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1. French recommendations for the diagnosis and management of lymphangioleiomyomatosis

Author: Vincent Cottin, Elodie Blanchard, Mallorie Kerjouan, Romain Lazor, Martine Reynaud-Gaubert, Camille Taille, Yurdagül Uzunhan, Lidwine Wemeau, Claire Andrejak, Dany Baud, Philippe Bonniaud, Pierre-Yves Brillet, Alain Calender, Lara Chalabreysse, Isabelle Court-Fortune, Nicolas Pierre Desbaillets, Gilbert Ferretti, Anne Guillemot, Laurane Hardelin, Marianne Kambouchner, Violette Leclerc, Mathieu Lederlin, Marie-Claire Malinge, Alain Mancel, Sylvain Marchand-Adam, Jean-Michel Maury, Jean-Marc Naccache, Mouhamad Nasser, Hilario Nunes, Gaële Pagnoux, Grégoire Prévot, Christine Rousset-Jablonski, Olivier Rouviere, Salim Si-Mohamed, Renaud Touraine, Julie Traclet, Ségolène Turquier, Stéphane Vagnarelli, Kaïs Ahmad, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Assistance Publique - Hôpitaux de Marseille (APHM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Plateforme F-CRIN, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Hôpital Avicenne [AP-HP], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, EA3920 University of Burgundy Franche-Comté Besançon, Equipe CADIR (LNC - U1231), 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)-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), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Centre pour l'innovation en cancérologie de Lyon (CICLY), Université de Lyon-Université de Lyon, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Centre Hospitalier Universitaire [Grenoble] (CHU)
Subjects: Pulmonary and Respiratory Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BackgroundThe present article is an English-language version of the French National Diagnostic and Care Protocol, a pragmatic tool to optimize and harmonize the diagnosis, care pathway, management and follow-up of lymphangioleiomyomatosis in France.MethodsPractical recommendations were developed in accordance with the method for developing a National Diagnosis and Care Protocol for rare diseases of the Haute Autorité de Santé and following international guidelines and literature on lymphangioleiomyomatosis. It was developed by a multidisciplinary group, with the help of patient representatives and of RespiFIL, the rare disease network on respiratory diseases.ResultsLymphangioleiomyomatosis is a rare lung disease characterised by a proliferation of smooth muscle cells that leads to the formation of multiple lung cysts. It occurs sporadically or as part of a genetic disease called tuberous sclerosis complex (TSC). The document addresses multiple aspects of the disease, to guide the clinicians regarding when to suspect a diagnosis of lymphangioleiomyomatosis, what to do in case of recurrent pneumothorax or angiomyolipomas, what investigations are needed to make the diagnosis of lymphangioleiomyomatosis, what the diagnostic criteria are for lymphangioleiomyomatosis, what the principles of management are, and how follow-up can be organised. Recommendations are made regarding the use of pharmaceutical specialties and treatment other than medications.ConclusionThese recommendations are intended to guide the diagnosis and practical management of pulmonary lymphangioleiomyomatosis.
Published: 2023
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2. A recurrent ZP1 variant is responsible for oocyte maturation defect with degenerated oocytes in infertile females

Author: Corinne Loeuillet, Magali Dhellemmes, Caroline Cazin, Zine‐Eddine Kherraf, Selima Fourati Ben Mustapha, Raoudha Zouari, Nicolas Thierry‐Mieg, Christophe Arnoult, Pierre F. Ray, Thierry-Mieg, Nicolas, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Grenoble, Clinique de Promotion des Sciences de la Reproduction [Tunis] (CPSR), Polyclinique les Jasmins [Tunis], Modèles et Algorithmes pour la Génomique (TIMC-MAGe), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), 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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), and Centre Hospitalier Universitaire [Grenoble] (CHU)
Subjects: [SDV.BDD.GAM] Life Sciences [q-bio]/Development Biology/Gametogenesis, zona pellucida, Zona Pellucida Glycoproteins, Cohort Studies, Oogenesis, Tubulin, Exome Sequencing, Genetics, Humans, oocytes, Female, OMD, infertility, Infertility, Female, [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis, Genetics (clinical)
Abstract: International audience; A female factor is present in approximately 70% of couple infertility, often due to ovulatory disorders. In oocyte maturation defect (OMD), affected patients have a primary infertility with normal menstrual cycles but produce no oocyte, degenerated (atretic) or abnormal oocytes blocked at different stages of maturation. Four genes have so far been associated with OMD: PATL2, TUBB8, WEE2, and ZP1. In our initial study, 6 out of 23 OMD subjects were shown to carry the same PATL2 homozygous loss of function variant and one patient had a TUBB8 truncating variant. Here, we included four additional OMD patients and reanalyzed all 27 subjects. In addition to the seven patients with a previously identified defect, five carried the same deleterious homozygous ZP1 variant (c.1097G>A; p.Arg366Gln). All the oocytes from ZP1-associated patients appeared shriveled and dark indicating that the abnormal ZP1 protein induced oocyte death and degeneration. Overall ZP1-associated patients had degenerated or absent oocytes contrary to PATL2-associated subjects who had immature oocytes blocked mainly at the germinal vesicle stage. In this cohort of North African OMD patients, whole exome sequencing permitted to diagnose 44% of the patients studied and to identify a new frequent ZP1 variant.
Published: 2022
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3. Exposure to a mixture of non-persistent environmental chemicals and neonatal thyroid function in a cohort with improved exposure assessment

Author: Ophélie Coiffier, Dorothy Nakiwala, Matthieu Rolland, Andres Malatesta, Sarah Lyon-Caen, Benoît Chovelon, Patrice Faure, Anne Sophie Gauchez, Dorra Guergour, Amrit K. Sakhi, Azemira Sabaredzovic, Cathrine Thomsen, Isabelle Pin, Rémy Slama, Christelle Corne, Claire Philippat, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut de Biologie et de Pathologie [CHU Grenoble] (IBP), Norwegian Institute of Public Health [Oslo] (NIPH), Centre Hospitalier Universitaire [Grenoble] (CHU), and Coiffier, Ophélie
Subjects: [SDE] Environmental Sciences, Phthalates, Thyroid hormones, [SDE]Environmental Sciences, Mixture, Parabens, Bisphenols, DINCH, Heel-prick blood spot, General Environmental Science
Abstract: International audience; Background: In vitro and toxicological studies have shown that non-persistent environmental chemicals can perturb thyroid hormone homeostasis. Epidemiological studies with improved exposure assessment (i.e., repeated urine samples) are needed to evaluate effects of these compounds, individually or as a mixture, in humans. We studied the associations between prenatal exposure to non-persistent environmental chemicals and neonatal thyroid hormones.Methods: The study population consisted of 442 mother–child pairs from the French SEPAGES mother–child cohort recruited between July 2014 and July 2017. For each participant, four parabens, five bisphenols, tri- closan, triclocarban, benzophenone-3 as well as metabolites of phthalates and of di(isononyl)cyclohexane-1,2- dicarboxylate were assessed in two pools of repeated urine samples (median: 21 spot urines per pool), collected in the 2nd and 3rd trimesters of pregnancy, respectively. Thyroid stimulating hormone (TSH) and total thyroxine (T4) levels were determined in newborns from a heel-prick blood spot. Maternal iodine and selenium were assessed in urine and serum, respectively. Adjusted linear regression (uni-pollutant model) and Bayesian Kernel Machine Regression (BKMR, mixture model) were applied to study overall and sex-stratified associations between chemicals and hormone concentrations.Results: Interaction with child sex was detected for several compounds. Triclosan, three parabens, and one phthalate metabolite (OH-MPHP) were negatively associated with T4 among girls in the uni-pollutant model. BKMR also suggested a negative association between the mixture and T4 in girls, whereas in boys the association was positive. The mixture was not linked to TSH levels, and for this hormone the uni-pollutant model revealed associations with only a few compounds.Conclusion: Our study, based on repeated urine samples to assess exposure, showed that prenatal exposure to some phenols and phthalates disturb thyroid hormone homeostasis at birth. Furthermore, both uni-pollutant and mixture models, suggested effect modification by child sex, while, to date underlying mechanisms for such sex-differences are not well understood.
Published: 2023
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4. The melanoma tumor glyco-code impacts human dendritic cells’ functionality and dictates clinical outcomes

Author: Sosa Cuevas, Eleonora, Roubinet, Benoît, Mouret, Stephane, Thépaut, Michel, de Fraipont, Florence, Charles, Julie, Fieschi, Franck, Landemarre, Ludovic, Chaperot, Laurence, Aspord, Caroline, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), GLYcoDiag, CHU Grenoble, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)
Subjects: glycan, MESH: Humans, MESH: Dendritic Cells, MESH: Melanoma, [SDV]Life Sciences [q-bio], Immunology, immune subversion, MESH: Glycosylation, MESH: Male, human DC subsets, MESH: Lectins, MESH: Polysaccharides, melanoma, lectin, Immunology and Allergy
Abstract: International audience; Subversion of immunity is a hallmark of cancer development. Dendritic cells (DCs) are strategic immune cells triggering anti-tumor immune responses, but tumor cells exploit their versatility to subvert their functions. Tumor cells harbor unusual glycosylation patterns, which can be sensed through glycan-binding receptors (lectins) expressed by immune cells that are crucial for DCs to shape and orientate antitumor immunity. Yet, the global tumor glyco-code and its impact on immunity has not been explored in melanoma. To decrypt the potential link between aberrant glycosylation patterns and immune evasion in melanoma, we investigated the melanoma tumor glyco-code through the GLYcoPROFILE™ methodology (lectin arrays), and depicted its impact on patients’ clinical outcome and DC subsets’ functionality. Specific glycan patterns correlated with clinical outcome of melanoma patients, GlcNAc, NeuAc, TF-Ag and Fuc motifs being associated with poor outcome, whereas Man and Glc residues elicited better survival. Strikingly, tumor cells differentially impacting cytokine production by DCs harbored distinct glyco-profiles. GlcNAc exhibited a negative influence on cDC2s, whereas Fuc and Gal displayed inhibitory impacts on cDC1s and pDCs. We further identified potential booster glycans for cDC1s and pDCs. Targeting specific glycans on melanoma tumor cells restored DCs’ functionality. The tumor glyco-code was also linked to the nature of the immune infiltrate. This study unveils the impact of melanoma glycan patterns on immunity, and paves the way for innovative therapeutic options. Glycans/lectins interactions arise as promising immune checkpoints to rescue DCs from tumor’ hijacking to reshape antitumor immunity and inhibit immunosuppressive circuits triggered by aberrant tumor glycosylation.
Published: 2023
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5. Force tuning through regulation of clathrin-dependent integrin endocytosis

Author: Alexander Kyumurkov, Anne-Pascale Bouin, Mathieu Boissan, Sandra Manet, Francesco Baschieri, Mathilde Proponnet-Guerault, Martial Balland, Olivier Destaing, Myriam Régent-Kloeckner, Claire Calmel, Alice Nicolas, François Waharte, Philippe Chavrier, Guillaume Montagnac, Emmanuelle Planus, Corinne Albiges-Rizo, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Dynamique des cellules tumorales (UMR1279), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Minatec, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ANR-17-CE13-0022,CODECIDE,Coincidence de detection dans l'identité cellulaire(2017), Chavrier, Philippe, Coincidence de detection dans l'identité cellulaire - - CODECIDE2017 - ANR-17-CE13-0022 - AAPG2017 - VALID, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Didactique André Revuz (LDAR (URP_4434)), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Lille-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris Cité (UPCité)-CY Cergy Paris Université (CY), Laboratoire des technologies de la microélectronique (LTM ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), BioImaging Cell and Tissue Core Facility (PICT-IBiSA), Institut Curie [Paris], Centre de recherche de l'Institut Curie [Paris], Dynamique moléculaire de la transformation hématopoïétique (Dynamo), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Talin, [SDV] Life Sciences [q-bio], Focal Adhesions, Integrin beta1, [SDV]Life Sciences [q-bio], Integrin beta3, Cell Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mechanotransduction, Cellular, Clathrin, Endocytosis
Abstract: International audience; Integrin endocytosis is essential for many fundamental cellular processes. Whether and how the internalization impacts cellular mechanics remains elusive. Whereas previous studies reported the contribution of the integrin activator, talin, in force development, the involvement of inhibitors is less documented. We identified ICAP-1 as an integrin inhibitor involved in mechanotransduction by co-working with NME2 to control clathrin-mediated endocytosis of integrins at the edge of focal adhesions (FA). Loss of ICAP-1 enables β3-integrin-mediated force generation independently of β1 integrin. β3-integrin-mediated forces were associated with a decrease in β3 integrin dynamics stemming from their reduced diffusion within adhesion sites and slow turnover of FA. The decrease in β3 integrin dynamics correlated with a defect in integrin endocytosis. ICAP-1 acts as an adaptor for clathrin-dependent endocytosis of integrins. ICAP-1 controls integrin endocytosis by interacting with NME2, a key regulator of dynamin-dependent clathrin-coated pits fission. Control of clathrin-mediated integrin endocytosis by an inhibitor is an unprecedented mechanism to tune forces at FA.
Published: 2023
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6. Sleep characterization with smart wearable devices

Author: Mathias Baumert, Martin R Cowie, Susan Redline, Reena Mehra, Michael Arzt, Jean-Louis Pépin, Dominik Linz, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H08 Experimental atrial fibrillation, SALAS, Danielle, University of Adelaide, King‘s College London, Royal Brompton Hospital, Brigham and Women's Hospital [Boston], Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Cleveland Clinic, University Hospital Regensburg, Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Laboratoire d’EFCR [Grenoble], Pôle Thorax et Vaisseaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre Hospitalier Universitaire [Grenoble] (CHU), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Radboud University Medical Center [Nijmegen], and University of Copenhagen = Københavns Universitet (UCPH)
Subjects: MEDICINE, [SDV]Life Sciences [q-bio], ARTIFICIAL-INTELLIGENCE, Reproducibility of Results, GUIDELINES, sleep apnea, [SDV] Life Sciences [q-bio], Wearable Electronic Devices, VARIABILITY, wearables, Physiology (medical), APNEA, AMERICAN ACADEMY, Humans, DIAGNOSTIC-ACCURACY, Neurology (clinical), POLYSOMNOGRAPHY, sleep, MONITORS
Abstract: The general public increasingly adopts smart wearable devices to quantify sleep characteristics and dedicated devices for sleep assessment. The rapid evolution of technology has outpaced the ability to implement validation approaches and demonstrate relevant clinical applicability. There are untapped opportunities to validate and refine consumer devices in partnership with scientists in academic institutions, patients, and the private sector to allow effective integration into clinical management pathways and facilitate trust in adoption once reliability and validity have been demonstrated. We call for the formation of a working group involving stakeholders from academia, clinical care and industry to develop clear professional recommendations to facilitate appropriate and optimized clinical utilization of such technologies.
Published: 2022
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7. Efficacy and safety of prostate artery embolization for patients with lower urinary tract symptoms and indwelling urinary catheter: A retrospective multicenter study

Author: Julien Frandon, Asmaa Belaouni, Olivier Pellerin, Nicolas Thiounn, Chris Serrand, Stéphane Droupy, François Petitpierre, Hélène Vernhet-Kovacsik, Thibaut Murez, Vincent Vidal, Julien Ghelfi, Gaele Pagnoux, Ricardo Codas, Hélène de Forges, Jean-Paul Beregi, Marc Sapoval, Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Interventionnelle Expérimentale (LIIE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL), Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), and Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)
Subjects: Male, MESH: Catheters, Indwelling, Urinary Catheters, MESH: Prostate, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Catheters, Indwelling, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Radiology, Nuclear Medicine and imaging, Lower urinary tract symptoms, MESH: Arteries, Aged, Retrospective Studies, MESH: Aged, MESH: Lower Urinary Tract Symptoms / therapy, Benign prostatic hyperplasia, MESH: Humans, MESH: Middle Aged, Radiological and Ultrasound Technology, Prostate, MESH: Urinary Catheters, MESH: Quality of Life, MESH: Retrospective Studies, General Medicine, Arteries, Middle Aged, MESH: Lower Urinary Tract Symptoms / etiology, MESH: Male, Prostatic artery embolization, Quality of Life, MESH: Urinary Catheterization, Urinary Catheterization, Predictive factors
Abstract: International audience; Purpose: the purpose of this multicenter study was to evaluate the clinical success at three months of prostate artery embolization (PAE), assess PAE safety in centers with various experiences and identify factors associated with PAE success.Patients and methods: this multicenter, retrospective study included patients who underwent PAE for lower urinary tract symptoms (LUTS) including those with indwelling urinary catheter. PAE clinical success was defined as either 25% improvement of the International Prostate Symptom Score (IPSS) or 1-point improvement of quality of life (QoL) score, or catheter removal at three months. Multivariable analyses were performed using a logistic regression adjusted on patient variables, technical parameters and center experience in PAE.Results: a total of 383 men (mean age, 68.4±9.7 [standard deviation] years; range: 46-94) with LUTS, including 99 (25.8%) patients with indwelling urinary catheter, were included in seven centers from January 2017 to March 2019. Five patients reported major complications (1.3%), three (0.8%) penile ulceration, three (0.8%) acute urinary retention, one (0.3%) prostatic abscess, and 56 (14.6%) minor complications. Follow up data were available for 271 patients (center 1: n= 159; other centers: n= 112). Clinical success was reported in 232 patients (85.6%). In multivariable analyses, presence of cardiovascular comorbidities (diabetes, stroke history, myocardial infarction and lower limb artery disease) was the single independent variable inversely associated with PAE clinical success (odds ratio= 0.396; 95% confidence interval: 0.17-0.91; P= 0.029). There was no center effect.Conclusion: our results show that PAE is safe and effective in centers with various PAE experiences. Cardiovascular comorbidity is the single independent variable associated with PAE failure.
Published: 2022
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8. The combined detection of Amphiregulin, Cyclin A1 and DDX20/Gemin3 expression predicts aggressive forms of oral squamous cell carcinoma

