Author: "Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM)" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM)"' showing total 192 results

Start Over Author "Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM)"

192 results on '"Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM)"'

1. Hepatitis A and B vaccine uptake and immunisation among men who have sex with men seeking PrEP: a substudy of the ANRS IPERGAY trial

Author: Paul, Le Turnier, Isabelle, Charreau, Audrey, Gabassi, Diane, Carette, Laurent, Cotte, Gilles, Pialoux, Cécile, Tremblay, Bruno, Spire, Marie-Laure, Chaix, Laurence, Meyer, Catherine, Capitant, Constance, Delaugerre, François, Raffi, Jean-Michel, Molina, N, Lorente, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), 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), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Université de Montréal (UdeM), CRSN/Faculté de médecine Université de Montréal, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hopital Saint-Louis [AP-HP] (AP-HP), and Université Sorbonne Paris Cité (USPC)
Subjects: Infectious Diseases, [SDV]Life Sciences [q-bio], Dermatology
Abstract: Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended in men who have sex with men (MSM). We assessed HAV and HBV vaccine uptake in the non-immune participants and their immunisation during follow-up of the ANRS IPERGAY (Intervention Préventive de l'Exposition aux Risques avec et pour les Gays) pre-exposure prophylaxis (PrEP) trial.During the ANRS IPERGAY trial among MSM (NCT 01473472), vaccination against HAV and HBV was offered free of charge to all non-immune participants at baseline. We assessed anti-HAV IgGs and anti-hepatitis B surface (HBs) antibodies (Abs) at baseline, 1–3 months after each vaccine dose and on the last follow-up visit. Vaccination uptake and immunisation were analysed in non-immune participants with at least 6 months of follow-up after the 1st vaccine dose.A total of 427 MSM with a median age of 34.8 years were analysed. Median follow-up was 2.2 years (Q1–Q3, 1.6–2.9). Absence of anti-HAV IgG at baseline (50.4%, 215/427) was associated with younger age (p=0.0001). Among HAV non-immune participants, 96.1% (197/205) received one or more vaccine doses and 91.0% (172/189) received two vaccine doses. Among HBV non-immune participants, 97.6 % (81/83) received one or more vaccine doses and 78.4% (58/74) received three doses. On the last-visit sample, anti-HAV IgG and anti-HBs Abs were respectively detected in 94.8% (95% CI 90.0% to 97.7%) and 79.6% (95% CI 66.5% to 89.4%) of participants with complete vaccination and in 80.0% (95% CI 51.9% to 95.7%) and 40.0% (95% CI 16.3% to 67.7%) of participants with incomplete vaccination.Vaccine acceptability against HAV and HBV infections was very high in MSM starting PrEP. Immunisation was high in participants with a full vaccination scheme. Physicians must consider PrEP visits as major opportunities to propose and complete HAV and HBV vaccination in at-risk non-immune subjects.
Published: 2022

2. Alix is required for activity-dependent bulk endocytosis at brain synapses

Author: Marine H. Laporte, Kwang Il Chi, Laura C. Caudal, Na Zhao, Yvonne Schwarz, Marta Rolland, José Martinez-Hernandez, Magalie Martineau, Christine Chatellard, Eric Denarier, Vincent Mercier, Florent Lemaître, Béatrice Blot, Eve Moutaux, Maxime Cazorla, David Perrais, Fabien Lanté, Dieter Bruns, Sandrine Fraboulet, Fiona J. Hemming, Frank Kirchhoff, Rémy Sadoul, Perrais, David, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Université de Genève = University of Geneva (UNIGE), Saarland University [Saarbrücken], Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Interdisciplinary Institute for Neuroscience [Bordeaux] (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), 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 de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-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), and ANR-17-CE16-0012,LocalEndoProbes,Contrôle Local de l'Endocytose dans les dendrites neuronales analysé par de nouvelles sondes optiques(2017)
Subjects: Neurons, General Immunology and Microbiology, [SDV]Life Sciences [q-bio], General Neuroscience, Calcium-Binding Proteins, Brain, Clathrin, Endocytosis, General Biochemistry, Genetics and Molecular Biology, [SDV] Life Sciences [q-bio], Mice, Synapses, Animals, General Agricultural and Biological Sciences
Abstract: International audience; In chemical synapses undergoing high frequency stimulation, vesicle components can be retrieved from the plasma membrane via a clathrin-independent process called activity-dependent bulk endocytosis (ADBE). Alix (ALG-2-interacting protein X/PDCD6IP) is an adaptor protein binding to ESCRT and endophilin-A proteins which is required for clathrin-independent endocytosis in fibroblasts. Alix is expressed in neurons and concentrates at synapses during epileptic seizures. Here, we used cultured neurons to show that Alix is recruited to presynapses where it interacts with and concentrates endophilin-A during conditions triggering ADBE. Using Alix knockout (ko) neurons, we showed that this recruitment, which requires interaction with the calcium-binding protein ALG-2, is necessary for ADBE. We also found that presynaptic compartments of Alix ko hippocampi display subtle morphological defects compatible with flawed synaptic activity and plasticity detected electrophysiologically. Furthermore, mice lacking Alix in the forebrain undergo less seizures during kainate-induced status epilepticus and reduced propagation of the epileptiform activity. These results thus show that impairment of ADBE due to the lack of neuronal Alix leads to abnormal synaptic recovery during physiological or pathological repeated stimulations.
Published: 2022
Full Text: View/download PDF

3. Predictors of Outcome After Mechanical Thrombectomy in Stroke Patients Aged ≥85 Years

Author: Céline Odier, Julie Haesebaert, Norbert Nighoghossian, Omer Eker, Marlène Lapierre, Laura C. Gioia, Alexandre Y Poppe, Jean Raymond, Marielle Buisson, Walid Alesefir, Nicole Daneault, Grégory Jacquin, Daniel Roy, Yan Deschaintre, Christian Stapf, Yves Berthezène, Dana Iancu, Alain Weill, Fatine Karkri, Laurent Derex, Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Service de neuroradiologie [Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Centre d'Investigation Clinique [Bron] (CIC1407), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupement Hospitalier Est [Bron], Direction générale (DG), Centre national du machinisme agricole, du génie rural, des eaux et forêts (CEMAGREF), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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), CarMeN, laboratoire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: medicine.medical_specialty, Stroke patient, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030204 cardiovascular system & hematology, Logistic regression, Brain Ischemia, 03 medical and health sciences, Elderly, 0302 clinical medicine, Modified Rankin Scale, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Thrombectomy, Aged, 80 and over, Ischemic stroke, business.industry, General Medicine, Thrombolysis, Odds ratio, 3. Good health, Stroke, [SDV] Life Sciences [q-bio], Mechanical thrombectomy, Treatment Outcome, Neurology, Reperfusion, Cohort, Neurology (clinical), business, Lower mortality, 030217 neurology & neurosurgery
Abstract: Background:The effectiveness of mechanical thrombectomy (MT) in elderly stroke patients remains debated. We aimed to describe outcomes and their predictors in a cohort of patients aged ≥ 85 years treated with MT.Methods:Data from consecutive patients aged ≥ 85 years undergoing MT at two stroke centers between January 2016 and November 2019 were reviewed. Admission National Institutes of Health Stroke Scale (NIHSS), pre-stroke, and 3-month modified Rankin scale (mRS) were collected. Successful recanalization was defined as modified thrombolysis in cerebral ischemia score ≥ 2b. Good outcome was defined as mRS 0–3 or equal to pre-stroke mRS at 3 months.Results:Of 151 included patients, successful recanalization was achieved in 74.2%. At 3 months, 44.7% of patients had a good outcome and 39% had died. Any intracranial hemorrhage (ICH) and symptomatic ICH occurred in 20.3% and 3.6%, respectively. Logistic regression analysis identiﬁed lower pre-stroke mRS score (adjusted odds ratio [aOR], 0.52; 95% CI, 0.36–0.76), lower admission NIHSS score (aOR, 0.90; 95% CI, 0.83–0.97), successful recanalization (aOR, 3.65; 95% CI, 1.32–10.09), and absence of ICH on follow-up imaging (aOR, 0.42; 95% CI, 0.08–0.75), to be independent predictors of good outcome. Patients with successful recanalization had a higher proportion of good outcome (45.3% vs 34.3%, p = 0.013) and lower mortality at 3 months (35.8% vs 48.6%, p = 0.006) compared to patients with unsuccessful recanalization.Conclusions:Among patients aged ≥ 85 years, successful recanalization with MT is relatively common and associated with better 3-month outcome and lower mortality than failed recanalization. Attempting to achieve recanalization in elderly patients using MT appears reasonable.
Published: 2021

4. Analysis of the Acoustic Transcranial Bone Conduction

Author: Catherine Dufour-Fournier, Arnaud Devèze, Jonathan Barbut, Erick Ogam, Issam Saliba, Catherine Masson, Department of Otolaryngology and Head and Neck Surgery, University of Montreal, Montreal, Université du Québec à Montréal = University of Québec in Montréal (UQAM), Department of Otology and Skull Base Surgery, Ramsay Health Care, Clairval Hospital, 317 Bd du Redon, 13009 Marseille, France, Clairval Hospital, Laboratoire de Biomécanique Appliquée (LBA UMR T24), Aix Marseille Université (AMU)-Université Gustave Eiffel, Ondes et Imagerie (O&I), Laboratoire de Mécanique et d'Acoustique [Marseille] (LMA ), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), and Université de Montréal (UdeM)-Université de Montréal (UdeM)
Subjects: otology, acoustic, bone conduction, BAHA, Otorhinolaryngology, sound transmission, otorhinolaryngologic diseases, [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph]
Abstract: International audience; Objectives: (1) To analyze the preferential pathways of sound transmission and sound waves travelling properties in the skull and (2) to identify the location(s) on the skull where bone conduction to the cochlea is optimal. Study design: Basic research Methods: Nine cadaveric heads were placed in an anechoic chamber and equipped with six Bone Anchored Hearing Aids (BAHA™) implants (Cochlear™, Sydney, NSW, Australia) and fifteen accelerometers. A laser velocimeter was used to measure cochlear response by placing a reflector on the round window. Different frequency sweeps were applied to each implant, and measurements were recorded simultaneously by the laser velocimeter and accelerometers. Results: Low-frequency sound waves mostly travel the frontal transmission pathways, and there is no clear predominant pattern for the high frequencies. The mean inter-aural time lag is 0.1 ms. Optimal sound transmission to the cochlea occurs between 1000 and 2500 Hz with a contralateral 5 to 10 dB attenuation. The implant location does not influence mean transmission to the cochlea. Conclusion: There is a pattern of transmission for low frequencies through a frontal pathway but none for high frequencies. We were also able to demonstrate that the localization of the BAHA™ implant on the skull had no significant impact on the sound transmission, either ipsi or contralaterally.
Published: 2022

5. Opt-out universal HCV and HIV screening in a Canadian emergency room: a cross-sectional study

Author: Valerie Martel-Laferriere, Jean-Guy Baril, Isabelle Alarie, Judith Leblanc, José Côté, Emmanuelle Jourdenais, Damy Horth, Gilles Lambert, Cécile Tremblay, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Université de Montréal (UdeM), CRSN/Faculté de médecine Université de Montréal, Faculté de médecine et des sciences de la santé [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS), CHUS – Centre Hospitalier Universitaire de Sherbrooke [Sherbrooke, QC, Canada], Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-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), Surveillance et modélisation des maladies transmissibles [iPLesp] (SUMO), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de Santé Publique du Québec [Canada] (INSPQ), Direction régionale de santé publique [Montréal, Canada], Centre intégré universitaire de santé et de services sociaux du Centre-Sud-de-l'Ile-de-Montréal (CIUSSS [Centre-Sud-de-l'Ile-de-Montréal]), and Gestionnaire, Hal Sorbonne Université
Subjects: Adult, Canada, virus diseases, HIV & AIDS, HIV Infections, General Medicine, Hepacivirus, Hepatitis C, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, hepatology, accident & emergency medicine, Medicine, Humans, Mass Screening, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Emergency Service, Hospital, Diagnostics
Abstract: Objectives To determine the prevalence of undiagnosed hepatitis C virus (HCV) and HIV cases in a population sample tested in the emergency room (ER) and to evaluate linkage-to-care. Setting Canadian university hospital. Participants Adults born after 1945 who consulted at ER for any condition and on any shift were included. Patients unable to opt-out were excluded. Interventions ER nurse confirmed patients’ eligibility and provided them with the option to opt-out. A physician met patients with a new diagnosis. Linkage-to-care was assessed 3 months postdiagnosis. Patients newly diagnosed with HCV were considered linked if they had an HCV RNA test, genotype, liver fibrosis evaluation, and if indicated, treatment prescription. Patients newly diagnosed with HIV were considered linked to care if they had an HIV serology confirmation test, viral load, CD4 cell count and started antiretroviral therapy. Primary and secondary outcome measures Primary objective: to determine the prevalence (overall and undiagnosed cases) of HIV and HCV among the patients who consult the ER. Secondary objectives: to determine the proportion of patients who opt-out, assess the adherence of emergency staff to the offer of testing, determine the proportion of patients linked to care at 3 months. Results Among 6350 eligible patients informed of the screening programme, 62.1% of patients were tested for at least one virus (HIV: 3905; HCV: 3910). 25% patients opted-out, 12% were not tested for organisational reasons, 0.3% (18) patients were HCV-HIV coinfected. Overall prevalence of HCV and HIV cases were 1.9% and 1.2%, respectively. Prevalence of new cases was 0.23% (95% CI 0.12% 0.45%) for HCV and 0.05% (95% CI 0.01% to 0.20%) for HIV. Among the new cases, only two HCV-infected and one HIV-infected patients were linked-to-care 3 months postdiagnosis. Conclusions Identification of new cases of HCV and HIV through universal screening at the ER and linkage-to-care were both low. Trial registration number NCT03595527; Results.
Published: 2022

6. Outdoor air pollution exposure and cognitive performance: findings from the enrolment phase of the CONSTANCES cohort

Author: Mohammad Javad Zare Sakhvidi, Jun Yang, Emeline Lequy, Jie Chen, Kees de Hoogh, Noémie Letellier, Marion Mortamais, Anna Ozguler, Danielle Vienneau, Marie Zins, Marcel Goldberg, Claudine Berr, Bénédicte Jacquemin, 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 ), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Utrecht University [Utrecht], Swiss Tropical and Public Health Institute [Basel], Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), The Caisse Nationale d’Assurance Maladie, and partly funded by Merck Sharp and Dohme and L’Oréal, the French National Research Agency, and Fondation de France., and Chard-Hutchinson, Xavier
Subjects: Adult, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Health (social science), Adolescent, Health Policy, Public Health, Environmental and Occupational Health, Medicine (miscellaneous), [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Environmental Exposure, Middle Aged, Young Adult, Cognition, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Air Pollution, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Particulate Matter, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Aged
Abstract: Background Air pollution exposure is one of the modifiable risk factors of cognitive decline. We aimed to test the association between exposure to several outdoor air pollutants and domain-specific cognitive performance. Methods In this cross-sectional study, we used data from the enrolment phase of the French CONSTANCES cohort. From the 220 000 people (aged 18-69 years) randomly recruited in the French CONSTANCES cohort, participants aged 45 years old or older (104 733 people) underwent a comprehensive cognitive assessment (verbal episodic memory, language skills, and executive functions). After exclusion of those who were not suitable for our analysis, 61 462 participants with available data were included in the analyses. We used annual mean concentrations at residential addresses, derived from land-use regression models, to assign exposure to particulate matter with aerodynamic diameters less than 2·5 μm (PM2·5), nitrogen dioxide (NO2), and black carbon. We used multiple linear regression models with different covariate adjustments to test the associations between each pollutant and cognitive outcomes. We did several sensitivity analyses, including multilevel modelling, meta-analysis by centre of recruitment, and exclusion of specific population groups. Findings We found significantly poorer cognitive function, especially on semantic fluency and domains of executive functions, with an increase in exposure to black carbon and NO2. Exposure to PM2·5 was mainly significant for the semantic fluency test. We found that decrease in cognitive performance with an increase of one interquartile range of exposure ranged from 1% to nearly 5%. The largest effect size (percentage decrease) for both PM2.5 and NO2 was found for the semantic fluency test (PM2.5 4·6%, 95% CI 2·1-6·9 and NO2 3·8%, 1·9-5·7), whereas for black carbon, the largest effect size was found for the digit symbol substitution test of the domains of executive functions (4·5%, 2·7-6·3). Monotonic and linear exposure-response associations were found between air pollution exposure and cognitive performance, starting from a low level of exposures. Interpretation Significantly poorer cognitive performance was associated with exposure to outdoor air pollution even at low levels of exposure. This highlights the importance of further efforts to reduce exposure to air pollution. Funding The Caisse Nationale d'Assurance Maladie, and partly funded by Merck Sharp & Dohme and L'Oréal, the French National Research Agency, and Fondation de France. Translation For the French translation of the abstract see Supplementary Materials section.
Published: 2022

7. Numerical investigation of particle aggregate steering with magnetic resonance navigation for targeted embolization

Author: Rezaei Adariani, Mahdi, Pešek, Jiří, Li, Ning, Debbaut, Charlotte, Soulez, Gilles, Vignon-Clementel, Irene, REZAEI ADARIANI, mahdi, SImulations en Médecine, BIOtechnologie et ToXicologie de systèmes multicellulaires (SIMBIOTX ), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), IBiTech-bioMMeda, and Universiteit Gent = Ghent University (UGENT)
Subjects: [SPI.MECA.MEFL] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph], [SPI.MECA.MEFL]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Fluids mechanics [physics.class-ph]
Abstract: International audience; Magnetic resonance navigation (MRN) has become a significant method to steer magnetized particles in medical applications by using MRI scanners. Dedicated MRN sequences have been successfully developed to track and steer such particle aggregates for selective chemoembolization of liver tumors. Particle aggregation is however a complex process and a comprehensive study of its shape and motion is needed to avoid damaging healthy tissues. Previous computational studies have considered non-aggregating particles or aggregates in 2D simplified settings. In this study, we investigate the forces acting on such micro-particle aggregation including drag, gravity, pressure gradient, virtual mass, magnetic gradient, dipole and contact forces. The code is developed in the OpenFOAM framework. Primary results are compared with bifurcation in vitro experimental data. Different sizes of clusters, directions of the magnetic field and gradient can be investigated to optimize aggregation form. This research represents an initial step towards complex in-vitro phantoms and in-vivo models.
Published: 2022

8. Incidence and risk factors for recurrent sexually transmitted infections among men who have sex with men on HIV pre-exposure prophylaxis

Author: Zeggagh, Jérémy, Bauer, Rebecca, Delaugerre, Constance, Carette, Diane, Fressard, Lisa, Charreau, Isabelle, Chidiac, Christian, Pialoux, Gilles, Tremblay, Cécile, Cua, Eric, Robineau, Olivier, Raffi, François, Capitant, Catherine, Spire, Bruno, Meyer, Laurence, Molina, Jean Michel, Institut National de la Santé et de la Recherche Médicale (INSERM), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon, CHU Tenon [AP-HP], Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Université de Montréal (UdeM), CRSN/Faculté de médecine Université de Montréal, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Gustave Dron [Tourcoing], Dat’AIDS Study Group, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Université Paris-Saclay, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), and Université Paris Cité (UPCité)
Subjects: [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Objective: High rates of sexually transmitted infections (STIs) have been reported among pre-exposure prophylaxis (PrEP) users. We wished to assess the incidence and risk factors for recurrent STIs.Design: The ANRS IPERGAY trial was a prospective study investigating PrEP among MSM and transgender women in outpatient clinics in France and Canada. In all, 429 participants were enrolled, offered up to 4 years of PrEP and screened for bacterial STIs (syphilis, chlamydia and gonorrhea) at baseline and every 6 months.Methods: STIs incidence was calculated yearly. Cox proportional hazards model regression was used to explore associations between participants characteristics at baseline and recurrent STI during follow-up.Results: Over a median follow-up of 23 months, bacterial STI incidence was 75, 33, 13, 32 and 30 per 100 person-years for all STIs, rectal STIs, syphilis, gonorrhea and chlamydia, respectively. STI incidence significantly increased from the first year to the fourth year of the study (55 vs. 90 per 100 person-years, P < 0.001). During the study period, 167 participants (39%) presented with more than one bacterial STIs which accounted for 86% of all STIs. Baseline risk factors associated with recurrent STIs in a multivariate analysis were an STI at baseline [hazards ratio: 1.48 (95% confidence interval (CI): 1.06-2.07), P = 0.02], more than eight sexual partners in prior 2 months [hazards ratio: 1.72 (95% CI: 1.21-2.43), P = 0.002] and the use of gamma-hydroxybutyrate [hazards ratio: 1.66 (95% CI: 1.16-2.38), P = 0.005].Conclusion: STI incidence was high and increased over time. Most STIs were concentrated in a high-risk group that should be targeted for future interventions.
Published: 2022

