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1. Diurnal symptoms of sleepiness and dysfunction predict future suicidal ideation in a French cohort of outpatients (FACE-DR) with treatment resistant depression: A 1-year prospective study about sleep markers

Author: Maruani, Julia, Molière, Fanny, Godin, Ophelia, Yrondi, Antoine, Bennabi, Djamila, Richieri, Raphaelle, El-Hage, Wissan, Allauze, Etienne, Anguill, Loic, Bouvard, Alexandra, Camus, Vincent, Dorey, Jean-Michel, Etain, Bruno, Fond, Guillaume, Genty, Jean-Baptiste, Haffen, Emmanuel, Holtzmann, Jérôme, Horn, Mathilde, Kazour, François, Nguon, Anne-Sophie, Petrucci, Jean, Rey, Romain, Stephan, Florian, Vaiva, Guillaume, Walter, Michel, Lejoyeux, Michel, Leboyer, Marion, Llorca, Pierre-Michel, Courtet, Philippe, Aouizerate, Bruno, Geoffroy, Pierre, Fondation FondaMental [Créteil], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), 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), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut FRESNEL (FRESNEL), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), UMR 1253 IBrain Imagerie & Cerveau Equipe 1 : 'Psychiatrie Neuro-Fonctionnelle' (PNF), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier Charles Perrens [Bordeaux], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Lille, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital de Bohars - CHRU Brest (CHU - BREST ), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (EA7479 SPURBO), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), GHU Paris Psychiatrie et Neurosciences, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), and FondaMental Advanced Centers of Expertise in Resistant Depression (FACE-DR) Collaborators
Subjects: MESH: Humans, MESH: Suicidal Ideation, MESH: Sleepiness, MESH: Sleep, Excessive daytime sleepiness, Circadian, MESH: Depressive Disorder, Major, Daytime dysfunction, MESH: Prospective Studies, MESH: Outpatients, MESH: Depressive Disorder, Treatment-Resistant, Psychiatry and Mental health, Clinical Psychology, MESH: Risk Factors, Suicidal ideation, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Treatment-resistant depression, Sleep
Abstract: International audience; Background: Patients suffering from treatment-resistant depression (TRD) are at risk of suicide. Sleep and circadian rhythm alterations are widely recognized as core symptoms of major depressive disorder and are associated with suicidal ideation. Thus, sleep and circadian rhythm alterations may be targeted to prevent suicide.Methods: Patients were recruited from a prospective cohort of the French network of TRD expert centers. Mood, sleep and circadian rhythms were assessed at baseline; suicidal risk was assessed both at baseline and during a one-year follow-up with standardized subjective questionnaires.Results: Excessive daytime sleepiness (adjusted odds ratio aOR = 1.7(1-3.3), p = 0.04) and daytime dysfunction (aOR = 1.81(1.16-2.81), p = 0.0085) increased the risk of suicidal thoughts over the one-year follow-up period in patients with TRD after adjustment on age, gender, depression, trauma, anxiety, impulsivity, current daily tobacco smoking and body mass index. Hypnotics intake is associated with a reduced risk of suicidal ideation at one-year follow-up after the same adjustments (OR = 0.73(0.56-0.95), p = 0.019). Other associations between sleep quality or circadian rhythms and suicidal ideations at either baseline or one year did not remain significant in multivariate analyses after the same adjustments.Limitations: Sleep assessments were based on self-reported questionnaires rather than objective measures.Conclusions: Daytime sleepiness and dysfunction are predictors of suicidal ideations, whereas hypnotics intake is associated with a reduced risk of suicidal ideations. Diurnal symptoms of sleep disturbances are therefore red flags to target for preventing suicide in depressed patients, and hypnotics seem efficient in preventing suicide for patients with TRD.
Published: 2023
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2. Profils chimiques des glandes à venin chez les reines, les fondatrices, les gynes pré-hivernantes et les ouvrières du frelon Vespa velutina nigrithorax

Author: Berville, Laurence, Lucas, Christophe, Haouzi, Mélissa, Khalil, Ali, Gévar, Jérémy, Bagnières, A.G., Darrouzet, Éric, Institut de recherche sur la biologie de l'insecte UMR7261 (IRBI), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut d'écologie et des sciences de l'environnement de Paris (iEES Paris ), Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, 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), This study received funding from the Centre-Val deLoire region, in the form of French regional grants forour FRELON and FRELON 2 projects, as well as fromVeto-pharma and the French administrative depart-ment of La Manche. The TQ-MS was funded by theregion Centre-Val de Loire (APR-IA 2012)., and Berville, Laurence
Subjects: [SDE] Environmental Sciences, Invasive species, Glande à venin, Espèces invasives, Venom gland, Building and Construction, Frelon à pattes jaunes, Communication chimique, Chemical communication, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, Vespidae, Yellow-legged hornet, [SDE]Environmental Sciences, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Electrical and Electronic Engineering
Abstract: Invasive species are permanently modifying the distribution and diversity of native species worldwide. For nearly two decades, a hornet, Vespa velutina nigrithorax (Hymenoptera: Vespidae), has been spreading in Europe. Due to its marked invasiveness, this yellow-legged hornet is of great economic and ecological concern, mainly because of the damage it causes to insects in general and bees in particular. Current management methods are sparse and ineffective. Naturally produced by insects, semio-chemicals have been proposed as integrated management tools in this context, either for disruption or mass trapping, as an alternative tool to conventional nonselective traps. Here, we focused on the venom gland, which produces the alarm pheromone. In previous studies, individuals showed marked diversity in their chemical profiles. However, to successfully conduct targeted pheromone-based trapping, the hornet's chemical ecology must be thoroughly characterized. Therefore, it was necessary to better understand the chemical composition of the alarm pheromone of not only workers but also other V. v. nigrithorax females. First, we evaluated the differences in venom gland profiles between the four types of females: queens, foundresses, pre-winter gynes, and workers. Next, we experimentally explored the venom gland profiles of V. velutina nigrithorax workers and pre-wintering gynes by in vivo and in vitro approaches. We found 13 new compounds in the venom gland, of which 9 were identified (chain lengths: C8 to C12). Two compounds were found exclusively in reproductive females. Profiles differed among pre-wintering gynes, foundresses, and queens but not between pre-wintering gynes and workers. This result indicates that the chemical signature of the female venom gland changes over the course of life history: from pre-wintering gynes to foundresses to queens., Les espèces invasives modifient en permanence la répartition et la diversité des espècesindigènes dans le monde entier. Depuis près de vingt ans, un frelon originaire d’Asie du Sud-Est,Vespa velutina nigrithorax (Hymenoptera : Vespidae), se répand en Europe. En raison de son caractèreinvasif marqué, ce frelon à pattes jaunes suscite de vives inquiétudes sur le plan économique etécologique, principalement en raison des dégâts qu’il cause aux insectes en général et aux abeillesen particulier. Les méthodes de gestion actuelles sont rares et inefficaces. Naturellement produits parles insectes, les produits sémio-chimiques ont été proposés comme outils de gestion intégrée. Dansce contexte, soit pour la perturbation, soit pour le piégeage de masse, en tant qu’outil alternatif auxpièges non sélectifs conventionnels. Ici, nous nous sommes concentrés sur la glande à venin, quiproduit la phéromone d’alarme. Des études antérieures ont montré que les femelles présentaientune variabilité dans les profils chimiques. Cependant, pour mener à bien un piégeage ciblé à basede phéromones, l’écologie chimique du frelon doit être caractérisée de manière approfondie. Il étaitdonc nécessaire de mieux comprendre la composition chimique de la phéromone d’alarme nonseulement des ouvrières, mais également des autres femelles de V. v. nigrithorax. Tout d’abord, nousavons examiné les différences dans les profils des glandes à venin entre les quatre types de femelles :les reines, les fondatrices, les gynes pré-hivernantes et les ouvrières. Ensuite, nous avons exploréexpérimentalement les profils des glandes à venin des ouvrières de V. velutina nigrithorax et des gynespré-hivernantes par des approches in vivo et in vitro. Nous avons constaté la présence de 13 nouveauxcomposés dans la glande à venin, dont 9 ont été identifiés (longueur des chaînes : C8 à C12). Deuxcomposés ont été trouvés exclusivement chez les femelles reproductrices. Les profils diffèrent entreles gynes pré-hivernantes, les fondatrices et les reines, mais pas entre les gynes pré-hivernantes et lesouvrières. Ce résultat indique que la signature chimique de la glande à venin femelle évolue au coursde l’histoire de vie : des gynes pré-hivernantes aux fondatrices, en passant par les reines.
Published: 2023
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3. Impact psychologique de l’implication des professionnels des CUMP dans le dispositif de soins médico-psychologique face à l’épidémie COVID-19

Author: Gaëlle Abgrall, Laura Moioli, Élise Neff, Wissam El-Hage, Alexis Vancappel, François Ducrocq, Nathalie Prieto, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Qualité de vie et Santé psychologique [Tours] (QualiPsy - E.E. 1901), Université de Tours (UT), Clinique Psychiatrique Universitaire [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Vancappel, Alexis
Subjects: Santé mentale, Coping (psychology), education, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cellule d’urgence médico-psychologique, Population, Context (language use), Crisis management, Burnout, Feedback, Article Original, Arts and Humanities (miscellaneous), Intervention (counseling), medicine, Retour d’expérience, Applied Psychology, Professionnel de santé, education.field_of_study, Modalities, Psychic adjustment, Soutien médico-psychologique, Sars cov-2, Health professional, Psychiatry and Mental health, Medical and psychological emergency unit, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Traumatisme psychique, Anxiety, medicine.symptom, Covid-19, Psychology, Clinical psychology
Abstract: International audience; Objectives: COVID-19 pandemic and its consequences have put into great difficulty health professionals, and the general population, fostering the emergence of various psychological and psychiatric disorders. Medical and psychological emergency units' mission is the medical and psychological emergency care of people impacted during a traumatic event. Given their expertise in crisis management, they set up an important medical and psychological support system adapted to the health crisis' characteristics. The unusual modalities of intervention, the specific clinic that these professionals faced in this context of great tension may have unsettled workers and generate a psychological impact. This study aims to assess the existence of such repercussions among medical and psychological emergency unit professionals involved in this new system.Method: In all, 313 medical and psychological emergency unit professionals agreed to participate at the online survey. They filled surveys and visual analog scales assessing the difficulties encountered in the system, as well as their level of satisfaction, post-traumatic stress, burnout, level of anxiety and depression and coping strategies put in place.Results: Results show few significant emotional difficulties. However higher scores are found among women, among professionals who felt a negative impact on their personal lives, as well as for those who thought they had been infected with COVID-19. The establishment of coping strategies such as active coping, planning, expressing feelings, positive reinterpretation and acceptance helped to decrease the level of emotional complexities and brought more compassionate satisfaction. We note that participants with more medical and psychological emergency unit experience tend to show less emotional hardship and more compassionate satisfaction. It appears that older as well as younger professionals have lower burnout scores, as do workers who conducted more interviews for the same person. Likewise, participants who were satisfied of the system organization and of the support - a majority in this study - report less emotional challenges and more compassionate satisfaction.Conclusion: Psychological impact in this new system among medical and psychological emergency unit professionals is overall low. It appears that some coping strategies, perceived usefulness, satisfaction with the organization and the received support are associated with a lower level of emotional difficulties. A supportive framework and an operative organization of the medical and psychological emergency unit system in times of crisis has a protective effect on the participants.
Published: 2023
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4. Effectiveness of a Therapeutic Educational Oral Health Program for Persons with Schizophrenia: A Cluster Randomized Controlled Trial and Qualitative Approach

Author: Denis, Frédéric, Rat, Corinne, Cros, Lucie, Bertaud-Gounot, Valerie, El-Hage, Wissam, Jonval, Lysiane, Soudry-Faure, Agnès, Éducation Éthique Santé EA 7505 (EES), Université de Tours (UT), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Guillaume Régnier [Rennes], 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 Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and This trial is funded by the French Ministry of Health (Direction Générale de l’Offre de Soins).
Subjects: schizophrenia, dental education, oral health, therapeutic educational program, [SDV.IB]Life Sciences [q-bio]/Bioengineering
Abstract: International audience; BACKGROUND: The oral health of people with schizophrenia (PWS) is very poor, suggesting a need for oral health promotion programmes with a high level of evidence. The aim of the EBENE study (Clinicaltrials.gov: NCT02512367) was to develop and evaluate the effectiveness of a multidisciplinary therapeutic educational programme in oral health (TEPOH) for PWS. METHODS: A multicentre cluster randomised controlled trial, with outpatient psychiatry centres as the unit of randomisation, was designed to compare the effectiveness of TEPOH (intervention group) versus standard care (control group). The trial was conducted in 26 outpatient psychiatry centres in France (14 in the intervention group, 12 in the control group). Eligible patients with a diagnosis of schizophrenia were enroled between 2016 and 2020 and followed for 6 months. The TEPOH group received a multicomponent intervention (comprising an introductory session, three educational sessions, and a debriefing session). The primary endpoint was the evaluation of periodontal disease as a community periodontal index (CPI) score ≥ 3 at Month 6. The trial was completed using a qualitative approach based on semi-structured interviews with caregivers conducted between July 2018 and December 2019. The trial was stopped early due to difficulties in recruiting patients. RESULTS: Overall, 81 patients (of 250 planned) were included, and 54 patients completed the trial: 40 in the TEPOH group and 14 in the control group. At baseline, the percentage of CPI ≥ 3 was 42.5% in the TEPOH group and 9.1% in the control group. At Month 6, the percentage of CPI ≥ 3 was 20% in the TEPOH group and 14.3% in the control group. The qualitative evaluation underlined that the professionals emphasised the "seriousness" and "assiduity" of the patients’ participation in this programme and that the TEPOH reinforced carers’ investment in oral hygiene. It also highlighted structural factors (lack of resources for professionals, lack of teeth in PWS, COVID-19 pandemic) that may have exacerbated the difficulties with enrolment and follow-up. CONCLUSIONS: The effectiveness of this TEPOH, developed for PWS as part of the EBENE study, has not been demonstrated. Certain aspects of the programme’s content and implementation need to be reconsidered. In particular, an adapted subjective measurement scale should be developed.
Published: 2023
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5. Mathematical modeling of adipocyte size distributions: identifiability and parameter estimation from rat data

Author: 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)
Subjects: 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.
Published: 2023