Author: Bourova-Flin, Ekaterina, Derakhshan, Samira, Goudarzi, Afsaneh, Wang, Tao, Vitte, Anne-Laure, Chuffart, Florent, Khochbin, Saadi, Rousseaux, Sophie, Aminishakib, Pouyan, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Iran University of Medical Sciences [Tehran, Iran] (IUMS), Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University, Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Khochbin, Saadi
Subjects: Male, Sequence Analysis, RNA, Squamous Cell Carcinoma of Head and Neck, [SDV]Life Sciences [q-bio], Gene Expression Profiling, Amphiregulin, Article, [SDV] Life Sciences [q-bio], stomatognathic diseases, DEAD Box Protein 20, Cell Line, Tumor, Biomarkers, Tumor, Data Mining, Humans, Female, Mouth Neoplasms, Neoplasm Invasiveness, Cyclin A1, Biomarkers, Cancer, Neoplasm Staging, Oligonucleotide Array Sequence Analysis, Retrospective Studies
Abstract: International audience; BACKGROUND: Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programmes. A specifically designed strategy was applied to oral squamous cell carcinomas (OSCC) in order to detect ectopic gene activations and develop a prognostic stratification test. METHODS: A dedicated original prognosis biomarker discovery approach was implemented using genome-wide transcriptomic data of OSCC, including training and validation cohorts. Abnormal expressions of silent genes were systematically detected, correlated with survival probabilities and evaluated as predictive biomarkers. The resulting stratification test was confirmed in an independent cohort using immunohistochemistry. RESULTS: A specific gene expression signature, including a combination of three genes, AREG, CCNA1 and DDX20, was found associated with high-risk OSCC in univariate and multivariate analyses. It was translated into an immunohistochemistry-based test, which successfully stratified patients of our own independent cohort. DISCUSSION: The exploration of the whole gene expression profile characterising aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Experimental targeting of CCNA1 in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting that CCNA1 could be a good target for therapeutic approaches.
Published: 2021
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9. Long-term air pollution exposure, greenspace and health-related quality of life in the ECRHS study

Author: Anne, Boudier, Iana, Markevych, Bénédicte, Jacquemin, Michael J, Abramson, Simone, Accordini, Bertil, Forsberg, Elaine, Fuertes, Judith, Garcia-Aymerich, Joachim, Heinrich, Ane, Johannessen, Bénédicte, Leynaert, Isabelle, Pin, Valérie, Siroux, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Grenoble, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Monash university, Università degli studi di Verona = University of Verona (UNIVR), Umeå University, Imperial College London, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Ludwig-Maximilians University [Munich] (LMU), University of Bergen (UiB), 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, Centre Hospitalier Universitaire [Grenoble] (CHU), The present analyses are part of the NEVADA project funded by the French Direction Générale de l'Offre de Soin (DGOS), call PHRC-2012.The local investigators and funding agencies for the European Community Respiratory Health Survey (ECRHS I, ECRHS II and ECRHS III) are reported in the online supplementary file.Coordination of the ECRHS I was supported by the European Commission as part of the 'Quality of Life' program and the authors and participants are grateful to the late C. Baya and M. Hallen for their help during the study and K. Vuylsteek and the members of the COMAC for their support. Coordination of the ECRHS II was supported by the European Commission as part of the 'Quality of Life' program (Grant: QLK4-CT-1999-01237). The coordination of the ECRHS 3 was funded through the Medical Research Council (Grant: 92091). NDVI calculations were conducted within the framework of the Ageing Lungs In European Cohorts study that was funded by the European Union's Horizon 2020 research and innovation program under (Grant: 633212). Iana Markevych is currently supported from the 'NeuroSmog: Determining the impact of air pollution on the developing brain' (Nr. POIR.04.04.00-1763/18-00) which is implemented as part of the TEAM-NET programme of the Foundation for Polish Science, co-financed from EU resources, obtained from the European Regional Development Fund under the Smart Growth Operational Programme. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the 'Centro de Excelencia Severo Ochoa 2019–2023' Program (CEX2018-000806-S), and the Generalitat de Catalunya through the CERCA Program., and Jonchère, Laurent
Subjects: Adult, Male, Environmental Engineering, greenness, PM, Epidemiology, Parks, Recreational, [SDV]Life Sciences [q-bio], Nitrogen Dioxide, Well-being, NO(2), NO2, rhinitis, well-being, Air Pollution, Humans, Environmental Chemistry, European Union, Waste Management and Disposal, Rhinitis, Air Pollutants, asthma, greenness, NO2, PM, well-being, Environmental Exposure, asthma, Health Surveys, Pollution, Asthma, [SDV] Life Sciences [q-bio], Greenness, Quality of Life, Female, Particulate Matter, epidemiology
Abstract: International audience; BACKGROUND: Associations of long-term exposure to air pollution and greenspace with health-related quality of life (HRQOL) are poorly studied and few studies have accounted for asthma-rhinitis status. OBJECTIVE: To assess the associations of air pollution and greenspace with HRQOL and whether asthma and/or rhinitis modify these associations. METHODS: The study was based on the participants in the second (2000-2002, n = 6542) and third (2011-2013, n = 3686) waves of the European Community Respiratory Health Survey (ECRHS) including 19 centres. The mean follow-up time was 11.3 years. HRQOL was assessed by the SF-36 Physical and Mental Component Summary scores (PCS and MCS). NO(2), PM(2.5) and PM(10) annual concentrations were estimated at the residential address from existing land-use regression models. Greenspace around the residential address was estimated by the (i) mean of the Normalized Difference Vegetation Index (NDVI) and by the (ii) presence of green spaces within a 300 m buffer. Associations of each exposure variable with PCS and MCS were assessed by mixed linear regression models, accounting for the multicentre design and repeated data, and adjusting for potential confounders. Analyses were stratified by asthma-rhinitis status. RESULTS: The mean (SD) age of the ECRHS-II and III participants was 43 (7.1) and 54 (7.2) years, respectively, and 48 % were men. Higher NO(2), PM(2.5) and PM(10) concentrations were associated with lower MCS (regression coefficients [95%CI] for one unit increase in the inter-quartile range of exposures were -0.69 [-1.23; -0.15], -1.79 [-2.88; -0.70], -1.80 [-2.98; -0.62] respectively). Higher NDVI and presence of forests were associated with higher MCS. No consistent associations were observed for PCS. Similar association patterns were observed regardless of asthma-rhinitis status. CONCLUSION: European adults who resided at places with higher air pollution and lower greenspace were more likely to have lower mental component of HRQOL. Asthma or rhinitis status did not modify these associations.
Published: 2022
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10. Impact of OSA primary therapy on antihypertensive drugs use

Author: Bruno Revol, Christel Castelli, Marie Joyeux-Faure, Jean-Louis Pépin, Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Laboratoire d’EFCR [Grenoble], Pôle Thorax et Vaisseaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre Hospitalier Universitaire [Grenoble] (CHU), Centre régional de pharmacovigilance de Grenoble [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Clinique Médicale Beausoleil, Dynamiques du droit (DD), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and SALAS, Danielle
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Physiology (medical), Neurology (clinical)
Abstract: International audience; No abstract available
Published: 2022
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11. Validation of the new 2021 EASL algorithm for the noninvasive diagnosis of advanced fibrosis in NAFLD

Author: Clémence M. Canivet, Charlotte Costentin, Katharina M. Irvine, Adèle Delamarre, Adrien Lannes, Nathalie Sturm, Frederic Oberti, Preya J. Patel, Thomas Decaens, Marie Irles‐Depé, Isabelle Fouchard, Paul Hermabessière, Marine Roux, Justine Barthelon, Paul Calès, Elizabeth E. Powell, Victor de Ledinghen, Jérôme Boursier, Département d'hépatologie (CHU Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), PRES Université Nantes Angers Le Mans (UNAM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches Cliniques de Montréal (IRCM), Université de Montréal (UdeM), Clinique Universitaire d'Hépato-Gastroentérologie, and CHU Grenoble
Subjects: Hepatology, [SDV]Life Sciences [q-bio]
Abstract: The European Association for the Study of the Liver (EASL) has recently proposed an algorithm for the diagnosis of advanced liver fibrosis. We aimed to evaluate the diagnostic accuracy of this algorithm in nonalcoholic fatty liver disease (NAFLD).One thousand fifty-one patients with NAFLD, liver biopsy, and four noninvasive tests (NITs; Fibrosis-4 [FIB4], vibration controlled transient elastography [VCTE], FibroMeter, Fibrotest) were included. The enhanced liver fibrosis (ELF) score was available in 396 patients. A cohort of 230 patients from primary care/diabetes clinics had FIB4, VCTE, and ELF. Compared with the performance of single NITs, agreement between two NITs (FIB4 and VCTE, VCTE and patented serum tests) increased specificity and positive predictive value by 20%, thus justifying the sequential use proposed in the EASL algorithm. The FIB4/VCTE/FibroMeter and FIB4/VCTE/Fibrotest algorithms performed similarly, providing 85% diagnostic accuracy and a liver biopsy requirement rate of only 10%. The FIB4/VCTE/ELF algorithm performed similarly in the subgroup where ELF was available. Simulations of algorithm accuracies at different prevalence showed that positive predictive values rapidly increased, reaching a plateau above 75% starting at 15% prevalence. Negative predictive values remained higher than 90% up to 25% prevalence. The rate of liver biopsy requirement remained stable, increasing by only 5% between low and high prevalence settings. When the EASL algorithm was applied in the primary care/diabetes clinic cohort, liver biopsy requirement was only 3%, and the agreement among the three steps provided 75% positive predictive value.Our study validates the algorithm proposed by the EASL in its latest 2021 guidelines for the diagnosis of advanced fibrosis in the setting of NAFLD.
Published: 2022
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12. 10q26 deletion syndrome: a French cohort study

Author: Thorn, Hugo, Odent, Sylvie, Levy, Jonathan, Tabet, Anne-Claude, Thevenon, Julien, Caignec, Cedric Le, Schaefer, Elise, Frebourg, Thierry, Schluth-Bolard, Caroline, Plutino, Morgane, Chehadeh, Salima El, Philippe, Anais, Scheidecker, Sophie, Calmels, Nadege, Schalk, Audrey, Goldenberg, Alice, Guerot, Anne-Marie, Meur, Nathalie Le, Cassinari, Kevin, Ruaud, Lyse, Rachid, Myriam, Januel, Louis, Bonnet-Dupeyron, Marie-Noëlle, Carneiro, Maryline, Bieth, Eric, Plaisancie, Julie, Coutton, Charles, Harbuz, Radu, Dieterich, Klaus, Nadeau, Gwenaël, Vieville, Gaelle, Fradin, Melanie, Poirsier, Celine, Spodenkiewicz, Marta, Landais, Emilie, Doco-Fenzy, Martine, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Grenoble, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Rouen, Normandie Université (NU), Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre hospitalier de Valence, Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Métropole Savoie [Chambéry], CHU Pontchaillou [Rennes], SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA), Wiener Medizinische Akademie GmbH, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), CHU Toulouse [Toulouse], and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; 10q26 deletion syndrome (OMIM #609625) is a rare autosomal dominant genetic disorder with about 100 patients reported. Most cases are sporadic. Global development delay, short stature, microcephaly and typical facial appearance with triangular face, large forehead, low-set malformed ears, hypertelorism, prominent nose and a thin vermilion of the upper lip constitute the main clinical features. The clinical spectrum is very heterogeneous and neurobehavioral manifestations, deafness, limb malformations, cardiac and urogenital abnormalities can be associated. Thus, patients with 10q26 chromosomal deletion need multidisciplinary management strategies from birth. One of the main reasons for this heterogeneity is the variety of 10qter region chromosomal deletions summarized into the “10q26 deletion syndrome”. Various studies proposed critical regions to explain the main phenotype (Yatzenko et al., 2009; Choucair et al., 2015; Lin S et al., 2016) or more specific features (Vera-Carbonell et al., 2015; Choucair et al., 2015). In addition, these studies proposed about 20 genes of interest such as DOCK1 and FGFR2 to explain the different clinical features observed. We report a French ACLF cohort of 35 patients from 9 centers presenting 10q26 complete or partial deletions (size: 64kb to 12.5Mb), complex chromosomal rearrangement and derivative chromosomes diagnosed using DNA-array, to bring a further insight of the genotype/phenotype correlation.
Published: 2022
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13. ERRα Expression in Bone Metastases Leads to an Exacerbated Antitumor Immune Response

Author: Soumaya El-Moghrabi, Martine Duterque-Coquillaud, Alexandra Lainé, Philippe Clézardin, Sandra Geraci, Cyril Boyault, Casina W.S. Kan, Emmanuelle Meugnier, Lamia Bouazza, Julien C. Marie, Yuji Yoshiko, Hector Hernandez-Vargas, Edith Bonnelye, Mathilde Proponnet-Guerault, Claire Benetollo, Mathilde Bouchet, Inflammasome NLRP3 – NLRP3 Inflammasome, 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)-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 Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Régulations métaboliques, nutrition et diabètes (RMND), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Institut de biologie de Lille - UMS 3702 (IBL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), ANR-10-LABX-0061,DEVWECAN,Development Cancer and Targeted Therapies(2010), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Centre de recherche en neurosciences de Lyon (CRNL), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Inserm UMR1069, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS), Médecine cellulaire et moléculaire (MCM), Université de Lille, Sciences et Technologies-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, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), 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-Centre Léon Bérard [Lyon], Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bonnelye, Edith, Development Cancer and Targeted Therapies - - DEVWECAN2010 - ANR-10-LABX-0061 - LABX - VALID, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Cardiovasculaire, métabolisme, diabétologie et nutrition [CarMeN], Institut de biologie de Lille - UMS 3702 [IBL], Médecine cellulaire et moléculaire [MCM], Institut National de la Santé et de la Recherche Médicale [INSERM], Institut de Génomique Fonctionnelle de Lyon [IGFL], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [IAB], Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases [LYOS], and Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Subjects: 0301 basic medicine, Cancer Research, Chemokine, T-Lymphocytes, [SDV]Life Sciences [q-bio], Apoptosis, Mice, 0302 clinical medicine, Tumor Cells, Cultured, Tumor Microenvironment, Cytotoxic T cell, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, biology, Prognosis, Primary tumor, 3. Good health, Gene Expression Regulation, Neoplastic, Receptors, Estrogen, Oncology, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Signal Transduction, [SDV.IMM] Life Sciences [q-bio]/Immunology, Mice, Nude, Bone Neoplasms, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 03 medical and health sciences, Transforming Growth Factor beta3, Breast cancer, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, medicine, Animals, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cell Proliferation, Chemokine CCL20, business.industry, medicine.disease, Xenograft Model Antitumor Assays, CCL20, 030104 developmental biology, Transforming growth factor, beta 3, biology.protein, Cancer research, Chemokine CCL17, business, Transforming growth factor
Abstract: Bone is the most common metastatic site for breast cancer. Although the estrogen-related receptor alpha (ERRα) has been implicated in breast cancer cell dissemination to the bone from the primary tumor, its role after tumor cell anchorage in the bone microenvironment remains elusive. Here, we reveal that ERRα inhibits the progression of bone metastases of breast cancer cells by increasing the immune activity of the bone microenvironment. Overexpression of ERRα in breast cancer bone metastases induced expression of chemokines CCL17 and CCL20 and repressed production of TGFβ3. Subsequently, CD8+ T lymphocytes recruited to bone metastases escaped TGFβ signaling control and were endowed with exacerbated cytotoxic features, resulting in significant reduction in metastases. The clinical relevance of our findings in mice was confirmed in over 240 patients with breast cancer. Thus, this study reveals that ERRα regulates immune properties in the bone microenvironment that contributes to decreasing metastatic growth. Significance: This study places ERRα at the interplay between the immune response and bone metastases of breast cancer, highlighting a potential target for intervention in advanced disease.
Published: 2020
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14. GNS561, a clinical-stage PPT1 inhibitor, is efficient against hepatocellular carcinoma via modulation of lysosomal functions

Author: Jonathan Stauber, Maximilian G. Plach, Ahmed Hamaï, Jean-Pierre Baudoin, Philippe Halfon, Marie Novello, Madani Rachid, Eloïne Bestion, Zuzana Macek Jilkova, Soraya Mezouar, Lise Vanderlynden, Gilles Lalmanach, Gaël S. Roth, Raphael Legouffe, Jennifer Tracz, Thomas Schubert, Firas Bassissi, Thomas Decaens, Sonia Brun, Christelle Ansaldi, Cindy Serdjebi, Eric Raymond, Cyrille Drouot, Jérôme Courcambeck, Guillaume Jacquemot, GenoScience Pharma [Marseille] (GSP), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), ImaBiotech, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 2bind GmbH [Regensburg, Germany], Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Lalmanach, Gilles
Subjects: Programmed cell death, autophagy, Cathepsin D, Caspase 3, Biology, Caspase 7, Cathepsin B, Cathepsin L, liver cancer, PPT1, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Lysosome, mtor, medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, Mechanistic target of rapamycin, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Cell Biology, Antitumor, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, medicine.anatomical_structure, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cancer research, biology.protein, lysosome
Abstract: International audience; Hepatocellular carcinoma is the most frequent primary liver cancer. Macroautophagy/autophagy inhibitors have been extensively studied in cancer but, to date, none has reached efficacy in clinical trials. In this study, we demonstrated that GNS561, a new autophagy inhibitor, whose anticancer activity was previously linked to lysosomal cell death, displayed high liver tropism and potent antitumor activity against a panel of human cancer cell lines and in two hepatocellular carcinoma in vivo models. We showed that due to its lysosomotropic properties, GNS561 could reach and specifically inhibited its enzyme target, PPT1 (palmitoyl-protein thioesterase 1), resulting in lysosomal unbound Zn2+ accumulation, impairment of cathepsin activity, blockage of autophagic flux, altered location of MTOR (mechanistic target of rapamycin kinase), lysosomal membrane permeabilization, caspase activation and cell death. Accordingly, GNS561, for which a global phase 1b clinical trial in liver cancers was just successfully achieved, represents a promising new drug candidate and a hopeful therapeutic strategy in cancer treatment.Abbreviations: ANXA5:annexin A5; ATCC: American type culture collection; BafA1: bafilomycin A1; BSA: bovine serum albumin; CASP3: caspase 3; CASP7: caspase 7; CASP8: caspase 8; CCND1: cyclin D1; CTSB: cathepsin B; CTSD: cathepsin D; CTSL: cathepsin L; CQ: chloroquine; iCCA: intrahepatic cholangiocarcinoma; DEN: diethylnitrosamine; DMEM: Dulbelcco's modified Eagle medium; FBS: fetal bovine serum; FITC: fluorescein isothiocyanate; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HCC: hepatocellular carcinoma; HCQ: hydroxychloroquine; HDSF: hexadecylsulfonylfluoride; IC50: mean half-maximal inhibitory concentration; LAMP: lysosomal associated membrane protein; LC3-II: phosphatidylethanolamine-conjugated form of MAP1LC3; LMP: lysosomal membrane permeabilization; MALDI: matrix assisted laser desorption ionization; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MKI67: marker of proliferation Ki-67; MTOR: mechanistic target of rapamycin kinase; MRI: magnetic resonance imaging; NH4Cl: ammonium chloride; NtBuHA: N-tert-butylhydroxylamine; PARP: poly(ADP-ribose) polymerase; PBS: phosphate-buffered saline; PPT1: palmitoyl-protein thioesterase 1; SD: standard deviation; SEM: standard error mean; vs, versus; Zn2+: zinc ion; Z-Phe: Z-Phe-Tyt(tBu)-diazomethylketone; Z-VAD-FMK: carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone.
Published: 2022
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15. Les macrophages associés à la tumeur