9. Long-term exposure to black carbon and mortality: A 28-year follow-up of the GAZEL cohort

Author: Yang, Jun, Sakhvidi, Mohammad Javad Zare, de Hoogh, Kees, Vienneau, Danielle, Siemiatyck, Jack, Zins, Marie, Goldberg, Marcel, Chen, Jie, Lequy, Emeline, Jacquemin, Bénédicte, 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), Jinan University [Guangzhou], Swiss Tropical and Public Health Institute [Basel], University of Basel (Unibas), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institute for Risk Assessment Sciences [Utrecht, The Netherlands] (IRAS), Utrecht University [Utrecht], This study was supported by ARC (Grant information OCAPOL, CANCAIR-201501234). Jun Yang is also supported by the National Natural Science Foundation of China (No. 82003552), and the Guangdong Basic and Applied Basic Research Foundation (No. 2020A1515011161)., Chard-Hutchinson, Xavier, 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 ), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP)
Subjects: [SDE] Environmental Sciences, Air Pollutants, [SDV]Life Sciences [q-bio], Long-term exposure, Air pollutant, Environmental Exposure, Carbon, [SDV] Life Sciences [q-bio], Environmental sciences, Black carbon, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Air Pollution, [SDE]Environmental Sciences, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Particulate Matter, GE1-350, Mortality, Cohort study, Follow-Up Studies
Abstract: International audience; BACKGROUND: The current evidence on health effects of long-term exposure to outdoor airborne black carbon (BC) exposure remains scarce. OBJECTIVES: To examine the association between long-term exposure to BC and mortality in a large population-based French cohort, with 28 years of follow-up. METHODS: Data from the GAZEL cohort were collected between 1989 and 2017. Land use regression model with temporal extrapolation wa used to estimate yearly BC and PM(2.5) exposure at the residential addresses from 1989 until censoring for 19,906 participants. Time-varying Cox models with attained age as time-scale was used to estimate the associations between BC and all-cause and cardiovascular mortality, after adjusting for individual and area-level covariates. To handle confounding by PM(2.5), we used the residual of BC regressed on PM(2.5) as an alternate exposure variable. For all-cause mortality, we also examined effect modification by sex, smoking status, BMI and fruit/vegetable intake. RESULTS: The median of 20-year moving average of BC exposure was 2.02 10(-5)/m in study population. We found significant associations between BC exposure and all-cause mortality (n = 2357) using both 20-year moving average of BC and residual of BC, with corresponding hazard ratios (HR) of 1.14 (95 %CI: 1.07-1.22) and 1.17 (95 %CI: 1.10-1.24) for an inter-quartile range (IQR) increase (0.86 10(-5)/m for BC and 0.57 10(-5)/m for residual of BC). We found a similar association between BC and cardiovascular mortality (n = 277) with a HR of 1.15 (95 %CI: 0.95-1.38). The dose-response relationship between BC and all-cause mortality was monotonic but nonlinear with a steeper slope at high BC levels. In addition, the effect of BC was higher among never-smokers and among those having fruit/vegetables less than twice a week. CONCLUSIONS: There was a positive association between long-term exposure to BC and increased mortality risk, reinforcing the emerging evidence that BC is a harmful component of PM(2.5).
Published: 2021

10. Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis

Author: Goubet, Anne-Gaëlle, Dubuisson, Agathe, Geraud, Arthur, Danlos, François-Xavier, Terrisse, Safae, Silva, Carolina Alves Costa, Drubay, Damien, Touri, Lea, Picard, Marion, Mazzenga, Marine, Silvin, Aymeric, Dunsmore, Garett, Haddad, Yacine, Pizzato, Eugenie, Ly, Pierre, Flament, Caroline, Melenotte, Cléa, Solary, Eric, Fontenay, Michaela, Garcia, Gabriel, Balleyguier, Corinne, Lassau, Nathalie, Maeurer, Markus, Grajeda-Iglesias, Claudia, Nirmalathasan, Nitharsshini, Aprahamian, Fanny, Durand, Sylvère, Kepp, Oliver, Ferrere, Gladys, Thelemaque, Cassandra, Lahmar, Imran, Fahrner, Jean-Eudes, Meziani, Lydia, Ahmed-Belkacem, Abdelhakim, Saïdani, Nadia, La Scola, Bernard, Raoult, Didier, Gentile, Stéphanie, Cortaredona, Sébastien, Ippolito, Giuseppe, Lelouvier, Benjamin, Roulet, Alain, Andre, Fabrice, Barlesi, Fabrice, Soria, Jean-Charles, Pradon, Caroline, Gallois, Emmanuelle, Pommeret, Fanny, Colomba, Emeline, Ginhoux, Florent, Kazandjian, Suzanne, Elkrief, Arielle, Routy, Bertrand, Miyara, Makoto, Gorochov, Guy, Deutsch, Eric, Albiges, Laurence, Stoclin, Annabelle, Gachot, Bertrand, Florin, Anne, Merad, Mansouria, Scotte, Florian, Assaad, Souad, Kroemer, Guido, Blay, Jean-Yves, Marabelle, Aurélien, Griscelli, Frank, Zitvogel, Laurence, Derosa, Lisa, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, 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, 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, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Champalimaud Centre for the Unknown [Lisbon], 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), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Intercommunal de Cornouaille (CHIC), 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 d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), National Institute for Infectious Diseases 'Lazzaro Spallanzani', Vaiomer, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), E-institute of Shanghai University Immunology Division, Shanghai University, Duke-NUS Medical School [Singapore], McGill University Health Center [Montreal] (MUHC), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, UNICANCER, Université Paris Cité (UPCité), Karolinska Institutet [Stockholm], 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), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Modèles de Cellules Souches Malignes et Thérapeutiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, National Infrastructure INGESTEM, Université Paris Sud, A-GG was supported by Fondation pour la Recherche Médicale (FRM). LD has received support by the Philanthropia Fondation Gustave Roussy. The Gustave Roussy sponsored clinical study on COVID-19 (ONCOVID, NCT NCT04341207 has been supported by the Fondation Gustave Roussy, the Dassault family, Malakoff Humanis, Agnès b., Izipizi, Ralph Lauren and Sanofi). LZ and GK were supported by RHU Torino Lumière (ANR-16-RHUS-0008), ONCOBIOME H2020 network, the Seerave Foundation, the Ligue contre le Cancer (équipe labelisée), Agence Nationale de la Recherche (ANR)—Projets blancs, ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases, Association pour la recherche sur le cancer (ARC), Cancéropôle Ile-de-France, FRM, a donation by Elior, the European Research Council (ERC), Fondation Carrefour, High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051), Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, LeDucq Foundation, the LabEx Immuno-Oncology, the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), CARE network (directed by Prof. Mariette, Kremlin Bicêtre AP-HP), and the SIRIC Cancer Research and Personalized Medicine (CARPEM). GI was supported by Italian Ministry of Health (grants Ricerca CorrenteLinea 1, 1 'Infezioni Emergenti e Riemergenti', projects COVID-2020-12371675 and COVID‐2020‐12371817). MMy and GG were supported by ANR Flash COVID-19 program and ARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University ICOViD programs (PI: GG)., ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), European Project: 825410,ONCOBIOME, École pratique des hautes études (EPHE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), COMBE, Isabelle, LUMIERE - - LUMIERE2016 - ANR-16-RHUS-0008 - RHUS - VALID, European Union’s Horizon 2020 research and innovation programme under grant agreement. - ONCOBIOME - 825410 - INCOMING, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Oncostat team [Villejuif], Institut Pasteur [Paris]-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 de Paris (UP), Unité BioMaps (BIOMAPS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Paris (UP), Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), 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), Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), and Université Paris Cité (UPC)
Subjects: Adult, DNA, Bacterial, Male, Time Factors, Adolescent, Article, Cohort Studies, Young Adult, Prognostic markers, Medical research, Enterobacteriaceae, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Lymphopenia, Nasopharynx, Neoplasms, Humans, Pandemics, Aged, Aged, 80 and over, SARS-CoV-2, COVID-19, Middle Aged, Prognosis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virus Shedding, Interferon Type I, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Viral, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Micrococcaceae
Abstract: International audience; Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B + FasL + , Eomes high TCF-1 high , PD-1 + CD8 + Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
Published: 2021

11. A Meta-Analysis of Semantic Memory in Mild Cognitive Impairment

Author: Ludovic Gardy, Emmanuel J. Barbeau, Mira Didic, Sven Joubert, Isabelle Rouleau, Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service de neurochirurgie [CHU Marseille], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-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)
Subjects: medicine.medical_specialty, Neurology, Cognitive Neuroscience, naming, [SHS.PSY]Humanities and Social Sciences/Psychology, Experimental and Cognitive Psychology, Audiology, behavioral disciplines and activities, 050105 experimental psychology, Mini Mental Status Examination, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Arts and Humanities (miscellaneous), mental disorders, medicine, Developmental and Educational Psychology, Semantic memory, 0501 psychology and cognitive sciences, 10. No inequality, Cognitive impairment, semantic memory, 05 social sciences, Neuropsychology, Alzheimer's disease, Random effects model, MCI, Feature (linguistics), meta-analysis, Neuropsychology and Physiological Psychology, Meta-analysis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: International audience; Introduction: Accumulating evidence over the past decade suggests that semantic deficits represent a consistent feature of Mild Cognitive Impairment (MCI). A meta-analysis was performed to examine if semantic deficits are consistently found in patients with MCI. Methods: Studies meeting all inclusion criteria were selected for the current meta-analysis. An effect size and a weight were calculated for each study. A random effect model was performed to assess the overall difference in semantic performances between MCI patients and healthy subjects. Results: 22 studies (476 healthy participants, 476 MCI patients, mean MMSE of the MCI patients: 27.05 ± 0.58) were included in the meta-analysis. Results indicate that MCI patients systematically performed significantly worse than healthy matched controls in terms of overall semantic performance (mean effect size of 1.02; 95% CI [0.80; 1.24]). Discussion: Semantic deficits are a key feature of MCI. Semantic tests should be incorporated in routine clinical assessments.
Published: 2021

12. Évaluer et promouvoir le partenariat entre les patients et les professionnels de santé: Co-construction de l'outil CADICEE pour les patients et leurs proches

Author: POMEY, Marie-Pascale, CLAVEL, Nathalie, NORMANDIN, Louise, DEL GRANDE, Claudio, GHADIRI DJAHANCHAH PHILIP, Sacha, FERNANDEZ MC AULEY, Isabel, BOIVIN, Antoine, FLORA, Luigi, JANVIER, Annie, KARAZIVAN, Philippe, PELLETIER, Jean-François, FERNANDEZ, Nicolas, PAQUETTE, Jesseca, DUMEZ, Vincent, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre d'Excellence du Partenariat avec les Patients et le Public (CEPPP, CR-CHUM), McGill University = Université McGill [Montréal, Canada], HEC Montréal (HEC Montréal), Risques, Epidémiologie, Territoire, INformations, Education et Santé (RETINES), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Centre d'Innovation du Partenariat avec les Patients et le Public, Faculté de médecine, Université Côte d'Azur (CI3P), Faculté de médecine, Université Côte d'Azur, Centre National de Ressources et Résilience (CN2R), Centre d'Etudes des Solidarités Sociales (Ass.1901) (CESOL), Association, Département de pédiatrie, division de néonatologie, centre de recherche, unité de recherche en étique et médecine de famille, Centre hospitalier universitaire Sainte-Justine, Université de Montréal, Montréal, Canada (CHU Sainte Justine, Université de Montréal), Direction Collaboration et Partenariat Patient, Faculté de médecine, Université de Montréal (DCPP), Institut universitaire en santé mentale de Montréal, Université de Montréal (UdeM), CENTRE PÉDAGOGIE APPLIQUÉE SCIENCES SANTÉ (CPASS), Réseau Québécois COVID-Pandemie (RQCP), FRQ-S (RQCCP-FRQ-S), and Flora, Luigi
Subjects: [SHS] Humanities and Social Sciences, ComputingMilieux_MISCELLANEOUS, [SHS]Humanities and Social Sciences
Abstract: International audience
Published: 2021

13. Long-term exposure to atmospheric metals assessed by mosses and mortality in France

Author: Lequy, Emeline, Siemiatycki, Jack, Leblond, Sébastien, Meyer, Caroline, Zhivin, Sergey, Vienneau, Danielle, de Hoogh, Kees, Goldberg, Marcel, Zins, Marie, Jacquemin, Bénédicte, Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Muséum national d'Histoire naturelle (MNHN), Swiss Tropical and Public Health Institute [Basel], 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 (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 ), CANCAIR-201501234, ARC FoundationARC Foundation, ADEMEADEME, Jonchère, Laurent, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), Université d'Angers (UA)-Université de Rennes 1 (UR1), and 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 )
Subjects: [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, lcsh:GE1-350, Air Pollutants, Time Factors, Bryophyta, Cohort Studies, Metals, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Air Pollution, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, lcsh:Environmental sciences, Environmental Monitoring, Proportional Hazards Models
Abstract: International audience; Background - Long-term exposure to air pollution affects health, but little is known about exposure to atmospheric metals. Estimating exposure to atmospheric metals across large spatial areas remains challenging. Metal concentrations in mosses could constitute a useful proxy. Here, we linked moss biomonitoring and epidemiological data to investigate the associations between long-term exposure to metals and mortality.Methods - We modelled and mapped 13 atmospheric metals from a 20-year national moss biomonitoring program to derive exposure estimates across France. In the population-based Gazel cohort, we included 11,382 participants from low to intermediate population density areas and assigned modelled metals to their residential addresses. We distinguished between airborne metals that are primarily of natural origin and those primarily of anthropogenic origin. Associations were estimated between exposure to metals and mortality (natural-cause, cardiovascular and respiratory), using Cox models, with confounder adjustment at individual level.Findings - Between 1996 and 2017, there were 1313 deaths in the cohort (including 181 cardiovascular and 33 respiratory). Exposure to the anthropogenic metals was associated with an increased risk of natural-cause mortality (hazard ratio of 1.16 [1.08-1.24] per interquartile range of exposure), while metals from natural sources were not.Interpretation - Some atmospheric anthropogenic metals may be associated with excess mortality - even in areas with relatively low levels of exposure to air pollution. Consistent with the previous literature, our findings support the use of moss biomonitoring as a tool to assess health effects of air pollution exposure at individual level.
Published: 2019

14. Influence of exposure assessment methods on associations between long-term exposure to outdoor fine particulate matter and risk of cancer in the French cohort Gazel

Author: Emeline Lequy, Mohammad Javad Zare Sakhvidi, Danielle Vienneau, Kees de Hoogh, Jie Chen, Jean-François Dupuy, Valérie Garès, Emilie Burte, Olivier Bouaziz, Alain Le Tertre, Vérène Wagner, Ole Hertel, Jesper Heile Christensen, Sergey Zhivin, Jack Siemiatycki, Marcel Goldberg, Marie Zins, Bénédicte Jacquemin, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), 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), Swiss Tropical and Public Health Institute [Basel], Utrecht University [Utrecht], Institut de Recherche Mathématique de Rennes (IRMAR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut Agro Rennes Angers, 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), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Aarhus University [Aarhus], and The Gazel Cohort Study was funded by EDF-GDF, and received grants from CAMIEG (Caisse d'assurance maladie des industries électrique et gazière) and the 'Comité de coordination des CMCAS'. This study was supported by the ARC French Foundation for cancer research (OCAPOL, CANCAIR-201501234).
Subjects: Air Pollutants, Environmental Engineering, PM, Epidemiology, [SDV]Life Sciences [q-bio], PM(2.5), Air pollution, Environmental Exposure, Survival analysis, Pollution, Air Pollution, Neoplasms, [SDE]Environmental Sciences, Humans, Environmental Chemistry, Particulate Matter, Lung cancer, Waste Management and Disposal
Abstract: Background: Many studies investigated the relationship between outdoor fine particulate matter (PM2.5) and cancer. While they generally indicated positive associations, results have not been fully consistent, possibly because of the diversity of methods used to assess exposure. Objectives: To investigate how using different PM2.5 exposure assessment methods influences risk estimates in the large French general population-based Gazel cohort (20,625 participants at enrollment) with a 26-year follow-up with complete residential histories. Methods: We focused on two cancer incidence outcomes: all-sites combined and lung. We used two distinct exposure assessment methods: a western European land use regression (LUR), and a chemistry-dispersion model (Gazel-Air) for France, each with a time series ≥20-years annual concentrations. Spearman correlation coefficient between the two estimates of PM2.5 was 0.71 across all person-years; the LUR tended to provide higher exposures. We used extended Cox models with attained age as time-scale and time-dependent cumulative exposures, adjusting for a set of confounders including sex and smoking, to derive hazard ratios (HRs) and their 95% confidence interval, implementing a 10-year lag between exposure and incidence/censoring. Results: We obtained similar two-piece linear associations for all-sites cancer (3711 cases), with a first slope of HRs of 1.53 (1.24–1.88) and 1.43 (1.19–1.73) for one IQR increase of cumulative PM2.5 exposure for the LUR and the Gazel-Air models respectively, followed by a plateau at around 1.5 for both exposure assessments. For lung cancer (349 cases), the HRs from the two exposure models were less similar, with largely overlapping confidence limits. Conclusion: Our findings using long-term exposure estimates from two distinct exposure assessment methods corroborate the association between air pollution and cancer risk.
Published: 2022

15. Contribution of Long-Term Exposure to Outdoor Black Carbon to the Carcinogenicity of Air Pollution: Evidence regarding Risk of Cancer in the Gazel Cohort

Author: Kees de Hoogh, Jean-François Dupuy, Jack Siemiatycki, Valérie Garès, Bénédicte Jacquemin, Ole Hertel, Danielle Vienneau, Emeline Lequy, Marcel Goldberg, Jesper H. Christensen, Marie Zins, Sergey Zhivin, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Swiss Tropical and Public Health Institute [Basel], Institut de Recherche Mathématique de Rennes (IRMAR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Aarhus University [Aarhus], 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), ARC Foundation (OCAPOL, CANCAIR-201501234), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université 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 ), and HAL UR1, Admin
Subjects: Adult, Fine particulate, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Air pollution, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Air Pollution, Neoplasms, medicine, Aerodynamic diameter, Humans, 030212 general & internal medicine, Carcinogen, 0105 earth and related environmental sciences, Air Pollutants, Research, Public Health, Environmental and Occupational Health, Carbon black, Environmental Exposure, Carbon, 3. Good health, [SDV] Life Sciences [q-bio], 13. Climate action, Cohort, Environmental science, Particulate Matter
Abstract: BACKGROUND: Black carbon (BC), a component of fine particulate matter [particles with an aerodynamic diameter ≤2:5 lm (PM2:5)], may contribute to carcinogenic effects of air pollution. Until recently however, there has been little evidence to evaluate this hypothesis. OBJECTIVE: This study aimed to estimate the associations between long-term exposure to BC and risk of cancer. This study was conducted within the French Gazel cohort of 20,625 subjects. METHODS: We assessed exposure to BC by linking subjects’ histories of residential addresses to a map of European black carbon levels in 2010 with back-and forward-extrapolation between 1989 and 2015. We used extended Cox models, with attained age as time-scale and time-varying cumulative exposure to BC, adjusted for relevant sociodemographic and lifestyle variables. To consider latency between exposure and cancer diagnosis, we implemented a 10-y lag, and as a sensitivity analysis, a lag of 2 y. To isolate the effect of BC from that of total PM2:5, we regressed BC on PM2:5 and used the residuals as the exposure variable. RESULTS: During the 26-y follow-up period, there were 3,711 incident cancer cases (all sites combined) and 349 incident lung cancers. Median base-line exposure in 1989 was 2.65 10−5 /m [interquartile range (IQR): 2.23–3.33], which generally slightly decreased over time. Using 10 y as a lag-time in our models, the adjusted hazard ratio per each IQR increase of the natural log-transformed cumulative BC was 1.17 (95% confidence interval: 1.06, 1.29) for all-sites cancer combined and 1.31 (0.93, 1.83) for lung cancer. Associations with BC residuals were also positive for both outcomes. Using 2 y as a lag-time, the results were similar. DISCUSSION: Our findings for a cohort of French adults suggest that BC may partly explain the association between PM2:5 and lung cancer. Additional studies are needed to confirm our results and further disentangle the effects of BC, total PM2:5, and other constituents. https://doi.org/10.1289/EHP8719.
Published: 2021

16. Quels enseignements tirer de l’expérience de la pandémie de la COVID-19 dans l’accompagnement des patients chroniques ?