6. Metadata Schema for 3D Data Publication and Archiving

Author: Grimaud, Valentin, Eusèbe, Sylvie, Tournon, Sarah, Chayani, Mehdi, Quantin, Matthieu, Jeanson, Loic, Marlet, Olivier, Rassat, Sylvain, Granier, Xavier, Laboratoire de recherche ARchéologie et Architecture (LARA), Centre de Recherche en Archéologie, Archéosciences, Histoire (CReAAH), Le Mans Université (UM)-Université de Rennes (UR)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC)-Nantes Université - UFR Histoire, Histoire de l'Art et Archéologie (Nantes Univ - UFR HHAA), Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Le Mans Université (UM)-Université de Rennes (UR)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC)-Nantes Université - UFR Histoire, Histoire de l'Art et Archéologie (Nantes Univ - UFR HHAA), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut national de recherches archéologiques préventives (Inrap), Archéosciences Bordeaux, Université de Bordeaux (UB)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ), Institut National d'Histoire de l'Art (INHA), INHA, Cités, Territoires, Environnement et Sociétés (CITERES), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Maison des Sciences de l'Homme Val de Loire (MSH VL), Université d'Orléans (UO)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Institut d'Optique Graduate School (IOGS), and Dariah -EU
Subjects: The French National 3D Data Repository, archive, metadata, FAIR, 3D, [SHS]Humanities and Social Sciences
Abstract: International audience; The French National 3D Data Repository, the C.I.N.E.S (National Computer Center for Higher Education) which offers long-term archiving of electronic data, and aLTAG3D - their companion software to document the deposits, use a unique and dedicated metadata scheme based on the work from 2014 to 2017 of the national consortium “3D for Humanities” from Huma-Num infrastructure. This first version is currently evolving to take into account the evolution of deposited data and research domains.Scientific Domains. The first scheme was focused on archaeology - the main domain in digital humanities that make use of 3D models. One of our goals is to offer such previously cited services to the entire Humanities and Social Sciences. For this purpose, we divide metadata into generic and domain specific ones, such as 3D restitutions or scans of “physical object” in archaeology.Automatic Extraction. The metadata are also categorized in two groups: those which can be extracted automatically for the data themselves (such as number of points in a 3D file, creation date from EXIF), and those which have to be filled manually. The automatic process simplifies the user work, and the remaining information volume is still quite large, and we are working on either making it smaller or easier to fill. For this purpose, we are pushing forward the experience gained in developing and experimenting the first scheme.Referencing data. While data redundancy is a guarantee of sustainability, this has an economic and environmental impact. This is even more important for our 3D deposit since, for an open science perspective, we recommend integrating all the documentation, independently of the format and the origin. To tackle this problem, we are integrating into the metadata scheme the possibility to outsource data curation, by using URI to refer to any data present of a sufficiently perennial and reliable infrastructure. We favor institutional hosting over private enterprise. Corresponding requested metadata has also to be harvested. This process is becoming easier with the development of FAIR and institutional infrastructures.Standards. The FAIR principles also impose the interoperability of our scheme with standard formats. For this purpose, we ensure the compatibility with Dublin Core, CIDOC CRM and with DOI. We also integrate the use of standard thesaurus such as PeriodO, GeoNames, PACTOLS.3D data definition. The structure of our metadata scheme has evolved due to our experience in understanding 3D data and their usage. Initially, our 3D object was only defined by a colored or textured mesh. However, it seemed important to include any kind of 3D, from volumetric data to CAO (used in the history of technologies). We need also to consider how to take into account the object's structure, appearance properties (reflection, etc.), animations, annotations, and everything that can be attached to a 3D object.Furthermore, the 3D data are intrinsically linked with the software and the hardware that have been used to process it and/or to interact with (e.g., in VR usage). We thus extend the metadata scheme in order to include them.
Published: 2023

7. SPQR@Deft2023 : Automatically answering to MCQ in the medical domain with similaritymeasures and domain-specific corpora

Author: Bezançon, Julien, Boubehziz, Toufik, Chutaux, Corina, Zine, Oumaima, Acensio, Laurie, Koudoro-Parfait, Caroline, Briglia, Andrea, Lejeune, Gaël, Équipe Linguistique computationnelle (STIH-LC), Sens, Texte, Informatique, Histoire (STIH), Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Center for Artificial Intelligence (SCAI), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Université de Technologie de Compiègne (UTC)-Institut National de Recherche en Informatique et en Automatique (Inria)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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)-Institut Européen d'administration des Affaires (INSEAD), UMR 1253 IBrain Imagerie & Cerveau Equipe 1 : 'Psychiatrie Neuro-Fonctionnelle' (PNF), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Sorbonne Université (SU), ATALA, and Adrien Bazoge, Béatrice Daille, Richard Dufour, Yanis Labrak, Emmanuel Morin, Mickael Rouvier (Éds.)
Subjects: QCM, pharmacologie, n-grammes de caractères, FrenchMedMCQA, systèmes de question-réponse MCQ, [INFO]Computer Science [cs], pharmacology, [SCCO.LING]Cognitive science/Linguistics, similarity, Question-answering systems, similarité, character n-grams
Abstract: International audience; We exhibit the approach of the SPQR team in the 2023 French Text Mining Challenge (DEFT). Thischallenge focused on automatically answering Multiple Choice Questions (MCQ) in the pharmacology domain. We proposed an approach that takes advantage of domain-specific corpora in order to find similarities between possible answers and sentences in the corpora.We compute a cosine similarity on character n-gram vectors to compare them. The best scores we obtained were 0,294 for the Hammingscore on the test set (0,305 on the dev set) and 0,997 for the Exact Match ratio ( 0,16 on the dev set).; Nous présentons le travail de SPQR (Sorbonne Question-Réponses) au DÉfi Fouille de Textes 2023 sur la réponse automatique à des questionnaires à choix multiples dans le domaine de la pharmacologie. Nous proposons une approche fondée sur la constitution de corpus de spécialité et la recherche de phrases similaires entre ces corpus et les différentes réponses possibles à une question. Nous calculons une similarité cosinus sur des vecteurs en n-grammes de caractères pour déterminer les bonnes réponses. Cette approche a obtenu un score maximal en Hamming de 0,249 sur les données de test (0,305 sur le dev) et de 0,0997 en Exact Match Ratio (0,16 sur le dev).
Published: 2023

8. Who gets injured at home? Evidence from older people in France

Author: Liliane Bonnal, Greivis Buitrago Gámez, Pascal Favard, Cornel Oros, Centre de recherche sur l'intégration économique et financière (CRIEF), Université de Poitiers, Toulouse School of Economics (TSE-R), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de recherche juridique interdisciplinaire (IRJI), Université de Tours (UT), Laboratoire d'Économie d'Orleans [2022-...] (LEO), and Université d'Orléans (UO)-Université de Tours (UT)-Université Clermont Auvergne (UCA)
Subjects: JEL: C - Mathematical and Quantitative Methods, Health problems, Economics and Econometrics, Home and leisure injuries, JEL: I - Health, Education, and Welfare/I.I2 - Education and Research Institutions, Olderpeople, Logit models, JEL: I - Health, Education, and Welfare/I.I0 - General, [SHS.ECO]Humanities and Social Sciences/Economics and Finance
Abstract: International audience; The study analyses unintentional home and leisure injuries (HLIs) for the French senior population using data from the 2012 wave of the French health, health care and insurance survey. The results of our logit models reveal that health status, age, and risky attitudes are the main characteristics associated with HLIs for older people. When the severity of injuries is taken into consideration, the highest exposure to HLIs concerns the oldest seniors, aged 85 years old or older, with deteriorated health. This result is confirmed in the case of severe indoor HLIs, whereas for severe outdoor injuries, the most vulnerable individuals seem to be younger seniors, that is, 75–79 years old. Moreover, our findings suggest that HLIs, and mainly severe home HLIs, generate a short-term influence on a person's health.
Published: 2022
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9. Diversity and Inclusion Activities in EGC - A 2022 Report

Author: Amer-Yahia, Sihem, Bonifati, Angela, Favre, Cécile, Fromont, Elisa, Labroche, Nicolas, Melançon, Guy, Sèdes, Florence, Soulet, Arnaud, Termier, Alexandre, Laboratoire d'Informatique de Grenoble (LIG), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Base de Données (BD), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Entrepôts, Représentation et Ingénierie des Connaissances (ERIC), Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Large Scale Collaborative Data Mining (LACODAM), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Bases de données et traitement des langues naturelles (BDTLN), Laboratoire d'Informatique Fondamentale et Appliquée de Tours (LIFAT), Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Systèmes d’Informations Généralisées (IRIT-SIG), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), and Université de Toulouse (UT)
Subjects: [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], Geography, Planning and Development, General Earth and Planetary Sciences, [INFO.INFO-SI]Computer Science [cs]/Social and Information Networks [cs.SI], [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Water Science and Technology
Abstract: International audience; EGC ("Extraction et Gestion des Connaissances"1 in French) started in 2001 and is the reference conference for the french community in Knowledge Extraction and Management (equivalent to the French KDD).
Published: 2022
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10. Dynamic Ride-Hailing with Electric Vehicles

Author: Martin Cousineau, Jorge E. Mendoza, Justin C. Goodson, Nicholas Kullman, Recherche Opérationnelle, Ordonnancement, Transport ERL 7002 (ROOT), Laboratoire d'Informatique Fondamentale et Appliquée de Tours (LIFAT), Université de Tours-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL)
Subjects: Service (business), 050210 logistics & transportation, 021103 operations research, Profit (accounting), Artificial neural network, Operations research, Computer science, 05 social sciences, 0211 other engineering and technologies, Transportation, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], 02 engineering and technology, Operator (computer programming), 0502 economics and business, Civil and Structural Engineering
Abstract: International audience; We consider the problem of an operator controlling a fleet of electric vehicles for use in a ride-hailing service. The operator, seeking to maximize profit, must assign vehicles to requests as they arise as well as recharge and reposition vehicles in anticipation of future requests. To solve this problem, we employ deep reinforcement learning, developing policies whose decision making uses [Formula: see text]-value approximations learned by deep neural networks. We compare these policies against a reoptimization-based policy and against dual bounds on the value of an optimal policy, including the value of an optimal policy with perfect information, which we establish using a Benders-based decomposition. We assess performance on instances derived from real data for the island of Manhattan in New York City. We find that, across instances of varying size, our best policy trained with deep reinforcement learning outperforms the reoptimization approach. We also provide evidence that this policy may be effectively scaled and deployed on larger instances without retraining.
Published: 2022
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11. A fuzzy/possibility approach for area coverage in wireless sensor networks

Author: boualem adda, Cyril De Runz, Marwane Ayaida, Herman Akdag, Bases de données et traitement des langues naturelles (BDTLN), Laboratoire d'Informatique Fondamentale et Appliquée de Tours (LIFAT), Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), COMmunications NUMériques - IEMN (COMNUM - IEMN), INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Université de Reims Champagne-Ardenne (URCA), Laboratoire Paragraphe (PARAGRAPHE), Université Paris 8 Vincennes-Saint-Denis (UP8)-CY Cergy Paris Université (CY), and This research was not funded. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Subjects: [INFO]Computer Science [cs], Geometry and Topology, Software, Theoretical Computer Science
Abstract: Deterministic methods used to address the coverage problem in an uncertain deployment environment have not proven to be very successful. For this purpose, the original idea of this paper is to deal with the coverage problem in an uncertain environment with uncertain theories. We consider the imperfection in the deployment environment and in the characteristics of the sensor nodes. The selection of a minimum number of nodes for a minimum number of clusters to guarantee coverage in WSN is uncertain. As a consequence, this paper proposes a hybrid FuzzyPossibilistic model to schedule the Active/ Passive state of sensor nodes. This model helps to plan the scheduling of node states (Active / Passive) based on the possibilistic information fusion to make a possibilistic decision for the node activation at each period. We evaluated the proposed model with (a) a running example, (b) a statistical evaluation (calculation of the confidence interface), and (c) a comparison with maximum sensing coverage region problem (MSCR), Coverage Maximization with Sleep Scheduling (CMSS), Spider Canvas Strategy, Semi-Random Deployment Strategy (SRDP) and PEAS with location information protocols. The simulation results highlight the benefits of using the fuzzy and possibility theories for treating the area coverage problem.
Published: 2023
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12. Long-time asymptotic of the Lifshitz-Slyozov equation with nucleation

Author: Calvo, Juan, Hingant, Erwan, Yvinec, Romain, Universidad de Granada = University of Granada (UGR), Laboratoire Amiénois de Mathématique Fondamentale et Appliquée - UMR CNRS 7352 (LAMFA), Université de Picardie Jules Verne (UPJV)-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), MINECO-Feder (grantRTI2018-098850-B-I00), Junta de Andalucía (grants PY18-RT-2422 and A-FQM-311-UGR18), ECOS-Sud project n. C20E03 (France –Chile), and Inria Associated team ANACONDA
Subjects: Mathematics - Analysis of PDEs, Nucleation theory, FOS: Mathematics, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Long-time behavior, Lifshitz-Slyozov equation, Entropy functional, Analysis of PDEs (math.AP)
Abstract: We consider the Lifshitz-Slyozov model with inflow boundary conditions of nucleation type. We show that for a collection of representative rate functions the size distributions approach degenerate states concentrated at zero size for sufficiently large times. The proof relies on monotonicity properties of some quantities associated to an entropy functional. Moreover, we give numerical evidence on the fact that the convergence rate to the goal state is algebraic in time. Besides their mathematical interest, these results can be relevant for the interpretation of experimental data.
Published: 2023

13. SOME REMARKS ABOUT THE WELL-POSEDNESS OF LIFSHITZ-SLYOZOV'S EQUATIONS WITH NUCLEATION KINETICS

Author: Calvo, Juan, Hingant, Erwan, Yvinec, Romain, Universidad de Granada = University of Granada (UGR), Laboratoire Amiénois de Mathématique Fondamentale et Appliquée - UMR CNRS 7352 (LAMFA), Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), 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), 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), and 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)
Subjects: [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP]
Abstract: The Lifshitz-Slyozov model is a nonlocal transport equation that can describe certain types of phase transitions in terms of the temporal evolution of a mixture of monomers and aggregates. Most applications of this model so far do not require boundary conditions. However, there is a recent interest in situations where a boundary condition might be needed-e.g. in the context of protein polymerization phenomena. Actually the boundary condition may change dynamically in time, depending on an activation threshold for the monomer concentration. This new setting poses a number of mathematical difficulties for which the existing literature is scarce. In this contribution we construct examples of solutions for which the boundary condition becomes activated (resp. deactivated) dynamically in time; we also discuss how to approach the well-posedness problem for such situations.
Published: 2023

14. Version francaise des recommandations de la declaration d'Ottawa sur la conception et la conduite ethique d'essais randomises en clusters, dans le contexte legislatif francais