Author: Malier, Marie, Gharzeddine, Khaldoun, Laverriere, Marie-Hélène, Decaens, Thomas, Roth, Gael, Millet, Arnaud, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), and Sciences, EDP
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; Le fluorouracile (5-FU) est un analogue de base pyrimidique utilisé dans de nombreuses combinaisons de chimiothérapie, notamment contre les cancers colorectaux. Malgré les progrès dans le traitement de ces cancers, le pronostic des formes avancées reste sombre, notamment en raison de la forte prévalence de la chimiorésistance au 5-FU. Les mécanismes impliqués dans cette chimiorésistance sont multiples : modulation du transport du 5-FU dans la cellule (ainsi que son exportation), métabolisme de la molécule, modification de sa cible, modification de l’équilibre entre facteurs apoptotiques et anti-apoptotiques, adaptation au microenvironnement tumoral, et transition épithélio-mésenchymateuse [1]. La plupart des études portant sur la chimiorésistance se sont focalisées sur la cellule cancéreuse elle-même, et l’importance du microenvironnement tumoral a été longtemps minimisée. Des travaux récents, dont ceux de notre laboratoire, montrent cependant que le microenvironnement joue en réalité un rôle beaucoup plus important dans la chimiorésistance des tumeurs.
Published: 2022
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16. Long-Term Noninvasive Ventilation in Chronic Obstructive Pulmonary Disease: Association between Clinical Phenotypes and Survival

Author: Janssens, Jean-Paul, Cantero, Chloé, Pasquina, Patrick, Jaksic, Cyril, Adler, Dan, Uldry, Christophe, Egger, Bernard, Prella, Maura, Younossian, Alain Bigin, Rabec, Claudio, Soccal Gasche, Paola, Pépin, Jean-Louis, Geneva University Hospitals and Geneva University, Université de Genève = University of Geneva (UNIGE), GHOL - Hôpital de Rolle [Rolle, Switzerland] (HR), Groupement Hospitalier de l'Ouest Lémanique (GHOL), Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hôpital de la Tour [Meyrin, Switzerland] (HT), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Laboratoire d’EFCR [Grenoble], Pôle Thorax et Vaisseaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Grenoble, All the investigators of the Geneva Lake Study., and SALAS, Danielle
Subjects: Noninvasive Ventilation, Survival, Chronic obstructive pulmonary disease, [SDV]Life Sciences [q-bio], Long-term mechanical ventilation, Prognosis, Chronic hypercapnic respiratory failure, Overlap syndrome, [SDV] Life Sciences [q-bio], Airway Obstruction, Hypercapnia, Phenotypes, Pulmonary Disease, Chronic Obstructive, Phenotype, Latent class analysis, Home mechanical ventilation, Humans, Respiratory Insufficiency
Abstract: International audience; Background: Long-term noninvasive ventilation (LTNIV) is widely used in patients with chronic hypercapnic respiratory failure (CHRF) related to COPD. Prognosis of these patients is however poor and heterogenous. Research Question: In COPD patients under LTNIV for CHRF, is it possible to identify specific phenotypes which are predictive of probability of pursuing NIV and survival? Study Design and Methods: A latent class analysis was performed in a COPD population under LTNIV included in a comprehensive database of patients in the Geneva Lake area, to determine clinically relevant phenotypes. The observation period of this subgroup of COPD was extended to allow assessment of survival and/or pursuit of NIV for at least 2 years after inclusion. A logistic regression was conducted to generate an equation accurately attributing an individual patient to a defined phenotype. The identified phenotypes were compared on a series of relevant variables, as well as for probability of pursuing NIV or survival. A competitive risk analysis allowed to distinguish death from other causes of cessation of NIV. Results: Two phenotypes were identified: a “respiratory COPD” profile with very severe airway obstruction, a low or normal body mass index, and a low prevalence of comorbidities and a “systemic COPD” profile of obese COPDs with moderate airway obstruction and a high rate of cardiovascular and metabolic comorbidities. The logistic regression correctly classified 95.7% of patients studied. Probability of pursuing NIV and survival were significantly related to these phenotypes, with a poorer prognosis for “respiratory COPD.” Probability of death 5 years after implementing NIV was 22.3% (95% CI: 15.4–32.2) for “systemic COPD” versus 47.2% (37.4–59.6) for “respiratory COPD” (p = 0.001). Conclusion: The two distinct phenotypes of COPD under LTNIV for CHRF identified appear to be strongly related to prognosis and require further validation in other cohort studies.
Published: 2022
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17. Early delivery following chronic and acute ambient temperature exposure: a comprehensive survival approach

Author: Ian Hough, Matthieu Rolland, Ariane Guilbert, Emie Seyve, Barbara Heude, Rémy Slama, Sarah Lyon-Caen, Isabelle Pin, Cécile Chevrier, Itai Kloog, Johanna Lepeule, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Ben-Gurion University of the Negev (BGU), 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), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and ANR-19-CE36-0003,EDeN,Exposition précoces aux perturbateurs endocriniens et neurodéveloppement de l'enfant : le rôle de l'axe hypothalamo-hypophysaire(2019)
Subjects: exposure windows, Epidemiology, [SDE]Environmental Sciences, preterm birth, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, heat, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, cold
Abstract: Background Ambient temperature, particularly heat, is increasingly acknowledged as a trigger for preterm delivery but study designs have been limited and results mixed. We aimed to comprehensively evaluate the association between ambient temperature throughout pregnancy and preterm delivery. Methods We estimated daily temperature throughout pregnancy using a cutting-edge spatiotemporal model for 5347 live singleton births from three prospective cohorts in France, 2002–2018. We performed Cox regression (survival analysis) with distributed lags to evaluate time-varying associations with preterm birth simultaneously controlling for exposure during the first 26 weeks and last 30 days of pregnancy. We examined weekly mean, daytime, night-time and variability of temperature, and heatwaves accounting for adaptation to location and season. Results Preterm birth risk was higher following cold (5th vs 50th percentile of mean temperature) 7–9 weeks after conception [relative risk (RR): 1.3, 95% CI: 1.0–1.6 for 2°C vs 11.6°C] and 10–4 days before delivery (RR: 1.6, 95% CI: 1.1–2.1 for 1.2°C vs 12.1°C). Night-time heat (95th vs 50th percentile of minimum temperature; 15.7°C vs 7.4°C) increased risk when exposure occurred within 5 weeks of conception (RR: 2.0, 95% CI: 1.05–3.8) or 20–26 weeks after conception (RR: 2.9, 95% CI: 1.2–6.8). Overall and daytime heat (high mean and maximum temperature) showed consistent effects. We found no clear associations with temperature variability or heatwave indicators, suggesting they may be less relevant for preterm birth. Conclusions In a temperate climate, night-time heat and chronic and acute cold exposures were associated with increased risk of preterm birth. These results suggest night-time heat as a relevant indicator. In the context of rising temperatures and more frequent weather hazards, these results should inform public health policies to reduce the growing burden of preterm births.
Published: 2022
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18. Deep Learning for the Automatic Quantification of Pleural Plaques in Asbestos-Exposed Subjects

Author: Ilyes Benlala, Baudouin Denis De Senneville, Gael Dournes, Morgane Menant, Celine Gramond, Isabelle Thaon, Bénédicte Clin, Patrick Brochard, Antoine Gislard, Pascal Andujar, Soizick Chammings, Justine Gallet, Aude Lacourt, Fleur Delva, Christophe Paris, Gilbert Ferretti, Jean-Claude Pairon, François Laurent, CHU Bordeaux [Bordeaux], Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Modélisation Mathématique pour l'Oncologie (MONC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), 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), CHRU de Nancy, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Bordeaux Pellegrin [Bordeaux], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Intercommunal de Créteil (CHIC), Institut Interuniversitaire de Médecine du Travail de Paris Ile-de-France (IIMTPIF), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), This research was funded by French National Health Insurance (Occupational Risk Prevention Department), French Ministry of Labour and Social Relations, French Agency for Food, Environmental and Occupational Health and Safety (ANSES grant 07-CRD-51, EST 2006/1/43, EST 2009/68)., Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Normandie Université (NU), Université de Bordeaux (UB), Aliments Bioprocédés Toxicologie Environnements (ABTE), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), CHU Rouen, 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), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire [Grenoble] (CHU), Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, Ministère du Travail, de l’Emploi, de la Formation Professionnelle et du Dialogue Social, and Admin, Oskar
Subjects: artificial intelligence, pleural plaques, asbestos exposure, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Asbestos, Deep Learning, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Artificial Intelligence, Occupational Exposure, Medicine, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Retrospective Studies
Abstract: International audience; OBJECTIVE: This study aimed to develop and validate an automated artificial intelligence (AI)-driven quantification of pleural plaques in a population of retired workers previously occupationally exposed to asbestos. METHODS: CT scans of former workers previously occupationally exposed to asbestos who participated in the multicenter APEXS (Asbestos PostExposure Survey) study were collected retrospectively between 2010 and 2017 during the second and the third rounds of the survey. A hundred and forty-one participants with pleural plaques identified by expert radiologists at the 2nd and the 3rd CT screenings were included. Maximum Intensity Projection (MIP) with 5 mm thickness was used to reduce the number of CT slices for manual delineation. A Deep Learning AI algorithm using 2D-convolutional neural networks was trained with 8280 images from 138 CT scans of 69 participants for the semantic labeling of Pleural Plaques (PP). In all, 2160 CT images from 36 CT scans of 18 participants were used for AI testing versus ground-truth labels (GT). The clinical validity of the method was evaluated longitudinally in 54 participants with pleural plaques. RESULTS: The concordance correlation coefficient (CCC) between AI-driven and GT was almost perfect (>0.98) for the volume extent of both PP and calcified PP. The 2D pixel similarity overlap of AI versus GT was good (DICE = 0.63) for PP, whether they were calcified or not, and very good (DICE = 0.82) for calcified PP. A longitudinal comparison of the volumetric extent of PP showed a significant increase in PP volumes (p < 0.001) between the 2nd and the 3rd CT screenings with an average delay of 5 years. CONCLUSIONS: AI allows a fully automated volumetric quantification of pleural plaques showing volumetric progression of PP over a five-year period. The reproducible PP volume evaluation may enable further investigations for the comprehension of the unclear relationships between pleural plaques and both respiratory function and occurrence of thoracic malignancy.
Published: 2022
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19. Enantioselective approach for expanding the three‐dimensional space of tetrahydroquinoline to develop bet bromodomain inhibitors

Author: Marie‐Ange Lespinasse, Kaiyao Wei, Justine Perrin, Matthias Winkler, Sieme Hamaidia, Alexis Leroy, Zuzana Macek Jilkova, Christian Philouze, Patrice N. Marche, Carlo Petosa, Jérôme Govin, Anouk Emadali, Yung‐Sing Wong, Département de pharmacochimie moléculaire (DPM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Département de Chimie Moléculaire (DCM), ANR-11-LABX-0003,ARCANE,Grenoble, une chimie bio-motivée(2011), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-18-CE18-0007,InhiBET,Développement de nouvelles molécules antifongiques ciblant les protéines BET(2018), wong, yung-sing, Grenoble, une chimie bio-motivée - - ARCANE2011 - ANR-11-LABX-0003 - LABX - VALID, CBH-EUR-GS - - CBH-EUR-GS2017 - ANR-17-EURE-0003 - EURE - VALID, and APPEL À PROJETS GÉNÉRIQUE 2018 - Développement de nouvelles molécules antifongiques ciblant les protéines BET - - InhiBET2018 - ANR-18-CE18-0007 - AAPG2018 - VALID
Subjects: [CHIM.ORGA]Chemical Sciences/Organic chemistry, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Organic Chemistry, Stereoisomerism, Antineoplastic Agents, General Chemistry, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, anti-inflammatory agent, Catalysis, tetrahydroquinoline, BET bromodomain inhibitor, Quinolines, za-ortho-quinone methide, organocatalysis
Abstract: International audience; The pharmaceutical industry has a pervasive need for chiral specific molecules with optimal affinity for their biological targets. However, the mass production of such compounds is currently limited by conventional chemical routes, that are costly and have an environmental impact. Here, we propose an easy access to obtain new tetrahydroquinolines, a motif found in many bioactive compounds, that is rapid and cost effective. Starting from simple raw materials, the procedure uses a proline-catalyzed Mannich reaction followed by the addition of BF3.OEt2, which generates a highly electrophilic aza-ortho-quinone methide intermediate capable of reacting with different nucleophiles to form the diversely functionalized tetrahydroquinoline. Moreover, this enantioselective one-pot process provides access for the first time to tetrahydroquinolines with a cis-2,3 and trans-3,4 configuration. As proof of concept, we demonstrate that a three-step reaction sequence, from simple and inexpensive starting compounds and catalysts, can generate a BD2-selective BET bromodomain inhibitor with anti-inflammatory effect.
Published: 2022
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20. Pregnancy Exposure to Phenols and Anthropometric Measures in Gestation and at Birth

Author: Paulina, Jedynak, Matthieu, Rolland, Isabelle, Pin, Cathrine, Thomsen, Amrit K, Sakhi, Azemira, Sabaredzovic, Claire, Philippat, Rémy, Slama, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Norwegian Institute of Public Health [Oslo] (NIPH), and Coiffier, Ophélie
Subjects: Male, [SDE] Environmental Sciences, Phenol, Infant, Newborn, Cohort, Phenol exposure, Bisphenol, Fetal growth, Triclosan, Fetal Development, Phenols, Pooled biospecimens, Maternal Exposure, Pregnancy, [SDE]Environmental Sciences, Birth Weight, Humans, Birth outcomes, Female, Paraben
Abstract: International audience; Background: Some synthetic phenols alter pathways involved in fetal development. Despite their high within-subject temporal variability, earlier studies relied on spot urine samples to assess pregnancy exposure. In this study, we examined associations between prenatal phenol exposure and fetal growth. Methods: We measured concentrations of two bisphenols, four parabens, benzophenone-3, and triclosan in 478 pregnant women in two weekly pools of 21 samples each, collected at 18 and 34 gestational weeks. We used adjusted linear regressions to study associations between phenol concentrations and growth outcomes assessed twice during pregnancy and at birth. Results: Benzophenone-3 was positively associated with all ultrasound growth parameters in at least one time point, in males but not females. In females, butylparaben was negatively associated with third-trimester abdominal circumference and weight at birth. We observed isolated associations for triclosan (negative) and for methylparaben and bisphenol S (positive) and late pregnancy fetal growth. Conclusions: Our results suggest associations between prenatal exposure to phenols and fetal growth. Benzophenone-3 was the exposure most consistently (positively) associated across all growth parameters.
Published: 2022
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21. Prediction of hepatocellular carcinoma in Hepatitis C patients with advanced fibrosis after sustained virologic response

Author: Azzi, Jessica, Dorival, Céline, Cagnot, Carole, Fontaine, Hélène, Lusivika-Nzinga, Clovis, Leroy, Vincent, de Ledinghen, Victor, Tran, Albert, Zoulim, Fabien, Alric, Laurent, Gournay, Jérôme, Bronowicki, Jean-Pierre, Decaens, Thomas, Riachi, Ghassan, Mikhail, Nabiel, Soliman, Reham, Shiha, Gamal, Pol, Stanislas, Carrat, Fabrice, Ganne-Carrié, Nathalie, Hepather, Anrs-Afef, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Hospices Civils de Lyon, Departement de Neurologie (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre hospitalier universitaire de Nantes (CHU Nantes), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire [Grenoble] (CHU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Assiut University, Port Said University, Mansoura University [Egypt], Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), AP-HP - Hôpitaux Universitaires Paris Seine-Saint-Denis (GHU 93), INSERM U1053, Université Bordeaux, Bordeaux, France., Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Purpan (CHU Purpan), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Inserm U1254, Centre Hospitalier Universitaire de Nancy (CHU Nancy), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt, Biostatistics and Cancer Epidemiology Department, South Egypt Cancer Institute, Assiut University, Assuit, Egypt., Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt., Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École pratique des hautes études (EPHE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)
Subjects: Liver Cirrhosis, Male, Carcinoma, Hepatocellular, Hepatology, Sustained Virologic Response, Hepatitis C virus, Liver Neoplasms, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hepacivirus, Hepatitis C, Chronic, Middle Aged, Antiviral Agents, Hepatitis C, Risk factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Risk score, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HCC, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Background & Aims: Prediction of hepatocellular carcinoma (HCC) occurrence in patients with chronic hepatitis C (HCV) who achieved a sustained virological response (SVR) after direct acting antivirals (DAAs) remains challenging.Methods: Among HCC-free HCV patients with advanced fibrosis enrolled in the ANRS CO22 HEPATHER cohort who achieved SVR 12 weeks after treatment with DAAs, HCC predictive models were developed using Cox multivariable regression. The derived score was externally validated in a large Egyptian cohort. Our main outcome was the HCC-free survival.Results: During follow-up (median 3.05 years), 153 out of 3531 patients developed a HCC. Main variables associated with HCC occurrence were: male gender, HCV genotype 3, esophageal varices, albumin < 40 g/L, total bilirubin >11 µmol/L and hypercholesterolemia before DAA initiation, together with age > 58 years, FIB-4 index ≥3.25 evaluated at SVR. A score was established allowing the stratification of patients by high (score ≥ 12/22), intermediate (7 ≤ score
Published: 2022
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22. Cost-Effectiveness Analysis of Sequential Treatment Strategies for Advanced Melanoma in Real Life in France