Author: Berkesse, Alexandre, Gross, Olivia, École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'Excellence du Partenariat avec les Patients et le Public (CEPPP, CR-CHUM), CAPPS Bretagne, Rennes, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Laboratoire éducations et promotion de la santé (LEPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, and CCSD, Accord Elsevier
Subjects: Patient experience, Organisations apprenantes, Démocratie en santé, Patient partnership, Health support, Pouvoir d’agir, Learning organizations, Expérience patient, Health democracy, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Partenariat patient, Empowerment, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Accompagnement
Abstract: From an ethical, sanitary, social and political perspective, the first months of the COVID-19 pandemic were – and still are – a destabilizing experience. This was particularly so for people living with one or more chronic diseases whose quality of life, and sometimes survival, depends on a large number of decisions and actions in which they rarely participate. Such healthcare practices and situations are not new, but this epidemic period has brought them to the fore. In general, among the difficulties encountered during the first months of the COVID-19 pandemic, the most fundamental were the difficulty of supporting and developing the autonomy of people and of integrating the patient experience to think, perform and organize healthcare and health services. Without practices of continuous adjustment of the health system to the concerns, expectations and needs of the actors of health, without having as a horizon the development of people's power to act, the health system found itself to concentrate the essential of its resources on a limited type of users and acts. However, even in this context, alternatives to healthcare and health services have emerged, in particular through the actions of patient associations. It is essential that we learn from these first months to refocus health decisions on participatory actions that are anchored in the individual and collective experiences of the actors of health. © 2020 Elsevier Masson SAS, Du point de vue éthique, sanitaire, social et politique, les premiers mois de l’épidémie (pandémie) à coronavirus 2019 (COVID-19) ont été – et restent – une expérience déstabilisante. Cela le fut en particulier pour les personnes vivant avec une ou plusieurs maladies chroniques, dont la qualité de vie, et parfois la survie, dépend d’un grand nombre de décisions et de coopérations auxquelles elles ne participent que rarement. De telles pratiques de soins et de telles situations ne sont pas nouvelles, mais cette période épidémique les a davantage mis en lumière. Parmi les difficultés rencontrées au cours des premiers mois de la pandémie de la COVID-19, les plus fondamentales furent la difficulté de soutenir et de développer l’autonomie des personnes et d’intégrer « l’expérience patient » pour penser, effectuer et organiser les soins et les services de santé. Sans pratiques d’ajustement continu du système de santé aux préoccupations, attentes et besoins des acteurs de la santé, sans avoir pour horizon le développement des pouvoirs d’agir des personnes, le système de santé s’est retrouvé à concentrer l’essentiel de ses ressources sur des types limités d’actes et d’usagers. Pourtant, même dans ce contexte, des alternatives de soins et de services de santé ont pu émerger, en particulier à travers les actions des associations de malades. Apprendre de ces premiers mois invite à recentrer les décisions en santé sur des modalités participatives qui soient ancrées dans les expériences individuelles et collectives des acteurs.
Published: 2021

17. miRNA repertoires of cystic fibrosis ex vivo models highlight miR‐181a and miR ‐101 that regulate WISP1 expression

Author: Emmanuelle Brochiero, Mireille Claustres, Magali Taulan-Cadars, Solenne Bleuse, Anne Bergougnoux, Alexandra Pommier, Jessica Varilh, Jennifer Bonini, Michel Koenig, Karine Deletang, Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), and Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM)
Subjects: 0301 basic medicine, Gene isoform, lung disease, Genetic enhancement, Gene Expression, miR-181a, wound healing, Biology, Cystic fibrosis, Deep sequencing, Pathology and Forensic Medicine, CCN Intercellular Signaling Proteins, cystic fibrosis, 03 medical and health sciences, 0302 clinical medicine, IsomiR, Cell Movement, Genes, Reporter, Proto-Oncogene Proteins, Gene expression, microRNA, isomiR, medicine, Humans, RNA, Messenger, Cell Proliferation, miRNA, WISP1, medicine.disease, miR-101, small RNAseq, gene therapy, Up-Regulation, 3. Good health, MicroRNAs, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Tissue Array Analysis, 030220 oncology & carcinogenesis, Cancer research, Ex vivo
Abstract: Cystic fibrosis (CF), a genetic disorder, is characterized by chronic lung disease. Small non-coding RNAs are key regulators of gene expression and participate in various processes, which are dysregulated in CF; however, they remain poorly studied. Here, we determined the complete microRNAs (miRNAs) expression pattern in three CF ex vivo models. The miRNA profiles of air-liquid interface cultures of airway epithelia (bronchi, nasal cells, and nasal polyps) samples from patients with CF and non-CF controls were obtained by deep sequencing. Compared with non-CF controls, several miRNAs were deregulated in CF samples; for instance, miR-181a-5p and the miR-449 family were upregulated. Moreover, mature miRNAs often showed variations (i.e. isomiRs) relative to their reference sequence, such as miR-101, suggesting that miRNAs consist of heterogeneous repertoires of multiple isoforms with different effects on gene expression. Analysis of miR-181a-5p and miR-101-3p roles indicated that they regulate the expression of WISP1, a key component of cell proliferation/migration programs. We showed that miR-101 and miR-181a-5p participated in aberrant recapitulation of wound healing programs by controlling WISP1 mRNA and protein level. Our miRNA expression data bring new insights into CF physiopathology and define new potential therapeutic targets in CF. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Published: 2021

18. Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

Author: Ajit S. Puri, Allan Taylor, Huynh Le Vu, Tatemi Todaka, Teddy Y. Wu, Octavio M. Pontes-Neto, Eytan Raz, Pedro Lylyk, Jasmine Johann, Roberta Novakovic, Hormuzdiyar H. Dasenbrock, Francisco Mont’Alverne, Nobuyuki Sakai, Melanie Walker, Hugh Stephen Winters, Ossama Mansour, Yohei Takenobu, Gregory Walker, Miki Fujimura, Saif Bushnaq, Odysseas Kargiotis, Nabeel Herial, Markus A Möhlenbruch, Malveeka Sharma, Hiroshi Tokimura, Maxim Mokin, Jean Raymond, Michael D. Hill, Amal Abou-Hamden, Leonardo Renieri, Serdar Geyik, Yuri Sugiura, Luisa Fonseca, Roberto Crosa, Fabricio O Lima, Ameer E Hassan, Viet Quy Nguyen, Jane G. Morris, Steven W. Hetts, Jawad F. Kirmani, Matthew S. Tenser, Muhammad M. Qureshi, Gianmarco Bernava, Mahmoud H Mohammaden, Verónica V. Olavarría, Jun Deguchi, André Beer-Furlan, Steve M. Cordina, Hiroshi Yamagami, Mohamad Abdalkader, Toshiyuki Fujinaka, Clifford J. Eskey, Rotem Sivan-Hoffmann, Hao Zhang, Anirudh Kulkarni, Brendan Steinfort, Özlem Aykaç, Barbara Voetsch, Alex Brehm, Italo Linfante, Wenguo Huang, Omer Eker, M. Luis Silva, Pascal Jabbour, Lissa Peeling, Mollie McDermott, Pascale Lavoie, Kazutaka Sonoda, Thomas Devlin, Alicia C. Castonguay, Jin Soo Lee, Diogo C Haussen, Dileep R. Yavagal, Thanh N. Nguyen, Umair Rashid, Vasu Saini, Raghid Kikano, Hiroyuki Hashimoto, Masaaki Uno, Saima Ahmad, Artem Kaliaev, Eiji Hagashi, Ajay K. Wakhloo, Romain Bourcier, Ryoo Yamamoto, Jesse M. Thon, Georgios Tsivgoulis, Dorothea Altschul, Achmad Fidaus Sani, Satoshi Yamada, Varsha Singh, David S Liebeskind, Tatsuo Amano, Anchalee Churojana, Juan F. Arenillas, Junichi Iida, Charles C. Matouk, Nobuyuki Ohara, Osama O. Zaidat, Mario Martínez-Galdámez, Chandril Chugh, Don Frei, Vanessa Chalumeau, Brijesh P Mehta, Marios Psychogios, Anna Luisa Kühn, Leticia C Rebello, Xianjin Shang, Hosam Al-Jehani, Hiroki Fukuda, Hong Gee Roh, Gisele Sampaio Silva, Rakesh Khatri, Kenichi Todo, Amal Al Hashmi, Alex Bou Chebl, Sunil A Sheth, Zhongming Qiu, Oriana Cornett, Zhengzhou Yuan, Wazim Izzath, Hesham Masoud, Rodrigo Rivera, Michel Piotin, Vikram Huded, Mamoru Murakami, Mohamed Teleb, Viktor Szeder, Ruchir Shah, Dheeraj Gandhi, John Thornton, Michael Chen, Vitor Mendes Pereira, Nadia Hammami, Alice Ma, Anna M. Cervantes-Arslanian, James E. Siegler, Seby John, Carlos Ynigo Lopez, Mudassir Farooqui, David Ozretić, Takuya Kanamaru, Romain Guile, Daisuke Watanabe, Kosuke Miyake, Alejandro Rodriguez Vasquez, Patrick Nicholson, Yuki Yamamoto, William J. Mack, Naoto Kimura, Simon Mathew John, Robert Fahed, Yuji Matsumaru, David Y. Chung, Rishi Gupta, Ryuhei Kono, Michael Frankel, Victor S. Lopez Rivera, Johanna T. Fifi, Raul G Nogueira, Paolo Machi, Tudor G. Jovin, Jordi Blasco, Emma Griffin, Salvatore Mangiafico, Masafumi Morimoto, Jun Luo, Santiago Ortega-Gutierrez, Monika Killer-Oberpfalzer, Daniel Giansante Abud, Syed I. Hussain, Fawaz Al-Mufti, Yusuke Sugimura, Atilla Özcan Özdemir, Stephan A. Mayer, Sumeet Multani, Adel Alhazzani, Alhamza R Al-Bayati, Michael Kelly, Lee A Birnbaum, Shadi Yaghi, Jeyaraj D Pandian, Ji Man Hong, Junsuke Shimbo, Johnny Ho-Yin Wong, Elena A. Cora, Laura Mechtouff, Pedro S.C. Magalhães, Pablo M. Lavados, Yuichi Murayama, Dong Hun Shin, Simon Nagel, Ken Wong, Jose Antonio Fiorot, Jeremy Payne, Randall C. Edgell, Adrienne Weeks, CarMeN, laboratoire, Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Emory University School of Medicine, Emory University [Atlanta, GA], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), National Hospital Organization Osaka National Hospital [Japon] (NHO Osaka National Hospital), Alexandria University [Alexandrie], Boston Medical Center [Boston, MA, USA] (BMC), Xinqiao Hospital [Chongqing, China] (XH), University of Cape Town, La Sagrada Familia Clinic/Clínica La Sagrada Familia [Buenos Aires, Argentina] (LSFC), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), 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), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Hospital General de Fortaleza [Fortaleza, Brazil] (HGF), Nottingham University Hospitals NHS Trust [UK], Kobe City Medical Center General Hospital [Kobe, Hyogo, Japan] (KCMCGH), Azienda Ospedaliero-Universitaria Careggi [Firenze, Toscana, Italy] (AOUC), University Hospital Centre Zagreb, Partenaires INRAE, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cleveland Clinic Abu Dhabi [Abou Dabi, Émirats arabes unis], Hôpital de Beaumont [Dublin, Ireland] (HB), Hospital-Estadual Central [Vitoria, Brazil] (HEC), Instituto de NeuroCirugía Asenjo, Institut national de neurologie Mongi-Ben Hamida [Tunis], Hue Central Hospital [Thua Thien Hue, Vietnam] (HCH), University of California [San Francisco] (UC San Francisco), University of California (UC), Centre hospitalier universitaire de Nantes (CHU Nantes), Washington University School of Medicine (WUSM), University of Washington [Seattle], Englewood Hospital and Medical Center [Englewood], Jefferson (Philadelphia University + Thomas Jefferson University), Westchester Medical Center [Valhalla, New York, USA] (WMC), Eskisehir Osmangazi University, University of Maryland School of Medicine, University of Maryland System, MAX Superspecialty Hospital [Saket, New Delhi, India] (MSH), Yale School of Medicine [New Haven, Connecticut] (YSM), Université Laval [Québec] (ULaval), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Rush University Medical Center [Chicago], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of Toronto, NH Mazumdar Shah Medical Center [Bangalore, India] (NHMSMC), IMS Tokyo-Katsushika General Hospital [Tokyo, Japan], Gachon University [Seongnam, Korea] (GU), Hospital Municipal Sao Jose [Joinville, Santa Catarina, Brazil] (HMSJ), Lau Medical Center [Beirut, Lebanon] (LMC), University of Iowa [Iowa City], Royal Adelaide Hospital [Adelaide Australia], Kyorin University [Tokyo, Japan], Yokohama Brain and Spine Center [Yokohama, Japan] (YBSC), Dalhousie University [Halifax], Rambam Health Care Campus [Haifa, Israel], Centro Endovascular Neurologico Medica Uruguaya [Montevideo, Uruguay] (CENMU), Heidelberg University Hospital [Heidelberg], Imam Abdulrahman bin Faisal University [Alkhobar, Saudi Arabia] (IAFU), McGovern Medical School [Houston, TX, USA] (McGMS), The University of Texas Health Science Center at Houston (UTHealth), Cooper Medical School of Rowan University [Camden] (CMSRU), Airlangga University [Jawa Timur, Indonesia] (AU), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Geneva University Hospitals and Geneva University, Universidade de São Paulo = University of São Paulo (USP), Beth Israel Lahey Health [Burlington, MA, USA] (BILH), New York University School of Medicine (NYU Grossman School of Medicine), Memorial Neuroscience Institute [Pembroke Pines, FL, USA] (MNI), Iwate Prefectural Central Hospital [Morioka, Iwate, Japan] (IPCH), Japanese Red Cross Musashino Hospital [Tokyo], Ajou University, University of Ottawa [Ottawa], Saga-ken Medical Centre Koseikan [Saga, Japan] (SMCK), University of South Alabama, Konkuk University [Seoul], Royal Free Hospital [London, UK], Hospital Clinico Universitario de Valladolid [Castilla y León, Spain] (HCUV), Universidad de Valladolid [Valladolid] (UVa), Instituto de Ciencia de Materiales de Aragón [Saragoza, España] (ICMA-CSIC), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Hospital Clínic de Barcelona [Catalonia, Spain], Centro Hospitalar Universitário de São João [Porto], Christchurch Hospital [Christchurch, New Zealand] (CH), University Hospital Basel [Basel], University of Southern California (USC), Kohnan Hospital - Sendai [Miyagi, Japan], University of Texas Southwestern Medical Center [Dallas], Nara City Hospital [Nara, Japan] (NCH), Toyonaka Municipal Hospital [Osaka, Japan] (TMH), Kagoshima City Hospita [Kagoshima, Japan] (KCH), Texas Tech University System [Lubbock, TX, USA] (TTUS), University of Saskatchewan [Saskatoon] (U of S), National Institute of Information and Communications Technology [Tokyo, Japan] (NICT), Royal Prince Alfred Hospital [Camperdown, Australia] (RPAH), Banner Desert Medical Center [Mesa, AZ, USA] (BDMC), Japanese Red Cross Matsue Hospital [Shimane, Japan] (JRCMH), Shiroyama Hospital [Osaka, Japan] (SH), Niigata City General Hospital [Niigata, Japan] (NCGH), Sugimura Hospital [Kumamoto, Japan] (SH), Kawasaki Medical School [Kurashiki, Japan] (KMS), Osaka Red Cross Hospital [Osaka, Japan] (ORCH), Université de Tsukuba = University of Tsukuba, Saiseikai Central Hospital [Tokyo, Japan] (SCH), Kinikyo Chuo Hospital - Sapporo [Hokkaido, Japan] (KCHS), NTT Medical Center Tokyo [Tokyo, Japan] (NTTMCT), Yokohama Shintoshi Neurosurgical Hospital [Yokohama, Japan]. (YSNH), Osaka General Medical Center [Osaka, Japan] (OGMC), University of Miami Leonard M. Miller School of Medicine (UMMSM), Bon Secours Mercy Health System [Toledo, OH, USA] (BSMHS), Maoming City Hospital [Guandong, China] (MCH), Miami Cardiac & Vascular Institute [Miami, FL, USA] (MC&VI), Hackensack University Medical Center [Hackensack], David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of Tennessee [Chattanooga] (UTC), The University of Texas at San Antonio (UTSA), Mianyang 404 Hospital [Sichuan, China] (M404H), Siriraj Hosital - Mahidol University [Bangkok, Thailand] (SHMU), SUNY Upstate Medical University, State University of New York (SUNY), Royal North Shore Hospital (RNSH), The University of Texas Rio Grande Valley [Harlingen, TX, USA] (UTRGV), Khoula Hospital [Muscat, Oman] (Ministry of Health - KH), University of Michigan [Ann Arbor], University of Michigan System, University of South Florida [Tampa] (USF), Henry Ford Health System [Detroit, MI, USA] (HFHS), Metropolitan Hospital [Piraeus, Greece] (MH), National and Kapodistrian University of Athens (NKUA), Maine Medical Center, Dartmouth Hitchcock Medical Center [Lebanon, NH, USA] (DHMC), Centro Universitário Feevale (BRAZIL), The Valley Hospital [Ridgewood, NJ, USA] (TVH), St Joseph's University Medical Center [Paterson, NJ, USA] (StJUMC), Christian Medical College and Hospital Ludhiana [Punjab, India] (CMCHL), Universidad del Desarrollo, University Graduate School of Medicine [Osaka, Japan], Tokushima University, Universidade Federal de São Paulo, Istanbul Aydin University [İstanbul, Turkey] (IAU), Swedish Medical Center [Englewood, CO, USA] (SMC), Bayhealth Medical Center [Dover, DE, USA] (BMC), Saiseikai Fukuoka General Hospital [Fukuoka, Japan] (SFGH), Osaka Rosai Hospital - Sakai [Osaka, Japan] (ORHS), King Saud University [Riyadh] (KSU), Mount Sinai Health System, University of Calgary, Huzhou University [Zhejiang], The Affiliated Hospital of Southwest Medical University - Luzhou [Sichuan, China] (TAHSMUL), Yijishan Hospital of Wannan Medical College [Wuhu, Anhui, China] (YHWMC), University of Toledo, WellStar Health System [Marietta, GA, USA] (WHS), Institut National de la Recherche Scientifique [Québec] (INRS), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), SVIN COVID-19 Registry, the Middle East North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO), Japanese Society of Vascular and Interventional Neurology Society (JVIN), University of California [San Francisco] (UCSF), University of California, Yale University School of Medicine, University of São Paulo (USP), and University of California-University of California
Subjects: [SDV]Life Sciences [q-bio], COVID-19, Subarachnoid Hemorrhage* / diagnostic imaging, 030204 cardiovascular system & hematology, Intracranial Aneurysm* / therapy, lcsh:RC346-429, 0302 clinical medicine, Pandemic, Myocardial infarction, Prospective Studies, Stroke, Original Research, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Intracranial Aneurysm* / diagnostic imaging, Cardiology, Subarachnoid haemorrhage, haemorrhage, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Subgroup analysis, subarachnoid, Intracranial Aneurysm* / epidemiology, 03 medical and health sciences, Aneurysm, Internal medicine, medicine, Humans, coil, cardiovascular diseases, Pandemics, lcsh:Neurology. Diseases of the nervous system, Retrospective Studies, business.industry, SARS-CoV-2, Intracranial Aneurysm, Subarachnoid Hemorrhage, medicine.disease, infection, nervous system diseases, Mechanical thrombectomy, Cross-Sectional Studies, aneurysm, Neurology (clinical), Subarachnoid Hemorrhage* / epidemiology, business, 030217 neurology & neurosurgery
Abstract: BackgroundDuring the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study’s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.MethodsWe conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March–31 May 2020. The prior 1-year control period (1 March–31 May 2019) was obtained to account for seasonal variation.FindingsThere was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI −24.3% to −20.7%, pInterpretationThere was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
Published: 2021