Author: A. Bourmaud, A. Fianu, C. Kervan, A. Verga-Gérard, I. Fournel, A. Dumas, J. Mancini, F. Alla, A. Omorou, B. Giraudeau, 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), Hôpital Robert Debré, Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Sud Saint Pierre [Ile de la Réunion], Centre d'Investigation Clinique de La Réunion - INSERM (CIC 1410), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut des sciences de la santé publique [Marseille] (ISSPAM), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), 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 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), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Ethics, Informed Consent, Epidemiology, Cluster randomized trial, Public Health, Environmental and Occupational Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; INTRODUCTION: There is growing evidence on the ethical challenges raised by cluster randomized trials. This specificity is not reflected in the legal texts regulating research, which creates difficulties for researchers implementing these experimental designs. The Ottawa Statement (Weijer et al. 2012) aims to provide detailed guidance on the ethical design, conduct and assessment of cluster trials. More broadly aims to help research stakeholders and decision-makers to make informed ethical decisions regarding the particularity of these experimental designs. It seems that this international statement, written in English, is not sufficiently accessible to all of the French professionals involved in health research. The aim of this article is to provide these professionals with a contextualized and illustrated French translation of the "Ottawa statement". METHOD: . The "complex design" working group of the RECaP network (Research in Clinical Epidemiology and Public Health), carried out this work. A first version was discussed by the authors in several meetings. It was completed by contextual explanations and examples of French studies currently conducted by the authors. The final version was obtained by consensus and validated by the group. RESULTS: . This work reports 15 recommendations grouped into 7 key questions: How to justify cluster design? How to submit an article to an ethics committee? How to identify research participants? How and when to obtain informed consent? Who are the gatekeepers? How to assess benefits and harm? How to protect vulnerable participants? Each of these recommendations is specific to cluster trials. The recommendations are explained and detailed through concrete examples. CONCLUSION: Without interfering with current French laws, this work provides a framework for the organization, conduct and ethical assessment of cluster randomized trials in France. In the present-day context, it is essential that all concerned groups can base their decisions on recommendations in line with the elementary principles of health research ethics.; INTRODUCTION : Il existe une littérature croissante sur les défis éthiques soulevés par les essais randomisés en clusters (ou en grappes). Cette spécificité n'est pas prise en compte dans les textes réglementaires qui régissent la recherche, ce qui est source de difficultés pour les chercheurs utilisant ces schémas expérimentaux. La Déclaration d'Ottawa (Weijer et al. 2012) vise à fournir des conseils détaillés sur l’éthique de la conception, de la conduite et de l’évaluation des essais en clusters. Elle a pour objectif d'aider l'ensemble des acteurs de la recherche (parties prenantes et décideurs) à prendre des décisions éclairées en termes d’éthique relative à la particularité de ces schémas expérimentaux. Il semble que cette déclaration internationale ne soit pas assez accessible auprès de l'ensemble des acteurs français de la recherche en santé. L'objectif de cet article est de proposer à ces professionnels une traduction française de l’« Ottawa Statement », contextualisée et illustrée. METHODE : Le groupe de travail « Design complexe » du réseau RECaP (Recherche en épidémiologie clinique et en santé publique) a réalisé ce travail. Une première version a été discutée par les auteurs au travers de plusieurs réunions. Elle a été complétée par des explications contextuelles et par des exemples d’études françaises actuellement menées par les auteurs. La dernière version a été obtenue par consensus et validée par le groupe. RESULTATS : Ce travail présente les 15 recommandations regroupées en sept grandes questions : quelle justification pour le design en clusters ? Comment soumettre à un comité d’éthique ? Comment identifier les participants à la recherche ? Quand et comment obtenir un consentement éclairé ? Qui sont les personnes référentes ? Comment évaluer les bénéfices et les risques ? Comment protéger les personnes vulnérables ? Chacune de ces recommandations porte spécifiquement sur les essais en clusters. Ces recommandations sont expliquées et détaillées au travers d'exemples. CONCLUSION : Ce travail permet de fournir un cadre pour la mise en place, la conduite et l’évaluation éthique des essais randomisés en clusters en France. Sans ingérence dans les lois actuelles françaises. Dans le contexte actuel, il est indispensable que l'ensemble des groupes concernés puissent appuyer leurs décisions sur des recommandations en accord avec les principes élémentaires de l’éthique de la recherche en santé.
Published: 2023
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15. Closeups of a not-so-domestic mite tritonymph

Author: Uzbekov, Rustem, Bouakaz, Ayache, Postema, Michiel, Tampere University, BioMediTech, Université de Tours (UT), UMR 1253 IBrain Imagerie & Cerveau Equipe 3 'Imagerie, Biomarqueurs & Thérapie' (IBT), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), LE STUDIUM (LE STUDIUM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de recherche pour le développement [IRD] : UR-Centre National de la Recherche Scientifique (CNRS), BioMediTech Institute [Tampere], University of Tampere [Finland], University of the Witwatersrand [Johannesburg] (WITS), and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Immunology and Allergy, 217 Medical engineering
Abstract: publishedVersion Non
Published: 2023
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16. Reproductives signature revealed by protein profiling and behavioral bioassays in termite

Author: Ruhland, Fanny, Gabant, Guillaume, Toussaint, Timothée, Nemcic, Matej, Cadène, Martine, Lucas, Christophe, Université de Tours (UT), Institut de recherche sur la biologie de l'insecte UMR7261 (IRBI), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO), Région Centre-Val de Loire (APR-IR 2017-00117111 BioControleTermite, APRIA MALDITOF 2018, APR-IA 2012, APR-IA SYMBIOMS 2010), European Project: 773324,ForestValue, and European Project: 508 2699-33931
Subjects: Multidisciplinary, [SDV]Life Sciences [q-bio], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Proteins are known to be social interaction signals in many species in the animal kingdom. Common mediators in mammals and aquatic species, they have seldom been identified as such in insects' behaviors. Yet, they could represent an important component to support social signals in social insects, as the numerous physical contacts between individuals would tend to favor the use of contact compounds in their interactions. However, their role in social interactions is largely unexplored: are they rare or simply underestimated? In this preliminary study, we show that, in the termite Reticulitermes flavipes, polar extracts from reproductives trigger body-shaking of workers (a vibratory behavior involved in reproductives recognition) while extracts from workers do not. Molecular profiling of these cuticular extracts using MALDI-TOF mass spectrometry reveals higher protein diversity in reproductives than in workers and a sex-specific composition exclusive to reproductives. While the effects observed with extracts are not as strong as with live termites, these results open up the intriguing possibility that social signaling may not be limited to cuticular hydrocarbons or other non-polar, volatile chemicals as classically accepted. Our results suggest that polar compounds, in particular some of the Cuticular Protein Compounds (CPCs) shown here by MALDI to be specific to reproductives, could play a significant role in insect societies. While this study is preliminary and further comprehensive molecular characterization is needed to correlate the body-shaking triggering effects with a given set of polar compounds, this exploratory study opens new perspectives for understanding the role of polar compounds such as proteins in caste discrimination, fertility signaling, or interspecific insect communication.
Published: 2023
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17. Clostridium difficile infection and immune checkpoint inhibitor–induced colitis in melanoma: 18 cases and a review of the literature

Author: Vuillamy, Chloé, Arnault, Jean-Philippe, Fumery, Mathurin, Mortier, Laurent, Monestier, Sandrine, Mansard, Sandrine, Bens, Guido, Duval-Modeste, Anne-Bénédicte, Funck-Brentano, Elisa, Jeudy, Géraldine, Machet, Laurent, Chaby, Guillaume, Dadban, Ali, Lok, Catherine, Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hôpital Ambroise Paré [AP-HP], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Dermatologie (CHU de Dijon), UMR 1253 IBrain Imagerie & Cerveau Equipe 3 'Imagerie, Biomarqueurs & Thérapie' (IBT), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Service de dermatologie [CHU d'Amiens-Picardie]
Subjects: [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Immunotherapy has become the standard of care for several types of cancer, such as melanoma. However, it can induce toxicity, including immune checkpoint inhibitor-induced colitis (CIC). CIC shares several clinical, histological, biological, and therapeutic features with inflammatory bowel disease (IBD). Clostridium difficile infection (CDI) can complicate the evolution of IBD. We aimed to characterize the association between CDI and CIC in patients treated with anti-CTLA-4 and anti-PD-1 for melanoma. Patients from nine centers treated with anti-CTLA-4 and anti-PD-1 for melanoma and presenting with CDI from 2010 to 2021 were included in this retrospective cohort. The primary endpoint was the occurrence of CIC. The secondary endpoints were findings allowing us to characterize CDI. Eighteen patients were included. Eleven were treated with anti-PD-1, four with anti-CTLA-4, and three with anti-PD-1 in combination with anti-CTLA-4. Among the 18 patients, six had isolated CDI and 12 had CIC and CDI. Among these 12 patients, eight had CIC complicated by CDI, three had concurrent CIC and CDI, and one had CDI followed by CIC. CDI was fulminant in three patients. Endoscopic and histological features did not specifically differentiate CDI from CIC. Nine of 11 patients required immunosuppressive therapy when CDI was associated with CIC. In nine cases, immunotherapy was discontinued due to digestive toxicity. CDI can be isolated or can complicate or reveal CIC. CDI in patients treated with immunotherapy shares many characteristics with CDI complicating IBD. Stool tests for Clostridium difficile should be carried out for all patients with diarrhea who are being treated with immunotherapy.
Published: 2023
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18. Prenatal diagnosis by trio exome sequencing in fetuses with ultrasound anomalies: A powerful diagnostic tool

Author: Tran Mau-Them, Frédéric, Delanne, Julian, Denommé-Pichon, Anne-Sophie, Safraou, Hana, Bruel, Ange-Line, Vitobello, Antonio, Garde, Aurore, Nambot, Sophie, Bourgon, Nicolas, Racine, Caroline, Sorlin, Arthur, Moutton, Sébastien, Marle, Nathalie, Rousseau, Thierry, Sagot, Paul, Simon, Emmanuel, Vincent-Delorme, Catherine, Boute, Odile, Colson, Cindy, Petit, Florence, Legendre, Marine, Naudion, Sophie, Rooryck, Caroline, Prouteau, Clément, Colin, Estelle, Guichet, Agnès, Ziegler, Alban, Bonneau, Dominique, Morel, Godelieve, Fradin, Mélanie, Lavillaureix, Alinoé, Quelin, Chloé, Pasquier, Laurent, Odent, Sylvie, Vera, Gabriella, Goldenberg, Alice, Guerrot, Anne-Marie, Brehin, Anne-Claire, Putoux, Audrey, Attia, Jocelyne, Abel, Carine, Blanchet, Patricia, Wells, Constance F., Deiller, Caroline, Nizon, Mathilde, Mercier, Sandra, Vincent, Marie, Isidor, Bertrand, Amiel, Jeanne, Dard, Rodolphe, Godin, Manon, Gruchy, Nicolas, Jeanne, Médéric, Schaeffer, Elise, Maillard, Pierre-Yves, Payet, Frédérique, Jacquemont, Marie-Line, Francannet, Christine, Sigaudy, Sabine, Bergot, Marine, Tisserant, Emilie, Ascencio, Marie-Laure, Binquet, Christine, Duffourd, Yannis, Philippe, Christophe, Faivre, Laurence, Thauvin-Robinet, Christel, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Unité fonctionnelle d' Innovation en Diagnostic Génomique des Maladies Rares (CHU Dijon) (UF6254), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), Laboratoire de Génétique Chromosomique et Moléculaire [CHU Dijon], Service de Gynécologie Obstétrique, Médecine Foetale et Stérilité Conjugale - Chirurgie Gynécologie et Oncologique [CHU de Dijon], Centre de Référence Maladies Rares Anomalies du Développement et Syndromes Malformatifs Nord, Centre Hospitalier Universitaire de Lille (CHU de Lille), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de référence Maladies Rares CLAD-Ouest [Rennes], Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Génétique Clinique, Hôpital Femme Mère Enfant, Centre Hospitalier Universitaire de Lyon, Service de Gynécologie et Obstétrique [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Génétique et Centre de Diagnostic Anténatal, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Equipe Maladies Génétiques de L'Enfant et de L'Adulte, Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée [Montpellier], Centre de Référence Anomalies du Développement et Syndromes Malformatifs [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Centre de Référence Anomalies du Développement et Syndromes Malformatifs [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Thorax [Nantes], Embryology and genetics of human malformation, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Génétique Médicale et Clinique, Hôpital Necker-Enfants Malades, Unité Fonctionnelle de Génétique Médicale, Cytogénétique, Génétique Médicale et Biologie de La Reproduction, Centre Hospitalier Intercommunal Poissy-Saint-Germain-en-Laye, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, UMR 1253 IBrain Imagerie & Cerveau Equipe 2 : 'Neurogénomique & Physiopathologie neuronale' (NPN), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Génétique Médicale, Pôle Femme, Mère, Enfants CHU de La Réunion-GH Sud Réunion-Saint-Pierre, Pôle Femme, Mère, Enfants, CHU de La Réunion-GH Sud Réunion-Saint-Pierre-CHU de La Réunion-GH Sud Réunion-Saint-Pierre, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Génétique Clinique Prénatale, Département de Génétique Médicale, Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), and This work was supported by grants from Dijon University Hospital, the ISITE-BFC (PIA ANR), the European Union through the FEDER programs, and the AnDDI-Rares network for ES performed in this study.
Subjects: prenatal, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, chromosomal microarray, exome sequencing (ES), diagnostic yield, Genetics, Molecular Medicine, fetal, Genetics (clinical)
Abstract: Introduction: Prenatal ultrasound (US) anomalies are detected in around 5%–10% of pregnancies. In prenatal diagnosis, exome sequencing (ES) diagnostic yield ranges from 6% to 80% depending on the inclusion criteria. We describe the first French national multicenter pilot study aiming to implement ES in prenatal diagnosis following the detection of anomalies on US.Patients and methods: We prospectively performed prenatal trio-ES in 150 fetuses with at least two US anomalies or one US anomaly known to be frequently linked to a genetic disorder. Trio-ES was only performed if the results could influence pregnancy management. Chromosomal microarray (CMA) was performed before or in parallel.Results: A causal diagnosis was identified in 52/150 fetuses (34%) with a median time to diagnosis of 28 days, which rose to 56/150 fetuses (37%) after additional investigation. Sporadic occurrences were identified in 34/56 (60%) fetuses and unfavorable vital and/or neurodevelopmental prognosis was made in 13/56 (24%) fetuses. The overall diagnostic yield was 41% (37/89) with first-line trio-ES versus 31% (19/61) after normal CMA. Trio-ES and CMA were systematically concordant for identification of pathogenic CNV.Conclusion: Trio-ES provided a substantial prenatal diagnostic yield, similar to postnatal diagnosis with a median turnaround of approximately 1 month, supporting its routine implementation during the detection of prenatal US anomalies.
Published: 2023
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19. A Lifschitz-Slyozov type model for adipocyte size dynamics : limit from Becker-Döring system and numerical simulation

Author: Meyer, Léo, Ribot, Magali, Yvinec, Romain, 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), and 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)
Subjects: [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP]
Abstract: Biological data show that the size distribution of adipose cells follows a bimodal distribution. In this work, we introduce a Lifshitz-Slyozov type model, based on a transport partial differential equation, for the dynamics of the size distribution of adipose cells. We prove a new convergence result from the related Becker-Döring model, a system composed of several ordinary differential equations, toward mild solutions of the Lifshitz-Slyozov model using distribution tail techniques. Then, this result allows us to propose a new advective-diffusive model, the second-order diffusive Lifshitz-Slyozov model, which is expected to better fit the experimental data. Numerical simulations of the solutions to the diffusive Lifshitz-Slyozov model are performed using a well-balanced scheme and compared to solutions to the transport model. Those simulations show that both bimodal and unimodal profiles can be reached asymptotically depending on several parameters. We put in evidence that the asymptotic profile for the second-order system does not depend on initial conditions, unlike for the transport Lifshitz-Slyozov model.
Published: 2023