Author: Marguerite Kandel, Aurélie Bardet, Stéphane Dalle, Clara Allayous, Laurent Mortier, Bernard Guillot, Caroline Dutriaux, Marie-Thérèse Leccia, Sophie Dalac, Henri Montaudie, Philippe Saiag, Delphine Legoupil, Florence Brunet-Possenti, Jean-Philippe Arnault, Julie De Quatrebarbes, Marie Beylot-Barry, Eve Maubec, Thierry Lesimple, François Aubin, Jean-Jacques Grob, Florence Granel-Brocard, Pierre-Emmanuel Stoebner, Alain Dupuy, Brigitte Dreno, Stefan Michiels, Céleste Lebbe, Isabelle Borget, Institut Gustave Roussy [IGR], Oncostat [U1018 (Équipe 2)], Centre Léon Bérard [Lyon], Immunologie humaine, physiopathologie & immunothérapie [HIPI (UMR_S_976 / U976)], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 [ONCO-THAI], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Centre Hospitalier Universitaire de Bordeaux [CHU de Bordeaux], Centre Hospitalier Universitaire [Grenoble] [CHU], Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Nice [CHU Nice], Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Régional Universitaire de Brest [CHRU Brest], AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Amiens-Picardie, Hôpital Avicenne [AP-HP], Centre Eugène Marquis [CRLCC], Centre Hospitalier Régional Universitaire de Besançon [CHRU Besançon], Hôpital de la Timone [CHU - APHM] [TIMONE], Service de Dermatologie et Allergologie [CHRU Nancy], Hôpital Universitaire Carémeau [Nîmes] [CHU Nîmes], Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM], CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes [CHU Nantes], Groupe de Recherche et d'Accueil en Droit et Economie de la Santé [GRADES], Institut Gustave Roussy (IGR), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-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 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, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Eugène Marquis (CRLCC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe de Recherche et d'Accueil en Droit et Economie de la Santé (GRADES), Université Paris-Saclay, and This research was funded by the French Institute National of Cancer (DOC 16-009).
Subjects: Proto-Oncogene Proteins B-raf, MESH: Melanoma, Cost-Benefit Analysis, Cost-Effectiveness Analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, JEL: I - Health, Education, and Welfare/I.I1 - Health/I.I1.I18 - Government Policy • Regulation • Public Health, Targeted therapy, Advanced melanoma, Cost-effectiveness analysis, Immunotherapy, Real-life clinical practice, Humans, Prospective Studies, Melanoma, MESH: Proto-Oncogene Proteins B-raf, MESH: Humans, MESH: Cost-Effectiveness Analysis, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, MESH: Prospective Studies, MESH: France, cost-effectiveness analysis, advanced melanoma, real-life clinical practice, immunotherapy, targeted therapy, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, MESH: Cost-Benefit Analysis
Abstract: International audience; Nine drugs have been marketed for 10 years for the treatment of advanced melanoma (AM). With half of patients reaching a second line, the optimal sequence of treatments remains unclear. To inform policy-makers about their efficiency, we performed a cost-effectiveness analysis of sequential strategies in clinical practice in France, for BRAF-mutated and wild-type patients. A multistate model was developed to describe treatment sequences, associated costs, and health outcomes over 10 years. Sequences, clinical outcomes, utility scores, and economic data were extracted from the prospective Melbase cohort, collecting individual data in 1518 patients since 2013, from their AM diagnosis until their death. To adjust the differences in patients’ characteristics among sequences, weighting by inverse probability was used. In the BRAF-mutated population, the MONO-targeted therapies (TT)-anti-PD1 sequence was the less expensive, whereas the anti-PD1-BI-TT sequence had an incremental cost-effectiveness ratio (ICER) of 180,441 EUR/QALY. Regarding the BRAF wild-type population, the three sequences constituted the cost-effective frontier, with ICERs ranging from 116 to 806,000 EUR/QALY. For BRAF-mutated patients, the sequence anti-PD1-BI-TT appeared to be the most efficient one in BRAF-mutated AM patients until 2018. Regarding the BRAF wild-type population until 2018, the sequence starting with IPI+NIVO appeared inefficient compared to anti-PD1, considering the extra cost for the QALY gained.
Published: 2022
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23. Terminal 6q deletions cause brain malformations, a phenotype mimicking heterozygous DLL1 pathogenic variants: A multicenter retrospective case series

Author: Marion Lesieur‐Sebellin, Marianne Till, Philippe Khau Van Kien, Bérénice Herve, Nicolas Bourgon, Céline Dupont, Anne‐Claude Tabet, Mathilde Barrois, Aurélie Coussement, Laurence Loeuillet, Eve Mousty, Vuthy Ea, Amal Assal, Laura Mary, Sylvie Jaillard, Claire Beneteau, Claudine Le Vaillant, Charles Coutton, Françoise Devillard, Carole Goumy, Amélie Delabaere, Sylvia Redon, Yves Laurent, Audrey Lamouroux, Jérôme Massardier, Catherine Turleau, Damien Sanlaville, Vincent Cantagrel, Pascale Sonigo, François Vialard, Laurent J. Salomon, Valérie Malan, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire d'Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), AP-HP Hôpital universitaire Robert-Debré [Paris], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Maternité Port-Royal [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHI Poissy-Saint-Germain, CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hospitalier universitaire de Nantes (CHU Nantes), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe Hospitalier Bretagne Sud (GHBS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), École nationale vétérinaire - Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Cytogénétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université de Brest (UBO), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de radiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Cité (UPCité), Service Obstétrique [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), Thérapie guidée par l'image (TGI), and SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)-SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, phenotype mimicking heterozygous, INTELLECTUAL DISABILITY, [SDV]Life Sciences [q-bio], Chromosome Disorders, Trisomy, LONG ARM, brain malformations, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 03 medical and health sciences, Pregnancy, FETUSES, MICROARRAY ANALYSIS, Humans, pathogenic variants, Genetics (clinical), 030304 developmental biology, Retrospective Studies, 0303 health sciences, Virulence, DEVELOPMENTAL DELAY, ABNORMALITIES, 030305 genetics & heredity, Calcium-Binding Proteins, REARRANGEMENTS, Obstetrics and Gynecology, Membrane Proteins, deletions, 3. Good health, NOTCH, Phenotype, DIFFERENTIATION, Chromosomes, Human, Pair 6, Female, MENTAL-RETARDATION
Abstract: International audience; OBJECTIVE: Terminal 6q deletion is a rare genetic condition associated with a neurodevelopmental disorder characterized by intellectual disability and structural brain anomalies. Interestingly, a similar phenotype is observed in patients harboring pathogenic variants in the DLL1 gene. Our study aimed to further characterize the prenatal phenotype of this syndrome as well as to attempt to establish phenotype-genotype correlations. METHOD: We collected ultrasound findings from 22 fetuses diagnosed with a pure 6qter deletion. We reviewed the literature and compared our 22 cases with 14 fetuses previously reported as well as with patients with heterozygous DLL1 pathogenic variants. RESULTS: Brain structural alterations were observed in all fetuses. The most common findings (>70%) were cerebellar hypoplasia, ventriculomegaly, and corpus callosum abnormalities. Gyration abnormalities were observed in 46% of cases. Occasional findings included cerebral heterotopia, aqueductal stenosis, vertebral malformations, dysmorphic features, and kidney abnormalities. CONCLUSION: This is the first series of fetuses diagnosed with pure terminal 6q deletion. Based on our findings, we emphasize the prenatal sonographic anomalies, which may suggest the syndrome. Furthermore, this study highlights the importance of chromosomal microarray analysis to search for submicroscopic deletions of the 6q27 region involving the DLL1 gene in fetuses with these malformations.
Published: 2021
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24. CYCLON and NPM1 Cooperate within an Oncogenic Network Predictive of R-CHOP Response in DLBCL

Author: Tatiana Raskovalova, Edwige Col, Caroline Algrin, Marie-Christine Jacob, Cyril Fournier, Anne McLeer, Anouk Emadali, Samuel Duley, Romain Aucagne, Antonin Bouroumeau, Mary Callanan, Claire Vettier, Hervé Sartelet, Christine Lefebvre, Patricia Betton-Fraisse, Thierry Bonnefoix, Yohann Couté, Lucile Bussot, Andrea Garcìa-Sandoval, Sieme Hamaidia, Annie Adrait, Simon Chevalier, Laurence David-Boudet, Anna Bergan-Dahl, Remy Gressin, Sylvain Carras, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier Universitaire [Grenoble] (CHU), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut Daniel Hollard [Grenoble], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Bruley, Christophe
Subjects: Oncology, Cancer Research, medicine.medical_specialty, NPM1, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Article, immune system diseases, Internal medicine, hemic and lymphatic diseases, medicine, CYCLON, nucleolus, R-CHOP, prognosis, R-IPI, Nuclear protein, Adverse effect, RC254-282, Rna processing, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, Immunotherapy, medicine.disease, Lymphoma, [SDV] Life Sciences [q-bio], Immunohistochemistry, business
Abstract: Simple Summary CYCLON is a nuclear protein, which has been associated with disease progression and treatment resistance in DLBCL, the most common form of aggressive B-cell lymphoma, but also represents a predictive factor of refractory disease and relapse for immuno-chemotherapy-treated DLBCL patients. The molecular mechanisms related to this unstructured protein remain largely uncharacterized. Here, we performed a mass-spectrometry-based identification of the CYCLON protein interactome that suggested it could exert nucleolar functions related to cell proliferation. Among the CYCLON oncogenic network, we performed an immunohistochemical evaluation of the multi-functional nucleolar protein NPM1 in a DLBCL cohort and showed that CYCLON/NPM1 concomitant expression delineates a poor prognosis subgroup of patients. Multivariate survival analyses demonstrated that specific sub-cellular localizations of CYCLON and NPM1 represent independent novel predictors specifically associated with refractory DLBCL. Abstract R-CHOP immuno-chemotherapy significantly improved clinical management of diffuse large B-cell lymphoma (DLBCL). However, 30–40% of DLBCL patients still present a refractory disease or relapse. Most of the prognostic markers identified to date fail to accurately stratify high-risk DLBCL patients. We have previously shown that the nuclear protein CYCLON is associated with DLBCL disease progression and resistance to anti-CD20 immunotherapy in preclinical models. We also recently reported that it also represents a potent predictor of refractory disease and relapse in a retrospective DLBCL cohort. However, only sparse data are available to predict the potential biological role of CYCLON and how it might exert its adverse effects on lymphoma cells. Here, we characterized the protein interaction network of CYCLON, connecting this protein to the nucleolus, RNA processing, MYC signaling and cell cycle progression. Among this network, NPM1, a nucleolar multi-functional protein frequently deregulated in cancer, emerged as another potential target related to treatment resistance in DLBCL. Immunohistochemistry evaluation of CYCLON and NPM1 revealed that their co-expression is strongly related to inferior prognosis in DLBCL. More specifically, alternative sub-cellular localizations of the proteins (extra-nucleolar CYCLON and pan-cellular NPM1) represent independent predictive factors specifically associated to R-CHOP refractory DLBCL patients, which could allow them to be orientated towards risk-adapted or novel targeted therapies.
Published: 2021
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25. Associations between a mixture of phenols and phthalates and child behaviour in a French mother–child cohort with repeated assessment of exposure

Author: Guilbert, Ariane, Rolland, Matthieu, Pin, Isabelle, Thomsen, Cathrine, Sakhi, Amrit, Sabaredzovic, Azemira, Slama, Rémy, Guichardet, Karine, Philippat, Claire, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA), Norwegian Institute of Public Health [Oslo] (NIPH), ANR-19-CE36-0003,EDeN,Exposition précoces aux perturbateurs endocriniens et neurodéveloppement de l'enfant : le rôle de l'axe hypothalamo-hypophysaire(2019), ANR-12-PDOC-0029,ANR-12-PDOC-0029-01,ANR-12-PDOC-0029-01, ANR-14-CE21-0007,SHALCOH,Expositions prénatales aux phénols et santé de l'enfant : analyse longitudinale(2014), ANR-18-CE36-0005,ETAPE,Exposition prénatale au tabac et à la pollution atmosphérique et effets sur la santé respiratoire et le neurodévelopment de l'enfant: rôle de la méthylation placentaire(2018), ANR-15-IDEX-0002,UGA,IDEX UGA(2015), ANR-15-IDEX-0005,ANR-15-IDEX5 ,ANR-15-IDEX5, European Project: 311765,EC:FP7:ERC,ERC-2012-StG_20111109,E-DOHAD(2013), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), ANR-15-IDEX5ANR-15-IDEX5ANR-15-IDEX-0005, ANR-12-PDOC-0029,PAPER,Grossesse, pollution atmospherique, epigenetique, et sante respiratoire(2012), BARBAGALLO, Maïlys, Exposition précoces aux perturbateurs endocriniens et neurodéveloppement de l'enfant : le rôle de l'axe hypothalamo-hypophysaire - - EDeN2019 - ANR-19-CE36-0003 - AAPG2019 - VALID, Retour Post-Doctorant - Grossesse, pollution atmospherique, epigenetique, et sante respiratoire - - PAPER2012 - ANR-12-PDOC-0029 - PDOC - VALID, Appel à projets générique - Expositions prénatales aux phénols et santé de l'enfant : analyse longitudinale - - SHALCOH2014 - ANR-14-CE21-0007 - Appel à projets générique - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Exposition prénatale au tabac et à la pollution atmosphérique et effets sur la santé respiratoire et le neurodévelopment de l'enfant: rôle de la méthylation placentaire - - ETAPE2018 - ANR-18-CE36-0005 - AAPG2018 - VALID, IDEX UGA - - UGA2015 - ANR-15-IDEX-0002 - IDEX - VALID, and Environmentally-induced Developmental Origins of Health and Disease - E-DOHAD - - EC:FP7:ERC2013-02-01 - 2018-01-31 - 311765 - VALID
Subjects: Male, Weighted quantile sum regression, Child behavior, [SDV]Life Sciences [q-bio], Phthalic Acids, [SCCO] Cognitive science, Environmental Exposure, Bisphenols, Mother-Child Relations, Triclosan, [SDV] Life Sciences [q-bio], Environmental sciences, [SCCO]Cognitive science, Phenols, Phthalates, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Pregnancy, Prenatal exposure, Humans, Environmental Pollutants, Female, GE1-350, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Child
Abstract: International audience; Background: Synthetic phenols and phthalates can interfere with biological pathways involved in brain development. Despite the high within-subject temporal variability of urinary concentrations observed for their metabolites, studies investigating effects of phenols and phthalates on child behaviour often relied on a limited number of spot biospecimens to assess exposure. Besides, the majority did not consider mixture effects.Objectives: To study the combined effect of prenatal exposure to synthetic phenols and phthalates on child behaviour using repeated exposure measurements.Methods: We assessed concentrations of 12 phenols, 13 phthalate and 2 non-phthalate plasticizer metabolites in within-subject pools of multiple urine samples (median = 21 samples per individual pool) collected at two distinct time points during pregnancy in 416 mother-child pairs from the French SEPAGES cohort. Child behaviour was evaluated at two years using the Child Behaviour Checklist 1.5-5 (CBCL). Associations between a mixture of biomarkers of exposure and externalizing and internalizing behaviour scores were studied using adjusted Weighted Quantile Sum (WQS) regressions with a repeated holdout validation (100 repetitions).Results: The positive WQS indexes were associated with both the externalizing and internalizing behaviour scores in the whole population, indicating greater risk of behavioural problems. Stratification for child sex suggested stronger associations in girls than boys. On average, girls externalizing and internalizing scores increased by 3.67 points (95% CI: 1.24, 6.10) and 2.47 points (95 %CI: 0.60, 4.33) respectively, for an increase of one tertile in the WQS index, compared with 1.70 points (95 %CI: -0.42, 3.81) and 1.17 points (95 %CI: -0.50, 2.84) in boys. Main contributors for the associations observed in girls were bisphenol A (weight of 18%), triclosan (17%) and monoethyl phthalate (MEP, 15%) for the externalizing score and MEP (19%), mono-benzyl phthalate (MBzP, 19%) and mono-n-butyl phthalate (MnBP, 16%) for the internalizing score.Discussion: Our results suggest adverse associations between in utero exposure to a mixture of phenols and phthalates and child behaviour, mainly in girls. Public health consequences may be substantial due to the widespread exposure of the population to these compounds.
Published: 2021
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26. Pre- and early post-natal exposure to phthalates and DINCH in a new type of mother-child cohort relying on within-subject pools of repeated urine samples