19. Cost-effectiveness of low-dose colchicine after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)

Author: François Roubille, Simon Kouz, Jean-Claude Tardif, Marie-Pierre Dubé, Rafael Diaz, Aldo P. Maggioni, Wolfgang Koenig, Marie-Claude Guertin, Fausto J. Pinto, Dominic Mitchell, Michelle Samuel, Lucie Blondeau, Nadia Bouabdallaoui, Habib Gamra, Jean Grégoire, Petr Ostadal, Philippe L. L’Allier, Colin Berry, Ghassan S. Kiwan, Andreas Orfanos, Reda Ibrahim, David D. Waters, Jacques LeLorier, Jose Lopez-Sendon, Mylène Provencher, Paul Khairy, Repositório da Universidade de Lisboa, Montreal Heart Institute - Institut de Cardiologie de Montréal, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Division of Cardiology, Zuckerberg San Francisco General Hospital, Department of Medicine, University of California, San Francisco, USA., Cardiology Department, CHULN, Centro Cardiovascular da Universidade de Lisboa, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal, Research Center [Associazione Nazionale Medici Cardiologi Ospedalieri] (ANMCO Research Center), Associazione Nazionale Medici Cardiologi Ospedalieri [Firenze] (ANMCO), Department of General Surgery. Surgical Oncology Unit, Reina Sofía University Hospital, Estudios Clinicos Latinoamerica, Rosario, Argentina, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Department of Internal Medicine II – Cardiology, Universität Ulm - Ulm University [Ulm, Allemagne], University of Ulm (UUlm), Department of Cardiology Cardiovascular Center, NaHomolce Hospital, Prague, Czech Republic, Na Homolce Hospital, Prague, Czech Republic., Cardiology department Hospital Universitario La Paz. UAM. IdiPaz. CIBER-CV, Madrid, Spain, CHU Fattouma Bourguiba [Monastir] (HFB), Bellevue Medical Center, Beirut, Lebanon, Montreal Health Innovations Coordinating Center [Montreal Heart Institute] (MHICC), Institut de Cardiologie et Pneumologie de Québec, Quebec City, Université Laval [Québec] (ULaval), Centre Hospitalier Régional de Lanaudière, Joliette, Canada, Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours, Logimetrix Inc, Canada, Montreal Health Innovation Coordination Center, Montreal Heart Institute Coordinating Centre (MHICC), Université de Montréal (UdeM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT), MORNET, Dominique, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Canada, medicine.medical_specialty, Heart disease, Cost effectiveness, Cost-Benefit Analysis, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Placebo, Angina, 03 medical and health sciences, 0302 clinical medicine, Myocardial infarction, Internal medicine, medicine, Humans, AcademicSubjects/MED00200, 030212 general & internal medicine, Stroke, health care economics and organizations, ComputingMilieux_MISCELLANEOUS, business.industry, Health Policy, Clopidogrel, medicine.disease, 3. Good health, Quality-adjusted life year, [SDV] Life Sciences [q-bio], Original Article, Quality-Adjusted Life Years, Cardiology and Cardiovascular Medicine, business, Colchicine, medicine.drug
Abstract: © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com, Aims: In the randomized, placebo-controlled Colchicine Cardiovascular Outcomes Trial (COLCOT) of 4745 patients enrolled within 30 days after myocardial infarction (MI), low-dose colchicine (0.5 mg once daily) reduced the incidence of the primary composite endpoint of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization. To assess the in-trial period and lifetime cost-effectiveness of low-dose colchicine therapy compared to placebo in post-MI patients on standard-of-care therapy. Methods and results: A multistate Markov model was developed incorporating the primary efficacy and safety results from COLCOT, as well as healthcare costs and utilities from the Canadian healthcare system perspective. All components of the primary outcome, non-cardiovascular deaths, and pneumonia were included as health states in the model as both primary and recurrent events. In the main analysis, a deterministic approach was used to estimate the incremental cost-effectiveness ratio (ICER) for the trial period (24 months) and lifetime (20 years). Over the in-trial period, the addition of colchicine to post-MI standard-of-care treatment decreased the mean overall per-patient costs by 47%, from $502 to $265 Canadian dollar (CAD), and increased the quality-adjusted life years (QALYs) from 1.30 to 1.34. The lifetime per-patient costs were further reduced (69%) and QALYs increased with colchicine therapy (from 8.82 to 11.68). As a result, both in-trial and lifetime ICERs indicated colchicine therapy was a dominant strategy. Conclusion: Cost-effectiveness analyses indicate that the addition of colchicine to standard-of-care therapy after MI is economically dominant and therefore generates cost savings.
Published: 2021

20. Application of two job indices for general occupational demands in a pooled analysis of case–control studies on lung cancer

Author: Neil E. Caporaso, Ann Olsson, Dana Mates, Cristina Fortes, Tamás Pándics, Simonato Lorenzo, Jolanta Lissowska, Kurt Straif, Beate Pesch, Jan Hovanec, Guillermo Fernández-Tardón, Hans Kromhout, Pascal Guénel, Karl-Heinz Jöckel, Eleonora Fabianova, Roel Vermeulen, Wolfgang Ahrens, Stefan Karrasch, Hermann Pohlabeln, John K. Field, Joachim Schüz, Vladimir Bencko, Beata Świątkowska, Thomas Brüning, Dario Consonni, Danièle Luce, Thomas Behrens, Maria Teresa Landi, David I. Conway, John R. McLaughlin, Per Gustavsson, Paolo Boffetta, Marie-Élise Parent, Vladimir Janout, Franco Merletti, Lorenzo Richiardi, Lenka Foretova, Heinz-Erich Wichmann, David Zaridze, Swaantje Casjens, Paul A. Demers, Jack Siemiatycki, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Ruhr-Universität Bochum [Bochum], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), University of Glasgow, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), 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, 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 (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 ), Ruhrlandklinik University Hospital, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Universität Bremen, Helmholtz Zentrum München = German Research Center for Environmental Health, Ludwig-Maximilians-Universität München (LMU), Karolinska Institute, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli studi di Torino = University of Turin (UNITO), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Toronto, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Universidad de Oviedo [Oviedo], CIBER de Epidemiología y Salud Pública (CIBERESP), N.N. Blokhin National Medical Research Center of Oncology, Nofer Institute of Occupational Medicine (NIOM), National Public Health Centre, Medical University of Warsaw - Poland, University of Liverpool, National Institute of Public Health [Romania] (INSP), Charles University [Prague] (CU), Masaryk Memorial Cancer Institute (MMCI), Palacky University Olomouc, Universiteit Utrecht, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Stony Brook University [SUNY] (SBU), State University of New York (SUNY), German Social Accident Insurance [FP 271], 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)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Helmholtz-Zentrum München (HZM), University of Turin, University Hospital of Padua, Masaryk Memorial Cancer Institute (RECAMO), Chard-Hutchinson, Xavier, Hovanec J., Siemiatycki J., Conway D.I., Olsson A., Guenel P., Luce D., Jockel K.-H., Pohlabeln H., Ahrens W., Karrasch S., Wichmann H.-E., Gustavsson P., Consonni D., Merletti F., Richiardi L., Simonato L., Fortes C., Parent M.-E., McLaughlin J.R., Demers P., Landi M.T., Caporaso N., Fernandez-Tardon G., Zaridze D., Swiatkowska B., Pandics T., Lissowska J., Fabianova E., Field J.K., Mates D., Bencko V., Foretova L., Janout V., Kromhout H., Vermeulen R., Boffetta P., Straif K., Schuz J., Casjens S., Pesch B., Bruning T., and Behrens T.
Subjects: Male, Lung Neoplasms, Occupational prestige, Short Communication, [SDV]Life Sciences [q-bio], Medizin, Logistic regression, 03 medical and health sciences, occupational demand, 0302 clinical medicine, Occupational Exposure, medicine, Odds Ratio, case–control, Humans, cancer, Risk factor, Occupations, Lung cancer, job index, business.industry, Environmental and Occupational Health, Smoking, Public Health, Environmental and Occupational Health, Cancer, Odds ratio, Social prestige, medicine.disease, 030210 environmental & occupational health, Confidence interval, Key terms job index, [SDV] Life Sciences [q-bio], lung cancer, Tumor subtype, Case-Control Studies, Female, Public Health, Public aspects of medicine, RA1-1270, business, Psychosocial, Tumor Subtype, Job index, Social Prestige, Demography
Abstract: The German Social Accident Insurance supported this study (grant number FP 271)., Hovanec J, Siemiatycki J, Conway DI, Olsson A, Guenel P, Luce D, Jöckel KH, Pohlabeln H, Ahrens W, Karrasch S, Wichmann HE, Gustavsson P, Consonni D, Merletti F, Richiardi L, Lorenzo S, Fortes C, Parent MÉ, McLaughlin JR, Demers P, Landi MT, Caporaso N, Fernández-Tardón G, Zaridze D, Świątkowska B, Pándics T, Lissowska J, Fabianova E, Field JK, Mates D, Bencko V, Foretova L, Janout V, Kromhout H, Vermeulen R, Boffetta P, Straif K, Schüz J, Casjens S, Pesch B, Brüning T, Behrens T.
Published: 2021

21. Echocardiographic evidence of left ventricular untwisting-filling interplay

Author: Amir Hodzic, Damien Garcia, Eric Saloux, Paula A.B. Ribeiro, Amélie Ethier, James D. Thomas, Paul Milliez, Hervé Normand, Francois Tournoux, Mobilités : Vieillissement, Pathologie, Santé (COMETE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie et de pathologie vasculaire [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Imagerie Ultrasonore, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bluhm Cardiovascular Institute at Northwestern Memorial Hospital, Garcia, Damien, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), 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)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Northwestern University [Chicago, Ill. USA]
Subjects: Adult, Male, [PHYS.PHYS.PHYS-FLU-DYN]Physics [physics]/Physics [physics]/Fluid Dynamics [physics.flu-dyn], lcsh:Diseases of the circulatory (Cardiovascular) system, Diastolic function, [INFO.INFO-TS] Computer Science [cs]/Signal and Image Processing, Heart Ventricles, [SDV]Life Sciences [q-bio], [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [SHS.PSY]Humanities and Social Sciences/Psychology, Ventricular Function, Left, Young Adult, Intraventricular pressure gradient, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Diastole, Ventricular Pressure, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Untwisting rate, Research, [SCCO.NEUR]Cognitive science/Neuroscience, Reproducibility of Results, Stroke Volume, [PHYS.PHYS.PHYS-FLU-DYN] Physics [physics]/Physics [physics]/Fluid Dynamics [physics.flu-dyn], Echocardiography, Doppler, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, lcsh:RC666-701, Female, Color Doppler M-mode, Blood Flow Velocity
Abstract: Background: Left ventricular untwisting generates an early diastolic intraventricular pressure gradient (DIVPG) than can be quantified by echocardiography. We sought to confirm the quantitative relationship between peak untwisting rate and peak DIVPG in a large adult population.Methods: From our echocardiographic database, we retrieved all the echocardiograms with a normal left ventricular ejection fraction, for whom color Doppler M-Mode interrogation of mitral inflow was available, and left ventricular untwisting rate was measurable using speckle tracking. Standard indices of left ventricular early diastolic function were assessed by Doppler (peaks E, e’ and Vp) and speckle tracking (peak strain rate Esr). Load dependency of DIVPG and untwisting rate was evaluated using a passive leg raising maneuver. Results: We included 154 subjects, aged between 18 to 77 years old, 63% were male. Test-retest reliability for color Doppler-derived DIVPG measurements was good, the intraclass correlation coefficients were 0.97 [0.91-0.99] and 0.97 [0.67-0.99] for intra- and inter-observer reproducibility, respectively. Peak DIVPG was positively correlated with peak untwisting rate (r = 0.73, P < 0.001). On multivariate analysis, peak DIVPG was the only diastolic parameter that was independently associated with untwisting rate. Age and gender were the clinical predictive factors for peak untwisting rate, whereas only age was independently associated with peak DIVPG. Untwisting rate and DIVPG were both load-dependent, without affecting their relationship. Conclusions: Color Doppler-derived peak DIVPG was quantitatively and independently associated with peak untwisting rate. It thus provides a reliable flow-based index of early left ventricular diastolic function.
Published: 2020

22. Immunodynamics of explanted human tumors for immuno‐oncology

Author: Dubuisson, Agathe, Fahrner, Jean Eudes, Goubet, Anne Gaëlle, Terrisse, Safae A., Voisin, Nicolas, Bayard, Charles, Lofek, Sébastien, Drubay, Damien, Bredel, Delphine, Mouraud, Séverine, Susini, Sandrine, Cogdill, Alexandria P., Rebuffet, Lucas, Ballot, Elise, Jacquelot, Nicolas, Thomas de Montpreville, Vincent, Casiraghi, Odile, Radulescu, Camélia, Ferlicot, Sophie, Figueroa, David J., Yadavilli, Sapna, Waight, Jeremy D., Ballas, Marc S., Hoos, Axel X., Condamine, Thomas, Parier, Bastien, Gaudillat, Christophe, Routy, Bertrand, Ghiringhelli, François, Derosa, Lisa, Breuskin, Ingrid, Rouanne, Mathieu, André, Fabrice, Lebacle, Cédric, Baumert, Hervé, Wislez, Marie, Fadel, Élie, Cremer, Isabelle, Albiges, Laurence, Geoerger, Birgit, Scoazec, Jean Yves, Loriot, Yohann, Kroemer, Guido, Marabelle, Aurélien, Bonvalet, Mélodie, Zitvogel, Laurence, Immunologie des tumeurs et immunothérapie (UMR 1015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), The University of Texas M.D. Anderson Cancer Center [Houston], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, The Walter and Eliza Hall Institute of Medical Research (WEHI), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Département de médecine oncologique [Gustave Roussy], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], Direction de la recherche [Gustave Roussy], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hôpital 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), Karolinska University Hospital [Stockholm], Chancellerie des Universités de Paris Agence Nationale de la Recherche, ANR Seerave Foundation Association pour la Recherche sur le Cancer, ARC ANR‐16‐RHUS‐0008 Ligue Contre le Cancer European Commission, EC Fondation pour la Recherche Médicale, FRM Institut National Du Cancer, INCa Institut Universitaire de France, IUF European Research Council, ERC Fondation Leducq RP170067 Association pour la Recherche sur le Cancer, ARC, LZ and GK were supported by the Ligue contre le Cancer (équipe labelisée), Agence Nationale de la Recherche (ANR) francogermanique ANR‐19‐CE15‐0029, ANR Projects blancs, ANR under the frame of E‐Rare‐2, the ERA‐Net for Research on Rare Diseases, Association pour la recherche sur le cancer (ARC), Bristol‐Myers Squibb Company (International Immuno‐Oncology Network), Cancéropôle Ile‐de‐France, Chancellerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM), a donation by Elior, the European Commission (ArtForce), the European Research Council (ERC), Fondation Carrefour, Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, LeDucq Foundation, the LabEx Immuno‐Oncology, the RHU Torino Lumière (ANR‐16‐RHUS‐0008), H2020 ONCOBIOME, the Seerave Foundation, the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), FHU CARE, Dassault, and Badinter Philantropia, and the Paris Alliance of Cancer Research Institutes (PACRI). AC is supported by the CPRIT Research Training Program (RP170067). JEF was supported by Transgene and AGG was supported by FRM. AM has been or is currently an investigator in clinical trials sponsored by BMS, MSD, GSK/Tesaro, Janssen, Roche/Genentech, Pfizer, Astra Zeneca (AZ), Amgen. AM has been or is currently a member of Clinical Trial Scientific Steering Committee for AZ and GSK. AM has been or is currently a member of the scientific advisory board of the following companies: Merck Serono, Novartis, BMS, Symphogen, Amgen, Tesaro/GSK, Pfizer, Astra Zeneca/Medimmune, Servier, Sanofi. AM has provided Scientific & Medical Consulting to the following companies: Roche, Sanofi. AM is a member of the Data Safety and Monitoring Board for the following trial NCT02423863 (TLR3 agonist, Oncovir). AM has received research funding and or drug supply for pre‐Clinical and clinical research projects from: BMS, Boehringer Ingelheim, Idera, MSD, Fondation MSD Avenir, SIRIC (INCa‐DGOS‐Inserm_12551)., ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), 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: Medicine (General), [SDV]Life Sciences [q-bio], Immunology, QH426-470, Medical Oncology, immune checkpoint inhibitors, R5-920, immunomonitoring, Report, precision oncology, Neoplasms, Genetics, “in sitro” assay, Tumor Microenvironment, cancer, Humans, Immunotherapy, Prospective Studies, Reports
Abstract: Decision making in immuno‐oncology is pivotal to adapt therapy to the tumor microenvironment (TME) of the patient among the numerous options of monoclonal antibodies or small molecules. Predicting the best combinatorial regimen remains an unmet medical need. Here, we report a multiplex functional and dynamic immuno‐assay based on the capacity of the TME to respond to ex vivo stimulation with twelve immunomodulators including immune checkpoint inhibitors (ICI) in 43 human primary tumors. This "in sitro" (in situ/in vitro) assay has the potential to predict unresponsiveness to anti‐PD‐1 mAbs, and to detect the most appropriate and personalized combinatorial regimen. Prospective clinical trials are awaited to validate this in sitro assay., To predict cancer resistance to PD‐1 blockade and design suitable combinations of immunomodulators, a 60‐h functional in sitro assay was set up in 43 tumors that allowed calculation of the “Immune Reactivity Score (IRS)” based on 17 TCR‐dependent‐ cytokines/chemokines.
Published: 2020

23. Changes in Sexual Behaviors in Men Who Have Sex with Men: A Comparison Between the Double-Blind and Open-Label Extension Phases of the ANRS-IPERGAY Trial

Author: Cécile Tremblay, Marie Suzan-Monti, Christian Chidiac, Jean-Michel Molina, Daniela Rojas Castro, Christel Protière, Mohamed Mimi, Laurence Meyer, Bruno Spire, Marion Di Ciaccio, Catherine Capitant, Luis Sagaon-Teyssier, Marie Préau, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), AIDES [Pantin, France], Coalition Internationale Sida [Pantin, France] (Programme Recherche Communautaire), Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS IPERGAY Study Group: J-M Molina, C Capitant, B Spire, G Pialoux, L Cotte, I Charreau, C Tremblay, J-M Le Gall, E Cua, A Pasquet, F Raffi, C Pintado, C Chidiac, J Chas, P Charbonneau, C Delaugerre, M Suzan-Monti, B Loze, J Fonsart, G Peytavin, A Cheret, J Timsit, G Girard, N Lorente, M Préau, J F Rooney, M A Wainberg, D Thompson, W Rozenbaum, V Doré, L Marchand, M-C Simon, N Etien, J-P Aboulker, L Meyer, J-F Delfraissy, C Pintado, B Loze, C Delaugerre, P Charbonneau, C Gatey, D Ponscarme, P Penot, L Niedbalski, R Veron, J Delgado, E Dalle, S Parlier, I Madelaine, J Fonsart, M Danet, N Mahjoub, N Mezreb, K Moudachirou, S Morel, G Conort, F Lorho, M Meunier, W Rozenbaum, J M Molina, J Chas, C Monfort, J Foucoin, B Boissavy, S Cousseau, S Huon, M Danet, A Djessima, V Berrebi, A Adda, S le Nagat, L Zarka, J Berdougo, G Pialoux, C Chidiac, N Mzoughi, F Clement, A Decouty, C Chapolard, M Godinot, C Adouard-Groslafeige, J Koffi, A Pansu, A Becker, S Pailhes, F Bonnet, F Jeanblanc, C Brochier, X Teruin, S Rouby, L Gilly, L Cotte, C Beauvais, P Arlotto, C Fortin, A Talbot, A Chamberland, A McKenzie, M Blanchette, R Rousseau, K Montheuth, D Thompson, M Morin, M Wainberg, C Tremblay, C Etienne, F Tolonin, S Breaud, V Péchenot, S Bagge, T Cepitelli, P M Roger, E Rosenthal, E Cua, A Cheret, P Cornavin, S Vandamme, J Lambec, N Dumon, O Leclanche, T Huleux, R Biekre, O Robineau, H Melliez, H Bazus, A Pasquet, C Bernaud, M Besnier, B Bonnet, N Hall, M Cavellec, H Hue, L Larmet, M Colas, R Choquet, F Raffi, Dupuis, Christine, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Male, Safe Sex, MESH: Sexual Behavior, [SDV]Life Sciences [q-bio], HIV Infections, Gee, law.invention, Men who have sex with men, 0302 clinical medicine, law, Medicine, MESH: Sexual Partners, MESH: Double-Blind Method, 030212 general & internal medicine, MESH: Anti-HIV Agents, Generalized estimating equation, MESH: Middle Aged, MESH: HIV Infections, Middle Aged, PrEP, 3. Good health, [SDV] Life Sciences [q-bio], Sexual Partners, Infectious Diseases, Sexual behavior, MESH: Risk-Taking, MESH: Young Adult, MESH: Risk Reduction Behavior, France, Open label, 0305 other medical science, Adult, Canada, Social Psychology, Anti-HIV Agents, ANRS-IPERGAY trial, Sexual Behavior, MESH: Safe Sex, Double blind, MESH: Homosexuality, Male, Young Adult, 03 medical and health sciences, Risk-Taking, Double-Blind Method, Condom, MESH: Canada, Humans, MSM, Homosexuality, Male, 030505 public health, MESH: Humans, business.industry, Public Health, Environmental and Occupational Health, HIV risk management, MESH: Adult, Odds ratio, MESH: Male, MESH: France, Behaviors, Pre-Exposure Prophylaxis, business, Risk Reduction Behavior, Demography, MESH: Pre-Exposure Prophylaxis
Abstract: International audience; Pre-Exposure Prophylaxis (PrEP) is changing the landscape of HIV prevention, and may bring changes in sexual behaviors. The double-blind phase (DBP) and open-label extension (OLE) study of the ANRS-IPERGAY trial allowed us to assess changes in sexual behavior of men who have sex with men (MSM) taking sexual activity-based (i.e., on-demand) PrEP. Generalized Estimating Equation (GEE) models found a significant decrease in the number of sexual partners (Coefficient [CI95%], p value; - 0.37[- 0.70 to - 0.04], p = 0.03) between the DBP and OLE as well as in the number of sexual relations (- 0.25 [- 0.49 to 0.00], 0.04). GEE estimates also showed that respondents' most recent sexual relation was less likely to have been with an unknown casual partner during the OLE than during the DBP (Odds Ratio [CI95%], p value: 0.75[0.62-0.92], 0.005). Furthermore, they showed an increase in the proportion of condomless anal sex in the OLE (1.32[1.04-1.67], 0.02), a decrease in the proportion of 'suboptimal PrEP adherence' over time (0.75[0.58-0.97], p = 0.03), a decrease in PrEP only use (0.73[0.55-0.96], 0.03) and in both PrEP and condom use over time (0.70[0.51-0.95], 0.02) and finally, a decrease in alcohol consumption between the DBP and OLE (0.74[0.61-0.90], 0.002). We observed both protective and risky behaviors in terms of HIV and STI risk after on-demand PrEP uptake in the OLE phase. Our findings are consistent with results from previous PrEP trials.
Published: 2020