20. Geometric and probabilistic results for the observability of the wave equation

Author: Emmanuel Humbert, Yannick Privat, Emmanuel Trélat, Institut Denis Poisson (IDP), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Université d'Orléans (UO), Institut de Recherche Mathématique Avancée (IRMA), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), TOkamaks and NUmerical Simulations (TONUS), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Control And GEometry (CaGE ), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT)-Université d'Orléans (UO), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Inria Nancy - Grand Est, Université d'Orléans (UO)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université d'Orléans (UO)-Université de Tours-Centre National de la Recherche Scientifique (CNRS), and Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], observability, [MATH.MATH-DG]Mathematics [math]/Differential Geometry [math.DG], General Mathematics, random set, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], wave equation, [MATH.MATH-OC]Mathematics [math]/Optimization and Control [math.OC], Riemannian geometry
Abstract: Given any measurable subset $\omega$ of a closed Riemannian manifold $(M,g)$ and given any $T>0$, we define $\ell^T(\omega)\in[0,1]$ as the smallest average time over $[0,T]$ spent by all geodesic rays in $\omega$. This quantity appears naturally when studying observability properties for the wave equation on $M$, with $\omega$ as an observation subset: the condition $\ell^T(\omega)>0$ is the well known \emph{Geometric Control Condition}.In this article we establish two properties of the functional $\ell^T$, one is geometric and the other is probabilistic.The first geometric property is on the maximal discrepancy of $\ell^T$ when taking the closure. We may have $\ell^T(\mathring{\omega})1/2$ then the Geometric Control Condition is satisfied and thus the wave equation is observable on $\omega$ in time $T$. The second property is of probabilistic nature. We take $M=\mathbb{T}^2$, the flat two-dimensional torus, and we consider a regular grid on it, a regular checkerboard made of $n^2$ square white cells. We construct random subsets $\omega_\varepsilon^n$ by darkening each cell in this grid with a probability $\varepsilon$. We prove that the random law $\ell^T(\omega_\varepsilon^n)$ converges in probability to $\varepsilon$ as $n\rightarrow+\infty$.As a consequence, if $n$ is large enough then the Geometric Control Condition is satisfied almost surely and thus the wave equation is observable on $\omega_\varepsilon^n$ in time $T$.
Published: 2022
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21. Analytical prediction of delayed Hopf bifurcations in a simplified stochastic model of reed musical instruments

Author: Baptiste Bergeot, Christophe Vergez, Dynamique interactions vibrations Structures (DivS), Laboratoire de Mécanique Gabriel Lamé (LaMé), Université d'Orléans (UO)-Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université d'Orléans (UO)-Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA), Laboratoire de Mécanique et d'Acoustique [Marseille] (LMA ), and Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Control and Systems Engineering, Applied Mathematics, Mechanical Engineering, [NLIN.NLIN-CD]Nonlinear Sciences [physics]/Chaotic Dynamics [nlin.CD], Aerospace Engineering, Ocean Engineering, Electrical and Electronic Engineering, [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph]
Abstract: International audience; This paper investigates the dynamic behavior of a simplified single reed instrument model subject to a stochastic forcing of white noise type when one of its bifurcation parameters (the dimensionless blowing pressure) increases linearly over time and crosses the Hopf bifurcation point of its trivial equilibrium position. The stochastic slow dynamics of the model is first obtained by means of the stochastic averaging method. The resulting averaged system reduces to a non-autonomous one-dimensional Itô stochastic differential equation governing the time evolution of the mouthpiece pressure amplitude. Under relevant approximations the latter is solved analytically treating separately cases where noise can be ignored and cases where it cannot. From that, two analytical expressions of the bifurcation parameter value for which the mouthpiece pressure amplitude gets its initial value back are deduced. These special values of the bifurcation parameter characterize the effective appearance of sound in the instrument and are called deterministic dynamic bifurcation point if the noise can be neglected and stochastic dynamic bifurcation point otherwise. Finally, for illustration and validation purposes, the analytical results are compared with direct numerical integration of the model in both deterministic and stochastic situations. In each considered case, a good agreement is observed between theoretical results and numerical simulations, which validates the proposed analysis.
Published: 2022
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22. Disability in a medieval village community: A unique case of facial dysmorphism

Author: Hélène Coqueugniot, Elisabeth Zadora-Rio, Boris Laure, Estelle Herrscher, Samuel Bédécarrats, Valentin Miclon, Matthieu Gaultier, Cités, Territoires, Environnement et Sociétés (CITERES), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de l'archéologie du département d'Indre-et-Loire (SADIL), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire méditerranéen de préhistoire Europe-Afrique (LAMPEA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), This work was funded by UMR CITERES 7324 – LAT., Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), École Pratique des Hautes Études (EPHE), Miclon, Valentin, Centre National de la Recherche Scientifique (CNRS)-Université de Tours, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Archeology, medicine.medical_specialty, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Paleopathology, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Population, Disease, Deafness, Care, Pathology and Forensic Medicine, Social life, 03 medical and health sciences, Facial dysmorphism, Treacher-Collins syndrome, Isotopes, medicine, Humans, 0601 history and archaeology, education, 030304 developmental biology, 0303 health sciences, education.field_of_study, [SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, 060101 anthropology, Bone collagen, Nitrogen Isotopes, Osteology, CT-scan, 06 humanities and the arts, Semiology, medicine.disease, Diet, [SHS.ANTHRO-BIO] Humanities and Social Sciences/Biological anthropology, Archaeology, [SHS.HIST] Humanities and Social Sciences/History, Female, [SHS.HIST]Humanities and Social Sciences/History, Psychology, Treacher Collins syndrome, Mandibulofacial Dysostosis, Clinical psychology
Abstract: International audience; Archaeological excavations carried out in the 1990s in the former rural parish of Rigny (Indre-et-Loire, France) uncovered 1738 graves. Among the individuals discovered, a female adult presents a series of cranial deformities characteristic of an extremely rare pathology, til then unknown in the archaeological record: the Treacher-Collins syndrome. It induces facial dysmorphism and is generally associated with hearing loss or even conductive deafness of the patient due to malformations of the hearing system.The retrospectif diagnosis of this individual was based on macroscopic analysis and computed tomography (CTscan). The use of 3D imaging made it possible to explore the impact of the pathology on the individual's hearing.In addition to the functional implications, the negative impacts of facial dysmorphic disorders in the social sphere are well known in today's societies while they are poorly documented for the medieval period.During this period, diet was an important social marker. The analysis of the individual affected by this syndrome’s diet, compared to those of other members of the Rigny village community, provide an opportunity to discuss the social significance of disability in a rural context in the Middle Ages. In this perspective, the isotopic ratios of carbon and nitrogen in this individual's bone collagen were compared to those of forty-seven other individuals found on the site.Archaeological, paleopathological and biochemical information are relevant to better characterize the functional repercussions of this syndrome on the Rigny individual and also to discuss the integration of this individual into this medieval village community.
Published: 2021
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23. EMDR for symptoms of depression, stress and burnout in health care workers exposed to COVID-19 (HARD): A study protocol for a trial within a cohort study

Author: Agnès Caille, Aude Allemang-Trivalle, Myriam Blanchin, Anne Rebion, Anne Sauvaget, Bénédicte Gohier, Philippe Birmes, Eric Bui, Eric Fakra, Marie-Odile Krebs, Cédric Lemogne, Nathalie Prieto, Isabelle Jalenques, Pierre Vidailhet, Bruno Aouizerate, Coraline Hingray, Wissam El-Hage, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), 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 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), MIP UR 4334 - T2 - Coordinations motrices (MIP T2), 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 (Nantes Univ)-Nantes Université (Nantes Univ)-Le Mans Université (UM)-Nantes Université - UFR des Sciences et Techniques des Activités Physiques et Sportives (Nantes Univ - UFR STAPS), Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Nantes Université - UFR Lettres et Langages (Nantes Univ - UFR LL), Nantes Université - pôle Humanités, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Humanités, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Massachusetts General Hospital [Boston], Université de Caen Normandie (UNICAEN), Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Psychiatric Disorders, Neuroscience Research and Clinical Research (PSYR2), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet - Saint-Étienne (UJM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Psychiatrie de l'Adulte A [CHU Clermont-Ferrand], CHU Clermont-Ferrand, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Fondation FondaMental [Créteil], Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Centre hospitalier Charles Perrens [Bordeaux], Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Psychothérapique de Nancy [Laxou] (CPN), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: trial within a cohort study, stress, burnout, [SDV]Life Sciences [q-bio], depression, COVID-19, EMDR, health care workers, study protocol, TwiC
Abstract: Background: Stressful events during a pandemic are a major cause of serious health problems, such as burnout, depression and posttraumatic stress disorder (PTSD) among health care workers (HCWs). During three years, HCWs, on the frontline to fight the COVID-19 pandemic, have been at an increased risk of high levels of stress, anxiety, depression, burnout and PTSD. Regarding potential psychological interventions, Eye Movement Desensitization & Reprocessing (EMDR) is a structured, strongly recommended therapy based on its well-known efficacy in reducing PTSD symptoms and anxiety. Objectives: This study, designed as a trial within a cohort (TwiC), aims to 1) estimate the prevalence of depression, burnout and PTSD in a sample of HCWs after experiencing the COVID-19 emergency (cohort part) and 2) assess the efficacy and acceptability of 'EMDR + usual care' for HCWs from the cohort who report significant psychological symptoms (trial part). Methods: The study, designed as a TwiC, consists of a prospective cohort study (n = 3000) with an embedded, pragmatic, randomized open-label superiority trial with two groups (n = 900). Participants included in the trial part are HCWs recruited for the cohort with significant symptoms on at least one psychological dimension (depression, burnout, PTSD) at baseline, 3 months or 6 months, determined by using the Patient Health Questionnaire (PHQ-9), Professional Quality of Life (ProQOL) scale, and PTSD Checklist for the DSM-5 (PCL-5). The intervention consists of 12 separate EMDR sessions with a certified therapist. The control group receives usual care. The trial has three primary outcomes: changes in depression, burnout and PTSD scores from randomization to 6 months. All participants are followed up for 12 months. Conclusions: This study provides empirical evidence about the impact of the COVID-19 pandemic and the mental health burden it places on HCWs and assesses the effectiveness of EMDR as a psychological intervention. Trial registration NCT04570202
Published: 2023
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24. Modélisation de la décomposition des matériaux énergétiques et de leurs sensibilités

Author: Claveau, Romain, Université de Tours (UT), CEA Le Ripault (CEA Le Ripault), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut franco-allemand de recherches de Saint-Louis (ISL), DGA-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), DGA (50%) - CEA (25%) - ISL (25%), Université de Tours (UT), Tours, FRA, and Mathieu Didier
Subjects: Decomposition modelling, Modélisation de la décomposition, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Energetic materials, Sensitivities modelling, Matériaux énergétiques, Modélisation des sensibilités
Abstract: Energetic materials (EMs) release considerable energy during their decomposition. For this reason, we use them forcivilian (propellants, fuels) and military (pyrotechnic compositions, explosives) applications. However, manydisadvantages go with their use. Indeed, an unintentional initiation can quickly have dramatic human, material, andenvironmental consequences.To measure the sensitivity of EMs, i.e., their propensity to initiate under more or less intense constraints, there arenumerous standardised experimental protocols. However, these procedures only apply to compounds that are availablein sufficient quantity and cannot be used to search for new compounds efficiently.In this case, modelling is necessary. Unfortunately, despite the abundant literature, there has yet to be a consensus onthe origin of sensitivity, as the problem's dimensionality prohibits any exhaustive study. These various observations areat the origin of this thesis. We wish to understand the origin of the sensitivity of EMs. In this thesis, we have favoured atheoretical rather than an empirical approach.To do this, we must describe many mechanisms involved, from applying the constraint to the decomposition of thesystem. We show that sensitivity is only a consequence of the tendency of a system to thermal runaway. Thus, weprovide a consequent physicochemical insight into the sensitivity of EMs.; Les matériaux énergétiques (MEs) libèrent une grande quantité d'énergie lors de leur décomposition. Pour cela, ils sontautant prisés pour des applications civiles (ergols, propergols, combustibles) que militaires (compositionspyrotechniques, explosifs). Cependant, leur utilisation est accompagnée de multiples inconvénients. En effet, uneinitiation involontaire peut rapidement entraîner des conséquences dramatiques, autant humaines, matériellesqu'environnementales.Afin de mesurer la sensibilité des MEs, c'est-à-dire leur propension à s'initier sous des contraintes plus ou moinsintenses, il existe de nombreux protocoles expérimentaux normalisés. Or, ces procédures s'appliquent uniquement auxcomposés disponibles en quantité suffisante et ne peuvent donc être employées pour en rechercher de nouveauxefficacement.Dans ce cas, la modélisation s'avère nécessaire. Malgré une littérature foisonnante, il n'existe à ce jour aucun consensussur l'origine de la sensibilité, la dimensionnalité du problème prohibant toute étude exhaustive. Ces divers constats sontà l'origine de cette thèse. Particulièrement, nous souhaitons comprendre l'origine de la sensibilité des MEs. Dans cemémoire, nous avons privilégié une approche théorique plutôt qu'empirique.Pour cela, nous devons décrire un grand nombre de mécanismes intervenants depuis l'application de la contraintejusqu'à la décomposition du système. Nous montrons que la sensibilité n'est qu'une conséquence de la tendance d'unsystème à l'emballement thermique. De ce fait, nous apportons ainsi un éclairage physico-chimique conséquent sur lasensibilité des MEs.
Published: 2023

25. SNORD90 induces glutamatergic signaling following treatment with monoaminergic antidepressants

Author: Rixing Lin, Aron Kos, Juan Pablo Lopez, Julien Dine, Laura M. Fiori, Jennie Yang, Yair Ben-Efraim, Zahia Aouabed, Pascal Ibrahim, Haruka Mitsuhashi, Tak Pan Wong, El Cherif Ibrahim, Catherine Belzung, Pierre Blier, Faranak Farzan, Benicio N. Frey, Raymond W. Lam, Roumen Milev, Daniel J. Müller, Sagar V. Parikh, Claudio Soares, Rudolf Uher, Corina Nagy, Naguib Mechawar, Jane A. Foster, Sidney H. Kennedy, Alon Chen, Gustavo Turecki, McGill Group for Suicide Studies, McGill University = Université McGill [Montréal, Canada]-Douglas Mental Health University Institute, Max Plank Institute of Psychiatry, Department of Stress Neurobiology and Neurogenetics, Department of Brain Sciences, Weizmann Institute of Science, Neuroscience Division, Douglas Research Centre, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), UMR 1253 IBrain Imagerie & Cerveau Equipe 1 : 'Psychiatrie Neuro-Fonctionnelle' (PNF), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Mood Disorders Research Unit, University of Ottawa Institute of Mental Health Research, eBrain Lab, Simon Fraser University, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario], Department of Psychiatry, University of British Columbia, Departments of Psychiatry and Psychology, Queens University, Centre for Mental Health, Department of Psychiatry, University Health Network, Krembil Research Institute, University of Toronto, University of Michigan Hospital, Department of Psychiatry, Nova Scotia Health Authority, Mood Disorders Program, St. Joseph's Healthcare Hamilton, and St Michael’s Hospital, Li Ka Shing Knowledge Institute, Centre for Depression and Suicide Studies, Toronto
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; Pharmacotherapies for the treatment of major depressive disorder were serendipitously discovered almost seven decades ago. From this discovery, scientists pinpointed the monoaminergic system as the primary target associated with symptom alleviation. As a result, most antidepressants have been engineered to act on the monoaminergic system more selectively, primarily on serotonin, in an effort to increase treatment response and reduce unfavorable side effects. However, slow and inconsistent clinical responses continue to be observed with these available treatments. Recent findings point to the glutamatergic system as a target for rapid acting antidepressants. Investigating different cohorts of depressed individuals treated with serotonergic and other monoaminergic antidepressants, we found that the expression of a small nucleolar RNA, SNORD90 , was elevated following treatment response. When we increased Snord90 levels in the mouse anterior cingulate cortex (ACC), a brain region regulating mood responses, we observed antidepressive-like behaviors. We identified neuregulin 3 ( NRG3 ) as one of the targets of SNORD90 , which we show is regulated through the accumulation of N 6 -methyladenosine modifications leading to YTHDF2-mediated RNA decay. We further demonstrate that a decrease in NRG3 expression resulted in increased glutamatergic release in the mouse ACC. These findings support a molecular link between monoaminergic antidepressant treatment and glutamatergic neurotransmission.
Published: 2023
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26. Sonoporation of the Round Window Membrane on a Sheep Model: A Safety Study