Author: Cathrine Thomsen, Isabelle Pin, Amrit Kaur Sakhi, Rémy Slama, Claire Philippat, Matthieu Rolland, Azemira Sabaredzovic, Sarah Lyon-Caen, Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Norwegian Institute of Public Health [Oslo] (NIPH), Anses (2019/1/039, 2018/1/264, EST-2016- 121), le Plan Cancer (projet Canc'Air) la Fondation française pour la recherche sur le cancer Association de Recherche sur le Cancer - ARC, le Fonds de dotation AGIR pour les maladies chroniques - APMC, PRENAPAR), le Fonds de dotation pour la santé respiratoire et le Fonds français - Fondation de France (CLIMATHES - 00081169)., ANR-15-IDEX-0002,UGA,IDEX UGA(2015), ANR-19-CE36-0003,EDeN,Exposition précoces aux perturbateurs endocriniens et neurodéveloppement de l'enfant : le rôle de l'axe hypothalamo-hypophysaire(2019), ANR-12-PDOC-0029,PAPER,Grossesse, pollution atmospherique, epigenetique, et sante respiratoire(2012), ANR-14-CE21-0007,SHALCOH,Expositions prénatales aux phénols et santé de l'enfant : analyse longitudinale(2014), ANR-17-CE34-0013,GUMME,Microbiote intestinal dans l'enfance et expositions environnementales maternelles(2017), ANR-18-CE36-0005,ETAPE,Exposition prénatale au tabac et à la pollution atmosphérique et effets sur la santé respiratoire et le neurodévelopment de l'enfant: rôle de la méthylation placentaire(2018), ANR-15-IDEX-0005,ANR-15- IDEX5,ANR-15- IDEX5, European Project: 311765,EC:FP7:ERC,ERC-2012-StG_20111109,E-DOHAD(2013), European Project, BARBAGALLO, Maïlys, IDEX UGA - - UGA2015 - ANR-15-IDEX-0002 - IDEX - VALID, Exposition précoces aux perturbateurs endocriniens et neurodéveloppement de l'enfant : le rôle de l'axe hypothalamo-hypophysaire - - EDeN2019 - ANR-19-CE36-0003 - AAPG2019 - VALID, Retour Post-Doctorant - Grossesse, pollution atmospherique, epigenetique, et sante respiratoire - - PAPER2012 - ANR-12-PDOC-0029 - PDOC - VALID, Appel à projets générique - Expositions prénatales aux phénols et santé de l'enfant : analyse longitudinale - - SHALCOH2014 - ANR-14-CE21-0007 - Appel à projets générique - VALID, Microbiote intestinal dans l'enfance et expositions environnementales maternelles - - GUMME2017 - ANR-17-CE34-0013 - AAPG2017 - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Exposition prénatale au tabac et à la pollution atmosphérique et effets sur la santé respiratoire et le neurodévelopment de l'enfant: rôle de la méthylation placentaire - - ETAPE2018 - ANR-18-CE36-0005 - AAPG2018 - VALID, ANR-15- IDEX5 - - ANR-15- IDEX5ANR-15-IDEX-0005 - INCOMING, Environmentally-induced Developmental Origins of Health and Disease - E-DOHAD - - EC:FP7:ERC2013-02-01 - 2018-01-31 - 311765 - VALID, FP7 / 2007–206 n ° 308333, le projet HELIx - INCOMING, and Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: Infancy, 010504 meteorology & atmospheric sciences, Intraclass correlation, Health, Toxicology and Mutagenesis, Metabolite, Within person, Phthalic Acids, Pools, Physiology, Urine, 010501 environmental sciences, Toxicology, 01 natural sciences, Article, chemistry.chemical_compound, Phthalates, Pregnancy, Medicine, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 0105 earth and related environmental sciences, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Repeated urines, business.industry, Phthalate, General Medicine, Environmental Exposure, DINCH, medicine.disease, Pollution, Mother-Child Relations, 3. Good health, chemistry, DPHP, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, Environmental Pollutants, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Biomarkers
Abstract: For non-persistent chemicals such as phthalates, a single spot urine sample only reflects exposure in the past few hours. Collecting repeated urine samples for each participant over windows of sensitivity is expected to improve exposure characterization but has rarely been done. We aimed to rely on within-subject pools of repeated urine samples to assess phthalate exposure during pregnancy and infancy. Women of the French SEPAGES mother-child cohort were asked to collect three urine samples per day over seven consecutive days, twice during their pregnancy (approximatively second (T2) and third (T3) trimesters). For their infants they also collected one sample per day during a week at two (M2) and twelve months (M12). Samples were pooled (within-subject, within-period) prior to phthalate and DINCH metabolite concentrations assessment. Number of pooled samples assayed was 477, 456, 152 and 100 for T2, T3, M2 and M12, respectively. All metabolites were detected in more than 95% of the pooled samples except for the two DINCH metabolites (oh- and oxo-MINCH), MMCHP and oh-MPHP at M2 for which detection frequencies ranged between 64% and 88%. Maternal concentrations of MiBP, MBzP, DEHP metabolites and oxo-MiNP decreased between 2014 and 2017, whereas concentrations of oh-MiNP and the two DINCH metabolites increased (Mann-Kendall p-values, Graphical abstract Image 1, Highlights • Repeated urine samples were collected and pooled within-subject, within period. • Metabolites of phthalates and DINCH were measured in pooled samples. • Frequencies of detection were overall high. • Pregnancy concentrations of MiBP, MBzP, DEHP and oxo-MINP decreased with time. • Pregnancy concentrations of oh-MiNP and DINCH metabolites increased with time., Relying on a recent cohort (2014–2017) with repeated urine samples collected during pregnancy and infancy, we showed that exposure to phthalates and DINCH is still widespread in the general population.
Published: 2021
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27. Mass Spectrometry-Based Proteomics Reveal Alcohol Dehydrogenase 1B as a Blood Biomarker Candidate to Monitor Acetaminophen-Induced Liver Injury

Author: Pailleux, Floriane, Maes, Pauline, Jaquinod, Michel, Barthelon, Justine, Darnaud, Marion, Lacoste, Claire, Vandenbrouck, Yves, Gilquin, Benoit, Louwagie, Mathilde, Hesse, Anne-Marie, Kraut, Alexandra, Garin, Jérôme, Leroy, Vincent, Zarski, Jean-Pierre, Bruley, Christophe, Couté, Yohann, Samuel, Didier, Ichai, Philippe, Faivre, Jamila, Brun, Virginie, Etude de la dynamique des protéomes (EDyP), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Clinique Universitaire d'Hépato-Gastroentérologie, CHU Grenoble, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Hôpital Paul Brousse, Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Bruley, Christophe, and ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
Subjects: Proteomics, QH301-705.5, [SDV]Life Sciences [q-bio], Alcohol Dehydrogenase, Computational Biology, bioinformatics, liver, Article, [SDV] Life Sciences [q-bio], Chemistry, blood, Limit of Detection, Tandem Mass Spectrometry, biomarker, Humans, International Normalized Ratio, Biology (General), Chemical and Drug Induced Liver Injury, QD1-999, Biomarkers, Chromatography, High Pressure Liquid, mass spectrometry, Acetaminophen
Abstract: International audience; Acute liver injury (ALI) is a severe disorder resulting from excessive hepatocyte cell death, and frequently caused by acetaminophen intoxication. Clinical management of ALI progression is hampered by the dearth of blood biomarkers available. In this study, a bioinformatics workflow was developed to screen omics databases and identify potential biomarkers for hepatocyte cell death. Then, discovery proteomics was harnessed to select from among these candidates those that were specifically detected in the blood of acetaminophen-induced ALI patients. Among these candidates, the isoenzyme alcohol dehydrogenase 1B (ADH1B) was massively leaked into the blood. To evaluate ADH1B, we developed a targeted proteomics assay and quantified ADH1B in serum samples collected at different times from 17 patients admitted for acetaminophen-induced ALI. Serum ADH1B concentrations increased markedly during the acute phase of the disease, and dropped to undetectable levels during recovery. In contrast to alanine aminotransferase activity, the rapid drop in circulating ADH1B concentrations was followed by an improvement in the international normalized ratio (INR) within 10\textendash 48 h, and was associated with favorable outcomes. In conclusion, the combination of omics data exploration and proteomics revealed ADH1B as a new blood biomarker candidate that could be useful for the monitoring of acetaminophen-induced ALI.
Published: 2021
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28. Long-term air pollution exposure, greenness and health-related quality of life (HRQOL) in ECRHS

Author: Bénédicte Jacquemin, Bénédicte Leynaert, Joachim Heinrich, Elaine Fuertes, Anne Boudier, Iana Markevych, Michael J. Abramson, Ane Johanessen, Judith Garcia-Aymerich, Isabelle Pin, Valérie Siroux, Simone Accordini, Bertil Forsberg, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Monash University [Melbourne], Università degli studi di Verona = University of Verona (UNIVR), Umeå University, Imperial College London, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Bergen (UiB), 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, and Centre Hospitalier Universitaire [Grenoble] (CHU)
Subjects: Quality of life, Health related quality of life, business.industry, [SDV]Life Sciences [q-bio], Environmental health, Air pollution exposure, Medicine, Environment, business, ComputingMilieux_MISCELLANEOUS, Asthma, Term (time)
Abstract: International audience
Published: 2021
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29. Bi-allelic truncating variants in CFAP206 cause male infertility in human and mouse

Author: Yunxia Cao, Véronique Satre, Chunyu Liu, Charles Coutton, Qunshan Shen, Marjorie Whitfield, Kuokuo Li, Julie Beurois, Hongbin Liu, Xiaojin He, Dan Liang, Pierre F. Ray, Guillaume Martinez, Marie Bidart, Tristan Celse, Nicolas Thierry-Mieg, Huan Wu, Feng Zhang, Zine-Eddine Kherraf, Fangbiao Tao, Caroline Cazin, Christophe Arnoult, Mingrong Lv, Bing Song, Amir Amiri-Yekta, Aminata Touré, Anhui Medical University, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Royan Institute for Reproductive Biomedicine [Tehran, Iran], Centre Hospitalier Universitaire [Grenoble] (CHU), Biologie Computationnelle et Modélisation (TIMC-BCM ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), 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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Fudan University [Shanghai], Anhui Medical University [Hefei, China], and Thierry-Mieg, Nicolas
Subjects: Male, [SDV]Life Sciences [q-bio], Biology, Flagellum, Frameshift mutation, Male infertility, Mice, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Animals, Humans, Frameshift Mutation, Infertility, Male, Genetics (clinical), Sperm motility, 030304 developmental biology, 0303 health sciences, Sperm flagellum, urogenital system, Calcium-Binding Proteins, Homozygote, Inner dynein arm, medicine.disease, Phenotype, Sperm, Cell biology, DNA-Binding Proteins, [SDV] Life Sciences [q-bio], Cytoskeletal Proteins, Sperm Tail, 030217 neurology & neurosurgery
Abstract: International audience; Spermatozoa are polarized cells with a head and a flagellum joined together by the connecting piece. Flagellum integrity is critical for normal sperm function, and flagellum defects consistently lead to male infertility. Multiple morphological abnormalities of the flagella (MMAF) is a distinct sperm phenotype consistently leading to male infertility due to a reduced or absent sperm motility associated with severe morphological and ultrastructural flagellum defects. Despite numerous genes recently described to be recurrently associated with MMAF, more than half of the cases analyzed remain unresolved, suggesting that many yet uncharacterized gene defects account for this phenotype. By performing a retrospective exome analysis of the unsolved cases from our initial cohort of 167 infertile men with a MMAF phenotype, we identified one individual carrying a homozygous frameshift variant in CFAP206, a gene encoding a microtubule-docking adapter for radial spoke and inner dynein arm. Immunostaining experiments in the patient's sperm cells demonstrated the absence of WDR66 and RSPH1 proteins suggesting severe radial spokes and calmodulin and spoke-associated complex defects. Using the CRISPR-Cas9 technique, we generated homozygous Cfap206 knockout (KO) mice which presented with male infertility due to functional, structural and ultrastructural sperm flagellum defects associated with a very low rate of embryo development using ICSI. Overall, we showed that CFAP206 is essential for normal sperm flagellum structure and function in human and mouse and that bi-allelic mutations in CFAP206 cause male infertility in man and mouse by inducing morphological and functional defects of the sperm flagellum that may also cause ICSI failures.
Published: 2021
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30. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Author: Xavier Cahu, Maxime Desmarets, Thibaut Leguay, Philippe Saas, Victoria Raggueneau, Delphine Binda, Maria Alessandra Rosenthal, Chrystelle Vidal, Olivier Adotevi, Fanny Angelot-Delettre, Françoise Solly, Anne-Cécile Galoisy, Alice Garnier, Sylvie Daliphard, Estelle Guérin, Marie-Pierre Gourin, Karim Maloum, Véronique Harrivel, Edouard Cornet, Felipe Suarez, Jacques Vargaftig, Fabrice Jardin, Caroline Mayeur-Rousse, Sylvain Thepot, Maïder Pagadoy, Thorsten Braun, Bernard Drenou, Yuriy Drebit, Marc Maynadié, Caroline Basle, Zehaira Benseddik, Frédéric Féger, Jean Feuillard, Christian Recher, Etienne Lengliné, Catherine Cordonnier, Rémi Letestu, Mathieu Puyade, Isabelle Arnoux, Remy Gressin, Nathalie Contentin, Jerome Tamburini, Pascale Saussoy, Mary Callanan, Elodie Dindinaud, Pierre-Simon Rohrlich, Julien Guy, Hind Bennani, Tony Petrella, Vincent Foissaud, Johann Rose, Natacha Maillard, Lucile Baseggio, Magali Le Garff-Tavernier, Vincent Barlogis, Denis Guyotat, Yohan Desbrosses, Caroline Bonmati, Damien Roos-Weil, Michel Ticchioni, Sandrine Puyraimond, Norbert Vey, Adriana Plesa, Blandine Guffroy, Daniel Lusina, Bérengère Gruson, Anne Roggy, Véronique Salaun, Eric Deconinck, Jean-Yves Cahn, Nathalie Jacques, Caroline Bret, Florian Renosi, Marie-Christine Béné, Alice Eischen, Stefan Wickenhauser, Benjamin Papoular, Francine Garnache-Ottou, François-Xavier Gros, Vahid Asnafi, Celia Salanoubat, Blandine Bénet, Elisabeth Macintyre, Lou Soret, Orianne Wagner-Ballon, Mohamad Mohty, Elsa Bera, Nicolas Freynet, Ludovic Lhermitte, Franck Trimoreau, Claude Preudhomme, Christophe Roumier, Sébastien Maury, Sabrina Bouyer, Eve Poret, Mikael Roussel, Romaric Lacroix, Christine Arnoulet, Françoise Schillinger, Patricia Okamba, Christine Lefebvre, Didier Blaise, Nicolas Lechevalier, Sabine Brechignac, Christophe Ferrand, Estelle Seilles, Richard Veyrat-Masson, Giorgia Battipaglia, Denis Caillot, Véronique Latger-Cannard, Bruno Quesnel, Didier Bouscary, Sophie Brun, Agathe Debliquis, Marie Loosveld, Franck Geneviève, Carinne Lafon, Lydia Campos, Thierry Fest, Ouda Ghoual, Marie-Christine Jacob, Pierre Peterlin, Valérie Bardet, Anne Arnaud, Véronique Dorvaux, Sabeha Biichle, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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 [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), European Project: IC18CT980373, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), 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), 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 de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de biologie hématologique, Garnache-Ottou, F., Vidal, C., Biichle, S., Renosi, F., Poret, E., Pagadoy, M., Desmarets, M., Roggy, A., Seilles, E., Soret, L., Schillinger, F., Puyraimond, S., Petrella, T., Preudhomme, C., Roumier, C., Macintyre, E. A., Harrivel, V., Desbrosses, Y., Gruson, B., Genevieve, F., Thepot, S., Drebit, Y., Leguay, T., Gros, F. -X., Lechevalier, N., Saussoy, P., Salaun, V., Cornet, E., Benseddik, Z., Veyrat-Masson, R., Wagner-Ballon, O., Salanoubat, C., Maynadie, M., Guy, J., Caillot, D., Jacob, M. -C., Cahn, J. -Y., Gressin, R., Rose, J., Quesnel, B., Guerin, E., Trimoreau, F., Feuillard, J., Gourin, M. -P., Plesa, A., Baseggio, L., Arnoux, I., Vey, N., Blaise, D., Lacroix, R., Arnoulet, C., Benet, B., Dorvaux, V., Bret, C., Drenou, B., Debliquis, A., Latger-Cannard, V., Bonmati, C., Bene, M. -C., Peterlin, P., Ticchioni, M., Rohrlich, P. -S., Arnaud, A., Wickenhauser, S., Bardet, V., Brechignac, S., Papoular, B., Raggueneau, V., Vargaftig, J., Letestu, R., Lusina, D., Braun, T., Foissaud, V., Tamburini, J., Bennani, H., Freynet, N., Cordonnier, C., Le Garff-Tavernier, M., Jacques, N., Maloum, K., Roos-Weil, D., Bouscary, D., Asnafi, V., Lhermitte, L., Suarez, F., Lengline, E., Feger, F., Battipaglia, G., Mohty, M., Bouyer, S., Ghoual, O., Dindinaud, E., Basle, C., Puyade, M., Lafon, C., Fest, T., Roussel, M., Cahu, X., Bera, E., Daliphard, S., Jardin, F., Campos, L., Solly, F., Guyotat, D., Galoisy, A. -C., Eischen, A., Mayeur-Rousse, C., Guffroy, B., Recher, C., Loosveld, M., Garnier, A., Barlogis, V., Rosenthal, M. A., Brun, S., Contentin, N., Maury, S., Callanan, M., Lefebvre, C., Maillard, N., Okamba, P., Ferrand, C., Adotevi, O., Saas, P., Angelot-Delettre, F., Binda, D., and Deconinck, E.
Subjects: Oncology, Vincristine, medicine.medical_specialty, Myeloid, Cyclophosphamide, Clinical Trials and Observations, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Plasmacytoid dendritic cell, Immunophenotyping, Clonal Evolution, 03 medical and health sciences, 0302 clinical medicine, Bone Marrow, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Neoplasm Metastasis, Neoplasm Staging, 030304 developmental biology, Chromosome Aberrations, 0303 health sciences, Leukemia, business.industry, Hematopoietic Stem Cell Transplantation, Disease Management, Myeloid leukemia, Dendritic Cells, Hematology, Prognosis, medicine.disease, Blood Cell Count, 3. Good health, Transplantation, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Acute Disease, business, Biomarkers, medicine.drug
Abstract: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.
Published: 2019
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31. Frameless ROSA® Robot-Assisted Lead Implantation for Deep Brain Stimulation: Technique and Accuracy