24. Early Antiretroviral Therapy Prevents Viral Infection of Monocytes and Inflammation in Simian Immunodeficiency Virus-Infected Rhesus Macaques

Author: Thibault Mesplèdes, Petronela Ancuta, Julien Clain, Ghita Benmadid-Laktout, Henintsoa Rabezanahary, Ouafa Zghidi-Abouzid, Gina Racine, Jérôme Estaquier, Chloé Borde, Guadalupe Andreani, Fabrizio Mammano, Université Laval [Québec] (ULaval), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Jewish General Hospital, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Mammano, Fabrizio, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: CD4-Positive T-Lymphocytes, viral reservoir, MESH: Inflammation, MESH: Spleen, [SDV]Life Sciences [q-bio], Simian Acquired Immunodeficiency Syndrome, HIV Infections, medicine.disease_cause, Systemic inflammation, MESH: Monocytes, MESH: Animals, 0303 health sciences, MESH: CD4-Positive T-Lymphocytes, MESH: HIV Infections, Viral Load, 3. Good health, [SDV] Life Sciences [q-bio], Intestines, medicine.anatomical_structure, Anti-Retroviral Agents, SIV, Simian Immunodeficiency Virus, medicine.symptom, MESH: Simian Acquired Immunodeficiency Syndrome, monocytes, MESH: Viral Load, IL-18, MESH: Intestines, CD14, Immunology, antiretroviral therapy, MESH: Simian Immunodeficiency Virus, Viremia, Spleen, Inflammation, Biology, CD16, Microbiology, MESH: Anti-Retroviral Agents, MESH: Macaca mulatta, 03 medical and health sciences, IL-1ra, Virology, medicine, Animals, Humans, MESH: Viremia, intestine, 030304 developmental biology, MESH: Humans, 030306 microbiology, Monocyte, HIV, Simian immunodeficiency virus, medicine.disease, Macaca mulatta, CD4, inflammation, Insect Science, Pathogenesis and Immunity, spleen
Abstract: International audience; Despite early antiretroviral therapy (ART), treatment interruption is associated with viral rebound, indicating early viral reservoir (VR) seeding and absence of full eradication of human immunodeficiency virus type 1 (HIV-1) that may persist in tissues. Herein, we address the contributing role of monocytes in maintaining VRs under ART, since these cells may represent a source of viral dissemination due to their ability to replenish mucosal tissues in response to injury. To this aim, monocytes with classical (CD14+), intermediate (CD14+ CD16+), and nonclassical (CD16+) phenotypes and CD4+ T cells were sorted from the blood, spleen, and intestines of untreated and early-ART-treated simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) before and after ART interruption. Cell-associated SIV DNA and RNA were quantified. We demonstrated that in the absence of ART, monocytes were productively infected with replication-competent SIV, especially in the spleen. Reciprocally, early ART efficiently (i) prevented the establishment of monocyte VRs in the blood, spleen, and intestines and (ii) reduced systemic inflammation, as indicated by changes in interleukin-18 (IL-18) and IL-1 receptor antagonist (IL-1Ra) plasma levels. ART interruption was associated with a rebound in viremia that led to the rapid productive infection of both CD4+ T cells and monocytes. Altogether, our results reveal the benefits of early ART initiation in limiting the contribution of monocytes to VRs and SIV-associated inflammation.IMPORTANCE Despite the administration of antiretroviral therapy (ART), HIV persists in treated individuals and ART interruption is associated with viral rebound. Persistent chronic immune activation and inflammation contribute to disease morbidity. Whereas monocytes are infected by HIV/SIV, their role as viral reservoirs (VRs) in visceral tissues has been poorly explored. Our work demonstrates that monocyte cell subsets in the blood, spleen, and intestines do not significantly contribute to the establishment of early VRs in SIV-infected rhesus macaques treated with ART. By preventing the infection of these cells, early ART reduces systemic inflammation. However, following ART interruption, monocytes are rapidly reinfected. Altogether, our findings shed new light on the benefits of early ART initiation in limiting VR and inflammation.
Published: 2020

25. Potential for virus endogenization in humans through testicular germ cell infection: the case of HIV

Author: Romain Mathieu, Claire Deleage, Luiz de Franca, Sylvain Lavoué, Nicolas Chomont, Antoine Rolland, Giulia Matusali, Dominique Mahé, Anne-Pascale Satie, Nathalie Dejucq-Rainsford, R. Alvarenga, Amelie Paggliuzza, Bernard Jégou, Laurent Houzet, 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 ), Federal University of Minas Gerais (UFMG), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Université de Montréal (UdeM), CHU Pontchaillou [Rennes], HHSN261200800001E, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Institut National de la Santé et de la Recherche Médicale, Sidaction, Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Campus France, Chard-Hutchinson, Xavier, 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 Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG)
Subjects: Male, Simian Acquired Immunodeficiency Syndrome, HIV Infections, integration, Virus Replication, Germline, Retrovirus, cell-associated infection, Chlorocebus aethiops, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, education.field_of_study, biology, male germ cells, gametes, 3. Good health, Virus-Cell Interactions, Seminoma, Rhesus macaque, SIV, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, entry, Simian Immunodeficiency Virus, antiviral defense, replication, Population, virus, testis, Virus, 03 medical and health sciences, Viral entry, evolution, Animals, Humans, education, 030304 developmental biology, 030306 microbiology, Macrophages, Prostatic Neoplasms, HIV, Virus Internalization, biology.organism_classification, Virology, restriction factors, Macaca mulatta, Spermatogonia, spermatogenesis, Germ Cells, Cell culture, endogenization, HIV-1, Human genome, germ line
Abstract: Viruses have colonized the host germ line on many occasions during evolution to eventually become endogenous. Here, we aimed at investigating whether human testicular germ cells (TGCs) can support such viral invasion by studying HIV interactions with TGCs in vitro. Our results indicate that isolated primary TGCs express alternative HIV-1 receptors, allowing virion binding but not entry. However, HIV-1 entered and integrated into TGCs upon cell-associated infection and produced low levels of viral proteins. In vivo, HIV-1 and SIV DNA was detected in a few TGCs. Molecular landscape analysis showed that TGCs have overall weak antiviral defenses. Altogether, our results indicate that human TGCs can support HIV-1 early replication, including integration, suggesting potential for endogenization in future generations., Viruses have colonized the germ line of our ancestors on several occasions during evolution, leading to the integration in the human genome of viral sequences from over 30 retroviral groups and a few nonretroviruses. Among the recently emerged viruses infecting humans, several target the testis (e.g., human immunodeficiency virus [HIV], Zika virus, and Ebola virus). Here, we aimed to investigate whether human testicular germ cells (TGCs) can support integration by HIV, a contemporary retrovirus that started to spread in the human population during the last century. We report that albeit alternative receptors enabled HIV-1 binding to TGCs, HIV virions failed to infect TGCs in vitro. Nevertheless, exposure of TGCs to infected lymphocytes, naturally present in the testis from HIV+ men, led to HIV-1 entry, integration, and early protein expression. Similarly, cell-associated infection or bypassing viral entry led to HIV-1 integration in a spermatogonial cell line. Using DNAscope, HIV-1 and simian immunodeficiency virus (SIV) DNA were detected within a few TGCs in the testis from one infected patient, one rhesus macaque, and one African green monkey in vivo. Molecular landscape analysis revealed that early TGCs were enriched in HIV early cofactors up to integration and had overall low antiviral defenses compared with testicular macrophages and Sertoli cells. In conclusion, our study reveals that TGCs can support the entry and integration of HIV upon cell-associated infection. This could represent a way for this contemporary virus to integrate into our germ line and become endogenous in the future, as happened during human evolution for a number of viruses. IMPORTANCE Viruses have colonized the host germ line on many occasions during evolution to eventually become endogenous. Here, we aimed at investigating whether human testicular germ cells (TGCs) can support such viral invasion by studying HIV interactions with TGCs in vitro. Our results indicate that isolated primary TGCs express alternative HIV-1 receptors, allowing virion binding but not entry. However, HIV-1 entered and integrated into TGCs upon cell-associated infection and produced low levels of viral proteins. In vivo, HIV-1 and SIV DNA was detected in a few TGCs. Molecular landscape analysis showed that TGCs have overall weak antiviral defenses. Altogether, our results indicate that human TGCs can support HIV-1 early replication, including integration, suggesting potential for endogenization in future generations.
Published: 2020

26. DNA hypomethylating agents increase activation and cytolytic activity of CD8

Author: Giselle M. Boukhaled, David G. Brooks, Felipe Campos de Almeida, David Allard, Sajid A. Marhon, David Roulois, Joaquín Arribas, Ilias Ettayebi, Tiago Medina, Parinaz Mehdipour, Gustavo P. Amarante-Mendes, Sandra Pommey, John Stagg, Daniel D. De Carvalho, Helen Loo Yau, Isabela M. Gonzaga, Shu Yi Shen, Ankur Chakravarthy, Christian Klein, Beatriz Morancho, Raymond Chen, Emma Bell, Charles A. Ishak, Rajat Singhania, University Health Network, University of Toronto, Universidade de São Paulo (USP), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Roche Pharma Research and Early Development [Basel] (pRED), F. Hoffmann-La Roche [Basel], 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 ), Institució Catalana de Recerca i Estudis Avançats (ICREA), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Natural Sciences and Engineering Research Council of Canada, Terry Fox Research Institute, Fundação de Amparo à Pesquisa do Estado de São Paulo, Breast Cancer Research Foundation, Instituto de Salud Carlos III, Canadian Institutes of Health Research, Universidade de São Paulo = University of São Paulo (USP), and 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 )
Subjects: Gene isoform, [SDV]Life Sciences [q-bio], NFATc1, epigenetic therapy, CD8-Positive T-Lymphocytes, Decitabine, Lymphocyte Activation, Granzymes, CITOCINAS, 03 medical and health sciences, 0302 clinical medicine, granzyme B, Cytotoxic T cell, Humans, Molecular Biology, cytolytic activity, 030304 developmental biology, 0303 health sciences, biology, NFATC Transcription Factors, Effector, Perforin, Cell Biology, DNA Methylation, 3. Good health, Cell biology, Granzyme B, Hypomethylating agent, Granzyme, killing potential, DNA methylation, biology.protein, CD8+ T cells, CpG Islands, 030217 neurology & neurosurgery, CD8
Abstract: International audience; We demonstrate that DNA hypomethylating agent (HMA) treatment can directly modulate the anti-tumor response and effector function of CD8(+) T cells. In vivo HMA treatment promotes CD8(+) T cell tumor infiltration and suppresses tumor growth via CD8(+) T cell-dependent activity. Ex vivo, HMAs enhance primary human CD8(+) T cell activation markers, effector cytokine production, and anti-tumor cytolytic activity. Epigenomic and transcriptomic profiling shows that HMAs vastly regulate T cell activation-related transcriptional networks, culminating with over-activation of NFATc1 short isoforms. Mechanistically, demethylation of an intragenic CpG island immediately downstream to the 3’ UTR of the short isoform was associated with antisense transcription and alternative polyadenylation of NFATc1 short isoforms. High-dimensional single-cell mass cytometry analyses reveal a selective effect of HMAs on a subset of human CD8(+) T cell subpopulations, increasing both the number and abundance of a granzyme B(high), perforin(high) effector subpopulation. Overall, our findings support the use of HMAs as a therapeutic strategy to boost anti-tumor immune response.
Published: 2020

27. A new tool for multi-block PLS discriminant analysis: application to metabolomic data in systems epidemiology

Author: Brandolini-Bunlon, Marion, Pétéra, Mélanie, Gaudreau, Pierrette, Comte, Blandine, Bougeard, Stéphanie, Pujos-Guillot, Estelle, Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaboHUB, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Laboratoire de Ploufragan-Plouzané-Niort [ANSES], and Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)
Subjects: Multi-block PLS discriminant analysis, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-OS]Computer Science [cs]/Operating Systems [cs.OS], metabolomics, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

28. INPUT OF DEEP PHENOTYPING IN THE METABOLIC SYNDROME STRATIFICATION

Author: Monnerie, Stéphanie, Pétéra, Mélanie, Canlet, Cécile, Castelli, Florence, Colsch, Benoit, Fenaille, Francois, Joly, Charlotte, Jourdan, Fabien, Lenuzza, Natacha, Lyan, Bernard, Martin, Jean-Francois, Migné, Carole, Morais, José A, Poupin, Nathalie, Vinson, Florence, Thevenot, Etienne, Junot, Christophe, Gaudreau, Pierrette, Comte, Blandine, Pujos-Guillot, Estelle, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Plateforme d’Exploration du Métabolisme, Institut National de la Recherche Agronomique (INRA), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), MetaboHUB, Service de Pharmacologie et Immunoanalyse (SPI), Laboratoire d'Etude du Métabolisme des Médicaments (LEMM), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Institut National de Recherche en Agriculture, Alimentation et Environnement (INRAE), Université Paris Saclay (COMUE), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Division de Gériatrie, Centre de recherche du Centre universitaire de santé McGill, McGill University, Département de médecine, Centre de Recherche du Centre hospitalier de l’Université de Montréal, Université de Montréal (UdeM), Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateforme Exploration du Métabolisme (PFEM), MetaboHUB-Clermont, MetaboHUB-MetaboHUB-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, MetaToul AXIOM (E20), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université de Toulouse (UT)-Université de Toulouse (UT), Laboratoire Sciences des Données et de la Décision (LS2D), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (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)-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)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, McGill University = Université McGill [Montréal, Canada], Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM)-Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-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 National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Plateforme d'Exploration du Métabolisme PFEM, Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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 National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], [CHIM.ANAL]Chemical Sciences/Analytical chemistry
Abstract: IntroductionMetabolic syndrome (MetS), defined as a cluster of cardiometabolic factors, is a public health challenge because of its growing prevalence. In the context of personalized medicine, new tools are necessary to bring additional knowledge about MetS etiology, better stratify populations and customise strategies for prevention. The objective of this study was to characterize the MetS phenotypic spectrum using complementary untargeted metabolomics platforms (HRMS, RMN).Technological and methodological innovationA case-control study was designed within the Quebec NuAge cohort1. Six complementary untargetedmetabolomic/lipidomic approaches were performed on serum samples collected at recruitment and 3 years later. Procedures were set up to guaranty the inter-laboratory standardisation from sample preparation to data processing, performed using reproducible online Galaxy workflows. A full feature selection strategy was developed to build a comprehensive molecular MetS signature, stable over time.Results and impactA wide range of metabolites (lipids, carbohydrates, amino-acids, peptides…) reflecting subject stability and providing new insights about underlying mechanisms, were found to be modulated. An optimized reduced signature was proposed, allowing good prediction performances (12% misclassification, AUC=0.95, CI:[0.92-0.98]). These results demonstrated the interest of a multidimensional molecular phenotyping as part of the next generation of medicine tools in the frame of noncommunicable diseases.References[1] Gaudreau P et al., 2007. Rejuvenation Res.10(3):377-386.
Published: 2020

29. The Impact of Work-Related Rhinitis on Quality of Life and Work Productivity: A General Workforce-Based Survey

Author: Eva Suarthana, Olivier Vandenplas, Nicole Le Moual, Jean Bousquet, Catherine Rifflart, Catherine Lemière, UCL - (MGD) Service de pneumologie, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, CHU UCL Namur, Université Catholique de Louvain = Catholic University of Louvain (UCL), Hôpital du Sacré-Coeur de Montréal, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA)
Subjects: Gerontology, Quality of life, Work productivity, Multivariate analysis, MESH: Workforce, Work-related rhinitis, Work related, Occupational safety and health, 03 medical and health sciences, MESH: Cross-Sectional Studies, 0302 clinical medicine, Nonallergic rhinitis, MESH: Belgium, Belgium, Surveys and Questionnaires, Immunology and Allergy, Medicine, Humans, 030212 general & internal medicine, MESH: Surveys and Questionnaires, Adverse effect, Rhinitis, MESH: Humans, business.industry, MESH: Rhinitis, MESH: Quality of Life, medicine.disease, Mental health, Cross-Sectional Studies, 030228 respiratory system, 8. Economic growth, Workforce, Quality of Life, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Background The specific burden of work-related rhinitis (WRR) on quality of life (QoL) and work productivity has received little attention. Objective The aim of this study was to investigate to what extent WRR affects QoL and work productivity as compared with subjects with rhinitis unrelated to work and those without rhinitis. Methods This cross-sectional survey was conducted among workers randomly recruited at the time of their periodic occupational health visit in the French-speaking part of Belgium. The survey instruments consisted of rhinitis-specific and generic questionnaires: Mini-Rhinitis QoL Questionnaire, Medical Outcome Study Short Form-8, and Work Productivity and Activity Impairment-General Health questionnaire. Eligible participants were categorized into 3 groups: non-WRR (current nasal symptoms not related to work, n = 329); WRR (current rhinitis with ≥2 nasal symptoms at work, n = 161); and controls (no nasal symptom; n = 1155). Results WRR showed significantly lower scores in all domains of the Mini-Rhinitis QoL Questionnaire compared with non-WRR. Multivariate analysis confirmed that WRR exerted an independent adverse effect on rhinitis-specific QoL. Both WRR and non-WRR were associated with greater impairment in the physical and mental health components of the Medical Outcome Study Short Form-8 instrument and the overall work productivity compared with controls, whereas these outcomes were more impacted in WRR than non-WRR. Multivariate analyses demonstrated that both WRR and non-WRR had an independent adverse impact on the physical and mental health status and overall work productivity. Conclusion WRR has an incremental adverse impact on QoL and work productivity that should be addressed in order to reduce the global burden of rhinitis.
Published: 2020

30. Metabolomic and Lipidomic Signatures of Metabolic Syndrome and its Physiological Components in Adults: A Systematic Review

Author: Blandine Comte, Pierrette Gaudreau, José A. Morais, Daniela Ziegler, Stéphanie Monnerie, Estelle Pujos-Guillot, Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Montréal, Université de Montréal (UdeM), Département de Gériatrie, McGill University = Université McGill [Montréal, Canada], Plateforme d’Exploration du Métabolisme, Institut National de la Recherche Agronomique (INRA), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Département de médecine, Centre Léon Bérard [Lyon], Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Université McGill [Montréal], and Centre de Recherche du CHUM
Subjects: Adult, Male, Risk, 0301 basic medicine, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Population, MEDLINE, lcsh:Medicine, 030209 endocrinology & metabolism, Type 2 diabetes, Computational biology, Article, 03 medical and health sciences, 0302 clinical medicine, Metabolomics, Lipidomics, Prevalence, Humans, Medicine, lcsh:Science, education, Aged, Glycemic, Metabolic Syndrome, education.field_of_study, Multidisciplinary, business.industry, Incidence, lcsh:R, Middle Aged, Lipid Metabolism, medicine.disease, Phenotype, 030104 developmental biology, Diabetes Mellitus, Type 2, Homogeneous, Female, lcsh:Q, Metabolic syndrome, business, Biomarkers
Abstract: The aim of this work was to conduct a systematic review of human studies on metabolite/lipid biomarkers of metabolic syndrome (MetS) and its components, and provide recommendations for future studies. The search was performed in MEDLINE, EMBASE, EMB Review, CINHAL Complete, PubMed, and on grey literature, for population studies identifying MetS biomarkers from metabolomics/lipidomics. Extracted data included population, design, number of subjects, sex/gender, clinical characteristics and main outcome. Data were collected regarding biological samples, analytical methods, and statistics. Metabolites were compiled by biochemical families including listings of their significant modulations. Finally, results from the different studies were compared. The search yielded 31 eligible studies (2005–2019). A first category of articles identified prevalent and incident MetS biomarkers using mainly targeted metabolomics. Even though the population characteristics were quite homogeneous, results were difficult to compare in terms of modulated metabolites because of the lack of methodological standardization. A second category, focusing on MetS components, allowed comparing more than 300 metabolites, mainly associated with the glycemic component. Finally, this review included also publications studying type 2 diabetes as a whole set of metabolic risks, raising the interest of reporting metabolomics/lipidomics signatures to reflect the metabolic phenotypic spectrum in systems approaches.
Published: 2020