Author: Sandrine Kerneis, Jean-Michel Escoffre, John J. Galvin, Ayache Bouakaz, Antoine Presset, Corentin Alix, Edward Oujagir, Antoine Lefèvre, Patrick Emond, Hélène Blasco, David Bakhos, Service ORL et chirurgie cervico-faciale [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, UMR 1253 IBrain Imagerie & Cerveau Equipe 3 'Imagerie, Biomarqueurs & Thérapie' (IBT), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT), The House Institute Foundation [Los Angeles, CA, USA] (THIF), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), UMR 1253 IBrain Imagerie & Cerveau Equipe 2 : 'Neurogénomique & Physiopathologie neuronale' (NPN), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), House Institute Foundation (HIF-121-5), and Escoffre, Jean-Michel
Subjects: inner ear, [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Pharmaceutical Science, sonoporation, perilymph, round window membrane, metabolomics
Abstract: International audience; Sonoporation using microbubble-assisted ultrasound increases the permeability of a biological barrier to therapeutic molecules. Application of this method to the round window membrane could improve the delivery of therapeutics to the inner ear. The aim of this study was to assess the safety of sonoporation of the round window membrane in a sheep model. To achieve this objective, we assessed auditory function and cochlear heating, and analysed the metabolomics profiles of perilymph collected after sonoporation, comparing them with those of the control ear in the same animal. Six normal-hearing ewes were studied, with one sonoporation ear and one control ear for each. A mastoidectomy was performed on both ears. On the sonoporation side, Vevo MicroMarker® microbubbles (MBs; VisualSonics—Fujifilm, Amsterdam, The Netherlands) at a concentration of 2 × 108 MB/mL were locally injected into the middle ear and exposed to 1.1 MHz sinusoidal ultrasonic waves at 0.3 MPa negative peak pressure with 40% duty cycle and 100 μs interpulse period for 1 min; this was repeated three times with 1 min between applications. The sonoporation protocol did not induce any hearing impairment or toxic overheating compared with the control condition. The metabolomic analysis did not reveal any significant metabolic difference between perilymph samples from the sonoporation and control ears. The results suggest that sonoporation of the round window membrane does not cause damage to the inner ear in a sheep model.
Published: 2023
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27. Multi-scale mechanical characterization of the interface in 3D printed concrete

Author: M. Taleb, D. Bulteel, D. Betrancourt, F. Roudet, S. Rémond, A. Montagne, D. Chicot, Laboratoire de Génie Civil et Géo-Environnement (LGCgE) - ULR 4515 (LGCgE), Université d'Artois (UA)-Université de Lille-Ecole nationale supérieure Mines-Télécom Lille Douai (IMT Lille Douai), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Génie Civil (GC), Laboratoire de Mécanique Gabriel Lamé (LaMé), Université d'Orléans (UO)-Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université d'Orléans (UO)-Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Laboratoire d'Automatique, de Mécanique et d'Informatique industrielles et Humaines - UMR 8201 (LAMIH), and Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France)
Subjects: [SPI]Engineering Sciences [physics], Mechanics of Materials, General Materials Science, Building and Construction, Civil and Structural Engineering
Abstract: International audience; To be printable, the cementitious ink may have contradictory properties. It must be fluid enough initially to be pumpable and extrudable, also should stiffen quickly after deposition to be buildable. This could be influential, along with other printing parameters, on its interlayer zone. Thus, the main purpose of this study is to compare experimental protocols allowing for its mechanical characterization and the assessment of a drop in bond strength. Classical microindentation tests are done perpendicularly to the interface. Furthermore, a new method to elaborate specimens on a lab-scale is proposed in this study allowing for multidirectional compression testing. Later, interfacial instrumented indentation measurements at the macroscopic scale were also performed. Results validate the new experimental procedure. Indentation profiles reveal a weakness and widening of the interface with time gap. Multidirectional compression tests show anisotropy while no influence of time gap was detected. Instrumented macroindentation indicates a lower adherence with time gap between layers.
Published: 2023
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28. Four functional profiles for fibre and mucin metabolism in the human gut microbiome

Author: Simon Labarthe, Sandra Plancade, Sebastien Raguideau, Florian Plaza Onate, Emmanuelle Le Chatelier, Marion Leclerc, Béatrice Laroche, from patterns to models in computational biodiversity and biotechnology (PLEIADE), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-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), Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-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), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Earlham Institute [Norwich], MetaGenoPolis (MGP (US 1367)), 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), Pendulum Therapeutics [San Francisco], 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), ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011), European Project: 609398,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,AGREENSKILLSPLUS(2014), and Labarthe, Simon
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: Background With the emergence of metagenomic data, multiple links between the gut microbiome and the host health have been shown. Deciphering these complex interactions require evolved analysis methods focusing on the microbial ecosystem functions. Despite the fact that host or diet-derived fibres are the most abundant nutrients available in the gut, the presence of distinct functional traits regarding fibre and mucin hydrolysis, fermentation and hydrogenotrophic processes has never been investigated. Results After manually selecting 91 KEGG orthologies and 33 glycoside hydrolases further aggregated in 101 functional descriptors representative of fibre and mucin degradation pathways in the gut microbiome, we used non-negative matrix factorization to mine metagenomic datasets. Four distinct metabolic profiles were further identified on a training set of 1153 samples and thoroughly validated on a large database of 2571 unseen samples from 5 external metagenomic cohorts. Profiles 1 and 2 are the main contributors to the fibre-degradation-related metagenome: they present contrasted involvement in fibre degradation and sugar metabolism and are differentially linked to dysbiosis, metabolic disease and inflammation. Profile 1 takes over Profile 2 inhealthy samples, and unbalance of these profiles characterize dysbiotic samples. Furthermore, high fibre diet favours a healthy balance between Profiles 1 and Profile 2. Profile 3 takes over Profile 2 during Crohn’s disease, inducing functional reorientations towards unusual metabolism such as fucose and H2S degradation or propionate, acetone and butanediol production. Profile 4 gathers under-represented functions, like methanogenesis. Two taxonomic makes up of the profiles were investigated, using either the covariation of 203 prevalent genomes or metagenomic species, both providing consistent results in line with their functional characteristics. This taxonomic characterization showed that Profiles 1 and 2 were respectively mainly composed of bacteria from the phyla Bacteroidetes and Firmicutes while Profile 3 is representative of Proteobacteria and Profile 4 of methanogens.Conclusions Integrating anaerobic microbiology knowledge with statistical learning can narrow down the metagenomic analysis to investigate functional profiles. Applying this approach to fibre degradation in the gut ended with 4 distinct functional profiles that can be easily monitored as markers of diet, dysbiosis, inflammation and disease.
Published: 2023

29. Experimental Study of Time Series Forecasting Methods for Groundwater Level Prediction

Author: Mbouopda, Michael Franklin, Guyet, Thomas, Labroche, Nicolas, Henriot, Abel, Laboratoire d'Informatique, de Modélisation et d'Optimisation des Systèmes (LIMOS), Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Inria Lyon, Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire d'Informatique Fondamentale et Appliquée de Tours (LIFAT), Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Bases de données et traitement des langues naturelles (BDTLN), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Guyet, T, Ifrim, G, Malinowski, S, Bagnall, A, Shafer, P, and Lemaire, V
Subjects: Time series, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Benchmark, Groundwater, Local and global forecasting, Forecasting
Abstract: International audience; Groundwater level prediction is an applied time series forecasting task with important social impacts to optimize water management as well as preventing some natural disasters: for instance, floods or severe droughts. Machine learning methods have been reported in the literature to achieve this task, but they are only focused on the forecast of the groundwater level at a single location. A global forecasting method aims at exploiting the groundwater level time series from a wide range of locations to produce predictions at a single place or at several places at a time. Given the recent success of global forecasting methods in prestigious competitions, it is meaningful to assess them on groundwater level prediction and see how they are compared to local methods. In this work, we created a dataset of 1026 groundwater level time series. Each time series is made of daily measurements of groundwater levels and two exogenous variables, rainfall and evapotranspiration. This dataset is made available to the communities for reproducibility and further evaluation. To identify the best configuration to effectively predict groundwater level for the complete set of time series, we compared different predictors including local and global time series forecasting methods. We assessed the impact of exogenous variables. Our result analysis shows that the best predictions are obtained by training a global method on past groundwater levels and rainfall data
Published: 2023
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30. NALCN-mediated sodium influx confers metastatic prostate cancer cell invasiveness

Author: Folcher, Antoine, Gordienko, Dmitri, Iamshanova, Oksana, Bokhobza, Alexandre, Shapovalov, George, Kannancheri-Puthooru, Dheeraj, Mariot, Pascal, Allart, Laurent, Desruelles, Emilie, Spriet, Corentin, Diez, Raquel, Oullier, Thibauld, Marionneau-Lambot, Séverine, Brisson, Lucie, Geraci, Sandra, Impheng, Hathaichanok, Lehen'Kyi, V'Yacheslav, Haustrate, Aurélien, Mihalache, Adriana, Gosset, Pierre, Chadet, Stéphanie, Retif, Stéphanie, Laube, Maryline, Sobilo, Julien, Lerondel, Stéphanie, Villari, Giulia, Serini, Guido, Pla, Alessandra Fiorio, Roger, Sébastien, Fromont-Hankard, Gaelle, Djamgoz, Mustafa, Clezardin, Philippe, Monteil, Arnaud, Prevarskaya, Natalia, Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Universidad de Extremadura - University of Extremadura (UEX), Cancéropôle du Grand Ouest, Université de Nantes (UN), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Naresuan University, Université catholique de Lille (UCL), EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Université de Tours (UT), Transgenèse et archivage d'animaux modèles (TAAM), Centre National de la Recherche Scientifique (CNRS), French National Infrastructure for Mouse Phenogenomics (PHENOMIN), Centre d'Imagerie du Petit Animal (CIPA), Université d'Orléans (UO), Università degli studi di Torino = University of Turin (UNITO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imperial College London, Cyprus International University, 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), LabEx Ion Channels Science and Therapeutics [France], and ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011)
Subjects: Sodium leak channel, calcium oscillations, invasion, oncochannelopathy, vesicle secretion, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
Abstract: International audience; There is growing evidence that ion channels are critically involved in cancer cell invasiveness and metastasis. However, the molecular mechanisms of ion signaling promoting cancer behavior are poorly understood and the complexity of the underlying remodeling during metastasis remains to be explored. Here, using a variety of in vitro and in vivo techniques, we show that metastatic prostate cancer cells acquire a specific Na+ /Ca2+ signature required for persistent invasion. We identify the Na+ leak channel, NALCN, which is overexpressed in metastatic prostate cancer, as a major initiator and regulator of Ca2+ oscillations required for invadopodia formation. Indeed, NALCN-mediated Na+ influx into cancer cells maintains intracellular Ca2+ oscillations via a specific chain of ion transport proteins including plasmalemmal and mitochondrial Na+ /Ca2+ exchangers, SERCA and store-operated channels. This signaling cascade promotes activity of the NACLN-colocalized proto-oncogene Src kinase, actin remodeling and secretion of proteolytic enzymes, thus increasing cancer cell invasive potential and metastatic lesions in vivo. Overall, our findings provide new insights into an ion signaling pathway specific for metastatic cells where NALCN acts as persistent invasion controller.
Published: 2023
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31. Co‐development of a school‐based and primary care‐based multicomponent intervention to improve HPV vaccine coverage amongst French adolescents (the PrevHPV Study)

Author: Bocquier, Aurélie, Bruel, Sébastien, Michel, Morgane, Le Duc-Banaszuk, Anne‐sophie, Bonnay, Stéphanie, Branchereau, Marion, Chevreul, Karine, Chyderiotis, Sandra, Gauchet, Aurélie, Giraudeau, Bruno, Hagiu, Dragos‐paul, Mueller, Judith E., Gagneux-Brunon, Amandine, Thilly, Nathalie, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Faculté de Médecine Jacques Lisfranc [Université Saint-Etienne], Université Jean Monnet - Saint-Étienne (UJM), Parcours santé systémique (P2S), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), 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)-Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital universitaire Robert-Debré [Paris], Centre Régional de Coordination des Dépistages des Cancers [Angers] (CRCDC Pays de la Loire), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-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 Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-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), Laboratoire Inter-universitaire de Psychologie : Personnalité, Cognition, Changement Social (LIP-PC2S), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), 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 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), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Département Méthodologie Promotion Investigation [CHRU Nancy] (MPI), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and The PrevPHV study is conducted with the support of IReSP and Inserm, and with financial support from ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé/National Alliance for Life Sciences and Health) within the framework of the Cancer Plan.
Subjects: vaccination behaviours, motivational interview, eHealth tools, complex Intervention, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, human papillomavirus, co-construction
Abstract: International audience; Introduction: Despite various efforts to improve human papillomavirus (HPV) vaccine coverage in France, it has always been lower than in most other high-income countries. The health authorities launched in 2018 the national PrevHPV research programme to (1) co-develop with stakeholders and (2) evaluate the impact of a multicomponent complex intervention aimed at improving HPV vaccine coverage amongst French adolescents.Objective: To describe the development process of the PrevHPV intervention using the GUIDance for rEporting of intervention Development framework as a guide.Methods: To develop the intervention, we used findings from (1) published evidence on effective strategies to improve vaccination uptake and on theoretical frameworks of health behaviour change; (2) primary data on target populations' knowledge, beliefs, attitudes, preferences, behaviours and practices as well as the facilitators and barriers to HPV vaccination collected as part of the PrevHPV Programme and (3) the advice of working groups involving stakeholders in a participatory approach. We paid attention to developing an intervention that would maximise reach, adoption, implementation and maintenance in real-world contexts.Results: We co-developed three components: (1) adolescents' and parents' education and motivation using eHealth tools (web conferences, videos, and a serious video game) and participatory learning at school; (2) general practitioners' e-learning training on HPV using motivational interviewing techniques and provision of a decision aid tool and (3) easier access to vaccination through vaccination days organised on participating middle schools' premises to propose free of charge initiation of the HPV vaccination.Conclusion: We co-developed a multicomponent intervention that addresses a range of barriers and enablers of HPV vaccination. The next step is to build on the results of its evaluation to refine it before scaling it up if proven efficient. If so, it will add to the small number of multicomponent interventions aimed at improving HPV vaccination worldwide.Patient or Public Contribution: The public (adolescents, their parents, school staff and health professionals) participated in the needs assessment using a mixed methods approach. The public was also involved in the components' development process to generate ideas about potential activities/tools, critically revise the successive versions of the tools and provide advice about the intervention practicalities, feasibility and maintenance.
Published: 2023
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32. A unique network of attack, defence and competence on the outer membrane of the periodontitis pathogen Tannerella forsythia

