà de l'hippocampe: Comment coder ses déplacements propres en tenant compte de l'environnement ?(2017), ANR-18-CE16-0010,RewInhib,Etude du circuit cérébelleux inhibiteur lors d'une tâche orienté vers la récompense(2018), ANR-17-CE16-0019,SynPredict,Rôle de la synapse pour le codage prédictif dans le cortex cérébelleux(2017), Paradis, Anne-Lise, la Navigation au delà de l'hippocampe: Comment coder ses déplacements propres en tenant compte de l'environnement ? - - NaviGPS2017 - ANR-17-CE37-0015 - AAPG2017 - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Etude du circuit cérébelleux inhibiteur lors d'une tâche orienté vers la récompense - - RewInhib2018 - ANR-18-CE16-0010 - AAPG2018 - VALID, and Rôle de la synapse pour le codage prédictif dans le cortex cérébelleux - - SynPredict2017 - ANR-17-CE16-0019 - AAPG2017 - VALID
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Neurons ,Hippocampus Introduction: Cerebellum and Spatial Cognition ,Cognition ,Multimodal sensory information ,Neurology ,Cerebellum ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SCCO.NEUR] Cognitive science/Neuroscience ,Neurology (clinical) ,Hippocampus ,Navigation ,Spatial cognition ,Spatial Navigation - Abstract
International audience; This review focuses on the functional and anatomical links between the cerebellum and the hippocampus and the role of their interplay in goal-directed navigation and spatial cognition. We will describe the interactions between the cerebellum and the hippocampus at different scales: a macroscopic scale revealing the joint activations of these two structures at the level of neuronal circuits, a mesoscopic scale highlighting the synchronization of neuronal oscillations, and finally a cellular scale where we will describe the activity of hippocampal neuronal assemblies following a targeted manipulation of the cerebellar system. We will take advantage of this framework to summarize the different anatomical pathways that may sustain this multiscale interaction. We will finally consider the possible influence of the cerebellum on pathologies traditionally associated with hippocampal dysfunction.
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- 2022
32. The scaffold-dependent function of RIPK1 in experimental non-alcoholic steatohepatitis
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Valeria Pistorio, Juliette Tokgozoglu, Vlad Ratziu, Jérémie Gautheron, University of Naples Federico II, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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Non-alcoholic Fatty Liver Disease ,Receptor-Interacting Protein Serine-Threonine Kinases ,[SDV]Life Sciences [q-bio] ,Drug Discovery ,Humans ,Molecular Medicine ,ComputingMilieux_MISCELLANEOUS ,Genetics (clinical) - Abstract
International audience; No abstract available
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- 2022
33. Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial
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Labro, Guylaine, Tubach, Florence, Belin, Lisa, Dubost, Jean-Louis, Osman, David, Muller, Grégoire, Quenot, Jean-Pierre, da Silva, Daniel, Zarka, Jonathan, Turpin, Matthieu, Mayaux, Julien, Lamer, Christian, Doyen, Denis, Chevrel, Guillaume, Plantefeve, Gaétan, Demeret, Sophie, Piton, Gaël, Manzon, Cyril, Ochin, Evelina, Gaillard, Raphael, Dautzenberg, Bertrand, Baldacini, Mathieu, Lebbah, Said, Miyara, Makoto, Pineton de Chambrun, Marc, Amoura, Zahir, Combes, Alain, Palmyre, Jessica, Gimeno, Linda, Kone, Assitan, Vialette, Cedric, Slimi, Ouramdane, Chommeloux, Juliette, Lefevre, Lucie, Schmidt, Matthieu, Hekimian, Guillaume, Luyt, Charles-Edouard, Stiel, Laure, Dureau, Anne-Florence, Khaldoun, Kuteifan, Eid, Hanna, Baldacini, Matthieu, Zyberfajn, Cecile, Manson, Julien, Charrier, Nathanael, Balabanian, Angelique, Contou, Damien, Pajot, Olivier, Fraisse, Megan, Desaint, Paul, Sarfati, Florence, Fartoukh, Muriel, Voirot, Guillaume, Elabbabi, Alexandre, Djibre, Michel, Desnos, Cyrielle, Garcon, Pierre, van Vong, Ly, Issad, Andrea, Pillot, Bertrand, Reither, Delphine, Rouge, Patrick, Foliot, Pascale, Bendjamar, Lynda, Pointurier, Valentin, Winiszewski, Hadrien, Capellier, Gilles, Navellou, Jean-Christophe, Tapponnier, Romain, Panicucci, Emilie, Morand, Lucas, Dellamonica, Jean, Saccheri, Clement, Weiss, Nicolas, Marois, Clemence, Le Guennec, Loic, Rohaut, Benjamin, Ensenat, Luis, Billiou, Cecilia, Aroca, Maria, Baron, Marie, Demoule, Alexandre, Beurton, Alexandra, Bureau, Come, Decavele, Maxens, Dres, Martin, Bayle, Frederique, Le, Quoc Viet, Liron, Lionel, Putegnat, Jean-Baptiste, Salord, Francois, Andreu, Pascal, Slimani, Hakim, Roudeau, Baptiste, Labruyere, Marie, Jacquier, Marine, Anguel, Nadia, Ayed, Soufia, Durand, Edgard, Guerin, Laurent, Lai, Christopher, Aboab, Jerome, Alviset, Sophie, Laine, Laurent, Azzi, Mathilde, Issoufaly, Tazime, Tric, Laurent, Knani, Lyes, Boumezrag, Chahrazad Bey, Viault, Nicolas, Barbier, Francois, Boulain, Thierry, Kamel, Toufik, Nay, Mai-Anh, Tollec, Sophie, Nguyen, an Hung, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Département de santé publique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier René Dubos - 6, avenue de l’Ile de France 95303 CERGY-PONTOISE, Service de Pneumologie et Réanimation Respiratoire [AP-HP Hôpital Bicêtre] (DHU TORINO), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Centre de Référence de l'Hypertension Pulmonaire Sévère, Centre Hospitalier Régional d'Orléans (CHRO), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), réanimation et soins continus [CH Saint-Denis], Centre Hospitalier de Saint-Denis [Ile-de-France], Grand Hôpital de l'Est Francilien (GHEF), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Médico-Universitaire APPROCHES, Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut Mutualiste de Montsouris (IMM), Hôpital l'Archet, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Sud Francilien, Centre Hospitalier Victor Dupouy, REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aigüE [CHU Pitié-Salpêtrière] (GRC RESPIRE), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Réanimation, Médipole Lyon Villeurbanne. Service de réanimation. 158 rue Léon Blum. 69100 VILLEURBANNE, France, Service de médecine intensive-réanimation Hôpital Simone Veil, Eaubonne, France, GHU Paris Psychiatrie et Neurosciences, Université Paris Cité (UPCité), Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Institut Arthur Vernes, Unité de Recherche Clinique des hôpitaux Pitié-Salpêtrière – Charles Foix [CHU Pitié Salpêtrière] (URC PSL-CFX), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Service de Réanimation Médicale [CHU Pitié-Salpétrière], and TUBACH, Florence