31. Trial watch : the gut microbiota as a tool to boost the clinical efficacy of anticancer immunotherapy

Author: Lucie Heinzerling, Sibylle Loilbl, Lars Engstrand, Lisa Derosa, Romain Daillère, Eva Budinská, I. Jolanda M. de Vries, Nicola Segata, Guido Kroemer, Carlos Caldas, Alessio Naccarati, Manuela Gariboldi, Bertrand Routy, Jacques Fieschi, Laurence Zitvogel, Mélodie Bonvalet, Valérie Zitvogel, Institut Gustave Roussy (IGR), Immunologie intégrative des tumeurs et immunothérapie des cancers (INTIM), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre for Integrative Biology (CIBIO), University of Trento (CIBIO), University of Trento [Trento], Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), IRCCS Istituto Nazionale dei Tumori [Milano], Research Centre for Toxic Compounds in the Environment [Brno] (RECETOX / MUNI), Faculty of Science [Brno] (SCI / MUNI), Masaryk University [Brno] (MUNI)-Masaryk University [Brno] (MUNI), Radboud University Medical Center [Nijmegen], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Cancer Research UK Cambridge Institute [Cambridge, Royaume-Uni] (CRUK), University of Cambridge [UK] (CAM), Karolinska Institutet [Stockholm], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), 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 de Paris (UP), Service de biologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), University of Science & Technology of China [Suzhou], Karolinska University Hospital [Stockholm], Centre d’Investigation Clinique en Biothérapies [CHU Pitié-Salpêtrière] (CIC-BT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, German Breast Group (GBG), 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), 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), ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), and European Project: 825410,ONCOBIOME
Subjects: 0301 basic medicine, Gut microbiota, anticancer therapeutics, clinical trials, Dysbiosis, Humans, Immunotherapy, Treatment Outcome, Gastrointestinal Microbiome, Neoplasms, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, Gut flora, Bioinformatics, digestive system, 03 medical and health sciences, 0302 clinical medicine, Immunology and Allergy, Medicine, RC254-282, ComputingMilieux_MISCELLANEOUS, Chemotherapy, biology, business.industry, Cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, RC581-607, medicine.disease, biology.organism_classification, Immune checkpoint, 3. Good health, Blockade, Clinical trial, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Oncology, Tumor progression, 030220 oncology & carcinogenesis, Immunologic diseases. Allergy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 220857.pdf (Publisher’s version ) (Open Access) Accumulating evidence demonstrates the decisive role of the gut microbiota in determining the effectiveness of anticancer therapeutics such as immunogenic chemotherapy or immune checkpoint blockade in preclinical tumor models, as well as in cancer patients. In synthesis, it appears that a normal intestinal microbiota supports therapeutic anticancer responses, while a dysbiotic microbiota that lacks immunostimulatory bacteria or contains overabundant immunosuppressive species causes treatment failure. These findings have led to the design of clinical trials that evaluate the capacity of modulation of the gut microbiota to synergize with treatment and hence limit tumor progression. Along the lines of this Trial Watch, we discuss the rationale for harnessing the gut microbiome in support of cancer therapy and the progress of recent clinical trials testing this new therapeutic paradigm in cancer patients.
Published: 2020

32. Whole-Genome Sequencing of Mycobacterium tilburgii Strain MEPHI

Author: Margaret M. Hannan, Michel Drancourt, Patrick Stapleton, Simon Grandjean Lapierre, Jamal Saad, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University College Dublin [Dublin] (UCD), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), ANR-10-IAHU-0003,Méditerranée Infection,I.H.U. Méditerranée Infection(2010), and European Project
Subjects: 0106 biological sciences, Mycobacterium genavense, 010603 evolutionary biology, 01 natural sciences, DNA sequencing, Mycobacterium triplex, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Immunology and Microbiology (miscellaneous), [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genetics, RefSeq, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Molecular Biology, 030304 developmental biology, Whole genome sequencing, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, biology, Contig, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, GenBank, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, GC-content
Abstract: International audience; Mycobacterium tilburgii is a fastidious mycobacterium which has previously been reported to cause severe disseminated infections. Genome sequencing of the M. tilburgii MEPHI clinical isolate yielded 3.14 Mb, with 66.3% GC content, and confirmed phylogenetic placement within the Mycobacterium simiae complex. O nly 13 cases of Mycobacterium tilburgii infection have been reported, highlighting host immunosuppression as a risk factor for M. tilburgii infection (1-3). M. tilburgii was never previously isolated in culture; its detection relied on the direct sequencing of internal transcribed spacer 1 (ITS1), hsp65, rpoB, and 16S rRNA genes from clinical material (2). We isolated M. tilburgii from a bone marrow sample by using a shell vial assay, as previously described (4, 5) (Fig. 1A). This organism had been previously detected in this immunocompromised patient in a biopsy specimen taken from a duodenal plaque by direct 16S rRNA gene sequencing. DNA (0.2 g/l) extracted using InstaGene matrix (Bio-Rad, Marnes-la-Coquette, France) was sequenced using MiSeq platform (Illumina, Inc., San Diego, CA, USA) paired-end sequencing and automated cluster generation with dual-indexed 2 ϫ 250-bp reads. A 535,000/mm 2 cluster density filter and a 96.3% cluster passing quality control filter were applied. A total of 8,690,521 reads were assembled using SPAdes version 3.12.0 with the option "-careful" in order to reduce the number of mismatches and short indels (6). Default parameters for k values, i.e., k-mer values of 127, 99, 77, 55, 33, and 21, were applied. A total of 977 human DNA contigs were removed via a BLASTn script that connected remotely to the NCBI database (nr/nt) (BLASTϩ 2.3.0). Annotation using Prokka version 1.13 (7) of the M. tilburgii strain MEPHI genome sequence (mean coverage depth, 6.5ϫ) comprises 102 contigs, with a total assembly size of 3,238,527 bp and 66.3% GC content (N 50 value, 56,170 bp; coverage, 5.6ϫ). One 19,595-bp contig (62.9 GC% content), exhibited 77% nucleotide similarity with Mycobacterium sp. strain KMS plasmid pMKMS02 (GenBank accession no. CP000520) using BLASTn. The M. tilburgii strain MEPHI genome was predicted to contain 4,207 genes, including 4,154 protein-coding genes, and 53 RNAs (49 tRNAs, 3 rRNAs, and one transfer-messenger RNA [tmRNA]). Phylogenetic trees based on the 3,504-bp rpoB and the 1,523-bp 16S RNA genes confirmed phylogenetic placement into the Mycobacterium simiae complex (Fig. 1B and C). The genomic similarities estimated using OrthoANI version 0.93.1 (8) and in silico DNA-DNA hybrid-ization estimated using the GGDC version 2.0 online tool (9) were 87.17% and 33.8% with M. simiae (GenBank assembly accession no. GCA_000455305), 87.15% and 33.6% with Mycobacterium sherrisii (GenBank assembly accession no. GCA_001722325), 82.88% and 26.8% with Mycobacterium triplex (GenBank assembly accession no. GCA_000689255), 82.76% and 26.6% with Mycobacterium florentinum (NCBI RefSeq accession no. NZ_LQOV00000000), 82.62% and 26.1% with Mycobacterium genavense
Published: 2019

33. Kankanet: An artificial neural network-based object detection smartphone application and mobile microscope as a point-of-care diagnostic aid for soil-transmitted helminthiases

Author: Liana Langdon-Embry, Nahid Bakhtari, Emile Redwood, Luis A. Marcos, Simon Grandjean Lapierre, Juan De Dios Santos, Armand Rafalimanantsoa, Astrid M. Knoblauch, Patricia Rakotomanga, Ariel Yang, Inès Vigan-Womas, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Unité des Mycobactéries [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité des Helminthiases [Antananarivo, Madagascar] (IPM), Uppsala University, Unité d'immunologie des maladies infectieuses [Antananarivo, Madagascar] (IPM), Swiss Tropical and Public Health Institute [Basel], AY received the David E Rogers Student Fellowship Award (New York Academy of Medicine, and We thank all communities involved in this study: the participants of the two villages investigated, the local authorities, the community health workers and facilitators. We would like to acknowledge the Centre ValBio health team: Fara Rakotoarison, Andri Andriami, Marie Solange Razanajaza, Marie Lizabelle Zaratambatra, Ando Rakotoniaina, Francis Daniel Lovasoa. We also thank Patricia Wright and Jesse McKinney of Centre Valbio for their mentorship and logistics coordination. We thank the Institut Pasteur de Madagascar team: Augustin Razanajatovo, Rado Lalaina Rakotoarison, and Mamy Donah Andrianatoandro. We thank the team at the Global Health Institute: Timothy Kobba, Jeanne O’Neil, Dr. Peter Small, Dr. Joe Brew, and Dr. Pierce Gardner. We thank Dr. Glenn Edosoa, Dr. Tahsin Kurc, Raza Hassan, Joseph Schurz, Rafael Tejada, Luke Lu, Rachel Yen, Dat Tran, and Harrison Kinsley for their contributions in microscope prototyping, Android application development, and Kankanet training.
Subjects: 0301 basic medicine, Ancylostomatoidea, Ascaris Lumbricoides, Microscope, Nematoda, RC955-962, Helminthiasis, Smartphone application, Diagnostic aid, law.invention, Geographical Locations, Feces, Soil, 0302 clinical medicine, law, Arctic medicine. Tropical medicine, Medicine and Health Sciences, Image Processing, Computer-Assisted, Computer vision, 2. Zero hunger, Microscopy, Artificial neural network, Pharmaceutics, Ascaris, Eukaryota, Public Health, Global Health, Social Medicine and Epidemiology, Miljövetenskap, Infectious Diseases, Soil transmitted helminthiases, Trichuris, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Helminth Infections, Engineering and Technology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Smartphone, Public aspects of medicine, RA1-1270, Research Article, Neglected Tropical Diseases, Computer and Information Sciences, Drug Administration, Point-of-Care Systems, 030231 tropical medicine, Equipment, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Sensitivity and Specificity, Microbiology in the medical area, 03 medical and health sciences, Hookworm Infections, Drug Therapy, Artificial Intelligence, Helminths, Mikrobiologi inom det medicinska området, Parasitic Diseases, Madagascar, Animals, Humans, Parasite Egg Count, Artificial Neural Networks, Point of care, Communication Equipment, Computational Neuroscience, business.industry, Public Health, Environmental and Occupational Health, Organisms, Drug administration, Biology and Life Sciences, Computational Biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Tropical Diseases, Invertebrates, Object detection, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 030104 developmental biology, Soil-Transmitted Helminthiases, Hookworms, People and Places, Africa, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Artificial intelligence, Neural Networks, Computer, Cell Phones, business, Environmental Sciences, Software, Neuroscience
Abstract: Background Endemic areas for soil-transmitted helminthiases often lack the tools and trained personnel necessary for point-of-care diagnosis. This study pilots the use of smartphone microscopy and an artificial neural network-based (ANN) object detection application named Kankanet to address those two needs. Methodology/Principal findings A smartphone was equipped with a USB Video Class (UVC) microscope attachment and Kankanet, which was trained to recognize eggs of Ascaris lumbricoides, Trichuris trichiura, and hookworm using a dataset of 2,078 images. It was evaluated for interpretive accuracy based on 185 new images. Fecal samples were processed using Kato-Katz (KK), spontaneous sedimentation technique in tube (SSTT), and Merthiolate-Iodine-Formaldehyde (MIF) techniques. UVC imaging and ANN interpretation of these slides was compared to parasitologist interpretation of standard microscopy.Relative to a gold standard defined as any positive result from parasitologist reading of KK, SSTT, and MIF preparations through standard microscopy, parasitologists reading UVC imaging of SSTT achieved a comparable sensitivity (82.9%) and specificity (97.1%) in A. lumbricoides to standard KK interpretation (97.0% sensitivity, 96.0% specificity). The UVC could not accurately image T. trichiura or hookworm. Though Kankanet interpretation was not quite as sensitive as parasitologist interpretation, it still achieved high sensitivity for A. lumbricoides and hookworm (69.6% and 71.4%, respectively). Kankanet showed high sensitivity for T. trichiura in microscope images (100.0%), but low in UVC images (50.0%). Conclusions/Significance The UVC achieved comparable sensitivity to standard microscopy with only A. lumbricoides. With further improvement of image resolution and magnification, UVC shows promise as a point-of-care imaging tool. In addition to smartphone microscopy, ANN-based object detection can be developed as a diagnostic aid. Though trained with a limited dataset, Kankanet accurately interprets both standard microscope and low-quality UVC images. Kankanet may achieve sensitivity comparable to parasitologists with continued expansion of the image database and improvement of machine learning technology., Author summary For rainforest-enshrouded rural villages of Madagascar, soil-transmitted helminthiases are more the rule than the exception. However, the microscopy equipment and lab technicians needed for diagnosis are a distance of several days’ hike away. We piloted a solution for these communities by leveraging resources the villages already had: a traveling team of local health care workers, and their personal Android smartphones. We demonstrated that an inexpensive, commercially available microscope attachment for smartphones could rival the sensitivity and specificity of a regular microscope using standard field fecal sample processing techniques. We also developed an artificial neural network-based object detection Android application, called Kankanet, based on open-source programming libraries. Kankanet was used to detect eggs of the three most common soil-transmitted helminths: Ascaris lumbricoides, Trichuris trichiura, and hookworm. We found Kankanet to be moderately sensitive and highly specific for both standard microscope images and low-quality smartphone microscope images. This proof-of-concept study demonstrates the diagnostic capabilities of artificial neural network-based object detection systems. Since the programming frameworks used were all open-source and user-friendly even for computer science laymen, artificial neural network-based object detection shows strong potential for development of low-cost, high-impact diagnostic aids essential to health care and field research in resource-limited communities.
Published: 2019

34. From Molecular Profiling to Precision Medicine in Metabolic Syndrome

Author: Comte, Blandine, Monnerie, Stéphanie, Brandolini-Bunlon, Marion, Canlet, Cécile, Castelli, Florence, Colsch, Benoit, Fenaille, Francois, Joly, Charlotte, Lenuzza, Natacha, Lyan, Bernard, Martin, Jean-Francois, Migné, Carole, Morais, José A., Pétéra, Mélanie, Thévenot, Etienne, Gaudreau, Pierrette, Junot, Christophe, Pujos-Guillot, Estelle, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-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 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 du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Département de médecine, Centre Léon Bérard [Lyon], MetaboHUB, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Centre de Recherche du CHUM, MetaToul AXIOM (E20), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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 National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], [CHIM.ANAL]Chemical Sciences/Analytical chemistry
Abstract: Session: From Molecular Profiling to Precision Medicine in Metabolic Syndrome Session: From Molecular Profiling to Precision Medicine in Metabolic SyndromeSession: From Molecular Profiling to Precision Medicine in Metabolic Syndrome; Metabolic syndrome (MetS), defined as a cluster of cardio-metabolic factors including obesity, hypertension, dysglycemia, and dyslipidemia, and mostly affecting older adults, is now a public health challenge because of its growing prevalence. In the context of personalized medicine/nutrition, new tools are necessary to bring additional knowledge about MetS etiology, better stratify populations and customise strategies for prevention. The objective of this study was to investigate the integration of data from complementary untargeted metabolomics platforms (HRMS, RMN) and technologies to characterize the MetS phenotypic spectrum. A case-control study was designed within the Quebec NuAge cohort1. Six complementary untargeted metabolomic/lipidomic approaches, available within the MetaboHUB infrastructure2, were performed on serum samples collected at recruitment and 3 years later. Standard operating procedures were designed to guaranty the inter-laboratory standardisationfrom sample preparation to data processing. Data analyses were performed using reproducible online Galaxy workflows3. A full feature selection strategy was developed to build a comprehensive molecular MetS signature, stable over time. Consistent cross-sectional and longitudinal data were observed with a wide range of metabolites (lipids, carbohydrates, amino-acids, peptides…) reflecting subject stability regarding MetS, and providingnew insights about underlying mechanisms. Correlation network analysis contributed to explore the links between the molecular signature and clinical parameters. Additionally, an optimized reduced signature was proposed, allowing good prediction performances (12% misclassification, AUC=0.96, CI:[0.94-0.98]), for future clinical application. These results demonstrated the interest of a multidimensional molecular phenotyping aspart of the next generation of medicine tools in the frame of non-communicable diseases.
Published: 2019

35. Multi-block PLS discriminant analysis for the joint analysis of metabolomic and epidemiological data

Author: Pierrette Gaudreau, Blandine Comte, Mélanie Pétéra, Stéphanie Bougeard, Marion Brandolini-Bunlon, Estelle Pujos-Guillot, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), MetaboHUB, Centre de Recherche du CHUM, Département de médecine, Centre Léon Bérard [Lyon], Laboratoires de Ploufragan-Plouzané, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), and Université de Montréal (UdeM)-Université de Montréal (UdeM)
Subjects: Computer science, Epidemiology, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, computer.software_genre, 01 natural sciences, Biochemistry, 03 medical and health sciences, Multiblock PLS discriminant analysis, Partial least squares regression, Discrimination, Humans, Metabolomics, Relevance (information retrieval), Least-Squares Analysis, 030304 developmental biology, Block (data storage), Complex data type, 0303 health sciences, 010401 analytical chemistry, Discriminant Analysis, Linear discriminant analysis, Data structure, 0104 chemical sciences, Metadata, Discriminant, Epidemiological Monitoring, Multi-block, Data mining, [INFO.INFO-OS]Computer Science [cs]/Operating Systems [cs.OS], computer, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Algorithms
Abstract: INTRODUCTION: Metabolomics is a powerful phenotyping tool in nutrition and health research, generating complex data that need dedicated treatments to enrich knowledge of biological systems. In particular, to investigate relations between environmental factors, phenotypes and metabolism, discriminant statistical analyses are generally performed separately on metabolomic datasets, complemented by associations with metadata. Another relevant strategy is to simultaneously analyse thematic data blocks by a multi-block partial least squares discriminant analysis (MBPLSDA) allowing determining the importance of variables and blocks in discriminating groups of subjects, taking into account data structure. OBJECTIVE: The present objective was to develop a full open-source standalone tool, allowing all steps of MBPLSDA for the joint analysis of metabolomic and epidemiological data. METHODS: This tool was based on the mbpls function of the ade4 R package, enriched with functionalities, including some dedicated to discriminant analysis. Provided indicators help to determine the optimal number of components, to check the MBPLSDA model validity, and to evaluate the variability of its parameters and predictions. RESULTS: To illustrate the potential of this tool, MBPLSDA was applied to a real case study involving metabolomics, nutritional and clinical data from a human cohort. The availability of different functionalities in a single R package allowed optimizing parameters for an efficient joint analysis of metabolomics and epidemiological data to obtain new insights into multidimensional phenotypes. CONCLUSION: In particular, we highlighted the impact of filtering the metabolomic variables beforehand, and the relevance of a MBPLSDA approach in comparison to a standard PLS discriminant analysis method.
Published: 2019

36. ERS statement on respiratory muscle testing at rest and during exercise

Author: Denis E. O'Donnell, Pierantonio Laveneziana, Frédéric Sériès, Brigitte Fauroux, Joaquim Gea, J. Alberto Neder, André Luis Pereira de Albuquerque, Ioannis Vogiatzis, Esther Barreiro, Bruno-Pierre Dubé, Samuel Verges, Christina M. Spengler, Martin Dres, Yuan Ming Luo, Daniel Langer, Andrea Rossi, Franco Laghi, Thomas Similowski, Jordan A. Guenette, Tony G. Babb, Hans-Joachim Kabitz, Roberto A Rabinovich, Michael I. Polkey, Anna L. Hudson, Andrea Aliverti, Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universidade de São Paulo = University of São Paulo (USP), Hospital Sírio-Libanês [São Paulo, Brazil], Politecnico di Milano [Milan] (POLIMI), Texas Health Presbyterian Hospital [Dallas, TX, USA], IMIM-Hospital del Mar, Generalitat de Catalunya, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Universitat Pompeu Fabra [Barcelona] (UPF), University of British Columbia (UBC), University of New South Wales [Sydney] (UNSW), Hochschule Konstanz (HTWG Konstanz), Loyola University [Chicago], Edward Hines, Jr. VA Hospital, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], The First Affiliated Hospital of Guangzhou Medical University (GMU), Queen's University [Kingston, Canada], Royal Brompton Hospital, University of Edinburgh, Royal Infirmary of Edinburgh, Università degli studi di Verona = University of Verona (UNIVR), Université Laval [Québec] (ULaval), Universität Zürich [Zürich] = University of Zurich (UZH), St. Paul’s Hospital - University of British Columbia [Vancouver, BC, Canada] (SPH-UBC), National and Kapodistrian University of Athens (NKUA), University of Northumbria at Newcastle [United Kingdom], Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and SALAS, Danielle
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Rest, Psychological intervention, Respiratory physiology, Electromyography, Disease, 030204 cardiovascular system & hematology, Structured light plethysmography, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, Respiratory muscle, Humans, Muscle Strength, Respiratory system, Exercise, Societies, Medical, medicine.diagnostic_test, Pulmons -- Músculs, business.industry, Transcranial Magnetic Stimulation, C600, Aparell respiratori -- Fisiologia, Respiratory Muscles, Respiratory Function Tests, [SDV] Life Sciences [q-bio], Europe, B900, 030228 respiratory system, Respiratory Mechanics, Breathing, business
Abstract: Assessing respiratory mechanics and muscle function is critical for both clinical practice and research purposes. Several methodological developments over the past two decades have enhanced our understanding of respiratory muscle function and responses to interventions across the spectrum of health and disease. They are especially useful in diagnosing, phenotyping and assessing treatment efficacy in patients with respiratory symptoms and neuromuscular diseases. Considerable research has been undertaken over the past 17 years, since the publication of the previous American Thoracic Society (ATS)/European Respiratory Society (ERS) statement on respiratory muscle testing in 2002. Key advances have been made in the field of mechanics of breathing, respiratory muscle neurophysiology (electromyography, electroencephalography and transcranial magnetic stimulation) and on respiratory muscle imaging (ultrasound, optoelectronic plethysmography and structured light plethysmography). Accordingly, this ERS task force reviewed the field of respiratory muscle testing in health and disease, with particular reference to data obtained since the previous ATS/ERS statement. It summarises the most recent scientific and methodological developments regarding respiratory mechanics and respiratory muscle assessment by addressing the validity, precision, reproducibility, prognostic value and responsiveness to interventions of various methods. A particular emphasis is placed on assessment during exercise, which is a useful condition to stress the respiratory system. ispartof: EUROPEAN RESPIRATORY JOURNAL vol:53 issue:6 ispartof: location:England status: published
Published: 2019