Author: Mirosław Książek, Theodoros Goulas, Danuta Mizgalska, Arturo Rodríguez-Banqueri, Ulrich Eckhard, Florian Veillard, Irena Waligórska, Małgorzata Benedyk-Machaczka, Alicja M. Sochaj-Gregorczyk, Mariusz Madej, Ida B. Thøgersen, Jan J. Enghild, Anna Cuppari, Joan L. Arolas, Iñaki de Diego, Mar López-Pelegrín, Irene Garcia-Ferrer, Tibisay Guevara, Vincent Dive, Marie-Louise Zani, Thierry Moreau, Jan Potempa, F. Xavier Gomis-Rüth, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Louisville School of Dentistry, Molecular Biology Institute of Barcelona (IBMB ), University of Thessaly [Lamia], Centre for Blood Research (CBR), University of British Columbia (UBC), Aarhus University [Aarhus], Université de Tours (UT), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des Oiseaux et Aviculture (BOA), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This study was supported in part by grants from Polish (National Science Centre and Ministry of Science and Higher Education), US (NIH/NIDR), Spanish, Danish and Catalan public and private bodies (grant/fellowship references PID2019-107725RG-I00 and PDC2022-133344-I00 by MICIN/AEI/10.13039/501100011033, 2017SGR3, 2016/21/B/NZ1/00292, 1306/MOB/IV/2015/0, 2019/35/B/NZ1/03118, DE026280, Fundació 'La Marató de TV3' 201815, and Novo Nordisk Foundation grant NNF18OC0032724)., National Science Centre (Poland), Ministry of Science and Higher Education (Poland), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundació La Marató de TV3, and Novo Nordisk Foundation
Subjects: [SDV]Life Sciences [q-bio], Tannerella forsythia, General Chemistry
Abstract: Periodontopathogenic Tannerella forsythia uniquely secretes six peptidases of disparate catalytic classes and families that operate as virulence factors during infection of the gums, the KLIKK-peptidases. Their coding genes are immediately downstream of novel ORFs encoding the 98–132 residue potempins (Pot) A, B1, B2, C, D and E. These are outer-membrane-anchored lipoproteins that specifically and potently inhibit the respective downstream peptidase through stable complexes that protect the outer membrane of T. forsythia, as shown in vivo. Remarkably, PotA also contributes to bacterial fitness in vivo and specifically inhibits matrix metallopeptidase (MMP) 12, a major defence component of oral macrophages, thus featuring a novel and highly-specific physiological MMP inhibitor. Information from 11 structures and high-confidence homology models showed that the potempins are distinct β-barrels with either a five-stranded OB-fold (PotA, PotC and PotD) or an eight-stranded up-and-down fold (PotE, PotB1 and PotB2), which are novel for peptidase inhibitors. Particular loops insert like wedges into the active-site cleft of the genetically-linked peptidases to specifically block them either via a new “bilobal” or the classic “standard” mechanism of inhibition. These results discover a unique, tightly-regulated proteolytic armamentarium for virulence and competence, the KLIKK-peptidase/potempin system., This study was supported in part by grants from Polish (National Science Centre and Ministry of Science and Higher Education), US (NIH/NIDR), Spanish, Danish and Catalan public and private bodies (grant/fellowship references PID2019-107725RG-I00 and PDC2022-133344-I00 by MICIN/AEI/10.13039/501100011033, 2017SGR3, 2016/21/B/NZ1/00292, 1306/MOB/IV/2015/0, 2019/35/B/NZ1/03118, DE026280, Fundació “La Marató de TV3” 201815, and Novo Nordisk Foundation grant NNF18OC0032724).
Published: 2023
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33. Identification of Lipid Biomarkers for Chronic Joint Pain Associated with Different Joint Diseases

Author: Spiro Khoury, Jenny Colas, Véronique Breuil, Eva Kosek, Aisha S. Ahmed, Camilla I. Svensson, Fabien Marchand, Emmanuel Deval, Thierry Ferreira, Lipotoxicity and Channelopathies - ConicMeds (LitCh), Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et Régulation des Transports Ioniques (PRéTI), Université de Poitiers, Mécanismes biologiques des Altérations du Tissu Osseux (MATOs), UMR E4320 (TIRO-MATOs), 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Pasteur [Nice] (CHU), Karolinska Institutet [Stockholm], Uppsala Universitet [Uppsala], Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and ANR-17-CE16-0018,JOINT-PAIN,Douleur articulaire chronique : vers de nouvelles cibles moléculaires.(2017)
Subjects: synovial fluid, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, inflammation, chronic joint pain, Biochemistry and Molecular Biology, lipidomics, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Molecular Biology, Biochemistry, Biokemi och molekylärbiologi, metabolic status
Abstract: International audience; Lipids, especially lysophosphatidylcholine LPC16:0, have been shown to be involved in chronic joint pain through the activation of acid-sensing ion channels (ASIC3). The aim of the present study was to investigate the lipid contents of the synovial fluids from controls and patients suffering from chronic joint pain in order to identify characteristic lipid signatures associated with specific joint diseases. For this purpose, lipids were extracted from the synovial fluids and analyzed by mass spectrometry. Lipidomic analyses identified certain choline-containing lipid classes and molecular species as biomarkers of chronic joint pain, regardless of the pathology, with significantly higher levels detected in the patient samples. Moreover, correlations were observed between certain lipid levels and the type of joint pathologies. Interestingly, LPC16:0 levels appeared to correlate with the metabolic status of patients while other choline-containing lipids were more specifically associated with the inflammatory state. Overall, these data point at selective lipid species in synovial fluid as being strong predictors of specific joint pathologies which could help in the selection of the most adapted treatment.
Published: 2023
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34. Modeling compartmentalization within intracellular signaling pathway

Author: Alamichel, Claire, Calvo, Juan, Hingant, Erwan, Latrach, Saoussen, Quiblier, Nathan, Yvinec, Romain, Laboratoire de Mathématiques et Modélisation d'Evry (LaMME), Université d'Évry-Val-d'Essonne (UEVE)-ENSIIE-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidad de Granada = University of Granada (UGR), Laboratoire Amiénois de Mathématique Fondamentale et Appliquée - UMR CNRS 7352 (LAMFA), Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Nord, La pharmacologie des neurones et des astrocytes à l’aide des sciences du numérique (AISTROSIGHT), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)- Theranexus [Lyon]-Inria Lyon, 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), 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), and ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011)
Subjects: Mathematics - Analysis of PDEs, FOS: Mathematics, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Analysis of PDEs (math.AP)
Abstract: We present a new modeling approach for G protein coupled receptors signaling systems, that take into account the compartmentalization of receptors and their effectors, both at plasma membrane and in dynamic intra-cellular vesicles called endosomes. The first building block of the model is about compartment dynamics. It takes into account creation of de-novo endosomes, i.e. endocytosis, recycling of endosomes back to plasma membrane, degradation through transfer into lysosomes as well as endosomes fusion through coagulation dynamics. The second building block is biochemical reactions into each compartments and the transfer of molecules between the dynamical compartments. In this work, we prove sufficient conditions to obtain exponentially ergodicity for the size distribution of intracellular compartments. We futher design a finite volume scheme to simulate our model and show two application cases for receptor trafficking and spatially biased second effector signaling.
Published: 2023
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35. Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the 64Cu-Labelling of Immunoconjugates

Author: Aurélie Maisonial-Besset, Tiffany Witkowski, Mercedes Quintana, Sophie Besse, Vincent Gaumet, Axel Cordonnier, Cyrille Alliot, Aurélien Vidal, Caroline Denevault-Sabourin, Sébastien Tarrit, Sophie Levesque, Elisabeth Miot-Noirault, Jean-Michel Chezal, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), GIP ARRONAX [Nantes], Université de Nantes (UN), GICC EA 7501, IMT (Innovation moléculaire et thérapeutique) (IMT), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, and Ligue contre le Cancer, Comité du Puy de Dôme
Subjects: copper-64, copper-64 chelating macrocycles NODAGA DOTA 15-5 trastuzumab, [CHIM.ORGA]Chemical Sciences/Organic chemistry, chelating macrocycles, NODAGA, DOTA, 15-5, trastuzumab, Organic Chemistry, Pharmaceutical Science, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Analytical Chemistry, Chemistry (miscellaneous), Drug Discovery, Molecular Medicine, Physical and Theoretical Chemistry, [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract: International audience; The development of 64 Cu-based immuno-PET radiotracers requires the use of copperspecific bifunctional chelators (BFCs) that contain functional groups allowing both convenient bioconjugation and stable copper complexes to limit in vivo bioreduction, transmetallation and/or transchelation. The excellent in vivo kinetic inertness of the pentaazamacrocyclic [ 64 Cu]Cu-15-5 complex prompted us to investigate its potential for the 64 Cu-labelling of monoclonal antibodies (mAbs), compared with the well-known NODAGA and DOTA chelators. To this end, three NODAGA, DOTA and 15-5-derived BFCs, containing a pendant azadibenzocyclooctyne moiety, were synthesised and a robust methodology was determined to form covalent bonds between them and azide-functionalised trastuzumab, an anti-HER2 mAb, using strain-promoted azide-alkyne cycloaddition. Unlike the DOTA derivative, the NODAGA-and 15-5-mAb conjugates were radiolabelled with 64 Cu, obtaining excellent radiochemical yields, under mild conditions. Although all the radioimmunoconjugates showed excellent stability in PBS or mouse serum, [ 64 Cu]Cu-15-5-and [ 64 Cu]Cu-NODAGA-trastuzumab presented higher resistance to transchelation when challenged by EDTA. Finally, the immunoreactive fraction of the radioimmunoconjugates (88-94%) was determined in HER-2 positive BT474 human breast cancer cells, confirming that the bioconjugation and radiolabelling processes implemented had no significant impact on antigen recognition.
Published: 2022
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36. The endocytic recycling compartment serves as a viral factory for hepatitis E virus

Author: Cyrine Bentaleb, Kévin Hervouet, Claire Montpellier, Charline Camuzet, Martin Ferrié, Julien Burlaud-Gaillard, Stéphane Bressanelli, Karoline Metzger, Elisabeth Werkmeister, Maliki Ankavay, Nancy Leon Janampa, Julien Marlet, Julien Roux, Clarence Deffaud, Anne Goffard, Yves Rouillé, Jean Dubuisson, Philippe Roingeard, Cécile-Marie Aliouat-Denis, Laurence Cocquerel, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Morphogénèse et antigénicité du VIH et du virus des Hépatites [MAVIVH - U1259 Inserm - CHRU Tours ], Institut de Biologie Intégrative de la Cellule [I2BC], Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS], BIOTEM [Apprieu], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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)-Centre National de la Recherche Scientifique (CNRS), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme IBISA de Microscopie Electronique [CHRU de Tours] (UNIV Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT), 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), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Institute of Microbiology [University of Lausanne] (IMUL), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Université de Tours, Plateformes Lilloises en Biologie et Santé - UMS 2014 - US 41 (PLBS), and This work has been funded by Inserm-Transfert (MAT-PI-17006), Pasteur Institute of Lille (DiagHepE), Region Hauts-de-France (DiagHepE), ANRS and the University of Tours.
Subjects: medicine.drug_class, viruses, Viral factories, [SDV]Life Sciences [q-bio], Endocytic recycling, RNA-dependent RNA polymerase, Infectious particles, Biology, medicine.disease_cause, Monoclonal antibody, Virus, Antibodies, Cellular and Molecular Neuroscience, 03 medical and health sciences, Hepatitis E virus, Viral factory, viral factories, medicine, Electron microscopy, Humans, AlphaFold2, Molecular Biology, 030304 developmental biology, Pharmacology, 0303 health sciences, 030306 microbiology, ORF2 capsid protein, Antibodies, Monoclonal, virus diseases, Biological Transport, Cell Biology, medicine.disease, Virology, digestive system diseases, 3. Good health, Endocytic recycling compartment, Rab11, Capsid, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, Capsid Proteins, Viral hepatitis, Viral Replication Compartments
Abstract: Background & AimsAlthough Hepatitis E virus (HEV) is the major leading cause of enterically transmitted viral hepatitis worldwide, many gaps remain in the understanding of the HEV lifecycle. Notably, viral factories induced by HEV have not been documented yet and it is currently unknown whether HEV infection leads to cellular membrane modelling as many positive-strand RNA viruses. HEV genome encodes three proteins, the ORF1 replicase, the ORF2 capsid protein and the ORF3 protein involved in virion egress. Previously, we demonstrated that HEV produces different ORF2 isoforms including the virion-associated ORF2i form. Here, we aimed to probe infectious particles and viral factories in HEV-producing cells, using antibodies directed against the different ORF2 isoforms.MethodsWe generated monoclonal antibodies that specifically recognize the particle-associated ORF2i form, and antibodies that recognize the different ORF2 isoforms. We used them in confocal and electron microscopy approaches to probe viral factories in HEV-producing cells. We performed an extensive colocalization study of viral proteins with subcellular markers. We analyzed the impact of silencing Rab11, a central player of the endocytic recycling compartment (ERC).ResultsOne of the antibodies, named P1H1 and targeting the N-terminus of ORF2i, recognized delipidated HEV particles. Confocal and ultrastructural microscopy analyses of HEV-producing cells revealed an unprecedented HEV-induced membrane network containing tubular and vesicular structures. These subcellular structures were enriched in ORF2 and ORF3 proteins, and were dependent on the ORF3 expression and ORF2i capsid protein assembly. Colocalization and silencing analyses revealed that these structures are derived from the ERC.ConclusionsOur study reveals that HEV hijacks the ERC and forms a membrane network of vesicular and tubular structures that might be the hallmark of HEV infection.Lay summaryHepatitis E virus (HEV) is the leading cause of acute hepatitis worldwide but many steps of its lifecycle are still elusive. Thanks to the development of new antibodies that recognize the different forms of the HEV capsid protein, we were able to visualize vesicular and tubular structures that were established by the virus in the host cell. In addition, extensive efforts to identify these structures led us to conclude that HEV hijacks the endocytic recycling compartment of the cell to form this network of vesicles and tubules, which might be the hallmark of HEV infection.
Published: 2022
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37. The French FRACTURE database: A way to improve knowledge on management of children with very rare tumors