Author: Sylvie Grand, Michel Lefranc, Lannie Liu, Stephan Chabardes, Eric Seigneuret, Sarah Giulia Mariani, Emmanuel de Schlichting, Centre Hospitalier Universitaire [Grenoble] (CHU), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)
Subjects: Deep brain stimulation, Deep Brain Stimulation, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Computed tomography, Rosa, Imaging, Three-Dimensional, Robotic Surgical Procedures, Subthalamic Nucleus, medicine, Humans, Robotic surgery, Lead (electronics), medicine.diagnostic_test, business.industry, Parkinson Disease, Magnetic resonance imaging, Robotics, Stylet, Surgery, Computer-Assisted, Surgery, Neurology (clinical), Tomography, Tomography, X-Ray Computed, Lead Placement, business, Nuclear medicine
Abstract: International audience; BACKGROUND: Frameless robotic-assisted surgery is an innovative technique for deep brain stimulation (DBS) that has not been assessed in a large cohort of patients.OBJECTIVE: To evaluate accuracy of DBS lead placement using the ROSA$^{(R)}$ robot (Zimmer Biomet) and a frameless registration.METHODS: All patients undergoing DBS surgery in our institution between 2012 and 2016 were prospectively included in an open label single-center study. Accuracy was evaluated by measuring the radial error (RE) of the first stylet implanted on each side and the RE of the final lead position at the target level. RE was measured on intraoperative telemetric X-rays (group 1), on intraoperative O-Arm$^{(R)}$ (Medtronic) computed tomography (CT) scans (group 2), and on postoperative CT scans or magnetic resonance imaging (MRI) in both groups.RESULTS: Of 144 consecutive patients, 119 were eligible for final analysis (123 DBS; 186 stylets; 192 leads). In group 1 (76 patients), the mean RE of the stylet was 0.57 $\pm$ 0.02 mm, 0.72 $\pm$ 0.03 mm for DBS lead measured intraoperatively, and 0.88 $\pm$ 0.04 mm for DBS lead measured postoperatively on CT scans. In group 2 (43 patients), the mean RE of the stylet was 0.68 $\pm$ 0.05 mm, 0.75 $\pm$ 0.04 mm for DBS lead measured intraoperatively; 0.86 $\pm$ 0.05 mm and 1.10 $\pm$ 0.08 mm for lead measured postoperatively on CT scans and on MRI, respectively No statistical difference regarding the RE of the final lead position was found between the different intraoperative imaging modalities and postoperative CT scans in both groups. CONCLUSION: Frameless ROSA (R) robot-assisted technique for DBS reached submillimeter accuracy. Intraoperative CT scans appeared to be reliable and sufficient to evaluatethe final lead position.
Published: 2019
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32. Chronic Oral Exposure to Synthetic Amorphous Silica (NM-200) Results in Renal and Liver Lesions in Mice

Author: Nathalie Sturm, Emilie Antier, Blandine Laurent, Michèle Cottier, Patrice N. Marche, Delphine Boudard, Anna Bencsik, Federica Aureli, Latifa Lakhdar, Andrea Raggi, Francesco Cubadda, Cytologie et Histologie Rénale [CHU Saint-Etienne] (UF6725), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Biologie intégrative du tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto Superiore di Sanità [Rome, Italy], Italian National Institute of Health, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Lyon, Plateforme Expérimentation Animale, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Plateforme d’expérimentation animale (PFEA), Laboratoire de Lyon [ANSES], Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and MARCHE, Patrice
Subjects: Pathology, medicine.medical_specialty, kidney, mice, Amyloid, Silicon dioxide, Transgene, 030232 urology & nephrology, E551, 030204 cardiovascular system & hematology, lcsh:RC870-923, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Translational Research, medicine, chronic oral exposure, Adverse effect, Kidney, business.industry, Amyloidosis, Wild type, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, medicine.anatomical_structure, chemistry, Vacuolization, Nephrology, silica, nanoparticles, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Introduction: Silicon dioxide, produced as synthetic amorphous silica (SAS), is made of nanoparticles (NPs), either present as such or as agglomerates and aggregates, and is widely used in many types of food processes and products as an additive. To assess whether repeated, long-term exposure to SAS NPs may result in adverse effects, mice were exposed for 18 months via drinking water to NM-200, one of the reference nanostructured silica used for applications related to food, at 4.8 mg NM-200/kg body weight per day, a dose relevant to the estimated dietary exposure to SAS in humans. Methods: The experiment focused on the kidney and liver as target organs and was carried out in parallel using 3 mouse lines (wild type and transgenic) differing for the expression of α-synuclein, that is, murine and human mutated (A53T). Sensitive determination of silicon revealed higher contents in liver and kidneys of NM-200–exposed mice compared with unexposed aged-matched controls. Results: Histological abnormalities, such as vacuolization of tubular epithelial cells, were detected in all kidneys, as well as inflammatory responses that were also detected in livers of exposed animals. Less frequent but more deleterious, amyloidosis lesions were observed in glomeruli, associated with perivascular amyloid accumulation in liver. Conclusion: These histological findings, in conjunction with the observation of detectable deposition of silica, highlight that chronic oral intake of SAS may pose a health risk to humans and need to be examined further. Keywords: chronic oral exposure, E551, kidney, mice, nanoparticles, silica
Published: 2019
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33. Discrimination of Escherichia coli and Shigella spp. by Nuclear Magnetic Resonance Based Metabolomic Characterization of Culture Media

Author: Isabelle Canard, Gilles J. P. Rautureau, Sonia Chatellier, Bénédicte Elena-Herrmann, Tony Lionel Palama, Alex van Belkum, Caroline Mirande, Centre Européen de Résonance Magnétique Nucléaire à Très Hauts Champs (CERMNTHC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, BIOMERIEUX, Unité de Microbiologie (MIC), Institut National de la Recherche Agronomique (INRA), R&D Microbiologie, bioMerieux SA, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de RMN à très hauts champs de Lyon (CRMN), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Microbiologie Environnement Digestif Santé (MEDIS), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), INRA Clermont-Ferrand-Theix-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Elena-Herrmann, Bénédicte
Subjects: 0301 basic medicine, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, metabolic footprint, 030106 microbiology, Biology, medicine.disease_cause, 03 medical and health sciences, exometabolome, Metabolomics, Nuclear magnetic resonance, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, Shigella, Escherichia coli, ComputingMilieux_MISCELLANEOUS, Therapeutic strategy, E. coli, Dysentery, medicine.disease, metabolomics, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, bacterial identification, NMR, 3. Good health, 030104 developmental biology, Infectious Diseases, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Infectious agent, Multivariate classification
Abstract: International audience; Dysentery is a major health threat that dramatically impacts childhood morbidity and mortality in developing countries. Various pathogenic agents cause dysentery, such as Shigella spp. and Escherichia coli, which are very closely related if not identical species. Sensitive and precise detection and identification of the infectious agent is important to target the best therapeutic strategy, but the differential diagnosis of these two groups remains a challenge using conventional methods. Here, we present a nuclear magnetic resonance (NMR) based multivariate classification model employing bacterial metabolic footprints in postculture growth media with remarkable segregation capability, including the discrimination of lactose negative E. coli and Shigella spp. Our results confirm the potential of metabolomic markers in the field of bacterial identification for the distinction of even very closely related species.
Published: 2019
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34. An Empirical Validation of the Within-subject Biospecimens Pooling Approach to Minimize Exposure Misclassification in Biomarker-based Studies

Author: Valérie Siroux, Enrique F. Schisterman, Sarah Lyon-Caen, Antonia M. Calafat, Céline Vernet, Claire Philippat, Pierre Hainaut, Xiaoyun Ye, Rémy Slama, Lydiane Agier, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centers for Disease Control and Prevention [Atlanta, GA, USA] (CDCP), Université Grenoble Alpes (UGA), Eunice Kennedy Shriver National Institute of Child Health and Human Development [Rockville, MD, USA], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Siroux, Valérie
Subjects: Oncology, exposure assessment, Epidemiology, Pooling, phenols, MESH: Epidemiologic Research Design, 01 natural sciences, 010104 statistics & probability, Empirical validity, MESH: Phenols, MESH: Pregnancy, 0302 clinical medicine, Pregnancy, MESH: Bias, Medicine, 030212 general & internal medicine, Follow up studies, MESH: Follow-Up Studies, MESH: Reproducibility of Results, within-subject variability, sampling design, Biomarker (medicine), Environmental Pollutants, Female, Environmental Monitoring, Adult, Validation study, medicine.medical_specialty, attenuation bias, MESH: Environmental Exposure, Within person, MEDLINE, Article, 03 medical and health sciences, Bias, exposure biomarkers, Internal medicine, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, pooling, 0101 mathematics, Exposure assessment, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, business.industry, Reproducibility of Results, Environmental Exposure, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Epidemiologic Research Design, MESH: Biomarkers, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Biomarkers, measurement error, Follow-Up Studies
Abstract: International audience; Background: Within-subject biospecimens pooling can theoretically reduce bias in dose-response functions from biomarker-based studies when exposure assessment suffers from classical-type error. However, collecting many urine voids each day is cumbersome. We evaluated the empirical validity of a within-subject pooling approach and compared several options to avoid sampling each void.Methods: In 16 pregnant women who collected a spot of each urine void over several nonconsecutive weeks, we compared concentrations of 10 phenols in daily, weekly, and pregnancy within-subject pools. We pooled either three or all daily samples. In a simulation study using these data, we quantified bias in dose-response functions when using one to 20 urine samples per subject to assess methylparaben (a compound with moderate within-subject variability) and bisphenol A (high variability) exposures.Results: Correlations between exposure estimates from pools of all and of only three voids per day were above 0.80 for all time windows and compounds, except for benzophenone-3 and triclosan in the daily time window (correlations, 0.57-0.68). With one spot sample to assess pregnancy exposure, correlations were all below 0.74. Using only one biospecimen led to attenuation bias in the dose-response functions of 29% (methylparaben) and 69% (bisphenol A); four samples for methylparaben and 18 for bisphenol A decreased bias to 10%.Conclusions: For nonpersistent chemicals, collecting and pooling three samples per day instead of all daily samples efficiently estimates exposures over a week or more. Collecting around 20 biospecimens can strongly limit attenuation bias for nonpersistent chemicals such as bisphenol A.
Published: 2019
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35. Which decreases in air pollution should be targeted to bring health and economic benefits and improve environmental justice?

Author: Stephan Gabet, Hélène Bouscasse, Rémy Slama, Xavier Morelli, Sandrine Mathy, Camille Rieux, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ATMO Auvergne-Rhône-Alpes (ATMO-AURA), Laboratoire d'Economie Appliquée de Grenoble (GAEL), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre d'Economie et de Sociologie Rurales Appliquées à l'Agriculture et aux Espaces Ruraux (CESAER), Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA), The present study is part of the QAMECS and MobilAir research projects, funded by the French Environment and Energy Management Agency (ADEME) and by the IDEX Program of Grenoble-Alpes University ComUE in the framework of the 'Investing for the future' Program of the French National Research Agency (ANR-15-IDEX-02). It was carried out as part of the 'Breathable city in 5 years' Program of the French Ministry of Ecological and Solidarity Transition for Grenoble conurbation., QAMECS, MobilAir, CCSD, Accord Elsevier, Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: 010504 meteorology & atmospheric sciences, Natural resource economics, Air pollution, 010501 environmental sciences, Social deprivation, medicine.disease_cause, complex mixtures, 01 natural sciences, Life Expectancy, Dispersion model, Social Justice, Order (exchange), Air Pollution, Economic cost, 11. Sustainability, medicine, Humans, Social inequality, [SHS.ECO] Humanities and Social Sciences/Economics and Finance, Lung cancer Fine particulate matter (PM2.5), lcsh:Environmental sciences, 0105 earth and related environmental sciences, General Environmental Science, Population Density, lcsh:GE1-350, Environmental justice, Air Pollutants, Health impact assessment, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Economic benefits, 3. Good health, 13. Climate action, Economic costs, Particulate Matter, Business
Abstract: Background: Fine particulate matter (PM2.5) exposure entails large health effects in many urban areas. Public measures aiming at decreasing air pollution are often designed without targeting an explicit health benefit. Our objective was to investigate the health and economic benefits and the social inequalities in exposure resulting from several scenarios of reduction of PM2.5 exposure, in order to support decisions about urban policies. Material and methods: In the French conurbations of Grenoble and Lyon (0.4 and 1.4 million inhabitants, respectively), PM2.5 yearly average exposure was estimated on a 10-m grid by coupling a PM2.5 dispersion model to population density. Changes in death cases, life expectancy, lung cancer and term low birth weight incident cases as well as associated health economic costs were estimated for ten PM2.5 reduction scenarios differing in terms of amplitude of reduction and spatial extent. Changes in social differences in PM2.5 exposure were also assessed. Results: During the 2015–2017 period, PM2.5 average exposure was 13.9 μg/m3 in Grenoble and 15.3 μg/m3 in Lyon conurbations. Exposure to PM2.5 led to an estimated 145 (95% Confidence Interval, CI, 90–199) and 531 (95% CI, 330–729) premature deaths, 16 (95% CI, 8–24) and 65 (95% CI, 30–96) incident lung cancers, and 49 (95% CI, 19–76) and 193 (95% CI, 76–295) term low birth weight cases each year in Grenoble and Lyon conurbations, respectively, compared to a situation without PM2.5 anthropogenic sources, i.e. a PM2.5 concentration of 4.9 μg/m3. The associated costs amounted to 495 (Grenoble) and 1767 (Lyon) M€/year for the intangible costs related to all-cause non-accidental mortality and 27 and 105 M€ for the tangible and intangible costs induced by lung cancer. A PM2.5 exposure reduction down to the WHO air quality guideline (10 μg/m3) would reduce anthropogenic PM2.5-attributable mortality by half while decreases by 2.9 μg/m3 (Grenoble) and 3.3 μg/m3 (Lyon) were required to reduce it by a third. Scenarios focusing only on the most exposed areas had little overall impact. Scenarios seeking to reach a homogeneous exposure in the whole study area were the most efficient in alleviating social inequalities in exposure. Conclusions: Reduction scenarios targeting only air pollution hotspots had little expected impact on population health. We provided estimates of the PM2.5 change required to reduce PM2.5-attributable mortality by one third or more. Our approach can help targeting air pollution reduction scenarios expected to entail significant benefits, and it could easily be transposed to other urban areas. Keywords: Dispersion model, Economic costs, Health impact assessment, Lung cancer, Fine particulate matter (PM2.5), Social deprivation
Published: 2019
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36. Spike discharge characteristic of the caudal mesencephalic reticular formation and pedunculopontine nucleus in MPTP-induced primate model of Parkinson disease

Author: Laurent Goetz, Olivier David, Brigitte Piallat, Stephan Chabardes, Hervé Mathieu, Manik Bhattacharjee, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), IRMaGe (IRMaGe ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Male, 0301 basic medicine, Deep brain stimulation, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Action Potentials, Biology, Reticular formation, lcsh:RC321-571, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dopamine, Micro electrode recording, Basal ganglia, Pedunculopontine Tegmental Nucleus, medicine, Animals, Cholinergic neuron, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Pedunculopontine nucleus, Neurons, Reticular Formation, MPTP, MPTP Poisoning, Macaca fascicularis, 030104 developmental biology, Neurology, chemistry, Cholinergic, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract: The pedunculopontine nucleus (PPN) included in the caudal mesencephalic reticular formation (cMRF) plays a key role in the control of locomotion and wake state. Regarding its involvement in the neurodegenerative process observed in Parkinson disease (PD), deep brain stimulation of the PPN was proposed to treat levodopa-resistant gait disorders. However, the precise role of the cMRF in the pathophysiology of PD, particularly in freezing of gait and other non-motor symptoms is still not clear. Here, using micro electrode recording (MER) in 2 primates, we show that dopamine depletion did not alter the mean firing rate of the overall cMRF neurons, particularly the putative non-cholinergic ones, but only a decreased activity of the regular neurons sub-group (though to be the cholinergic PPN neurons). Interestingly, a significant increase in the relative proportion of cMRF neurons with a burst pattern discharge was observed after MPTP intoxication. The present results question the hypothesis of an over-inhibition of the CMRF by the basal ganglia output structures in PD. The decreased activity observed in the regular neurons could explain some non-motor symptoms in PD regarding the strong involvement of the cholinergic neurons on the modulation of the thalamo-cortical system. The increased burst activity under dopamine depletion confirms that this specific spike discharge pattern activity also observed in other basal ganglia nuclei and in different pathologies could play a mojor role in the pathophysiology of the disease and could explain several symptoms of PD including the freezing of gait. The present data will have to be replicated in a larger number of animals and will have to investigate more in details how the modification of the spike discharge of the cMRF neurons in the parkinsonian state could alter functions such as locomotion and attentional state. This will ultimely allow a better comprehension of the pathophysiology of freezing of gait.
Published: 2019
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37. Elemental imaging using laser-induced breakdown spectroscopy: latest medical applications

Author: Marine Leprince, Vincent Motto-Ros, Benoit Busser, Jean-Luc Coll, Lucie Sancey, Spectrométrie des biomolécules et agrégats (SPECTROBIO), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), VIDAL, Armelle, and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: [PHYS]Physics [physics], 0303 health sciences, [SPI] Engineering Sciences [physics], 010401 analytical chemistry, General Medicine, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, [PHYS] Physics [physics], 0104 chemical sciences, [SPI]Engineering Sciences [physics], 03 medical and health sciences, 13. Climate action, [CHIM] Chemical Sciences, [CHIM]Chemical Sciences, 030304 developmental biology
Abstract: Multi-elemental imaging of soft tissues using Laser-induced breakdown spectroscopy, also known as LIBS, allows for the direct visualization of the distribution of endogenous or exogenous elements within tissues. LIBS was used to image the kinetics of metal nanoparticles in elimination organs, but also the physiological distribution of biological elements in situ and the topography of chemicals or metals in exposed human tissues. Based on our experience and recent literature in the field of imaging the elemental content of animal and human specimens, this review describes the principle and characteristics of the instrument, technical considerations for setting up experiments with LIBS, its advantages, limitations and possibilities for pre-clinical and medical applications., L’imagerie multi-élémentaire des tissus biologiques grâce à la spectroscopie LIBS (laser-induced breakdown spectroscopy) permet la visualisation directe de la distribution des éléments endogènes ou exogènes. Cette technologie est notamment utilisée pour mettre en image la cinétique des nanoparticules métalliques dans les organes d’élimination, mais également pour analyser la distribution physiologique des éléments biologiques in situ, et pour révéler la topographie des éléments chimiques, comme les métaux, dans des tissus humains qui ont été exposés à des agents extérieurs potentiellement toxiques. Fondée sur notre expérience et les travaux les plus récents dans le domaine de l’imagerie du contenu élémentaire des tissus animaux et humains, cette revue décrit les principes et les caractéristiques de l’instrumentation LIBS, présente certains aspects techniques pour mettre en place des expériences avec cet outil, montre les avantages et les limites de cette technologie, et s’intéresse aux différentes possibilités qu’offre l’imagerie LIBS pour des applications précliniques et médicales.
Published: 2019
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38. COVIZ

Author: Behrooz Omidvar-Tehrani, Valérie Siroux, Jean-Louis Pépin, Cicero A. L. Pahins, Sihem Amer-Yahia, João Luiz Dihl Comba, Jean-Christian Borel, Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), Laboratoire d'Informatique de Grenoble (LIG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Grenoble, Agir à dom., ANR-19-P3IA-0003,MIAI,MIAI @ Grenoble Alpes(2019), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Information retrieval, Computer science, Patient demographics, 05 social sciences, General Engineering, 020207 software engineering, 02 engineering and technology, 050905 science studies, Data structure, 3. Good health, Cohort, 0202 electrical engineering, electronic engineering, information engineering, Key (cryptography), [INFO]Computer Science [cs], 0509 other social sciences
Abstract: International audience; We demonstrate COVIZ, an interactive system to visually form and explore patient cohorts. COVIZ seamlessly integrates visual cohort formation and exploration, making it a single destination for hypothesis generation. COVIZ is easy to use by medical experts and offers many features: (1) It provides the ability to isolate patient demographics (e.g., their age group and location), health markers (e.g., their body mass index), and treatments (e.g., Ventilation for respiratory problems), and hence facilitates cohort formation; (2) It summarizes the evolution of treatments of a cohort into health trajectories, and lets medical experts explore those trajectories; (3) It guides them in examining different facets of a cohort and generating hypotheses for future analysis; (4) Finally, it provides the ability to compare the statistics and health trajectories of multiple cohorts at once. COVIZ relies on QDS, a novel data structure that encodes and indexes various data distributions to enable their efficient retrieval. Additionally, COVIZ visualizes air quality data in the regions where patients live to help with data interpretations. We demonstrate two key scenarios. In the ecological scenario, we show how COVIZ can be used to explore patient data to generate hypotheses on the health evolution of cohorts. In the case cross-over scenario, we show how COVIZ can be used to generate hypotheses on cohort health and pollution data. A video demonstration of COVIZ is accessible via http://bit.ly/video-coviz.
Published: 2019
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39. Whole exome sequencing of men with multiple morphological abnormalities of the sperm flagella reveals novel homozygous QRICH2 mutations

Author: Caroline Cazin, Pierre F. Ray, Christophe Arnoult, Seyedeh Hanieh Hosseini, Amir Amiri-Yekta, Nicolas Thierry-Mieg, Selima Fourati Ben Mustapha, Zine-Eddine Kherraf, Raoudha Zouari, Magalie Boguenet, Aminata Touré, Mahmoud Kharouf, Guillaume Martinez, Charles Coutton, Hamid Gourabi, Abbas Daneshipour, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Clinique de Promotion des Sciences de la Reproduction - Les Jasmins (CPSR), Clinique de Promotion des Sciences de la Reproduction, Polyclinique les Jasmins [Tunis], Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACER, Tehran, 16635-148, Iran., Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Clinique de la reproduction les Jasmins, AGeing and IMagery (AGIM), Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Axoneme, Iran, 030105 genetics & heredity, Flagellum, Biology, Male infertility, Cohort Studies, 03 medical and health sciences, Africa, Northern, Genetics, medicine, Humans, Abnormalities, Multiple, Gene, ComputingMilieux_MISCELLANEOUS, Infertility, Male, Genetics (clinical), Exome sequencing, Sperm flagellum, Homozygote, medicine.disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Spermatozoa, Sperm, Phenotype, 3. Good health, Europe, Cytoskeletal Proteins, 030104 developmental biology, Sperm Tail, Mutation, Microtubule Proteins, Spermatogenesis
Abstract: Multiple morphological anomalies of the sperm flagella (MMAF syndrome) is a severe male infertility phenotype which has so far been formally linked to the presence of biallelic mutations in nine genes mainly coding for axonemal proteins overexpressed in the sperm flagellum. Homozygous mutations in QRICH2, a gene coding for a protein known to be required for stabilizing proteins involved in sperm flagellum biogenesis, have recently been identified in MMAF patients from two Chinese consanguineous families. Here, in order to better assess the contribution of QRICH2 in the etiology of the MMAF phenotype, we analyzed all QRICH2 variants from whole exome sequencing data of a cohort of 167 MMAF-affected subjects originating from North Africa, Iran, and Europe. We identified a total of 14 potentially deleterious variants in 18 unrelated individuals. Two unrelated subjects, representing 1% of the cohort, carried a homozygous loss-of-function variant: c.3501C>G [p.Tyr1167Ter] and c.4614C>G [p.Tyr1538Ter], thus confirming the implication of QRICH2 in the MMAF phenotype and human male infertility. Sixteen MMAF patients (9.6%) carried a heterozygous QRICH2 potentially deleterious variant. This rate was comparable to what was observed in a control group (15.5%) suggesting that the presence of QRICH2 heterozygous variants is not associated with MMAF syndrome.
Published: 2019
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40. CYP46A1 gene therapy deciphers the role of brain cholesterol metabolism in Huntington’s disease

Author: Antonin Lamaziere, Coline Mounier, Wilhelm Christaller, Sandrine Betuing, Peter Vanhoutte, Satish Sasidharan Nair, Jocelyne Caboche, Nicolas Heck, Radhia Kacher, Vincent Kappes, Nathalie Cartier, Valérie Messent, Gaëtan Despres, Elodie Perrin, Laurent Venance, Frédéric Saudou, Yulia Dembitskaya, Christian Neri, Université Pierre et Marie Curie - Paris 6 (UPMC), Signalisation Neuronale et Régulations Géniques = Neuronal Signaling and Gene Regulation (NPS-02), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Team Dynamic and Pathophysiology of Neuronal Networks, Center for Interdisciplinary Research in Biology (CIRB), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), 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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), 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)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chaire Neuropharmacologie (INSERM U114), Collège de France (CdF (institution)), Régulations cellulaires et oncogenèse (RCO), Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-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), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL), Centre Hospitalier Universitaire [Grenoble] (CHU), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Collège de France (CdF)-PSL Research University (PSL), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurobiologie pharmacologique, Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Dynamics and Pathophysiology of neuronal networks, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Vanhoutte, Peter, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), and Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Huntingtin, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Tropomyosin receptor kinase B, Disease, Axonal Transport, Mice, 0302 clinical medicine, Neural Pathways, Medicine, Gene Knock-In Techniques, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, Huntingtin Protein, Membrane Glycoproteins, Brain, Oxysterols, Dependovirus, Protein-Tyrosine Kinases, 3. Good health, Huntington Disease, Neuroprotective Agents, neuroprotection, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Proteasome Endopeptidase Complex, autophagy, Genetic Vectors, Mice, Transgenic, Endosomes, Protein Aggregation, Pathological, Neuroprotection, 03 medical and health sciences, Huntington's disease, mental disorders, Cholesterol 24-Hydroxylase, Animals, Humans, synaptic transmission, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Brain-derived neurotrophic factor, business.industry, Brain-Derived Neurotrophic Factor, Autophagy, cholesterol, Genetic Therapy, medicine.disease, Corpus Striatum, Mice, Inbred C57BL, 030104 developmental biology, Proteasome, Rotarod Performance Test, Neurology (clinical), business, transcriptome, Neuroscience, 030217 neurology & neurosurgery
Abstract: Dysfunctions in brain cholesterol homeostasis have been extensively related to brain disorders. The main pathway for brain cholesterol elimination is its hydroxylation into 24S-hydroxycholesterol by the cholesterol 24-hydrolase, CYP46A1. Increasing evidence suggests that CYP46A1 has a role in the pathogenesis and progression of neurodegenerative disorders, and that increasing its levels in the brain is neuroprotective. However, the mechanisms underlying this neuroprotection remain to be fully understood. Huntington’s disease is a fatal autosomal dominant neurodegenerative disease caused by an abnormal CAG expansion in huntingtin’s gene. Among the multiple cellular and molecular dysfunctions caused by this mutation, altered brain cholesterol homeostasis has been described in patients and animal models as a critical event in Huntington’s disease. Here, we demonstrate that a gene therapy approach based on the delivery of CYP46A1, the rate-limiting enzyme for cholesterol degradation in the brain, has a long-lasting neuroprotective effect in Huntington’s disease and counteracts multiple detrimental effects of the mutated huntingtin. In zQ175 Huntington’s disease knock-in mice, CYP46A1 prevented neuronal dysfunctions and restored cholesterol homeostasis. These events were associated to a specific striatal transcriptomic signature that compensates for multiple mHTT-induced dysfunctions. We thus explored the mechanisms for these compensations and showed an improvement of synaptic activity and connectivity along with the stimulation of the proteasome and autophagy machineries, which participate to the clearance of mutant huntingtin (mHTT) aggregates. Furthermore, BDNF vesicle axonal transport and TrkB endosome trafficking were restored in a cellular model of Huntington’s disease. These results highlight the large-scale beneficial effect of restoring cholesterol homeostasis in neurodegenerative diseases and give new opportunities for developing innovative disease-modifying strategies in Huntington’s disease.
Published: 2019
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41. Prise en charge aux urgences de patients avec cancer thoracique et défaillance d’organe

Author: M. Giaj Levra, Maxime Maignan, L. Ferrer, C. Paquier, Denis Moro-Sibilot, Damien Viglino, C. Collart, Anne-Claire Toffart, Carole Schwebel, CHU Grenoble, Pôle Thorax et Vaisseaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Réanimation Médicale [Grenoble], CHU Grenoble-Hôpital Michallon, Radiopharmaceutiques biocliniques (LRB), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: Pulmonary and Respiratory Medicine, Gynecology, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, 030220 oncology & carcinogenesis, medicine, Lung cancer, business
Abstract: Resume Contexte Lorsqu’un patient atteint d’un cancer du poumon se presente aux urgences avec une defaillance d’organe, la question d’une admission en reanimation se pose. Notre objectif est de decrire le processus aboutissant aux soins proposes. Methodes Retrospectivement, tous les patients admis aux urgences entre decembre 2010 et janvier 2015 et un diagnostic CIM-10 C34.9 (cancer du poumon) ont ete etudies. Ceux avec au moins une defaillance d’organe ont ete inclus. Resultats Les dossiers de 561 patients ont ete etudies, 79 (14 %) presentaient au moins une defaillance d’organe. La majorite de ces patients ont recu des soins medicaux maximaux (59 %), 25 % des soins de confort exclusifs et 15 % des soins intensifs. L’indice de performance, le statut metastatique et l’efficacite du traitement anti-tumoral etaient consignes dans le dossier medical des urgences dans 20 %, 66 % et 74 % des cas, respectivement. Un avis a ete pris aupres de l’oncologue dans 44 % des cas et aupres du reanimateur dans 41 % des cas. Aucun avis exterieur n’a ete pris dans 27 % des cas. Conclusion Dans la majorite des cas, la decision sur l’intensite des soins a proposer aux patients atteints d’un cancer du poumon avec une defaillance d’organe a ete prise de facon collegiale.
Published: 2019
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42. Air pollution modeling and exposure assessment during pregnancy in the French Longitudinal Study of Children (ELFE)

Author: Elsa Real, Laure Malherbe, Julien Bernard, Fabrice Dugay, Emmanuel Riviere, Emie Seyve, Damien Piga, Anne Laborie, Pierre-Yves Robic, Jonathan Virga, Jérôme Cortinovis, Marie Cheminat, Johanna Lepeule, Cécile Zaros, Agnès Hulin, Marie-Aline Charles, François Ducroz, Atmo Grand Est, Atmo Nouvelle-Aquitaine, Atmo Sud, AIRPARIF - Surveillance de la qualité de l'air en Île-de-France, Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Atmo Normandie, Air Pays de la Loire, ATMO, Institut National de l'Environnement Industriel et des Risques (INERIS), Atmo Occitanie, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Civs, Gestionnaire, EFS-Institut national d'études démographiques (INED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: [SDE] Environmental Sciences, Atmospheric Science, Longitudinal study, 010504 meteorology & atmospheric sciences, Scale (ratio), Air pollution, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, Spearman's rank correlation coefficient, 11. Sustainability, Statistics, medicine, COHORT, 0105 earth and related environmental sciences, General Environmental Science, Exposure assessment, Pollutant, Simulation modeling, Atmospheric dispersion modeling, EXPOSURE ASSESSMENT, 3. Good health, AIR POLLUTION, PREGNANCY, 13. Climate action, [SDE]Environmental Sciences, Environmental science, DISPERSION MODELING
Abstract: We developed a nation-wide exposure model to NO2, PM10 and PM2.5 at a fine spatial and temporal resolution for France in order to study air pollutants exposure during pregnancy for the French Longitudinal Study of Children (ELFE). The exposure to air pollutants was estimated daily for years 2010 and 2011 by combining three simulation models at the national and regional scale (CHIMERE) and at the local urban scale (ADMS-Urban or SIRANE). The spatial resolution was 4 km for the national scale model, 3–4 km for regional models and from 10 to 200 m for urban-scale models. We developed a confidence index (from 0 to 10) based on the target plot to identify the best model to estimate exposure for a given address, year and pollutant. Air pollution exposure during pregnancy was then estimated using each modeling scale for the 17,427 women participating in the ELFE cohort. We described the exposure of the women during different time windows of pregnancy using each of the three models and using the most suitable model as estimated by the confidence index. The exposure estimates obtained from the three models were quite similar and highly correlated (spearman correlation between 0.64 and 0.96), especially for the national and regional models. For NO2 and PM10 predicted by the urban models, the minimum values were lower and the maximum values and the variability were higher, compared to the regional and national models. The averaged confidence indexes were comprised between 5.6 and 8 depending on the pollutant, year and exposure model considered. The best confidence index was observed for urban modeling (10) and the lowest for the regional modeling (0). In average during pregnancy, using the most suitable model, women were exposed to 21 μg/m3 for NO2, 16 μg/m3 for PM2.5 and 24 μg/m3 for PM10. To our knowledge, this is the first study combining three modeling tools available at different scales to estimate NO2, PM10 and PM2.5 concentrations at a fine spatial and temporal resolution over a large geographical area. The confidence index provides guidance in the choice of the exposure model. These exposure estimates will be used to investigate potential effects of air pollutants on the pregnant woman health and on health of the fetus and development of the child.
Published: 2019
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43. Exposure to phthalate metabolites, phenols and organophosphate pesticide metabolites and blood pressure during pregnancy

Author: Jeroen de Bont, Isabelle Pin, Sarah Lyon-Caen, Charline Warembourg, Xavier Basagaña, Valérie Siroux, Maribel Casas, Berit Granum, Cyntia B. Manzano-Salgado, Rémy Slama, Chiara Seminati, Cathrine Thomsen, Martine Vrijheid, Amrit Kaur Sakhi, Jose Urquiza, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), CIBER de Epidemiología y Salud Pública (CIBERESP), Norwegian Institute of Public Health [Oslo] (NIPH), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de chirurgie pédiatrique [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes (UGA), Siroux, Valérie, and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: [SDE] Environmental Sciences, Physiology, Blood Pressure, Urine, 010501 environmental sciences, 01 natural sciences, chemistry.chemical_compound, MESH: Pregnancy, MESH: Phenols, 0302 clinical medicine, Phthalates, Pregnancy, MESH: Organophosphorus Compounds, Organophosphate pesticides, 030212 general & internal medicine, 2. Zero hunger, Organophosphate, Phthalate, MESH: Blood Pressure, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, MESH: Environmental Pollutants, [SDE]Environmental Sciences, Gestation, Environmental Pollutants, Female, Biological Monitoring, Adult, Offspring, Phthalic Acids, 03 medical and health sciences, Organophosphorus Compounds, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Phenols, medicine, Humans, MESH: Pesticides, Pesticides, Pregnancy Trimesters, 0105 earth and related environmental sciences, MESH: Humans, business.industry, Public Health, Environmental and Occupational Health, MESH: Adult, MESH: Phthalic Acids, medicine.disease, Blood pressure, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Biological Monitoring, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: International audience; Introduction: Hypertensive disorders during pregnancy are one of the leading causes of maternal and offspring mortality and morbidity. Exposure to environmental chemicals is suspected to increase blood pressure (BP) but few studies have investigated the impact of non-persistent chemicals, in particular among pregnant women.Methods: Women included in the study were 152 volunteer participants in the Human Early-Life Exposome (HELIX) project. They provided 3 urine samples daily over one week in two pregnancy trimesters (at around 18 and 32 weeks of gestation) to assess their exposure to phthalates (10 metabolites), phenols (7 compounds) and organophosphate pesticides (4 metabolites). BP was measured at the end of the two collection weeks. Associations between biomarkers of exposure and BP were investigated using generalized estimating equations (GEE) and linear regression, and adjusted for potential confounders.Results: A significant decrease in systolic and/or diastolic BP was observed with exposure to some phthalate metabolites, BPA, and parabens (e.g. β GEE models for systolic BP = -0.91 mmHg (95%CI: -1.65; -0.17) per doubling of BPA concentrations). These associations were more frequently observed in the second trimester of pregnancy and remained statistically significant after correction for multiple testing for BPA only. No associations were observed with organophosphate pesticides.Conclusion: This study investigates the effect of exposure to non-persistent chemicals assessed using multiple biospecimens per subject on BP during pregnancy and suggests that higher exposure to some phthalates and phenols but not pesticides is associated with lower BP during pregnancy.
Published: 2019
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44. Performance of approaches relying on multidimensional intermediary data to decipher causal relationships between the exposome and health: A simulation study under various causal structures

Author: Cadiou, Solène, Basagaña, Xavier, Gonzalez, Juan R., Lepeule, Johanna, Vrijheid, Martine, Siroux, Valérie, Slama, Rémy, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), CIBER de Epidemiología y Salud Pública (CIBERESP), BARBAGALLO, Maïlys, and Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: Reverse causality, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Variable selection, Omics, Environmental Exposure, Causality, Environmental sciences, Epigenome, Exposome, Sensitivity, Pregnancy, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Multilayer, Specificity, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Environmental Pollutants, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, GE1-350
Abstract: Challenges in the assessment of the health effects of the exposome, defined as encompassing all environmental exposures from the prenatal period onwards, include a possibly high rate of false positive signals. It might be overcome using data dimension reduction techniques. Data from the biological layers lying between the exposome and its possible health consequences, such as the methylome, may help reducing exposome dimension. We aimed to quantify the performances of approaches relying on the incorporation of an intermediary biological layer to relate the exposome and health, and compare them with agnostic approaches ignoring the intermediary layer. We performed a Monte-Carlo simulation, in which we generated realistic exposome and intermediary layer data by sampling with replacement real data from the Helix exposome project. We generated a Gaussian outcome assuming linear relationships between the three data layers, in 2381 scenarios under five different causal structures, including mediation and reverse causality. We tested 3 agnostic methods considering only the exposome and the health outcome: ExWAS (for Exposome-Wide Association study), DSA, LASSO; and 3 methods relying on an intermediary layer: two implementations of our new oriented Meet-in-the-Middle (oMITM) design, using ExWAS and DSA, and a mediation analysis using ExWAS. Methods' performances were assessed through their sensitivity and FDP (False-Discovery Proportion). The oMITM-based methods generally had lower FDP than the other approaches, possibly at a cost in terms of sensitivity; FDP was in particular lower under a structure of reverse causality and in some mediation scenarios. The oMITM-DSA implementation showed better performances than oMITM-ExWAS, especially in terms of FDP. Among the agnostic approaches, DSA showed the highest performance. Integrating information from intermediary biological layers can help lowering FDP in studies of the exposome health effects; in particular, oMITM seems less sensitive to reverse causality than agnostic exposome-health association studies. The study has received funding from the European Commission Program H2020-EU.3.1.2 under grant agreement no 874583 – ATHLETE (Advancing Tools for Human Early Lifecourse Exposome Research and Translation). We also received support from Région Auvergne-Rhône-Alpes for collaborations with Catalunya.
Published: 2021
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45. Chronic T cell receptor stimulation unmasks NK receptor signaling in peripheral T cell lymphomas via epigenetic reprogramming

Author: Carras, Sylvain, Chartoire, Dimitri, Mareschal, Sylvain, Heiblig, Maël, Marçais, Antoine, Robinot, Rémy, Urb, Mirjam, Pommier, Roxane, Julia, Edith, Chebel, Amel, Verney, Aurélie, Bertheau, Charlotte, Bardel, Emilie, Fezelot, Caroline, Courtois, Lucien, Lours, Camille, Bouska, Alyssa, Sharma, Sunandini, Lefebvre, Christine, Rouault, Jean-Pierre, Sibon, David, Ferrari, Anthony, Iqbal, Javeed, de Leval, Laurence, Gaulard, Philippe, Traverse-Glehen, Alexandra, Sujobert, Pierre, Blery, Mathieu, Salles, Gilles, Walzer, Thierry, Bachy, Emmanuel, Genestier, Laurent, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Activation et transduction du signal dans les lymphocytes - Lymphocyte activation and signaling (LYACTS), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], University of Nebraska Medical Center, University of Nebraska System, Centre Hospitalier Universitaire [Grenoble] (CHU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Lausanne (UNIL), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, CHU Henri Mondor, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Innate Pharma, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), 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), Université de Lausanne = University of Lausanne (UNIL), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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)-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), Fondation Synergie Lyon Cancer [Lyon], Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications (ERL 8254), and CHU Henri Mondor [Créteil]
Subjects: [SDV]Life Sciences [q-bio], Immunology, T cells, hemic and immune systems, Lymphomas, Hematology, T cell receptor
Abstract: International audience; Peripheral T cell lymphomas (PTCLs) represent a significant unmet medical need with dismal clinical outcomes. The T cell receptor (TCR) is emerging as a key driver of T lymphocyte transformation. However, the role of chronic TCR activation in lymphomagenesis and in lymphoma cell survival is still poorly understood. Using a mouse model, we report that chronic TCR stimulation drove T cell lymphomagenesis, whereas TCR signaling did not contribute to PTCL survival. The combination of kinome, transcriptome, and epigenome analyses of mouse PTCLs revealed a NK cell-like reprogramming of PTCL cells with expression of NK receptors (NKRs) and downstream signaling molecules such as Tyrobp and SYK. Activating NKRs were functional in PTCLs and dependent on SYK activity. In vivo blockade of NKR signaling prolonged mouse survival, demonstrating the addiction of PTCLs to NKRs and downstream SYK/mTOR activity for their survival. We studied a large collection of human primary samples and identified several PTCLs recapitulating the phenotype described in this model by their expression of SYK and the NKR, suggesting a similar mechanism of lymphomagenesis and establishing a rationale for clinical studies targeting such molecules.
Published: 2021
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46. GNS561, a New Autophagy Inhibitor Active against Cancer Stem Cells in Hepatocellular Carcinoma and Hepatic Metastasis from Colorectal Cancer

Author: Soraya Mezouar, Elena Patricia Gifu, Philippe Halfon, Julie Pannequin, Firas Bassissi, Thomas Decaens, Sonia Brun, Philippe Merle, Claude Caron de Fromentel, Zuzana Macek-Jilkova, Eloïne Bestion, Jean-Marc Pascussi, Jérôme Courcambeck, Guanxiong Wang, GenoSciencePharma, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microbes évolution phylogénie et infections (MEPHI), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Guerineau, Nathalie C.
Subjects: Programmed cell death, cancer stem cell, Colorectal cancer, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, liver cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer stem cell, medicine, CD90, education, GNS561, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, 0303 health sciences, education.field_of_study, therapy, business.industry, medicine.disease, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cancer cell, Cancer research, lysosome, Liver cancer, business, Research Paper
Abstract: Patients with advanced hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC) have a very poor prognosis due to the lack of efficient treatments. As observed in several other tumors, the effectiveness of treatments is mainly hampered by the presence of a highly tumorigenic sub-population of cancer cells called cancer stem cells (CSCs). Indeed, CSCs are resistant to chemotherapy and radiotherapy and have the ability to regenerate the tumor bulk. Hence, innovative drugs that are efficient against both bulk tumor cells and CSCs would likely improve cancer treatment. In this study, we demonstrated that GNS561, a new autophagy inhibitor that induces lysosomal cell death, showed significant activity against not only the whole tumor population but also a sub-population displaying CSC features (high ALDH activity and tumorsphere formation ability) in HCC and in liver mCRC cell lines. These results were confirmed in vivo in HCC from a DEN-induced cirrhotic rat model in which GNS561 decreased tumor growth and reduced the frequency of CSCs (CD90+CD45-). Accordingly, GNS561, which was in a global phase 1b clinical trial in liver cancers that was recently successful, offers great promise for cancer therapy by exterminating both the tumor bulk and the CSC sub-population.
Published: 2021
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47. A missense mutation in IFT74, encoding for an essential component for intraflagellar transport of Tubulin, causes asthenozoospermia and male infertility without clinical signs of Bardet-Biedl Syndrome

Author: Catherine Patrat, Patrick Lorès, Laurence Stouvenel, Marjorie Whitfield, Zine-Eddine Kherraf, Pierre F. Ray, Amir Amiri-Yekta, Raoudha Zouari, Caroline Cazin, Selima Fourati Ben Mustapha, Emma Cavarocchi, Christophe Arnoult, Seyedeh-Hanieh Hosseini, Aminata Touré, Marie-Astrid Llabador, Abbas Daneshipour, Lucile Ferreux, Charles Coutton, Nicolas Thierry-Mieg, Emmanuel Dulioust, 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), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Royan Institute for Reproductive Biomedicine [Tehran, Iran], CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Biologie Computationnelle et Modélisation (TIMC-BCM ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), 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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Hôpitaux Universitaires Paris Centre (CHU Paris Centre), Polyclinique les Jasmins [Tunis], Thierry-Mieg, Nicolas, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Axoneme, Male, [SDV]Life Sciences [q-bio], Mutation, Missense, Biology, Ciliopathies, 03 medical and health sciences, Bardet–Biedl syndrome, Intraflagellar transport, Tubulin, Exome Sequencing, Genetics, medicine, Missense mutation, Animals, Humans, IFT74, Cilia, Bardet-Biedl Syndrome, Genetics (clinical), Infertility, Male, 030304 developmental biology, 0303 health sciences, Sperm flagellum, Intra Flagellar Transport, Cilium, 030305 genetics & heredity, Homozygote, medicine.disease, Sperm, Cell biology, [SDV] Life Sciences [q-bio], Ciliopathy, Cytoskeletal Proteins, Protein Transport, Asthenozoospermia, Flagella, Sperm Tail, Infertility, MMAF, RNA Splice Sites
Abstract: International audience; Cilia and flagella are formed around an evolutionary conserved microtubule-based axoneme and are required for fluid and mucus clearance, tissue homeostasis, cell differentiation and movement. The formation and maintenance of cilia and flagella require bidirectional transit of proteins along the axonemal microtubules, a process called intraflagellar transport (IFT). In humans, IFT defects contribute to a large group of systemic diseases, called ciliopathies, which often display overlapping phenotypes. By performing exome sequencing of a cohort of 167 non-syndromic infertile men displaying multiple morphological abnormalities of the sperm flagellum (MMAF) we identified two unrelated patients carrying a homozygous missense variant adjacent to a splice donor consensus site of IFT74 (c.256G>A;p.Gly86Ser). IFT74 encodes for a core component of the IFT machinery that is essential for the anterograde transport of tubulin. We demonstrate that this missense variant affects IFT74 mRNA splicing and induces the production of at least two distinct mutant proteins with abnormal subcellular localization along the sperm flagellum. Importantly, while IFT74 deficiency was previously implicated in two cases of Bardet-Biedl Syndrome (BBS), a pleiotropic ciliopathy with variable expressivity, our data indicate that this missense mutation only results in primary male infertility due to MMAF, with no other clinical features. Taken together, our data indicate that the nature of the mutation adds a level of complexity to the clinical manifestations of ciliary dysfunction, thus contributing to the expanding phenotypical spectrum of ciliopathies.
Published: 2021
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48. MALDI-TOF MS in a Medical Mycology Laboratory: On Stage and Backstage

Author: Yvan Caspar, Danièle Maubon, Muriel Cornet, Cécile Garnaud, Marvin Jacquet, Léa Pondérand, Tahinamandranto Rasamoelina, Marie Bidart, Aurélie Hennebique, Marie-Gladys Robert, Harmonie Durand, Centre Hospitalier Universitaire [Grenoble] (CHU), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), 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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Groupe Pathogenèse Bactérienne et Réponses Cellulaires / Bacterial Pathogenesis and Cellular Responses Group (IBS-PBRC), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Translational microbial Evolution and Engineering (TIMC-TrEE), Université Grenoble Alpes (UGA)-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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Centre d’Infectiologie Charles-Mérieux, Université d’Antananarivo - Madagascar, Université d'Antananarivo, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)
Subjects: 0301 basic medicine, Microbiology (medical), Antifungal, medicine.medical_specialty, Medical mycology, medicine.drug_class, Computer science, QH301-705.5, diagnosis, [SDV]Life Sciences [q-bio], 030106 microbiology, Review, Microbiology, 03 medical and health sciences, Virology, medicine, MALDI-TOF MS, Medical physics, Biology (General), Daily routine, Fungemia, antifungal susceptibility testing, medicine.disease, 3. Good health, 030104 developmental biology, microorganism identification, Typing methods, fungi, medical mycology
Abstract: International audience; The implementation of MALDI-TOF MS in medical microbiology laboratories has revolutionized practices and significantly reduced turnaround times of identification processes. However, although bacteriology quickly benefited from the contributions of this technique, adjustments were necessary to accommodate the specific characteristics of fungi. MALDI-TOF MS is now an indispensable tool in clinical mycology laboratories, both for the identification of yeasts and filamentous fungi, and other innovative uses are gradually emerging. Based on the practical experience of our medical mycology laboratory, this review will present the current uses of MALDI-TOF MS and the adaptations we implemented, to allow their practical execution in a daily routine. We will also introduce some less mainstream applications, like those for fungemia, or even still under development, as is the case for the determination of sensitivity to antifungal agents or typing methods.
Published: 2021
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49. Deep learning: step forward to high-resolution in vivo shortwave infrared imaging

Author: Xavier Le Guével, Vladimir A. Baulin, Yves Usson, Departament de Química Física i Inorganica, Universitat Rovira i Virgili, Universitat Rovira i Virgili, Univ. Grenoble Alpes, CNRS, CHU Grenoble Alpes, Grenoble INP*, TIMC-IMAG, Grenoble, France, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Biologie Computationnelle et Modélisation (TIMC-BCM ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), 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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-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)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Usson, Yves
Subjects: Infrared Rays, Radio Waves, Computer science, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV]Life Sciences [q-bio], General Physics and Astronomy, High resolution, microvessels, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Shortwave infrared, 010309 optics, [SPI]Engineering Sciences [physics], [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], 0103 physical sciences, Redundancy (engineering), Animals, General Materials Science, [INFO]Computer Science [cs], High resolution imaging, Remote sensing, Artificial neural network, business.industry, Noise (signal processing), Deep learning, 010401 analytical chemistry, General Engineering, deep learning, [INFO.INFO-LG] Computer Science [cs]/Machine Learning [cs.LG], General Chemistry, 0104 chemical sciences, SWIR, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Neural Networks, Computer, Artificial intelligence, fluorescence, business, Preclinical imaging
Abstract: International audience; In vivo optical imaging is a fast growing field that offers great perspectives for biomedical applications. In particular, imaging in the shortwave infrared window (SWIR: 1000-1700 nm) represents major improvement compared to the NIR-I region (700-900 nm) in terms of temporal and spatial resolutions in depths down to 4 mm. SWIR is a fast and cheap alternative to more precise methods such as X-ray and optoacoustic imaging. Main obstacles in SWIR imaging are the noise and scattering from tissues and skin that reduce the precision of the method. We demonstrate the combination of SWIR in vivo imaging in the NIR-IIb region (1500-1700 nm) with advanced deep learning image analysis allows to overcome these obstacles and making a large step forward to high resolution imaging: it allows to precisely segment vessels from tissues and noise, provides morphological structure of the vessels network, with learned 1 pseudo-3D shape, their relative position, dynamic information of blood vascularization in depth in small animals and distinguish the vessels types: artieries and veins. For demonstration we use neural the network IterNet that exploits structural redundancy of the blood vessels (L. Li, et.al., The IEEE WACV, 2020), which provides a useful analysis tool for raw SWIR images.
Published: 2021
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50. Tonnerre de Brest ! Des Journées de Recherche Respiratoires 2020 pas comme les autres…

Author: Christelle Guibert, Nelly Frossard, C Morelot, membres du comité J R, Philippe Gosset, Mustapha Si-Tahar, Isabelle Vachier, Carole Planès, I Annesi-Maesano, Grégory Bouchaud, Laurent Boyer, Laurent Plantier, Stefan Matecki, Delphine Gras, Myriam Polette, Charles Pilette, Christophe Guignabert, Camille Taillé, B Mari, Philippe Bonniaud, Sylvie Gazzeri, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Innovation Thérapeutique (LIT), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Team 'RNA splicing, cell signaling and response to therapies' (U1209 Inserm - CNRS UMR5309 - UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), 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), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR_S 999 «Pulmonary Hypertension: Pathophysiology and Novel Therapies», Hôpital Marie Lannelongue, 92350 Le Plessis-Robinson, France, Institut de pharmacologie moléculaire et cellulaire (IPMC), 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), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Sorbonne Université - Faculté de médecine [CHU Pitié Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Faculté de Médecine et Médecine Dentaire [UCLouvain], Université Catholique de Louvain = Catholic University of Louvain (UCL), Groupe Hospitalier Universitaire Paris Seine-Saint-Denis (GHUPSSD), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), CHU Montpellier, 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 National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université - Faculté de médecine Pitié Salpétrière, Université de Paris - UFR Médecine [Santé] (UP Médecine), Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service de pneumologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité - UFR Médecine [Santé] (UPC UFR Médecine), and Université Paris Cité (UPC)
Subjects: Pulmonary and Respiratory Medicine, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, media_common.quotation_subject, [SDV]Life Sciences [q-bio], 030212 general & internal medicine, Art, Humanities, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, media_common
Abstract: International audience; Tentons un peu d’oublier l’année 2020, mais pas complètement . . . C’est une année qui nousaura conduits à des envies et des visions différentes. Les rencontres conviviales et bien-veillantes qui ponctuent nos journées chaque année au mois d’octobre depuis 2005 n’ontpu se dérouler comme prévues, mais nous étions tous présents pour les 16esJournées deRecherche Respiratoire (J2R) le 16 octobre 2020, bien que devant nos écrans !Nous y avons cru jusqu’au bout et pensions pouvoir bénéficier de la fin de la fenêtreestivale, le programme était prêt et nos hôtes Brestois (nous ne remercierons jamais assezles équipes des Prs Francis Couturaud et Christophe Leroyer) avaient pensé à toutes lessolutions pour maintenir la distanciation, mais force fut de constater fin septembre qu’iln’était plus réaliste de poursuivre l’aventure en présentiel !!!Qu’à cela ne tienne, le plus important était de permettre aux jeunes, dont les résumésavaient suscité suffisamment d’intérêt et d’appétit pour une communication orale, deprésenter leurs travaux. Les J2R 2020 seraient donc organisées en format virtuel. Noustenons à remercier la SPLF pour son soutien logistique qui a permis cette transformation,ainsi que nos sponsors qui nous permettent de faire vivre les J2R depuis 16 ans.C’est ainsi que nos 19 jeunes étudiants chercheurs ont présenté et discuté leurs travauxsous forme de communications orales lors du Webinaire J2R. Tous les thèmes étaient repré-sentés (asthme, BPCO, cancer bronchique, maladies vasculaires, maladies inflammatoirespulmonaires, infectiologie, épidémiologie et la physiologie. . .) et ces communications,comme à l’accoutumée d’excellente qualité, ont pu être écoutées par quelques 135 per-sonnes connectées. Merci à tous des efforts consentis qui ont permis ce succès.
Published: 2021
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