37. A new tool for multi-block PLS discriminant analysis of metabolomic data: application to systems epidemiology

Author: Brandolini-Bunlon, Marion, Pétéra, Mélanie, Gaudreau, Pierrette, Comte, Blandine, Bougeard, Stephanie, Pujos-Guillot, Estelle, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), MetaboHUB, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre Hospitalier Universitaire de Montréal, Département de médecine, Centre Léon Bérard [Lyon], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), and Centre de Recherche du CHUM
Subjects: multi block PLS discriminant analysis, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, metabolomics
Abstract: Metabolomics is a powerful phenotyping tool in nutrition and health research, generating massive and complex data that need dedicated treatments to enrich our knowledge of biological systems. In particular, to deeper investigate relations between environmental factors, phenotypes and metabolism, discriminant statistical analyses performed separately on metabolomic datasets, are often complemented by associations with metadata (anthropometric, clinical, nutritional and physical activity data…). Another relevant strategy is to perform a multi-block partial least squares discriminant analysis (MBPLSDA) that simultaneously analyses data available from different sources, allowing determining the importance of variables and variable blocks in discriminating groups of subjects, taking into account data structure in thematic blocks.In order to propose a full open-source standalone tool, the present objective was to develop an R package allowing all steps of MBPLSDA analysis for the joint analysis of metabolomic and additional data.The tool was based on the mbpls function of the ade4 R package, enriched with different functionalities, including some dedicated to discriminant analysis. Provided indicators help to determine the optimal number of components, to check the MBPLSDA model validity, and to evaluate the variability of its parameters and predictions. To illustrate the potential of the proposed tool and the associated procedure, MBPLSDA was applied to a real case study involving metabolomics, nutritional and clinical data from a human cohort.The availability of the different functionalities in a single R package allowed optimizing parameters for an efficient joint analysis of metabolomics and epidemiological data to obtain new insights into multidimensional phenotypes. In particular, we highlighted the impact of filtering the metabolomic variables beforehand, and the relevance of a MBPLSDA approach in comparison to a standard PLS-discriminant analysis method.
Published: 2019

38. On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post-hoc analysis of the ANRS IPERGAY trial

Author: Laurence Meyer, Julie Chas, Jean-Guy Baril, Véronique Doré, Michel Morin, Jean-Pierre Aboulker, Marine Saouzanet, Isabelle Durant-Zaleski, Marie Suzan-Monti, Emmanuelle Netzer, Françoise Euphrasie, Nathalie Bajos, Séverine Gibowski, Soizic Le Mestre, Gilles Peytavin, Jean-François Delfraissy, Constance Delaugerre, David Thompson, Brigitte Guillon, Gilles Pialoux, Alpha Diallo, Nicolas Etien, Christian Chidiac, Michel Besnier, Isabelle Charreau, Benoit Trottier, Baptiste Demoulin, Julie Timsit, Bruno Spire, Joanne Otis, Laurent Cotte, Julien Fonsart, W. Rozenbaum, Mark A. Wainberg, Gabriel Girard, Eric Cua, Guillemette Antoni, Daniela Rojas Castro, Catherine Capitant, Luis Sagaon-Teyssier, Antoine Cheret, Marie-Christine Simon, Cécile Tremblay, Nicolas Leturque, Johan Binesse, Diane Carette, Valérie Foubert, Anaïs Mennecier, Grégoire Cattin, Jean-Michel Molina, Yacine Saïdi, Nicolas Lorente, Elias Choucair, François Raffi, Cecile Rabian, Armelle Pasquet, Marie Préau, Thomas Huleux, 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, Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Archet 2 [Nice] (CHU), Coalition PLUS [Pantin, France] (Community Research Laboratory Pantin), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Gustave Dron [Tourcoing], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), the Canadian HIV Trials Network, Fonds Pierre Bergé (Sidaction), Gilead Sciences, and the Bill & Melinda Gates Foundation., ANRS IPERGAY study group: Jean-Pierre Aboulker, Nathalie Bajos, Jean-Guy Baril, Michel Besnier, Johan Binesse, Diane Carette, Grégoire Cattin, Antoine Chéret, Christian Chidiac, Elias Choucair, Jean-François Delfraissy, Baptiste Demoulin, Alpha Diallo, Isabelle Durant-Zaleski, Véronique Doré, Nicolas Etien, Françoise Euphrasie, Julien Fonsart, Valérie Foubert, Séverine Gibowski, Gabriel Girard, Brigitte Guillon, Soizic Le Mestre, France Lert, Nicolas Leturque, Nicolas Lorente, Anaïs Mennecier, Michel Morin, Emmanuelle Netzer, Joanne Otis, Armelle Pasquet, Gilles Peytavin, Gilles Pialoux, Marie Préau, Cécile Rabian, Willy Rozenbaum, Luis Sagaon-Teyssier, Yacine Saïdi, Marine Saouzanet, Marie-Christine Simon, Marie Suzan-Monti, David Thompson, Julie Timsit, Benoît Trottier, Mark Wainberg, Dupuis, Christine, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Male, MESH: Sexual Behavior, Epidemiology, [SDV]Life Sciences [q-bio], HIV Infections, Men who have sex with men, MESH: HIV-1, Pre-exposure prophylaxis, Sexual and Gender Minorities, 0302 clinical medicine, MESH: Tenofovir, Medicine, MESH: Double-Blind Method, 030212 general & internal medicine, MESH: Incidence, MESH: Anti-HIV Agents, education.field_of_study, Incidence (epidemiology), Incidence, MESH: HIV Infections, 3. Good health, [SDV] Life Sciences [q-bio], MESH: Sexual and Gender Minorities, Infectious Diseases, Pill, France, medicine.drug, Adult, medicine.medical_specialty, Canada, Anti-HIV Agents, Sexual Behavior, Immunology, Population, Placebo, Emtricitabine, Medication Adherence, MESH: Homosexuality, Male, 03 medical and health sciences, Double-Blind Method, MESH: Canada, Virology, Internal medicine, Humans, Homosexuality, Male, education, Tenofovir, MESH: Humans, business.industry, MESH: Adult, MESH: Medication Adherence, 030112 virology, MESH: Male, MESH: France, Sexual intercourse, HIV-1, Pre-Exposure Prophylaxis, business, MESH: Pre-Exposure Prophylaxis
Abstract: Summary Background ANRS IPERGAY found that on-demand pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine was associated with an 86% relative reduction of HIV-1 incidence compared with placebo among men who have sex with men at high risk of HIV. We aimed to investigate whether on-demand PrEP was similarly effective among individuals with lower exposure to HIV risk. Methods Participants in the ANRS IPERGAY trial were randomly assigned to receive PrEP (fixed-dose combination of 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine per pill) or placebo. The primary endpoint was the diagnosis of HIV-1 infection. Pill uptake was assessed by counting returned pills at each follow-up and by estimating tenofovir concentration from frozen plasma samples. Participants were interviewed at each visit to assess the pattern of PrEP use. All participants enrolled in the modified intention-to-treat population of the double-blind phase of the ANRS IPERGAY trial were eligible for this post-hoc analysis. We calculated the total follow-up time for periods of less frequent sexual intercourse with high PrEP adherence (15 pills or fewer per month taken systematically or often during sexual intercourse). To estimate the time of HIV acquisition, fourth-generation HIV-1/2 ELISA assays, plasma HIV-1 RNA assays, and western blot analyses were done with use of frozen samples, and the stage of HIV infection was defined according to Fiebig staging. HIV incidence was compared between the two treatment groups among individuals who had less frequent sexual intercourse with high PrEP adherence. The ANRS IPERGAY trial is registered with ClinicalTrials.gov , NCT01473472 . Findings 400 participants who were randomly assigned to receive PrEP (n=199) or placebo (n=201) between Feb 22, 2012, and Oct 17, 2014, were included in this analysis. 270 participants had at least one period of less frequent sexual intercourse with high PrEP adherence during the study, representing 134 person-years of follow-up and 31% of the total study follow-up. During these periods, participants in both groups reported a median of 5·0 (IQR 2·0–10·0) episodes of sexual intercourse per month and used a median of 9·5 (6·0–13·0) pills per month. Six HIV-1 infections were diagnosed in the placebo group (HIV incidence of 9·2 per 100 person-years; 95% CI 3·4–20·1) and none were diagnosed in the tenofovir disoproxil fumarate plus emtricitabine arm (HIV incidence of 0 per 100 person-years; 0–5·4; p=0·013), with a relative reduction of HIV incidence of 100% (95% CI 39–100). Interpretation A choice between daily or on-demand PrEP regimens could be offered to men who have sex with men who have less frequent sexual intercourse. Funding ANRS (France Recherche Nord and Sud Sida-HIV Hepatites), the Canadian HIV Trials Network, Fonds Pierre Berge (Sidaction), Gilead Sciences, and the Bill & Melinda Gates Foundation.
Published: 2019

39. The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system

Author: Luc Pénicaud, Demetra Rodaros, Khalil Bouyakdan, Bouchra Taïb, Hugo Martin, Eric Biron, Xavier Fioramonti, Lionel Budry, Daniela Cota, Thierry Alquier, F. Liénard, Chloé Chrétien, Zoé Husson, Stephanie Fulton, Laboratory of Molecular Genetics [Montréal, Canada], Institut De Recherches Cliniques De Montreal - IRCM [Canada], Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Laboratory of Molecular Genetics, Institut de recherches cliniques de Montréal, Centre de recherche du Chum [Montréal] (CRCHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université Laval, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-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), STROMALab, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), CRCHUM, Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Université Laval [Québec] (ULaval), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (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)-École normale supérieure - Paris (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), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Grants from the Canadian Institutes of Health Research (MOP115042 and PJT153035 to TA), Marie Curie Foundation (CIG NeuROSenS PCIG09-GA-2011-293738 to XF), Société Francophone du Diabète and Diabète Québec (to TA) and Réseau cardiométabolique, diabète & obésité from Fonds de Recherche Québec-Santé (CMDO-FRQS to TA and XF) and from INSERM, Agence Nationale Recherche ANR-13-BSV4-0006, ANR-18-CE14-0029-02 (to DC) and ANR-10-LABX-43 Labex BRAIN (to DC and XF). HM and CC were supported by a fellowship from the department AlimH INRA and the Région Nouvelle Aquitaine or Région Bourgogne, respectively. XF and LP were also supported by the PARI Région Bourgogne. TA, SF and EB were supported by a salary award from FRQS. KB and BT were supported by a fellowship from Diabète Québec and LB by a fellowship from Diabetes Canada., and 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Pro-Opiomelanocortin, Gliotransmitter, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hyperphagia, Energy homeostasis, Cell Line, neuroscience, 03 medical and health sciences, Eating, Mice, 0302 clinical medicine, Proopiomelanocortin, Central melanocortin system, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Obesity, ComputingMilieux_MISCELLANEOUS, Diazepam Binding Inhibitor, Mice, Knockout, Neurons, Arc (protein), biology, Chemistry, GABAA receptor, General Medicine, Viral rescue, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Cell biology, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Astrocytes, biology.protein, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Melanocortin, Energy Metabolism, metabolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract: International audience; Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-lineage neural cells, promoted diet-induced hyperphagia and obesity in both male and female mice, an effect prevented by viral rescue of ACBP in ARC astrocytes. ACBP-astrocytes were observed in apposition with proopiomelanocortin (POMC) neurons and ODN selectively activated POMC neurons through the ODN-GPCR but not GABAA, and supressed feeding while increasing carbohydrate utilization via the melanocortin system. Similarly, ACBP overexpression in ARC astrocytes reduced feeding and weight gain. Finally, the ODN-GPCR agonist decreased feeding and promoted weight loss in ob/ob mice. These findings uncover ACBP as an ARC gliopeptide playing a key role in energy balance control and exerting strong anorectic effects via the central melanocortin system.
Published: 2019

40. Nuna vu à travers le cinéma des jeunes Nunavimmiuts

Author: Hermann, Thora Martina, Chanteloup, Laine, Joliet, Fabienne, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), L’Observatoire Hommes-Milieux International (OHMI (Labex DRIIHM)), Espaces et Sociétés (ESO), Le Mans Université (UM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université d'Angers (UA)-AGROCAMPUS OUEST-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN), Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université d'Angers (UA)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Le Mans Université (UM)
Subjects: [SDE.ES]Environmental Sciences/Environmental and Society, [SHS]Humanities and Social Sciences
Published: 2019

41. Walking, trip purpose, and exposure to multiple environments: A case study of older adults in Luxembourg

Author: Sylvain Klein, Yan Kestens, Benoit Thierry, Basile Chaix, Ruben Brondeel, Philippe Gerber, Rania Wasfi, Geoffrey Caruso, Camille Perchoux, Olivier Klein, Martin Dijst, Julie Vallée, Chaix, Basile, Luxembourg Institute of Socio-Economic Research (LISER), Université de Montréal (UdeM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Université du Luxembourg (Uni.lu), Géographie-cités (GC (UMR_8504)), Université Paris 1 Panthéon-Sorbonne (UP1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: [SDV]Life Sciences [q-bio], Poison control, 030209 endocrinology & metabolism, Transportation, Trip purpose, Suicide prevention, Occupational safety and health, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Distance traveled, Injury prevention, Utilitarian walking, 030212 general & internal medicine, Safety, Risk, Reliability and Quality, Built environment, Multi-place exposure, Health Policy, Public Health, Environmental and Occupational Health, Human factors and ergonomics, Pollution, [SDV] Life Sciences [q-bio], Travel behavior, Older adults, Residence, [SHS] Humanities and Social Sciences, Psychology, human activities, Safety Research, Demography
Abstract: International audience; PurposeUnderstanding the geographical and environmental triggers for active transport among older adults is crucial to promote healthy and independent lifestyles. While transportation research has long considered trip purpose as a major determinant of transport mode choices, “place and health” research has paid little attention to it, and even less in connection with environmental determinants. To avoid an oversimplification of how neighborhood built environments influence utilitarian walking, it is critical to account simultaneously for trip purposes, the locations of visited places, and the related exposure to surrounding environments.MethodsBased on a cohort of 471 older adults in Luxembourg, this study examines the influence of trip purposes on utilitarian walking, and the potential interaction effects with characteristics of multiple geographic environments and distance to the place of residence. Information related to demographics, health status, and regularly visited destinations was collected in 2015 and 2016. Associations between trip purpose, environment, distance, and walking were analyzed using multilevel logistic regressions, accounting for demographics, neighborhood self-selection, and health status.ResultsAfter accounting for environmental attributes, distance, and confounding factors, trip purpose remained a strong correlate of walking among older adults. Associations between distance and walking strongly differed by trip purpose (Wald Chi2 test p
Published: 2019

42. Autologous endometrial cell co-culture improves human embryo development to high-quality blastocysts: a randomized controlled trial

Author: S. Phillips, Bernard Couturier, François Bissonnette, Sandra Bisotto, Cécile Le Saint, Isaac Jacques Kadoch, John S. Sampalis, Karen Buzaglo, Samir Hamamah, Melissa Stutz, Jean-Noël Gouze, Amélie Bourdiec, Kimberley Crespo, Salvy-Córdoba, Nathalie, Clinique Ovo (Ovo Labo), Ovo Labo - Clinique Ovo, Department of Obstetrics Gynecology [Montréal], Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC)-McGill University Health Center [Montreal] (MUHC)-McGill University = Université McGill [Montréal, Canada], Centre Hospitalier Universitaire Montréal - Hôpital Saint-Luc, Partenaires INRAE, Ovo Labo - (Clinique Ovo), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Clinique Ovo (Labo Ovo), Université du Québec à Montréal = University of Québec in Montréal (UQAM), JSS Research (JSS Medical Research), Laboratoires Genévrier, JSS Medical Research (JSS), Développement embryonnaire précoce humain et pluripotence EmbryoPluripotency (UMR 1203), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-CHU Montpellier, and Clinique Ovo (Ovo R&D)
Subjects: Pregnancy Rate, medicine.medical_treatment, Good-quality blastocysts, Intracytoplasmic sperm injection, law.invention, Embryo Culture Techniques, Endometrium, 0302 clinical medicine, Randomized controlled trial, Pregnancy, law, reproductive and urinary physiology, 0303 health sciences, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Pregnancy Outcome, Obstetrics and Gynecology, Autologous endometrial co-culture, 3. Good health, Treatment Outcome, medicine.anatomical_structure, IVF, embryonic structures, Female, Live Birth, Adult, Infertility, medicine.medical_specialty, Randomization, Embryonic Development, Fertilization in Vitro, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, ICSI, 03 medical and health sciences, Double-Blind Method, MESH: Blastocyst / cytology, Embryo Culture Techniques / methods, Embryonic Development / physiology, Endometrium / cytology, Fertilization in Vitro / methods, medicine, Humans, Blastocyst, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, 030304 developmental biology, Gynecology, Assisted reproductive technology, business.industry, Embryo culture, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Embryo Transfer, medicine.disease, Coculture Techniques, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Reproductive Medicine, Oocytes, business, Developmental Biology, Endometrial biopsy
Abstract: International audience; Does autologous endometrial cell co-culture (AECC) improve the number of good-quality blastocysts obtained by IVF/intracytoplasmic sperm injection (ICSI), compared with conventional embryo culture medium in a broad group of patients referred to assisted reproductive technology (ART)?Design: This interventional, randomized, double-blind study took place at Clinique Ovo from March 2013 to October 2015 and included 207 healthy patients undergoing an IVF or ICSI protocol, of which 71 were excluded before randomization. On the previous cycle, all participants underwent an endometrial biopsy at D5 to D7 post-ovulation, following which the endometrial cells were prepared for AECC.Results: The data demonstrated that AECC significantly increased the incidence of good-quality blastocysts compared with culture in conventional media (42.6% vs 28.4%, P < 0.001). No significant differences were found in pregnancy and live birth rates.Conclusion: This study demonstrated the benefits of AECC on blastocyst quality compared with conventional embryo culture medium, in a broader category of patients referred to ART as opposed to other studies that concentrated on specific causes of infertility only. However, limitations of the study design should be taken into consideration; the analysis was performed using embryos rather than patients and a follow-up of children born following the treatments could not be conducted
Published: 2019