Author: Coralie Mallebranche, Yves Reguerre, Brice Fresneau, Nicolas Andre, Claire Berger, Claire Briandet, Marie‐Pierre Castex, Anne‐Sophie Defachelles, Cécile Faure‐Conter, Julien Lejeune, Sébastien Klein, Guy Leverger, Aude Marie‐Cardine, Caroline Oudot, Claire Freycon, Stéphanie Proust, Marianne Roumy, Estelle Thebaud, Cécile Verite, Brigitte Lacour, Daniel Orbach, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), Unité d'Immuno-Hémato-Oncologie Pédiatrique [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Service d'hémato-immuno-oncologie pédiatrique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'Immunologie Hématologie et Oncologie pédiatriques [CHU Angers], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Pellegrin Tripode, Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent (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), Registre National des Tumeurs Solides de l'Enfant (RNTSE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Institut Curie [Paris]
Subjects: very rare tumors, Adolescent, Databases, Factual, Incidence, [SDV]Life Sciences [q-bio], Hematology, FRACTURE database, national registry, childhood malignancies, Oncology, Neoplasms, Pediatrics, Perinatology and Child Health, Humans, Registries, France, Child
Abstract: International audience; Introduction: Very rare pediatric tumors (VRTs), defined by an annual incidence ≤2 per million inhabitants, represent a heterogeneous group of cancers. Due to their extremely low incidence, knowledge on these tumors is scant. Since 2012, the French Very Rare Tumors Committee (FRACTURE) database has recorded clinical data about VRTs in France. This study aims: (a) to describe the tumors registered in the FRACTURE database; and (b) to compare these data with those registered in the French National Registry of Childhood Cancer (RNCE).Methods: Data recorded in the FRACTURE database between January 1, 2012 and December 31, 2018 were analyzed. In addition, these data were compared with those of the RNCE database between 2012 and 2015 to evaluate the completeness of the documentation and understand any discrepancies.Results: A total of 477 patients with VRTs were registered in the FRACTURE database, representing 97 histological types. Of the 14 most common tumors registered in the RNCE (772 patients), only 19% were also registered in the FRACTURE database. Total 39% of children and adolescent VRTs registered in the RNCE and/or FRACTURE database (323 of a total of 828 patients) were not treated in or linked to a specialized pediatric oncology unit.Conclusion: VRTs represent many different heterogenous entities, which nevertheless account for 10% of all pediatric cancers diagnosed each year. Sustainability in the collection of these rare tumor cases is therefore important, and a regular systematic collaboration between the FRACTURE database and the RNCE register helps to provide a more exhaustive picture of these VRTs and allow research completeness for some peculiar groups of patients.
Published: 2022
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38. Geotechnical Behavior and Physico-Chemical Changes of Lime-Treated and Cement-Treated Silty Soil

Author: Muzahim Al-Mukhtar, Mylène Martin, Naima Belayachi, Kévin Beck, Fawzi Bouras, Nouffou Tapsoba, Serge Sabio, Génie Civil (GC), Laboratoire de Mécanique Gabriel Lamé (LaMé), Université d'Orléans (UO)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Tours (UT)-Université d'Orléans (UO)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Tours (UT)
Subjects: Ettringite, Materials science, Aluminate, 0211 other engineering and technologies, Soil Science, 02 engineering and technology, engineering.material, 010502 geochemistry & geophysics, complex mixtures, 01 natural sciences, chemistry.chemical_compound, Architecture, Ultimate tensile strength, ComputingMilieux_MISCELLANEOUS, 021101 geological & geomatics engineering, 0105 earth and related environmental sciences, Lime, Cement, [SPI.GCIV.GEOTECH]Engineering Sciences [physics]/Civil Engineering/Géotechnique, Metallurgy, Geology, California bearing ratio, Geotechnical Engineering and Engineering Geology, 6. Clean water, Compressive strength, chemistry, engineering, Pozzolanic reaction
Abstract: An investigation performed on the interactions of silty soil treated with cement or lime demonstrates the strong relationship between microstructural phenomena and their engineering behavior. Cement hydration induces a rapid improvement in soil properties while the progressive pozzolanic reaction of lime leads to long-term improvement. Moreover, the cement-treated soil presents better mechanical properties (California bearing ratio and unconfined compressive strength). X-ray diffraction tests and thermo-gravimetric analyses show calcium aluminate hydrates in lime-treated soil and ettringite in cement-treated soil. Mineralogical changes and new hydrates formed in the treated soil demonstrate their positive effect on the engineering behavior of the soil. Swelling and indirect tensile strength indicate the soil suitability for treatment with specific amounts of binders. Cement-treated soil resists the immersion test, as ettringite and new calcium aluminate hydrate are detected by XRD after immersion, whereas dissolution of the unreacted lime and part of the calcium hydrates during the immersion test imply a low resistance to immersion of lime-treated soil.
Published: 2021
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39. Wavelet-based multiresolution analysis coupled with deep learning to efficiently monitor cracks in concrete

Author: Sébastien Jacques, Ahcene Arbaoui, Abdeldjalil Ouahabi, Madina Hamiane, Université Mohamed Akli Ouelhadj de Bouira (UMAOB), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), GREMAN (matériaux, microélectronique, acoustique et nanotechnologies) (GREMAN - UMR 7347), Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Royal University for Women (RUW), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Jacques, Sebastien, Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Identification scheme, 010504 meteorology & atmospheric sciences, Computer science, Multiresolution analysis, 0211 other engineering and technologies, TA630-695, 02 engineering and technology, 01 natural sciences, Convolutional neural network, Wavelet, crack monitoring, TJ1-1570, Mechanical engineering and machinery, [SPI.MECA.GEME] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Mechanical engineering [physics.class-ph], wavelet-based multiresolution analysis, 021101 geological & geomatics engineering, 0105 earth and related environmental sciences, [SPI.ACOU]Engineering Sciences [physics]/Acoustics [physics.class-ph], [SPI.ACOU] Engineering Sciences [physics]/Acoustics [physics.class-ph], Artificial neural network, Structural engineering (General), business.industry, Mechanical Engineering, Deep learning, Ultrasonic testing, deep learning, Pattern recognition, non-destructive ultrasonic testing, [SPI.MECA.GEME]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Mechanical engineering [physics.class-ph], [SPI.GCIV]Engineering Sciences [physics]/Civil Engineering, Mechanics of Materials, Pattern recognition (psychology), [SPI.GCIV] Engineering Sciences [physics]/Civil Engineering, concrete, Artificial intelligence, business
Abstract: International audience; This paper proposes an efficient methodology to monitor the formation of cracks in concrete after non-destructive ultrasonic testing of a structure. The objective is to be able to automatically detect the initiation of cracks early enough, i.e. well before they are visible on the concrete surface, in order to implement adequate maintenance actions on civil engineering structures. The key element of this original approach is the wavelet-based multiresolution analysis of the ultrasonic signal received from a sample or a specimen of the studied material subjected to several types of solicitation. This analysis is finally coupled to an automatic identification scheme of the types of cracks based on artificial neural networks (ANNs), and in particular deep learning by convolutional neural networks (CNNs); a technology today at the cutting edge of machine learning, in particular for all applications of pattern recognition. Wavelet-based multiresolution analysis does not add any value in detecting fractures in concrete visible by optical inspection. However, the results of its implementation coupled with different CNN architectures show cracks in concrete can be identified at an early stage with a very high accuracy, i.e. around 98%, and a loss function of less than 0.1, regardless of the implemented learning architecture.
Published: 2021
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40. Ear Recognition Based on Deep Unsupervised Active Learning

Author: Yacine Khaldi, Abdeldjalil Ouahabi, Amir Benzaoui, Abdelmalik Taleb-Ahmed, Sébastien Jacques, Université de Bouira, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), U 1016/ UMR 8104 Institut Cochin, Plate-Forme Séquençage et Génomique (Genom'IC), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université Polytechnique Hauts-de-France (UPHF), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), GREMAN (matériaux, microélectronique, acoustique et nanotechnologies) (GREMAN - UMR 7347), Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), COMmunications NUMériques - IEMN (COMNUM - IEMN), INSA Institut National des Sciences Appliquées Hauts-de-France (INSA Hauts-De-France), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), and Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA)
Subjects: Scheme (programming language), AMI dataset, Biometrics, Active learning (machine learning), Computer science, Feature extraction, 02 engineering and technology, Machine learning, computer.software_genre, 01 natural sciences, Facial recognition system, USTB2 dataset, Image (mathematics), [SPI]Engineering Sciences [physics], ear recognition, active learning, 0202 electrical engineering, electronic engineering, information engineering, 0101 mathematics, Electrical and Electronic Engineering, Instrumentation, computer.programming_language, AWE dataset, business.industry, 010102 general mathematics, Process (computing), 020206 networking & telecommunications, GAN, ComputingMethodologies_PATTERNRECOGNITION, Knowledge base, Artificial intelligence, business, computer
Abstract: International audience; Cooperative machine learning has many applications, such as data annotation, where an initial model trained with partially labeled data is used to predict labels for unseen data continuously. Predicted labels with a low confidence value are manually revised to allow the model to be retrained with the predicted and revised data. In this paper, we propose an alternative to this approach: an initial training process called Deep Unsupervised Active Learning. Using the proposed training scheme, a classification model can incrementally acquire new knowledge during the testing phase without manual guidance or correction of decision making. The training process consists of two stages: the first stage of supervised training using a classification model, and an unsupervised active learning stage during the test phase. The labels predicted during the test phase, with high confidence, are continuously used to extend the knowledge base of the model. To optimize the proposed method, the model must have a high initial recognition rate. To this end, we exploited the Visual Geometric Group (VGG16) pre-trained model applied to three datasets: Mathematical Image Analysis (AMI), University of Science and Technology Beijing (USTB2), and Annotated Web Ears (AWE). This approach achieved impressive performance that shows a significant improvement in the recognition rate of the USTB2 dataset by coloring its images using a Generative Adversarial Network (GAN). The obtained performances are interesting compared to the current methods: the recognition rates are 100.00%, 98.33%, and 51.25% for the USTB2, AMI, and AWE datasets, respectively.
Published: 2021
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41. Backtesting Marginal Expected Shortfall and Related Systemic Risk Measures

Author: Christophe Hurlin, Olivier Scaillet, Jeremy Leymarie, Denisa Banulescu Radu, Laboratoire d'Économie d'Orleans [UMR7322] (LEO), Université d'Orléans (UO)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), ANR-16-CE26-0015,MultiRisk,Méthodes Econométriques pour la Modélisation des Risques Multiples(2016), Laboratoire d'Économie d'Orleans (LEO), Université d'Orléans (UO)-Université de Tours (UT), and Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Université d'Orléans (UO)
Subjects: Estimation, Measure (data warehouse), 050208 finance, Actuarial science, business.industry, Strategy and Management, 05 social sciences, Sample (statistics), Management Science and Operations Research, Discount points, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Expected shortfall, Market risk, 0502 economics and business, Independence test, Econometrics, Systemic risk, Economics, Early warning system, 050207 economics, business, Risk management, Statistical hypothesis testing
Abstract: This paper proposes an original approach for backtesting systemic risk measures. This backtesting approach makes it possible to assess the systemic risk measure forecasts used to identify the financial institutions that contribute the most to the overall risk in the financial system. Our procedure is based on simple tests similar to those generally used to backtest the standard market risk measures such as value-at-risk or expected shortfall. We introduce a concept of violation associated with the marginal expected shortfall (MES), and we define unconditional coverage and independence tests for these violations. We can generalize these tests to any MES-based systemic risk measures such as the systemic expected shortfall (SES), the systemic risk measure (SRISK), or the delta conditional value-at-risk ([Formula: see text]CoVaR). We study their asymptotic properties in the presence of estimation risk and investigate their finite sample performance via Monte Carlo simulations. An empirical application to a panel of U.S. financial institutions is conducted to assess the validity of MES, SRISK, and [Formula: see text]CoVaR forecasts issued from a bivariate GARCH model with a dynamic conditional correlation structure. Our results show that this model provides valid forecasts for MES and SRISK when considering a medium-term horizon. Finally, we propose an early warning system indicator for future systemic crises deduced from these backtests. Our indicator quantifies how much is the measurement error issued by a systemic risk forecast at a given point in time which can serve for the early detection of global market reversals. This paper was accepted by Kay Giesecke, finance.
Published: 2021
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42. Quality of evidence of the efficacy of therapeutic interventions on patient-important outcomes in Cochrane's systematic reviews’ abstracts: A survey

Author: Nemat Jaafari, Hélène Vaillant-Roussel, Benoit Tudrej, Denis Pouchain, Elodie Tawil, Caroline Huas, Rémy Boussageon, Christine Maynié-François, Florian Naudet, Collège Universitaire de Médecine Générale [Lyon] (CUMG), Université de Lyon, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Département de Médecine Générale, Université de Poitiers (DMG), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers-Université de Poitiers, 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], Fondation santé des Etudiants de France, Fondation Santé des Etudiants de France, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Tours (UT), AutomédiCation aCcompagnement Pluriprofessionnel PatienT (ACCePPT), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre de Recherches sur la Cognition et l'Apprentissage (CeRCA), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), 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 Tours, and Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Université de Poitiers
Subjects: Evidence-based medicine, medicine.medical_specialty, 030309 nutrition & dietetics, education, Psychological intervention, Placebo, 03 medical and health sciences, 0302 clinical medicine, Intervention (counseling), parasitic diseases, Clinical endpoint, Medicine, Pharmacology (medical), GRADE approach, Intensive care medicine, 0303 health sciences, Cochrane collaboration, business.industry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 030205 complementary & alternative medicine, 3. Good health, Quality of evidence, Patient-important outcome, Systematic review, business
Abstract: International audience; OBJECTIVE: The objective of this study was to evaluate the proportion of therapeutics that have proven their efficacy on patient-important outcomes with a high quality of evidence among Cochrane systematic reviews (SRs). METHODS: We surveyed a random sample of 400 SRs’ abstracts published between September 2012 and December 2015, which compared therapeutic interventions with at least a placebo or no intervention control. The primary endpoint was the proportion of SRs with a statistically significant efficacy on a patient-important outcome and with a high quality of evidence. RESULTS: Among the 400 abstracts surveyed, 32 (8%) found efficacy on a patient-important outcome with a high quality of evidence. Half of the 400 SRs (50.2%) evaluated a pharmacological intervention and 12% of these found efficacy of the intervention on a patient-important outcome with a reported high quality of evidence. CONCLUSION: Based on an analysis of 400 abstracts of SRs from the Cochrane Collaboration, we found that there is a low number of therapeutic interventions which have proven their efficacy on patient-important outcomes with a high quality of evidence.
Published: 2021
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43. Table-ronde sur les Enjeux de la Science Ouverte pour l'archéologie, Colloque MASA (Tours, 2 dec 2022)

Author: Bouiron, Marc, Brissaud, Laurence, Callou, Cécile, Laura, Favreau, Guichard, Vincent, Joffres, Adeline, Rodier, Xavier, Culture et Environnements, Préhistoire, Antiquité, Moyen-Age (CEPAM), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Archéologies d'Orient et d'Occident et Sciences des textes (AOROC), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Musée gallo-romain de Saint-Romain-en-Gal - Vienne, MUSEES DE FRANCE, Bases de données sur la Biodiversité, Ecologie, Environnement et Sociétés (BBEES), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Archéozoologie, archéobotanique : sociétés, pratiques et environnements (AASPE), Musée du Louvre, BIBRACTE EPCC, Huma-Num : la TGIR des humanités numériques (Huma-Num), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Cités, Territoires, Environnement et Sociétés (CITERES), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Maison des Sciences de l'Homme Val de Loire (MSH VL), Université d'Orléans (UO)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Consortium MASA - Mémoires des Archéologues et des Sites Archéologiques (MASA), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Archéologie, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Science Ouverte, [SHS]Humanities and Social Sciences
Abstract: National audience
Published: 2022

44. Dissipative hyperelastic model for highly compressible elastomeric seals

Author: Bour, Manon, Méo, Stéphane, Chalon, Florent, Le Quilliec, Guenhael, Raymond, Matthieu, Picart, Didier, Mécanique des Matériaux et Procédés (MMP), Laboratoire de Mécanique Gabriel Lamé (LaMé), Université d'Orléans (UO)-Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université d'Orléans (UO)-Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), CEA Le Ripault (CEA Le Ripault), Direction des Applications Militaires (DAM), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: [PHYS.MECA.MEMA]Physics [physics]/Mechanics [physics]/Mechanics of materials [physics.class-ph], [PHYS.MECA.STRU]Physics [physics]/Mechanics [physics]/Structural mechanics [physics.class-ph], [PHYS.MECA.SOLID]Physics [physics]/Mechanics [physics]/Solid mechanics [physics.class-ph], [PHYS.MECA.MSMECA]Physics [physics]/Mechanics [physics]/Materials and structures in mechanics [physics.class-ph]
Abstract: International audience
Published: 2022
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45. Les « Bibliotheques françoises » (BibFr) – Avancée de l’indexation de La Croix du Maine et élaboration du modèle de données

Author: Uetani, Toshinori, Porte, Guillaume, Centre d'études supérieures de la Renaissance UMR 7323 (CESR), Ministère de la Culture et de la Communication (MCC)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Bibliothèques Virtuelles Humanistes (BVH), Ministère de la Culture et de la Communication (MCC)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Arts, civilisation et histoire de l'Europe (ARCHE), Université de Strasbourg (UNISTRA), Programme de recherche « Bibliothèques Virtuelles Humanistes », Programe de recherche « Bibliothèques Virtuelles Humanistes », Bibliotheques françoises (Equipex Biblissima, 2012), PROC : 'Pratiques de Référencement dans les Œuvres Composites des XVIe-XVIIe siècles' (AAP Recherche MISHA 2023-2024), ANR-21-ESRE-0005,Biblissima+,Biblissima+, Observatoire des cultures écrites anciennes, de l'argile à l'imprimé(2021), ANR-11-EQPX-0007,BIBLISSIMA,Bibliotheca bibliothecarum novissima : un observatoire du patrimoine écrit du Moyen Âge et de la Renaissance (arabe, français, grec, hébreu, latin)(2011), and European Project: 675570,H2020,H2020-INFRADEV-1-2015-1,HaS-DARIAH(2015)
Subjects: Bibliothèques virtuelles humanistes CESR, Patrimoine écrit, Livres anciens, Bilan, Édition numérique, Notices bio-bibliographiques, Bases de données, XML-TEI, Histoire du Livre, Histoire des Bibliothèques, [SHS]Humanities and Social Sciences
Abstract: International audience
Published: 2022

46. Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece

Author: Arnaud W, Thille, Arnaud, Gacouin, Rémi, Coudroy, Stephan, Ehrmann, Jean-Pierre, Quenot, Mai-Anh, Nay, Christophe, Guitton, Damien, Contou, Guylaine, Labro, Jean, Reignier, Gael, Pradel, Gaëtan, Beduneau, Laurence, Dangers, Clement, Saccheri, Gwénaël, Prat, Guillaume, Lacave, Nicholas, Sedillot, Nicolas, Terzi, Béatrice, La Combe, Jean-Paul, Mira, Antoine, Romen, Marie-Ange, Azais, Anahita, Rouzé, Jérôme, Devaquet, Agathe, Delbove, Martin, Dres, Jeremy, Bourenne, Alexandre, Lautrette, Joe, de Keizer, Stéphanie, Ragot, Jean-Pierre, Frat, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier Victor Dupouy, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Henri Mondor d'Aurillac, Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Groupe de Recherche sur le Handicap Ventilatoire et Neurologique (GRHVN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre Hospitalier Universitaire de Nice (CHU Nice), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier de Versailles André Mignot (CHV), Centre Hospitalier Fleyriat [Bourg en Bresse], CHU Grenoble, Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Groupe Hospitalier Bretagne Sud (GHBS), 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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier de Pau, Centre Hospitalier Loire Vendée Océan, CHU Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Foch [Suresnes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Supported by a grant (18-007) from the Programme Hospitalier de Recherche Clinique National 2018 of the French Ministry of Health., REVA Research Network: Anne Veinstein, Delphine Chatellier, Florence Boissier, Maeva Rodriguez, Céline Deletage, Céline Abonneau, Adel Maamar, Florian Reizine, Jean-Marc Tadie, Charlotte Salmon-Gandonniere, Emmanuelle Mercier, Stefan Mankikian, Pascal Andreu, Marine Jacquier, Marie Labruyère, Dalila Benzekri-Lefevre, Grégoire Muller, Armelle Mathonnet, Nicolas Chudeau, Mickaël Landais, Cédric Darreau, Gaëtan Plantefève, Paul Desaint, Radj Cally, Pierre Oudeville, Valentin Pointurier, Yannick Rabouel, Gauthier Blonz, Maité Agbakou, Thi My-Hue Nguyen, Marie-Hélène Hausermann, Christophe Girault, Dorothée Carpentier, Chloé Combe, Amélie Renou, Jean Dellamonica, Lucas Morand, Pierre Bailly, Christelle Teiten, Marine Paul, Hugo Bellut, Clio Torres, Camille Bouisse, Guillaume Rigault, Louis-Marie Galerneau, Pierre Bouju, Roland Smoning, Driss Laghlam, Morgane Bertrix, Alexandre Massri, Ugo Gouedard, Saad Nseir, Benjamin Zuber, Yannick Fedun, Côme Bureau, Julien Carvelli, Guillaume Gayraud, Quentin Levrat, Emmanuel Vivier, Christophe Leroy, Laurent Argaud, Alexandre Demoule, Gaetan Beduneau, Jean Dellamonica, Claude Guerin, Samir Jaber, Armand Mekontso-Dessap, Alain Mercat, Saad Nseir, Jean Roeseler, Matthieu Schmidt, Nicolas Terzi, Arnaud W Thille, Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), and MORNET, Dominique
Subjects: Positive-Pressure Respiration, [SDV] Life Sciences [q-bio], Recurrence, Respiration, [SDV]Life Sciences [q-bio], Airway Extubation, Humans, General Medicine, Respiratory Insufficiency, Respiration, Artificial, Ventilator Weaning
Abstract: International audience; Background: Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown.Methods: In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were >65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation.Results: A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group).Conclusions: Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.).
Published: 2022
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47. Microbubble-assisted ultrasound for imaging and therapy of melanoma skin cancer: A systematic review

Author: François Avry, Coralie Mousset, Edward Oujagir, Ayache Bouakaz, Valérie Gouilleux-Gruart, Rose-Anne Thépault, Sylvaine Renault, Sylviane Marouillat, Laurent Machet, Jean-Michel Escoffre, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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), and Escoffre, Jean-Michel
Subjects: therapy, Microbubbles, Skin Neoplasms, Acoustics and Ultrasonics, Radiological and Ultrasound Technology, ultrasound, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Biophysics, microbubble, Contrast Media, imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.CAN] Life Sciences [q-bio]/Cancer, drug delivery, Humans, Radiology, Nuclear Medicine and imaging, Melanoma, Ultrasonography
Abstract: International audience; Recent technological developments in ultrasound (US) imaging and ultrasound contrast agents (UCAs) have improved the diagnostic confidence in echography. In the clinical management of melanoma, contrast-enhanced ultrasound (CEUS) imaging complements conventional US imaging (i.e., high-resolution US and Doppler imaging) for clinical examination and therapeutic follow-up. These developments have set into motion the combined use of ultrasound and UCAs as a new modality for drug delivery. This modality, called sonoporation, has emerged as a noninvasive, targeted, and safe method for the delivery of therapeutic drugs into melanoma. This review focuses on the results and prospects of using US and UCAs as dual modalities for CEUS imaging and melanoma treatment.
Published: 2022
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48. An overview of deep learning applications in precocious puberty and thyroid dysfunction

Author: Misbah Razzaq, Frédérique Clément, Romain Yvinec, 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), 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), and 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)
Subjects: thyroid dysfunction, Endocrinology, Diabetes and Metabolism, Thyroid Gland, Puberty, Precocious, deep learning, artificial intelligence, supervised learning, Hormones, precocious puberty, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], endocrinology, Humans, imbalanced data, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; In the last decade, deep learning methods have garnered a great deal of attention in endocrinology research. In this article, we provide a summary of current deep learning applications in endocrine disorders caused by either precocious onset of adult hormone or abnormal amount of hormone production. To give access to the broader audience, we start with a gentle introduction to deep learning and its most commonly used architectures, and then we focus on the research trends of deep learning applications in thyroid dysfunction classification and precocious puberty diagnosis. We highlight the strengths and weaknesses of various approaches and discuss potential solutions to different challenges. We also go through the practical considerations useful for choosing (and building) the deep learning model, as well as for understanding the thought process behind different decisions made by these models. Finally, we give concluding remarks and future directions.
Published: 2022
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49. Low-dose aspirin to prevent preeclampsia and growth restriction in nulliparous women identified by uterine artery Doppler as at high risk of preeclampsia: A double blinded randomized placebo-controlled trial

Author: Diguisto, Caroline, Le Gouge, Amelie, Marchand, Marie-Sara, Megier, Pascal, Ville, Yves, Haddad, Georges, Winer, Norbert, Arthuis, Chloé, Doret, Muriel, Debarge, Veronique Houfflin, Flandrin, Anaig, Delmas, Hélène Laurichesse, Gallot, Denis, Mares, Pierre, Vayssiere, Christophe, Sentilhes, Loïc, Cheve, Marie-Therese, Paumier, Anne, Durin, Luc, Schaub, Bruno, Equy, Veronique, Giraudeau, Bruno, Perrotin, Franck, 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), Maternité Olympe de Gouges [CHRU Tours], 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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), CHU Lille, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Clermont-Ferrand, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aix-Marseille Université - École de maïeutique (AMU SMPM EM), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Le Mans (CH Le Mans), Polyclinique de l’Atlantique, Partenaires INRAE, Elsan Polyclinique du Parc - Caen, CHU de la Martinique [Fort de France], CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, and Université de Tours (UT)
Subjects: Male, Uterine Artery, Pregnancy Trimester, First, Multidisciplinary, Pre-Eclampsia, Aspirin, Pregnancy, [SDV]Life Sciences [q-bio], Infant, Newborn, Humans, Birth Weight, Female
Abstract: Introduction This trial evaluates whether daily low-dose aspirin initiated before 16 weeks of gestation can reduce preeclampsia and fetal growth restriction in nulliparous women identified by first-trimester uterine artery Dopplers as at high risk of preeclampsia. Methods This randomized, blinded, placebo-controlled, parallel-group trial took place in 17 French obstetric departments providing antenatal care. Pregnant nulliparous women aged ≥ 18 years with a singleton pregnancy at a gestational age < 16 weeks of gestation with a lowest pulsatility index ≥ 1.7 or a bilateral protodiastolic notching for both uterine arteries on an ultrasound performed between 11+0 and 13+6 weeks by a certified sonographer were randomized at a 1:1 ratio to 160 mg of low-dose aspirin or to placebo to be taken daily from inclusion to their 34th week of gestation. The main outcome was preeclampsia or a birthweight ≤ 5th percentile. Other outcomes included preeclampsia, severe preeclampsia, preterm preeclampsia, preterm delivery before 34 weeks, mode of delivery, type of anesthesia, birthweight ≤ 5th percentile and perinatal death. Results The trial was interrupted due to recruiting difficulties. Between June 2012 and June 2016, 1104 women were randomized, two withdrew consent, and two had terminations of pregnancies. Preeclampsia or a birthweight ≤ 5th percentile occurred in 88 (16.0%) women in the low-dose aspirin group and in 79 (14.4%) in the placebo group (proportion difference 1.6 [-2.6; 5.9] p = 0.45). The two groups did not differ significantly for the secondary outcomes. Conclusion Low-dose aspirin was not associated with a lower rate of either preeclampsia or birthweight ≤ 5th percentile in women identified by their first-trimester uterine artery Doppler as at high risk of preeclampsia. Trial registration (NCT0172946).
Published: 2022
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50. Outcomes after allogeneic hematopoietic stem cell transplantation for adults with primary mediastinal B cell lymphoma: a SFGM-TC and LYSA study

Author: Baptiste Le Calvez, Benoit Tessoullin, Loïc Renaud, Carmen Botella-Garcia, Micha Srour, Steven Le Gouill, Gaelle Guillerm, Rémy Gressin, Stéphanie Nguyen Quoc, Sabine Furst, Adrien Chauchet, David Sibon, Philippe Lewalle, Xavier Poiré, Natacha Maillard, Alban Villate, Michael Loschi, Jérôme Paillassa, Yves Beguin, Rémy Dulery, Jean-Jacques Tudesq, Amandine Fayard, Marie C. Béné, Vincent Camus, Patrice Chevallier, Amandine Le Bourgeois, Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez [Lille], CHU Lille, Université de Lille, Institut Curie [Paris], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire [Grenoble] (CHU), 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 Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Cliniques universitaires St Luc [Bruxelles], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Laboratoire d'Hematologie [CHU Nantes], and Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Adult, Lymphoma, B-Cell, Oncology, Recurrence, [SDV]Life Sciences [q-bio], Remission Induction, Hematopoietic Stem Cell Transplantation, Humans, Graft vs Host Disease, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine, Retrospective Studies
Abstract: Background: Despite therapeutic progress, 10 to 30% of adult patients with primary mediastinal B cell lymphoma (PMBCL) are primary refractory or experience early relapse (R/R). Allogeneic stem cell transplantation (allo-HSCT) thus remains a potentially curative option in this setting. Material and Methods: In this multicenter retrospective study, the outcomes of 33 French and Belgian adult patients allo-transplanted for R/R PMBCL between January 1999 and December 2018, were examined. Results: At allo-HSCT time, patients had received a median of 3 treatment lines, 50% of them were in complete response, 40% in partial response and 10% had a progressive disease. Forty-two percent of the donors were siblings and 39% matched related. The median follow-up for alive patients was 78 months (3.5-157). Considering the whole cohort, 2-year overall survival (OS), progression free survival (PFS) and graft-versus-host disease-free/relapse-free survival (GRFS) were 48% (95%CI: 33-70), 47% (95%CI: 33-68) and 38.5% (95%CI: 25-60) respectively. Cumulative incidence of relapse and non-relapse mortality rates were respectively 34% (95%CI: 18-50) and 18% (95%CI: 7-34). Disease status at transplant was the only factor predicting survivals, patients with progressive disease showing significant lower 2-year PFS (HR: 6.12, 95%CI: 1.32-28.31, p = 0.02) and OS (HR: 7.04, 95%CI: 1.52-32.75, p = 0.013). A plateau was observed for OS and PFS after 4 years with 10 patients alive after this date, suggesting that almost one third of the patients effectively salvaged and undergoing allo-SCT could be cured. Conclusion: This study indicates that allo-HSCT is a valid therapeutic option for R/R PMBCL, providing durable remissions.
Published: 2022
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