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Adult ,Male ,Nicotine ,[SDV]Life Sciences [q-bio] ,Acute respiratory failure ,Critical Care and Intensive Care Medicine ,MESH: Nicotine ,Nicotinic receptor ,Double-Blind Method ,MESH: COVID-19 ,Humans ,MESH: SARS-CoV-2 ,MESH: Double-Blind Method ,MESH: Respiration, Artificial ,MESH: Treatment Outcome ,MESH: Humans ,SARS-CoV-2 ,COVID-19 ,MESH: Adult ,Respiration, Artificial ,Ventilation ,MESH: Male ,[SDV] Life Sciences [q-bio] ,Intensive Care Units ,Treatment Outcome ,Artificial ,MESH: Intensive Care Units ,Female ,Randomized trial ,MESH: Female - Abstract
Epidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia.In this multicentre, double-blind, placebo-controlled trial conducted in 18 intensive care units in France, we randomly assigned adult patients (non-smokers, non-vapers or who had quit smoking/vaping for at least 12 months) with proven COVID-19 pneumonia receiving invasive mechanical ventilation for up to 72 h to receive transdermal patches containing either nicotine at a daily dose of 14 mg or placebo until 48 h following successful weaning from mechanical ventilation or for a maximum of 30 days, followed by 3-week dose tapering by 3.5 mg per week. Randomization was stratified by centre, non- or former smoker status and Sequential Organ Function Assessment score ( or ≥ 7). The primary outcome was day-28 mortality. Main prespecified secondary outcomes included 60-day mortality, time to successful extubation, days alive and free from mechanical ventilation, renal replacement therapy, vasopressor support or organ failure at day 28.Between November 6th 2020, and April 2nd 2021, 220 patients were randomized from 18 active recruiting centers. After excluding 2 patients who withdrew consent, 218 patients (152 [70%] men) were included in the analysis: 106 patients to the nicotine group and 112 to the placebo group. Day-28 mortality did not differ between the two groups (30 [28%] of 106 patients in the nicotine group vs 31 [28%] of 112 patients in the placebo group; odds ratio 1.03 [95% confidence interval, CI 0.57-1.87]; p = 0.46). The median number of day-28 ventilator-free days was 0 (IQR 0-14) in the nicotine group and 0 (0-13) in the placebo group (with a difference estimate between the medians of 0 [95% CI -3-7]). Adverse events likely related to nicotine were rare (3%) and similar between the two groups.In patients having developed severe COVID-19 pneumonia requiring invasive mechanical ventilation, transdermal nicotine did not significantly reduce day-28 mortality. There is no indication to use nicotine in this situation.
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- 2022
34. A straightforward meta‐analysis approach for oncology phase I dose‐finding studies
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Tim Friede, Moreno Ursino, Sarah Zohar, Christian Röver, University Medical Center Göttingen (UMG), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE)
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FOS: Computer and information sciences ,Statistics and Probability ,Dose-Response Relationship, Drug ,Maximum Tolerated Dose ,Shrinkage estimation ,Epidemiology ,[SDV]Life Sciences [q-bio] ,Bayes Theorem ,Medical Oncology ,Bayesian statistics ,[STAT]Statistics [stat] ,Methodology (stat.ME) ,Logistic Models ,Research Design ,Dose-escalation trial ,Humans ,Computer Simulation ,Monte Carlo Method ,Statistics - Methodology ,Random-effects meta-analysis - Abstract
Phase I early-phase clinical studies aim at investigating the safety and the underlying dose-toxicity relationship of a drug or combination. While little may still be known about the compound's properties, it is crucial to consider quantitative information available from any studies that may have been conducted previously on the same drug. A meta-analytic approach has the advantages of being able to properly account for between-study heterogeneity, and it may be readily extended to prediction or shrinkage applications. Here we propose a simple and robust two-stage approach for the estimation of maximum tolerated dose(s) (MTDs) utilizing penalized logistic regression and Bayesian random-effects meta-analysis methodology. Implementation is facilitated using standard R packages. The properties of the proposed methods are investigated in Monte-Carlo simulations. The investigations are motivated and illustrated by two examples from oncology., Comment: 30 pages, 11 figures, 8 tables
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- 2022
35. Adenoma detection rate is enough to assess endoscopist performance: a population-based observational study of FIT-positive colonoscopies
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Bernard Denis, Isabelle Gendre, Nicolas Tuzin, Juliette Murris, Anne Guignard, Philippe Perrin, Gabriel Rahmi, Hôpital pasteur [Colmar], Association pour le dépistage du cancer colorectal en Alsace (ADECA Alsace), Centre Régional de Coordination du Dépistage des Cancers [Grand Est] (CRCDC-GE), CHU Strasbourg, Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
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[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Pharmacology (medical) - Abstract
Background and study aims Neoplasia-related indicators, such as adenoma detection rate (ADR), are a priority in the quality improvement process for colonoscopy. Our aim was to assess and compare different detection and characterization indicators in fecal immunochemical test (FIT)-positive colonoscopies, to determine associated factors, and to propose benchmarks. Patients and methods Retrospective analysis of prospectively collected data from all colonoscopies performed between 2015 and 2019 after a positive quantitative FIT in the population-based colorectal cancer screening program conducted in Alsace, part of the French national program. Detection indicators included ADR, mean number of adenomas per colonoscopy, and proximal serrated lesion (SL) detection rate. Characterization indicators included rate of non-neoplastic polyp (NNP) detection. Results Overall, 13,067 FIT-positive colonoscopies were evaluated, performed by 80 community gastroenterologists. The overall ADR was 57.6 %, and a 10 µg/g increase in fecal hemoglobin concentration was significantly associated with higher ADR (odds ratio [95 % confidence interval] = 1.02 [1.02–1.03]). Endoscopists whose ADR was ≥ 55 % were high detectors for all neoplasia, including proximal SLs and number of adenomas. The rate of detection of NNPs was 39.5 % in highest detectors (ADR > 70 %), significantly higher than in lower detectors (21.4 %) (P Conclusions A single indicator, ADR, is enough to assess endoscopist performance for both detection and characterization in routine practice provided the minimum target standard is raised and a maximum standard is added: 55 % and 70 % for FIT-positive colonoscopies, respectively.
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- 2022
36. Relationships between pelvic nerves and levator ani muscle for posterior sacrocolpopexy: an anatomic study
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Rocher, Grégoire, Azaïs, Henri, Favier, Amélia, Uzan, Catherine, Castela, Mathieu, Moawad, Gaby, Lavoué, Vincent, Morandi, Xavier, Nyangoh Timoh, Krystel, Canlorbe, Geoffroy, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Scarcell Therapeutics, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Universitaire de Cancérologie [Paris] (IUC)
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Mesh ,Sacrocolpopexy ,Hypogastric Plexus ,Ligaments ,Pararectal fossa ,Pelvic Floor ,Inferior hypogastric plexus ,Pelvic organ prolapse ,Pathology and Forensic Medicine ,Humans ,Female ,Laparoscopy ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,Radiology, Nuclear Medicine and imaging ,Surgery ,Anatomy ,Levator ani muscle - Abstract
International audience; BACKGROUND: The placement of posterior mesh during pelvic organ prolapse laparoscopic surgery has been incriminated as responsible for postoperative adverse outcomes such as digestive symptoms, chronic pelvic pain, and sexual dysfunction. These complications may be related to neural injuries that occur during the fixation of the posterior mesh on the levator ani muscle. OBJECTIVES: The aim of our study was to describe the course of the autonomic nerves of the pararectal space and their anatomical relationship with the posterior mesh fixation zone on the levator ani muscle. STUDY DESIGN: Twenty hemi-pelvis specimens from 10 fresh female cadavers were dissected. We measured the distance between the posterior mesh fixation zone on the levator ani, and the nearest point of adjacent structures: the hypogastric nerve, inferior hypogastric plexus, uterosacral ligament, uterine artery, and ureter. Measurements were repeated starting from the inferior hypogastric plexus. RESULTS: Nerve fibers of the inferior hypogastric plexus spread out systematically above the superior aspect of the levator ani muscle. Median distance from the posterior mesh fixation zone and the inferior hypogastric plexus was around 2.8 (range 2.1-3.5) cm. CONCLUSIONS: The inferior hypogastric plexus lies above the superior aspect of the levator ani muscle. A short distance between the posterior mesh fixation zone on the levator ani muscle and inferior hypogastric plexus could explain in part postoperative digestive symptoms. These observations support the development of nerve-sparing procedures for posterior mesh placement in the context of pelvic organ prolapse repair and suggest that postoperative complications could be improved by changing the fixation zone.
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- 2022
37. Comparison of 8 versus 15 days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial
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Adrien, Bouglé, Sophie, Tuffet, Laura, Federici, Marc, Leone, Antoine, Monsel, Thomas, Dessalle, Julien, Amour, Claire, Dahyot-Fizelier, François, Barbier, Charles-Edouard, Luyt, Olivier, Langeron, Bernard, Cholley, Julien, Pottecher, Tarik, Hissem, Jean-Yves, Lefrant, Benoit, Veber, Matthieu, Legrand, Alexandre, Demoule, Pierre, Kalfon, Jean-Michel, Constantin, Alexandra, Rousseau, Tabassome, Simon, Arnaud, Foucrier, Nora, Soussi, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Sud Francilien, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut 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 d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Strasbourg, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), CHU Rouen, Normandie Université (NU), Hôpital Lariboisière-Fernand-Widal [APHP], Hôpital Louis Pasteur [Chartres], CHU Clermont-Ferrand, Centre de Ressources Biologiques APHP-SU (PASS-CRB-APHP-SU), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Hôpital Beaujon [AP-HP]
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Adult ,MESH: Humans ,Survival ,Pneumonia, Ventilator-Associated ,MESH: Adult ,MESH: Pneumonia, Ventilator-Associated ,Antibiotic therapy ,Critical Care and Intensive Care Medicine ,Respiration, Artificial ,Anti-Bacterial Agents ,Ventilator-associated pneumonia ,Intensive Care Units ,Recurrence ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,MESH: Anti-Bacterial Agents ,MESH: Intensive Cate Units ,MESH: Pseudomonas aeruginosa ,Pseudomonas aeruginosa ,Humans ,MESH: Respiration, Artificial - Abstract
International audience; Purpose: Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in VAP due to PA (PA-VAP).Methods: We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8 days) or a long-duration treatment (15 days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days.Results: The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay.Conclusions: Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.
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- 2022
38. Therapeutic indications and metabolic effects of metreleptin in patients with lipodystrophy syndromes: Real‐life experience from a national reference network
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Héléna Mosbah, Marie‐Christine Vantyghem, Estelle Nobécourt, Fabrizio Andreelli, Francoise Archambeaud, Elise Bismuth, Claire Briet, Maryse Cartigny, Benjamin Chevalier, Bruno Donadille, Anne Daguenel, Mathilde Fichet, Jean‐François Gautier, Sonja Janmaat, Isabelle Jéru, Carole Legagneur, Lysiane Leguier, Julie Maitre, Elise Mongeois, Christine Poitou, Eric Renard, Yves Reznik, Anne Spiteri, Florence Travert, Bruno Vergès, Jamila Zammouri, Corinne Vigouroux, Camille Vatier, Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
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Adult ,Leptin ,Adolescent ,Lipodystrophy ,Endocrinology, Diabetes and Metabolism ,Syndrome ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,Middle Aged ,Young Adult ,Endocrinology ,Lipodystrophy, Congenital Generalized ,Internal Medicine ,Humans ,Retrospective Studies - Abstract
International audience; Aims: To describe baseline characteristics and follow-up data in patients with lipodystrophy syndromestreated with metreleptin in a national reference network, in a real-life setting.Patients and Methods: Clinical and metabolic data from patients receiving metreleptin in France wereretrospectively collected, at baseline, one year and at the latest follow-up during treatment.Results: Forty-seven patients with lipodystrophy including generalized lipodystrophy (GLD, n=28) andpartial lipodystrophy (PLD, n=19) received metreleptin over the last decade. At baseline, age was 29.3[16.6-47.6] (years, median [interquartile range]); BMI 23.8 kg/m2 [21.2-25.7]; serum leptin 3.2 [1.0-4.9] ng/mL); 94% of patients had diabetes (66% insulin-treated), 53% hypertension, and 87%dyslipidemia. Metreleptin therapy, administered during 31.7 [14.2-76.0] months, was ongoing in 77%of patients at the latest follow-up. In patients with GLD, HbA1c (%) and fasting triglycerides (mmol/L)significantly decreased from baseline to one year-metreleptin treatment, from 8.4 [6.5-9.9] to 6.8 [5.6-7.4], and 3.6 [1.7-8.5] to 2.2 [1.1-3.7] respectively (p
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- 2022
39. The ‘Alu-ome’ shapes the epigenetic environment of regulatory elements controlling cellular defense
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Mickael Costallat, Eric Batsché, Christophe Rachez, Christian Muchardt, Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and MUCHARDT, Christian
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Epigenomics ,biology ,Alu element ,RNA polymerase II ,Promoter ,Regulatory Sequences, Nucleic Acid ,Cell biology ,Epigenesis, Genetic ,Histone Code ,Transcription (biology) ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,DNA methylation ,biology.protein ,Genetics ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,H3K4me3 ,Epigenetics ,Enhancer ,Promoter Regions, Genetic - Abstract
Promoters and enhancers are sites of transcription initiation (TSSs) and carry active histone modifications, including H3K4me1, H3K4me3, and H3K27ac. Yet, the principles governing the boundaries of such regulatory elements are still poorly characterized. Alu elements are good candidates for a boundary function, being highly abundant in gene-rich regions, while essentially excluded from regulatory elements. Here, we show that the interval from the TSS to the first upstream Alu accommodates essentially all H3K4me3 marks, while excluding DNA methylation. In contrast, enhancer-enriched H3K4me1 and H3K27ac marks eventually cross the first-Alu limit, consistent with enhancer-annotation occasionally overlapping with Alu elements. Remarkably, the average length of TSS-to-first Alu intervals greatly varies in-between tissues, being longer in stem- and shorter in immune-cells. Shortest TSS-to-Alu intervals were observed at promoters active in T cells, particularly at immune genes, correlating with serendipitous RNA polymerase II transcription and accumulation of H3K4me1 signal at the first-Alu. At several T-cell first-Alus, the DNA methylation was further found to evolved with age, regressing from young to middle-aged, then recovering later in life. Thus, the first-Alu upstream of TSSs functions as a dynamic boundary for regulatory elements, initiating the upstream DNA-methylation landscape, while also participating in the recording of immune gene transcriptional events.
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- 2022
40. Single-cell transcriptomics reveals age-resistant maintenance of cell identities, stem cell compartments and differentiation trajectories in long-lived naked mole-rats skin
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Aleksandra Savina, Thierry Jaffredo, Frederic Saldmann, Chris G. Faulkes, Philippe Moguelet, Christine Leroy, Delphine Del Marmol, Patrice Codogno, Lucy Foucher, Antoine Zalc, Mélanie Viltard, Gérard Friedlander, Selim Aractingi, Romain H. Fontaine, Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Migration et différenciation des cellules souches hématopoiétiques = Migration and differentiation of hematopoietic stem cells (LBD-E06), Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire de Biologie du Développement [IBPS] (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement [IBPS] (LBD), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), School of Biological and Chemical Sciences, Queen Mary University of London (QMUL), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université de Namur [Namur] (UNamur), Centre de recherche biomédicale (CRBM), École nationale vétérinaire - Alfort (ENVA)-Université Paris-Est (UPE), 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), Fondation pour la Recherche en Physiologie [Bruxelles], UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CITI Centre of Innovation in Telecommunications and Integration of services (CITI), 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)-Institut National de Recherche en Informatique et en Automatique (Inria), Robots coopératifs et adaptés à la présence humaine en environnements (CHROMA), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-CITI Centre of Innovation in Telecommunications and Integration of services (CITI), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-Inria Lyon, and Institut National de Recherche en Informatique et en Automatique (Inria)
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skin ,Aging ,naked mole-rat ,Mole Rats ,[SDV]Life Sciences [q-bio] ,Longevity ,Wound healing ,wound healing ,Stem cells ,Cell Biology ,Naked mole-rat ,Mice ,naked mole-rat skin stem cells wound healing aging ,stem cells ,Animals ,Transcriptome ,Skin - Abstract
International audience; Naked mole-rats (NMR) are subterranean rodents characterized by an unusual longevity coupled with an unexplained resistance to aging. In the present study, we performed extensive in situ analysis and single-cell RNA-sequencing comparing young and older animals. At variance with other species, NMR exhibited a striking stability of skin compartments and cell types, which remained stable over time without aging-associated changes. Remarkably, the number of stem cells was constant throughout aging. We found three classical cellular states defining a unique keratinocyte differentiation trajectory that were not altered after pseudotemporal reconstruction. Epidermal gene expression did not change with aging either. Langerhans cell clusters were conserved, and only a higher basal stem cell expression of Igfbp3 was found in aged animals. In accordance, NMR skin healing closure was similar in young and older animals. Altogether, these results indicate that NMR skin is characterized by peculiar genetic and cellular features, different from those previously demonstrated for mice and humans. The remarkable stability of the aging NMR skin transcriptome likely reflects unaltered homeostasis and resilience.
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- 2022
41. Foveal Hypoplasia Grading in 95 Cases of Congenital Aniridia: Correlation to Phenotype and PAX6 Genotype
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ALEJANDRA DARUICH, MATTHIEU P. ROBERT, CAMILLE LEROY, NATHALIE DE VERGNES, CAROLINE BEUGNET, VALERIE MALAN, SOPHIE VALLEIX, DOMINIQUE BREMOND-GIGNAC, Service d'ophtalmologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie des maladies oculaires : innovations thérapeutiques = Physiopathology of ocular diseases: Therapeutic innovations [CRC], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique moléculaire [CHU Necker], Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], and Gestionnaire, Hal Sorbonne Université
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[SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Genotype ,PAX6 Transcription Factor ,genetic structures ,Vision Disorders ,aniridia ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,eye diseases ,Pedigree ,PAX6 ,Ophthalmology ,Phenotype ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Mutation ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,[SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Humans ,foveal hypoplasia ,sense organs ,Eye Proteins ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,Retrospective Studies ,iris - Abstract
International audience; Purpose: To correlate the degree of foveal hypoplasia in congenital aniridia with visual acuity, iris phenotype, and PAX6 mutations.Design: Retrospective case series.Methods: 95 consecutive patients with high quality Spectral-domain optical coherence tomography (SD-OCT) records and available genotype were included in a single referral center. Iris hypoplasia was classified as complete, presence of iris root or remnants and mild atypical aniridia. SD-OCT images were assessed to classify foveal hypoplasia as Grade 1 to 4 and to determine mean thicknesses for retinal layers. For statistical analysis one eye for each patient have been used and one member of the same family has been included (n=76 eyes).Results: Most eyes (93.5%) showed variable degree of foveal hypoplasia. PAX6-positive patients presented higher degree of foveal hypoplasia than patients negative for PAX6 (p
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- 2022
42. Titin copy number variations associated with dominant inherited phenotypes
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Perrin, Aurélien, Métay, Corinne, Savarese, Marco, Yaou, Rabah Ben, Demidov, German, Solé, Guilhem, Péréon, Yann, Bertini, Enrico, Fattori, Fabiana, D’amico, Adele, Ricci, Federica, Ginsberg, Mira, Seferian, Andreea, Boespflug-Tanguy, Odile, Servais, Laurent, Chapon, Françoise, Lagrange, Emmeline, Gaudon, Karen, Nelson, Isabelle, Guyant-Maréchal, Lucie, Johari, Mridul, Goethem, Charles Van, Fardeau, Michel, Juntas-Morales, Raul, Udd, Bjarne, Bonne, Gisèle, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
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[SDV.GEN]Life Sciences [q-bio]/Genetics ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics - Published
- 2023
43. Caveolae and Bin1 form ring-shaped platforms for T-tubule initiation
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Eline Lemerle, Jeanne Lainé, Marion Benoist, Gilles Moulay, Anne Bigot, Clémence Labasse, Angéline Madelaine, Alexis Canette, Perrine Aubin, Jean-Michel Vallat, Norma B Romero, Marc Bitoun, Vincent Mouly, Isabelle Marty, Bruno Cadot, Laura Picas, Stéphane Vassilopoulos, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Microscopie Electronique [IBPS] (IBPS-ME), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Université Grenoble Alpes (UGA), Hôpital Dupuytren [CHU Limoges], [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Montpellier (UM), ANR-21-CE13-0018,CLASS,Plaques de clathrine: Structure, fonction et implication dans les maladies neuromusculaires(2021), and ANR-18-CE17-0006,DynaTher,Thérapie par modulation de l'expression de la Dynamine 2(2018)
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General Immunology and Microbiology ,General Neuroscience ,[SDV]Life Sciences [q-bio] ,General Medicine ,General Biochemistry, Genetics and Molecular Biology - Abstract
International audience; Excitation-contraction coupling requires a highly specialized membrane structure, the triad, composed of a plasma membrane invagination, the T-tubule, surrounded by two sarcoplasmic reticulum terminal cisternae. Although the precise mechanisms governing T-tubule biogenesis and triad formation remain largely unknown, studies have shown that caveolae participate in T-tubule formation and mutations of several of their constituents induce muscle weakness and myopathies. Here, we demonstrate that, at the plasma membrane, Bin1 and caveolae composed of caveolin-3 assemble into ring-like structures from which emerge tubes enriched in the dihydropyridine receptor. Bin1 expression lead to the formation of both rings and tubes and we show that Bin1 forms scaffolds on which caveolae accumulate to form the initial T-tubule. Cav3 deficiency caused by either gene silencing or pathogenic mutations results in defective ring formation and perturbed Bin1-mediated tubulation that may explain defective T-tubule organization in mature muscles. Our results uncover new pathophysiological mechanisms that may prove relevant to myopathies caused by Cav3 or Bin1 dysfunction.
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- 2023
44. The UAS thioredoxin-like domain of UBXN7 regulates E3 ubiquitin ligase activity of RNF111/Arkadia
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Sadek Amhaz, Batiste Boëda, Mouna Chouchène, Sabrina Colasse, Florent Dingli, Damarys Loew, Julien Henri, Céline Prunier, Laurence Levy, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Polarité cellulaire, Migration et Cancer - Cell Polarity, Migration and Cancer, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Curie [Paris], Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and S.A. was funded by a PhD fellowship from Ministère de l’enseignement supérieur et de la recherche. C.P. was supported by Grants from La Ligue Contre le Cancer (Comité de Paris—grant R18059DD) and Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC—grant R18115DD)
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RNF111 ,TGF-β ,RING ,Physiology ,TOPORS ,Cell Biology ,Plant Science ,General Biochemistry, Genetics and Molecular Biology ,UBXN7 ,E3 ubiquitin ligase ,Structural Biology ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,General Agricultural and Biological Sciences ,Thioredoxin ,SKIL ,Ecology, Evolution, Behavior and Systematics ,Developmental Biology ,Biotechnology ,RNF165 - Abstract
Background E3 ubiquitin ligases play critical roles in regulating cellular signaling pathways by inducing ubiquitylation of key components. RNF111/Arkadia is a RING E3 ubiquitin ligase that activates TGF-β signaling by inducing ubiquitylation and proteasomal degradation of the transcriptional repressor SKIL/SnoN. In this study, we have sought to identify novel regulators of the E3 ubiquitin ligase activity of RNF111 by searching for proteins that specifically interacts with its RING domain. Results We found that UBXN7, a member of the UBA-UBX family, directly interacts with the RING domain of RNF111 or its related E3 RNF165/ARK2C that shares high sequence homology with RNF111. We showed that UBXN7 docks on RNF111 or RNF165 RING domain through its UAS thioredoxin-like domain. Overexpression of UBXN7 or its UAS domain increases endogenous RNF111, while an UBXN7 mutant devoid of UAS domain has no effect. Conversely, depletion of UBXN7 decreases RNF111 protein level. As a consequence, we found that UBXN7 can modulate degradation of the RNF111 substrate SKIL in response to TGF-β signaling. We further unveiled this mechanism of regulation by showing that docking of the UAS domain of UBXN7 inhibits RNF111 ubiquitylation by preventing interaction of the RING domain with the E2 conjugating enzymes. By analyzing the interactome of the UAS domain of UBXN7, we identified that it also interacts with the RING domain of the E3 TOPORS and similarly regulates its E3 ubiquitin ligase activity by impairing E2 binding. Conclusions Taken together, our results demonstrate that UBXN7 acts as a direct regulator for the E3 ubiquitin ligases RNF111, RNF165, and TOPORS and reveal that a thioredoxin-like domain can dock on specific RING domains to regulate their E3 ubiquitin ligase activity.
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- 2023
45. The histone demethylase Kdm3 prevents auto-immune piRNAs production in Drosophila
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Karine Casier, Julie Autaa, Nathalie Gueguen, Valérie Delmarre, Pauline P. Marie, Stéphane Ronsseray, Clément Carré, Emilie Brasset, Laure Teysset, Antoine Boivin, Laboratoire de Biologie du Développement [IBPS] (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)
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[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics ,Multidisciplinary ,[SDV]Life Sciences [q-bio] - Abstract
SUMMARYIn animals, genome integrity of the germ line is protected from transposable element (TE) activity by small, non-coding, dedicated RNAs acting as an immune system against TEs, and called PIWI-interacting RNAs (piRNAs) 1,2. In Drosophila, the production of piRNAs is initiated from heterochromatic loci containing remnants of TEs and enriched in histone H3 trimethylated on lysine 9 (H3K9me3) 3–5. These loci, called piRNA clusters, constitute a memory of past TE invasions. Little is known about how piRNA clusters are genetically defined. Using a genetic screen combined with a bimodal epigenetic state piRNA cluster (BX2), we identified the splicing factor Half pint (Hfp) and the histone demethylase KDM3 as being able to prevent BX2 piRNA production. Furthermore, we showed that Hfp is needed to splice Kdm3 transcripts. Germline expression of Kdm3 coding sequence (splicing-independent) rescued the hfp germline knock-down (GLKD) effect demonstrating that Kdm3 is sufficient to prevent BX2 piRNA production. Our data revealed that in the absence of Kdm3, dozens of gene-containing regions become bona fide germinal dual strand piRNA clusters. Indeed, they produce piRNAs originating from both DNA strands, become transcribed in a Moonshiner-dependent manner and enriched in di-and tri-methylation of lysine 9 of histone H3 (H3K9me2/3) and in Rhino, an HP1-like protein. Eggs laid by Kdm3 GLKD females do not hatch and show developmental defects phenocopying loss of function of genes included into the new piRNA clusters, suggesting an inheritance of functional ovarian “auto-immune” piRNAs. Our results demonstrate that some gene-containing regions are actively prevented for piRNA production by proteins that counteract piRNA cluster emergence. Hence, a non-piRNA-producing state is therefore not a “by default” state but rather a cellular lock that is actively controlled for some genomic loci.KEY FACTSHfp regulates the expression of Kdm3 via its splicingKdm3 prevents genomic regions containing coding genes from becoming piRNA clustersEmbryos from Kdm3 mutant females show developmental phenotypes suggesting that auto-immune piRNAs are functional and alter the expression of genes embedded in newly established piRNA clusters
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- 2023
46. Escape from oncogene-induced senescence is controlled by POU2F2 and memorized by chromatin scars
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Ricardo Iván Martínez-Zamudio, Alketa Stefa, José Américo Nabuco, Themistoklis Vasilopoulos, Mark Simpson, Gregory Doré, Pierre-François Roux, Mark A. Galan, Ravi J. Chokshi, Oliver Bischof, Utz Herbig, Rutgers University [Newark], Rutgers University System (Rutgers), Rutgers, The State University of New Jersey [New Brunswick] (RU), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Biologie des ARN de Plasmodium - Plasmodium RNA Biology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Rutgers New Jersey Medical School (NJMS), Centre National de la Recherche Scientifique (CNRS), This study was supported by the National Cancer Institute of the NIH (R01CA136533)., and Bischof, Oliver
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[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,Genetics ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Article - Abstract
SummaryAlthough oncogene-induced senescence (OIS) is a potent tumor-suppressor mechanism, recent studies revealed that cells can escape from OIS with features of transformed cells. However, the mechanisms that promote OIS escape remain unclear, and evidence of post-senescent cells in human cancers is missing. Here, we unravel the regulatory mechanisms underlying OIS escape using dynamic multidimensional profiling. We demonstrate a critical role for AP1 and POU2F2 transcription factors for escape from OIS and identify ‘senescence-associated chromatin scars (SACS)’ as an epigenetic memory of OIS, detectable during colorectal cancer progression. POU2F2 levels are elevated already in precancerous lesions and as cells escape from OIS, and its expression and binding activity to cis-regulatory elements are associated with decreased patient survival. Our results support a model in which POU2F2 exploits a precoded enhancer landscape to promote senescence escape and reveal POU2F2 gene signatures and SACS as valuable biomarkers with diagnostic and prognostic potential.
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- 2023
47. Deep Learning on Bone Scintigraphy to Detect Abnormal Cardiac Uptake at Risk of Cardiac Amyloidosis
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Marc-Antoine Delbarre, François Girardon, Lucien Roquette, Paul Blanc-Durand, Marc-Antoine Hubaut, Éric Hachulla, Franck Semah, Damien Huglo, Nicolas Garcelon, Etienne Marchal, Isabelle El Esper, Christophe Tribouilloy, Nicolas Lamblin, Pierre Duhaut, Jean Schmidt, Emmanuel Itti, Thibaud Damy, CHU Amiens-Picardie, CODOC SAS [Paris] (CS), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Roger Salengro [Lille], Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Troubles cognitifs vasculaires et dégénératifs, Université de Lille, Sciences et Technologies, Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and CHU Henri Mondor [Créteil]
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Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; BackgroundCardiac uptake on technetium-99m whole-body scintigraphy (WBS) is almost pathognomonic of transthyretin cardiac amyloidosis. The rare false positives are often related to light-chain cardiac amyloidosis. However, this scintigraphic feature remains largely unknown, leading to misdiagnosis despite characteristic images. A retrospective review of all WBSs in a hospital database to detect those with cardiac uptake may allow the identification of undiagnosed patients.ObjectivesThe authors sought to develop and validate the first deep learning–based model that automatically detects significant cardiac uptake (≥Perugini grade 2) on WBS from large hospital databases in order to retrieve patients at risk of cardiac amyloidosis.MethodsThe model is based on a convolutional neural network with image-level labels. The performance evaluation was performed with C-statistics using a 5-fold cross-validation scheme stratified so that the proportion of positive and negative WBSs remained constant across folds and using an external validation data set.ResultsThe training data set consisted of 3,048 images: 281 positives (≥Perugini 2) and 2,767 negatives. The external validation data set consisted of 1,633 images: 102 positives and 1,531 negatives. The performance of the 5-fold cross-validation and external validation was as follows: 98.9% (± 1.0) and 96.1% for sensitivity, 99.5% (± 0.4) and 99.5% for specificity, and 0.999 (SD = 0.000) and 0.999 for the area under the curve of the receiver-operating characteristic curves. Sex, age
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- 2023
48. Filopodia-like protrusions of adjacent somatic cells shape the developmental potential of oocytes
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Flora Crozet, Gaëlle Letort, Rose Bulteau, Christelle Da Silva, Adrien Eichmuller, Anna Francesca Tortorelli, Joséphine Blévinal, Morgane Belle, Julien Dumont, Tristan Piolot, Aurélien Dauphin, Fanny Coulpier, Alain Chédotal, Jean-Léon Maître, Marie-Hélène Verlhac, Hugh J Clarke, Marie-Emilie Terret, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Biologie du système neuromusculaire - Biology of the neuromuscular system [Maisons-Alfort] (BNMS - Team 10), École nationale vétérinaire - Alfort (ENVA)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), The STED microscopy was performed at the Orion Platform (member of France-Bioimaging ANR-10-INBS-XX) of the Center for Interdisciplinary Research in Biology (UMR7241/U1050) of Collège de France. The OMX microscopy was performed at the Cell and Tissue Imaging Platform-PICT-IBiSA of the Genetics and Developmental Biology Department (UMR3215/U934) of Institut Curie. This work was supported by the Fondation pour la Recherche Médicale (FRM Label EQU201903007796 to M-H Verlhac), by the Agence Nationale de la Recherche (ANR-18-CE13 to M-H Verlhac and Auguste Genovesio, IBENS/ENS, ANR-16-CE13 to M-E Terret), and by the France Canada Research Fund (FCRF 2017 to M-E Terret and Hugh J Clarke, McGill University). F Crozet obtained a grant from the Fondation pour la Recherche Médicale for her fourth PhD year (FDT202001010906). This work has received support from the Fondation Bettencourt Schueller.., ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-10-LABX-0054,MEMOLIFE,Memory in living systems: an integrated approach(2010), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), and European Project: 250367,EC:FP7:ERC,ERC-2009-AdG,EPIGENETIX(2010)
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Ecology ,Health, Toxicology and Mutagenesis ,[SDV]Life Sciences [q-bio] ,Plant Science ,Biochemistry, Genetics and Molecular Biology (miscellaneous) - Abstract
The oocyte must grow and mature before fertilization, thanks to a close dialogue with the somatic cells that surround it. Part of this communication is through filopodia-like protrusions, called transzonal projections (TZPs), sent by the somatic cells to the oocyte membrane. To investigate the contribution of TZPs to oocyte quality, we impaired their structure by generating a full knockout mouse of the TZP structural component myosin-X (MYO10). Using spinning disk and super-resolution microscopy combined with a machine-learning approach to phenotype oocyte morphology, we show that the lack ofMyo10decreases TZP density during oocyte growth. Reduction in TZPs does not prevent oocyte growth but impairs oocyte-matrix integrity. Importantly, we reveal by transcriptomic analysis that gene expression is altered in TZP-deprived oocytes and that oocyte maturation and subsequent early embryonic development are partially affected, effectively reducing mouse fertility. We propose that TZPs play a role in the structural integrity of the germline–somatic complex, which is essential for regulating gene expression in the oocyte and thus its developmental potential.
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- 2023
49. Actes de la journée d'étude sur la Similarité entre Patients, SimPa 2023
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Coulet, Adrien, Gérardin, Christel, Névéol, Aurélie, Tannier, Xavier, Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Épidémiologie clinique des maladies virales chroniques [iPLesp] (CLEPIVIR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Sciences et Technologies des Langues (STL), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord
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[INFO.INFO-TT]Computer Science [cs]/Document and Text Processing ,Données de patients ,[INFO]Computer Science [cs] ,Similarité ,Texte clinique ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Représentation de patients ,[INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI] - Abstract
La notion de similarité est importante pour représenter les connaissances médicales et traiter les documents véhiculant des informations de santé. Les développements méthodologiques récents en traitement automatique de la langue ont permis d’explorer différentes facettes de la similarité en santé en s’appuyant sur la représentation des contenus structurés ou non-structurés typiquement présents dans les entrepôts de données de santé. Dans ce contexte, il nous a semblé intéressant d’examiner les approches proposées dans les communautés de l’informatiquemédicale, de la gestion de connaissances et du traitement automatique de la langue sur des questions telles que la définition et l’identification des phénomènes de similarité textuelle en santé, explorant un continuum allant de l’identité des chaînes de caractères à la similarité sémantique et thématique entre documents ; l’identification de « cas similaires » (par exemple pour la définition de cohortes, l’inclusion dans des essais cliniques ou la détection de dossiers patients dupliqués) ; la représentation de patients ; la création de jumeaux numériques par génération de données patient synthétiques. L’objectif de la journée SimPa était double : — documenter les cas pratiques en santé dans lesquels les méthodes de calcul de similarité entre patients sont utiles ;— documenter les solutions existantes, par exemple, mais sans y être limité, pour les systèmes fondées sur des méthodes d’apprentissage automatique. En bref, nous souhaitions que cette journée permette une rencontre des communautés d’informatique médicale, santé publique et traitement automatique de la langue et des échanges sur la recherche de contenus textuels « similaires » en TAL. Elle a bien rempli cet objectif en permettant de rassembler 45 personnes (30 en présentiel, 15 à distance) autour de la thématique de similarité entre patients.
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- 2023
50. Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3)
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Jean Reignier, Gaetan Plantefeve, Jean-Paul Mira, Laurent Argaud, Pierre Asfar, Nadia Aissaoui, Julio Badie, Nicolae-Vlad Botoc, Laurent Brisard, Hoang-Nam Bui, Delphine Chatellier, Louis Chauvelot, Alain Combes, Christophe Cracco, Michael Darmon, Vincent Das, Matthieu Debarre, Agathe Delbove, Jérôme Devaquet, Louis-Marie Dumont, Olivier Gontier, Samuel Groyer, Laurent Guérin, Bertrand Guidet, Yannick Hourmant, Samir Jaber, Fabien Lambiotte, Christophe Leroy, Philippe Letocart, Benjamin Madeux, Julien Maizel, Olivier Martinet, Frédéric Martino, Virginie Maxime, Emmanuelle Mercier, Mai-Anh Nay, Saad Nseir, Johanna Oziel, Walter Picard, Gael Piton, Jean-Pierre Quenot, Florian Reizine, Anne Renault, Jack Richecoeur, Jean-Philippe Rigaud, Francis Schneider, Daniel Silva, Michel Sirodot, Bertrand Souweine, Fabienne Tamion, Nicolas Terzi, Didier Thévenin, Guillaume Thiery, Nathalie Thieulot-Rolin, Jean-Francois Timsit, Francois Tinturier, Patrice Tirot, Thierry Vanderlinden, Isabelle Vinatier, Christophe Vinsonneau, Sebastian Voicu, Jean-Baptiste Lascarrou, Amélie Le Gouge, Damien Contou, Olivier Pajot, Paul Jaubert, Nathalie Marin, Marie Simon, Martin Cour, Satar Mortaza, Vincent Souday, Marie Lemerle, Sylvain Malfroy, Fernando Berdaguer Ferrari, Bertrand Rozec, Didier Gruson, Charline Sazio, Suzanne Champion, Florence Boissier, Anne Veinstein, Loredana Baboi, Jean-Christophe Richard, Hodane Yonis, Loïc Le Guennec, Lucie Lefevre, Juliette Chommeloux, Guillaume Hékimian, Virginie Lemiale, Eric Mariotte, Sandrine Valade, Joanna Tirolien, Yannick Fedun, Charles Cerf, Guillaume Tachon, Jérôme Roustan, Sylvie Vimeux, Michel Bonnivard, Nadia Anguel, David Osman, Karim Asehnoune, Antoine Roquilly, Fouad Belafia, Matthieu Conseil, Moussa Cisse, Bouras Chaouki, Rémi Espenel, Christine Brasse, Sébastien Ena, Arnaud Delahaye, Jeremy Castanera, Thierry Dulac, Philippe Petua, Yoann Zerbib, Clément Brault, Djillali Annane, Rania Bounab, Nicholas Heming, Thierry Boulain, Sophie Jacquier, Grégoire Muller, Raphael Favory, Sébastien Préau, Julien Poissy, Alexandre Massri, Floriane Lissonde, Hadrien Winiszewski, Thibault Vieille, Marine Jacquier, Marie Labruyère, Pascal Andreu, Jean-Marc Tadié, Laetitia Bodenes, Danièle Combaux, David Luis, Antoine Marchalot, Jean-Etienne Herbrecht, Raphaël Clere-Jehl, David Schnell, Jérôme Aboad, David Bougon, Etienne Escudier, Elisabeth Coupez, Claire Dupuis, Zoe Demailly, Louis-Marie Galerneau, Jonathan Chelly, Franck Pourcine, Ly Van Vong, Sonia Abid, Etienne De Montmollin, Romain Sonneville, Christophe Guitton, Nicolas Chudeau, Mickaël Landais, Vincent Pages, Caroline Séjourné, Imen Rahmani, Ghada Sbouj, Bruno Megarbane, Nicolas Deye, Isabelle Malissin, Motricité, interactions, performance UR 4334 / Movement - Interactions - Performance (MIP), Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier Argenteuil (CH Argenteuil), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), CH de Saint-Malo [Broussais], Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de Réanimation Médicale [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Croix-Rousse [CHU - HCL], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier d'Angoulême (CH Angoulême), Hopital Saint-Louis [AP-HP] (AP-HP), Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Centre hospitalier Saint-Brieuc, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Hôpital Foch [Suresnes], Hôpital Louis Mourier - AP-HP [Colombes], Hôpitaux de Chartres [Chartres], Centre hospitalier de Montauban (CH Montauban), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre hospitalier [Valenciennes, Nord], Centre Hospitalier Emile Roux [AP-HP], Hôpital Jacques Puel - Bourran [Rodez] (HJPB), Centre Hospitalier de Bigorre [Tarbes], CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Unité de Soins Intensifs [CHU La Réunion], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Hôpital Raymond Poincaré [Garches], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'interculturalité et la circulation médiatique des savoirs (CRICS (EA_3965)), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional d'Orléans (CHRO), CHU Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Centre hospitalier de Pau, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, 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)-Université de Montpellier (UM), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université de Bourgogne (UB), Centre Hospitalier Universitaire [Rennes], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier de Beauvais, Centre hospitalier de Dieppe, Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier de Lens, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Intensive Care Unit, Groupe Hospitalier Sud Ile de France, 270 avenue Marc Jacquet, 77000, Melun, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier Le Mans (CH Le Mans), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL), Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and French Ministry of Health.
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Pulmonary and Respiratory Medicine ,[SDV]Life Sciences [q-bio] - Abstract
Also written with the NUTRIREA-3 Trial Investigators and the Clinical Research in Intensive Care and Sepsis (CRICS-TRIGGERSEP) Group; International audience; BackgroundThe optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets.MethodsThe pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2–0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0–1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed.FindingsOf 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference –1·5%, 95% CI –5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0–14·0) in the low group and 9·0 days (5·0–17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p
- Published
- 2023
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