43. Cellular Senescence: Defining a Path Forward

Author: John M. Sedivy, Paul D. Robbins, Cleo L. Bishop, Vassilis G. Gorgoulis, Konstantinos Vougas, Konstantinos Evangelou, Valery Krizhanovsky, Dorothy C. Bennett, Eiji Hara, Diana Jurk, Gerardo Ferbeyre, Judith Campisi, Masashi Narita, Laura J. Niedernhofer, Manuel Serrano, Clemens A. Schmitt, Peter D. Adams, Oliver Bischof, Andrea Alimonti, Marco Demaria, Jesús Gil, Daohong Zhou, Manuel Collado, Thomas von Zglinicki, Andrea B. Maier, João F. Passos, Institut Pasteur [Paris], National and Kapodistrian University of Athens (NKUA), University of Manchester [Manchester], Biomedical Research Foundation of the Academy of Athens (BRFAA), Institute of Cancer Sciences [Glasgow, UK] (CR-UK Beatson Institute), University of Glasgow, Sanford Burnham Prebys Medical Discovery Institute, Oncology Institute of Southern Switzerland (IOSI), Università della Svizzera italiana = University of Italian Switzerland (USI), Universita degli Studi di Padova, Veneto Institute of Molecular Medicine [Padova, Italy] (VIMM), University of London [London], Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Bart's and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Buck Institute for Research on Aging, Universidade de Santiago de Compostela [Spain] (USC ), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Université de Montréal (UdeM), MRC London Institute of Medical Sciences (LMC), Imperial College London, Research Institute for Microbial Diseases [Osaka, Japan] (RIMD), Osaka University [Osaka], Department of Molecular Cell Biology [Rehovot], Weizmann Institute of Science [Rehovot, Israël], Robert and Arlene Kogod Center on Aging [Rochester, MN, USA], Mayo Clinic, Vrije Universiteit Amsterdam [Amsterdam] (VU), University of Melbourne, University of Cambridge [UK] (CAM), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Kepler University Hospital, Brown University, Newcastle University [Newcastle], University of Florida [Gainesville] (UF), Institute for Research in Biomedicine [Barcelona, Spain] (IRB), University of Barcelona-Barcelona Institute of Science and Technology (BIST), Institució Catalana de Recerca i Estudis Avançats (ICREA), University of Groningen [Groningen], European Research Institute for the Biology of Ageing [Groningen] (ERIBA), University Medical Center Groningen [Groningen] (UMCG), M.D. is funded by the Dutch Cancer Foundation, Netherlands (grant ID 10989). V.G., K.E., and K.V. were financially supported by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grants agreement no. 722729 (SYNTRAIN), the Welfare Foundation for Social & Cultural Sciences (KIKPE), Greece, the KIKPE Foundation, Athens, Greece, Pentagon Biotechnology, UK, DeepMed IO, UK, grant no. 775 from the Hellenic Foundation for Research and Innovation (HFRI), and NKUA-SARG grants 70/3/9816, 70/3/12128, and 70/3/15603. M.S.: is funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and 'laCaixa' Foundation., We would like to thank Nikolaos Kastrinakis, Panagiotis V.S. Vasileiou, Gkikas Magiorkinis, Eleni Fitsiou, and Michela Borghesan for their valuable support to this work. We apologize in advance that, for reason of space, we have omitted the citations of relevant papers and reviews., National and Kapodistrian University of Athens = University of Athens (NKUA | UoA), Organisation Nucléaire et Oncogenèse - Nuclear Organization and Oncogenesis, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], University of Santiago de Compostela [Spain] (USC), Centre de recherche du Chum [Montréal] (CRCHUM), Université de Montréal [Montréal], Research Institute for Microbial Diseases, Weizmann Institute of Science, University of Minnesota [Twin Cities], Max Delbrück Center for Molecular Medicine [Berlin], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, University of Florida [Gainesville], University of Barcelona, Università degli Studi di Padova = University of Padua (Unipd), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Narita, Masashi [0000-0001-7764-577X], and Apollo - University of Cambridge Repository
Subjects: Senescence, EXPRESSION, Aging, Cell cycle checkpoint, [SDV]Life Sciences [q-bio], Cell, DNA-DAMAGE RESPONSE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Mitochondrion, Biology, General Biochemistry, Genetics and Molecular Biology, CHROMATIN LANDSCAPE, 03 medical and health sciences, 0302 clinical medicine, MITOCHONDRIA, ONCOGENE-INDUCED SENESCENCE, medicine, Humans, OXIDATIVE STRESS, Senolytic, Cellular Senescence, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, P53, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Genetic Diseases, Inborn, DARK SIDE, Cell Cycle Checkpoints, 06 Biological Sciences, CANCER, Chromatin, medicine.anatomical_structure, Gene Expression Regulation, CELLS, Developmental biology, 030217 neurology & neurosurgery, Biomarkers, Developmental Biology
Abstract: International audience; Cellular senescence is a cell state implicated in various physiological processes and a wide spectrum of age-related diseases. Recently, interest in therapeutically targeting senescence to improve healthy aging and age-related disease, otherwise known as senotherapy, has been growing rapidly. Thus, the accurate detection of senescent cells, especially in vivo, is essential. Here, we present a consensus from the International Cell Senescence Association (ICSA), defining and discussing key cellular and molecular features of senescence and offering recommendations on how to use them as biomarkers. We also present a resource tool to facilitate the identification of genes linked with senescence, SeneQuest (available at http://Senequest.net). Lastly, we propose an algorithm to accurately assess and quantify senescence, both in cultured cells and in vivo.
Published: 2019
Full Text: View/download PDF

44. Analytic correlation filtration: A new tool to reduce analytical complexity of metabolomic datasets

Author: Monnerie, Stéphanie, Pétéra, Mélanie, Lyan, Bernard, Gaudreau, Pierrette, Comte, Blandine, Pujos-Guillot, Estelle, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), MetaboHUB, Centre de Recherche du CHUM, Département de médecine, Centre Léon Bérard [Lyon], Centre Hospitalier Universitaire de Montréal, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), and Université de Montréal (UdeM)-Université de Montréal (UdeM)
Subjects: filtration, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, analytical redundancies, workflow, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, lcsh:QR1-502, high-resolution mass spectrometry, data filtration, metabolomics, lcsh:Microbiology, Article
Abstract: Session: Analytic correlation filtration: A new tool to reduce analytical complexity of metabolomic datasets Poster P-501* (*AWARD WINNERS) Session: Analytic correlation filtration: A new tool to reduce analytical complexity of metabolomic datasets Poster P-501* (*AWARD WINNERS)Session: Analytic correlation filtration: A new tool to reduce analytical complexity of metabolomic datasetsPoster P-501* (*AWARD WINNERS); Metabolomics generates complex data that need dedicated workflows to extract the meaningful information. For biological interpretation, experts are mainly focusing on metabolites rather than on the redundant different analytical species. Moreover, the high degree of correlation in datasets is a constraint for the use of statistical methods. In this context, we developed a new tool to detect analytical correlation into datasets.The algorithm principle is to group features from the same analyte and to propose one single representative per group. The user can define grouping criteria with various options including correlation coefficient, retention time, mass defect information. The representative feature can be determined following four methods according to the analytical technology. The present tool was compared to one of the most commonly used free package proposing a grouping method: ‘CAMERA’, using its Galaxy version ‘CAMERA.annotate’ available in workflow4Metabolomics (W4M; http://workflow4metabolomics.org). To illustrate its functionalities, a published dataset available on W4M (Thevenot et al., 2015) was used as an example. Within the 3,120 ions of the dataset, the tool allowed creating 2,651 groups, meaning that 15% of ions are proposed to be filtered because of analytical redundancies. The proposed tool subdivided more than 20 groups of more than 10 ions into smaller ones corresponding to individualannotated metabolites, thus demonstrating the efficiency and relevance of the present approach. As a key element in metabolomics data analysis, the tool will be available via the web-based galaxy platform W4M with different output files for network vizualisation and for further data analysis within workflows.
Published: 2019

45. In the the Eyes of Inuit and Cree Youth: Homeland Videos in Nunavik (Kuujjuarapik,Kangiqsujuaq, Whapmagoostui)

Author: Joliet, Fabienne, Chanteloup, Laine, Hermann, Thora Martina, Espaces et Sociétés (ESO), Le Mans Université (UM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université d'Angers (UA)-AGROCAMPUS OUEST-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN), L’Observatoire Hommes-Milieux International (OHMI (Labex DRIIHM)), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université d'Angers (UA)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Le Mans Université (UM)
Subjects: [SHS.SOCIO]Humanities and Social Sciences/Sociology, [SDE.ES]Environmental Sciences/Environmental and Society, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

46. γ-Aminobutyric acid receptor alpha 1 subunit loss of function causes genetic generalized epilepsy by impairing inhibitory network neurodevelopment

Author: Eric Samarut, Patrick Cossette, Liselotte Dufour, Marc Allard, Nadia Soussi-Yanicostas, Solène Renault, Rahma Hassan-Abdi, Pierre Drapeau, Amrutha Swaminathan, Meijiang Liao, Raphaëlle Riché, Department of Neurosciences [Montréal, QC, Canada], Université de Montréal (UdeM)-Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Molecular Biology and Genetics Unit [Bangalore, India] (Transcription and Disease Laboratory), Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR)-Indian Institute of Science, Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de l'Université de Montréal (CHUM), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), and Centre de recherche du Chum [Montréal] (CRCHUM)
Subjects: 0301 basic medicine, Embryo, Nonmammalian, Light, [SDV]Life Sciences [q-bio], Green Fluorescent Proteins, Gene Expression, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Inhibitory postsynaptic potential, Epileptogenesis, Clonazepam, Animals, Genetically Modified, Gabra1 loss of function, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, medicine, Anti-epileptic drugs, Animals, MESH: Epilepsy, Gabra1 loss of function, Zebrafish, High‐throughput antiepileptic drug screening, Anti-epileptic drugs, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Generalized epilepsy, Zebrafish, Loss function, Neurons, biology, Glutamate Decarboxylase, Mortality, Premature, Brain, Gene Expression Regulation, Developmental, medicine.disease, biology.organism_classification, Receptors, GABA-A, High‐throughput antiepileptic drug screening, Disease Models, Animal, 030104 developmental biology, Neurology, Neurodevelopmental Disorders, Larva, Mutation, GABAergic, Axon guidance, Anticonvulsants, Epilepsy, Generalized, Neurology (clinical), Transcriptome, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Objective: In humans, mutations of the γ-aminobutyric acid receptor subunit 1 (GABRA1) cause either mild or severe generalized epilepsy. Although these epilepsy causing mutations have been shown to disrupt the receptor activity in vitro, their in vivo consequences on brain development and activity are not known. Here, we aim at unraveling the epileptogenesis mechanisms of GABRA1 loss of function. Methods: We generated a gabra1 −/− zebrafish mutant line displaying highly pen-etrant epileptic seizures. We sought to identify the underlying molecular mechanisms through unbiased whole transcriptomic assay of gabra1 −/− larval brains. Results: Interestingly, mutant fish show fully penetrant seizures at juvenile stages that accurately mimic tonic-clonic generalized seizures observed in patients. Moreover , highly penetrant seizures can be induced by light stimulation, thus providing us with the first zebrafish model in which evident epileptic seizures can be induced by nonchemical agents. Our transcriptomic assay identified misregulated genes in several pathways essential for correct brain development. More specifically, we show that the early development of the brain inhibitory network is specifically affected. Although the number of GABAergic neurons is not altered, we observed a drastic reduction in the number of inhibitory synapses and a decreased complexity of the GABAergic network. This is consistent with the disruption in expression of many genes involved in axon guidance and synapse formation. Significance: Together with the role of GABA in neurodevelopment, our data identify a novel aspect of epileptogenesis, suggesting that the substratum of GABRA1-deficiency epilepsy is a consequence of early brain neurodevelopmental defects, in particular at the level of inhibitory network wiring.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Published: 2018

47. Combining social network and activity space data for health research: tools and methods

Author: Kestens Yan, Basile Chaix, Sueur Cédric, Naud Alexandre, Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Montréal (UdeM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation (MESRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and CCSD, Accord Elsevier
Subjects: Health (social science), Computer science, Relational database, Geography, Planning and Development, Population health, Name generator, Space (commercial competition), Social Environment, Sciences du Vivant [q-bio]/Santé publique et épidémiologie, Article, Social Networking, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Humans, 030212 general & internal medicine, Built Environment, Healthy aging, 030505 public health, Social network, business.industry, Public Health, Environmental and Occupational Health, Science non linéaire [physics]/Adaptation et Systèmes auto-organisés [nlin.AO], Data science, [SHS] Humanities and Social Sciences, 0305 other medical science, business, Network analysis
Abstract: Contextual factors influencing population health have received substantial attention, especially with regard to people’s social networks and the roles of built environments in their activity spaces. Yet little health research has considered spatial and social contexts simultaneously, often because of a lack of existing data. This paper presents a tool for collecting relational data on social network and activity space that extends an existing map-based questionnaire with the addition of a name generator. We then illustrate how network analysis provides a useful framework for studying connections between social and spatial contexts using data collected in the Contrasted Urban settings for Healthy Aging research project., Highlights • An interactive tool to collect linked social network and activity space data. • Socio-spatial relations are defined by the location of face-to-face interactions. • Collected data can be modeled as complex networks. • A method to connect social and spatial contexts in health research.
Published: 2020

48. International AIDS Society global scientific strategy: towards an HIV cure 2016

Author: Deeks, Sg, Lewin, Sr, Ross, Al, Ananworanich, J, Benkirane, M, Cannon, P, Chomont, N, Douek, D, Lifson, Jd, Lo, Yr, Kuritzkes, D, Margolis, D, Mellors, J, Persaud, D, Tucker, Jd, Barre-Sinoussi, F, International Aids Society Towards a Cure Working Group, International Aids Society Towards a Cure Working Group, Alter, G, Auerbach, J, Autran, B, Barouch, Dh, Behrens, G, Cavazzana, M, Chen, Z, Cohen, Ea, Corbelli, Gm, Eholié, S, Eyal, N, Fidier, S, Garcia, L, Grossman, C, Henderson, G, Henrich, Tj, Jefferys, R, Kiem, Hp, Mccune, J, Moodley, K, Newman, Pa, Nijhuis, M, Nsubuga, Ms, Ott, M, Palmer, S, Richman, D, Saez-Cirion, A, Sharp, M, Siliciano, J, Silvestri, G, Singh, J, Spire, B, Taylor, J, Tolstrup, M, Valente, S, van Lunzen, J, Walensky, R, Wilson, I, Zack, J, Department of Medicine [San Francisco], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia, International and Scientific Relations Office, ANRS, Paris, France, Walter Reed Army Institute of Research, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of Southern California (USC), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), National Institutes of Health [Bethesda] (NIH), Frederick National Laboratory for Cancer Research (FNLCR), World Health Organization Regional Office for the Western Pacific, Manila, Philippines, Brigham and Women's Hospital [Boston], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Institut Pasteur [Paris] (IP), Ragon Institute of MGH, MIT and Harvard, Centre d'Immunologie et de Maladies Infectieuses (CIMI), 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), Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Clinic for Immunology and Rhematology, Hannover Medical School, Hanover, Germany, Département de Biothérapie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AIDS Institute, The University of Hong Kong, Pok Fu Lam, Hong Kong, Institut de Recherches Cliniques de Montréal (IRCM), Université de Montréal (UdeM), European AIDS Treatment Group, Italy, Programme PAC-CI, Centre Hospitalier Universitaire de Treichville, Abidjan, Côte d'Ivoire, Harvard School of Public Health, Imperial College London, The B-Change Group, Manila, Philippines, Treatment Action Group (TAG), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Stellenbosch University, Factor-Inwentash Faculty of Social Work, University of Toronto, Toronto, Ontario, Canada, University Medical Center [Utrecht], Joint Clinical Research Centre, University of California (UC), The Westmead Institute for Medical Research, University of California [San Diego] (UC San Diego), Independent HIV Education and Advocacy Consultant, San Francisco, California, USA, Emory University [Atlanta, GA], Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CARE Collaboratory Community Advisory Board, Palm Springs, California, USA., Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark., The Scripps Research Institute [La Jolla, San Diego], ViiV Healthcare, London, United Kingdom., Massachusetts General Hospital [Boston], Brown University School of Public Health, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California [San Francisco] (UCSF), University of California-University of California, Institut Pasteur [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Department of Medicine, Imperial College London, London, United Kingdom, University of California, Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Scripps Research Institute, Imperial College Healthcare NHS Trust- BRC Funding, American Foundation for AIDS Research, Medical Research Council (MRC), MRC DCS, British HIV Association (BHIVA), and Larose, Catherine
Subjects: CD4(+) T-CELLS, 0301 basic medicine, International Cooperation, [SDV]Life Sciences [q-bio], VIRAL RESERVOIR, Human immunodeficiency virus (HIV), Stakeholder engagement, HIV Infections, [SDV.GEN] Life Sciences [q-bio]/Genetics, Research & Experimental Medicine, medicine.disease_cause, Medicine, Societies, Medical, IN-VIVO, ComputingMilieux_MISCELLANEOUS, HIGHLY PATHOGENIC SIV, virus diseases, LATENT HIV-1, 11 Medical And Health Sciences, General Medicine, TREATMENT INTERRUPTION, 3. Good health, [SDV] Life Sciences [q-bio], International AIDS Society Towards a Cure Working Group, Medicine, Research & Experimental, Goals, Life Sciences & Biomedicine, BROADLY NEUTRALIZING ANTIBODIES, Biochemistry & Molecular Biology, medicine.medical_specialty, RALTEGRAVIR INTENSIFICATION, Immunology, education, Article, General Biochemistry, Genetics and Molecular Biology, HISTONE DEACETYLASE INHIBITOR, 03 medical and health sciences, Global population, Acquired immunodeficiency syndrome (AIDS), SUPPRESSIVE ANTIRETROVIRAL THERAPY, Journal Article, Humans, Organizational Objectives, Acquired Immunodeficiency Syndrome, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, business.industry, Research, Cell Biology, medicine.disease, Antiretroviral therapy, 030104 developmental biology, Treatment interruption, Family medicine, business
Abstract: Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.
Published: 2016

49. Mass or total surface area with aerosol size distribution as exposure metrics for inflammatory, cytotoxic and oxidative lung responses in rats exposed to titanium dioxide nanoparticles

Author: Alexandra Noël, Karim Maghni, Michel Charbonneau, Yves Cloutier, Ginette Truchon, Robert Tardif, Institut de recherche en santé publique, Université de Montréal, Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Département de santé environnementale et de santé au travail, and Université de Montréal (UdeM)
Subjects: Male, 0301 basic medicine, Pulmonary toxicity, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, Metal Nanoparticles, 010501 environmental sciences, Dinoprost, Toxicology, medicine.disease_cause, 01 natural sciences, chemistry.chemical_compound, Surface area, Cytotoxicity, Lung, Titanium, Inhalation Exposure, Cell Death, Chemistry, nanoparticle, Oxidants, medicine.anatomical_structure, Neutrophil Infiltration, Environmental chemistry, nanotoxicology, exposure metric, Bronchoalveolar Lavage Fluid, Surface Properties, Respiratory Mucosa, 03 medical and health sciences, Toxicity Tests, Acute, medicine, Animals, Particle Size, pulmonary toxicity, 0105 earth and related environmental sciences, Aerosols, Dose-Response Relationship, Drug, 030111 toxicology, Public Health, Environmental and Occupational Health, Rats, Inbred F344, Aerosol, Oxidative Stress, Nanotoxicology, Titanium dioxide, Biophysics, Biomarkers, Oxidative stress
Abstract: There is currently no consensus on the best exposure metric(s) for expressing nanoparticle (NP) dose. Although surface area has been extensively studied for inflammatory responses, it has not been as thoroughly validated for cytotoxicity or oxidative stress effects. Since inhaled NPs deposit and interact with lung cells based on agglomerate size, we hypothesize that mass concentration combined with aerosol size distribution is suitable for NP risk assessment. The objective of this study was to evaluate different exposure metrics for inhaled 5 nm titanium dioxide aerosols composed of small (SA < 100 nm) or large (LA > 100 nm) agglomerates at 2, 7, and 20 mg/m3 on rat lung inflammatory, cytotoxicity, and oxidative stress responses. We found a significant positive correlation ( r = 0.98, p < 0.01) with the inflammatory reaction, measured by the number of neutrophils and the mass concentration when considering all six (SA + LA) aerosols. This correlation was similar ( r = 0.87) for total surface area. Regarding cytotoxicity and oxidative stress responses, measured by lactate dehydrogenase and 8-isoprostane, respectively, and mass or total surface area as an exposure metric, we observed significant positive correlations only with SA aerosols for both the mass concentration and size distribution ( r > 0.91, p < 0.01), as well as for the total surface area ( r > 0.97, p < 0.01). These data show that mass or total surface area concentrations alone are insufficient to adequately predict oxidant and cytotoxic pulmonary effects. Overall, our study indicates that considering NP size distribution along with mass or total surface area concentrations contributes to a more mechanistic discrimination of pulmonary responses to NP exposure.
Published: 2016

50. Residential buffer, perceived neighborhood, and individual activity space: New refinements in the definition of exposure areas – The RECORD Cohort Study

Author: Yan Kestens, Ruben Brondeel, Camille Perchoux, Basile Chaix, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Montréal (UdeM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), École des Hautes Études en Santé Publique [EHESP] (EHESP), and Chaix, Basile
Subjects: Male, Health (social science), Parks, Recreational, media_common.quotation_subject, Geography, Planning and Development, Environment, Destinations, Space (commercial competition), [SHS]Humanities and Social Sciences, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Residence Characteristics, Environmental health, Perception, 11. Sustainability, Humans, Perceived residential neighborhood, Social inequality, Activity space, 030212 general & internal medicine, Built environment, media_common, Spatial Analysis, 030505 public health, Public Health, Environmental and Occupational Health, Selective daily mobility bias, Environmental exposure, Middle Aged, Geography, Socioeconomic Factors, Female, Residence, [SHS] Humanities and Social Sciences, 0305 other medical science, Residential buffer, Cohort study
Abstract: International audience; Neighborhood effects on health have been widely investigated; yet the definition of neighborhoods is usually arbitrary. This study analyses how disparities in environmental exposure according to urbanicity vary when considering a home-centered network-buffer, the perceived residential neighborhood, or the activity space. Exposures to the density of destinations and proportion of green space were compared for three spatial definitions of exposure areas, overall and stratified by urbanicity of the residence. Environmental exposure levels and gradients by urbanicity were found to vary depending on the spatial definition of the exposure area.
Published: 2016

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

192 results on '"Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM)"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources