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Andre Olivier

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https://read.qxmd.com/read/30773432/development-of-a-novel-nurr1-not-agonist-from-hit-to-lead-and-candidate-for-the-potential-treatment-of-parkinson-s-disease
#1
Dominique Lesuisse, André Malanda, Jean-François Peyronel, Yannick Evanno, Patrick Lardenois, Danielle De-Peretti, Pierre-Yves Abécassis, Pascal Barnéoud, Pascale Brunel, Marie-Claude Burgevin, Céline Cegarra, Florian Auger, Amélie Dommergue, Corinne Lafon, Luc Even, Joanna Tsi, Thy Phuong Hieu Luc, Antonio Almario, Anne Olivier, Marie-Noëlle Castel, Véronique Taupin, Thomas Rooney, Xavier Vigé
In the course of a programme aimed at identifying Nurr1/NOT agonists for potential treatment of Parkinson's disease, a few hits from high throughput screening were identified and characterized. A combined optimization pointed to a very narrow and stringent structure activity relationship. A comprehensive program of optimization led to a potent and safe candidate drug displaying neuroprotective and anti-inflammatory activity in several in vitro and in vivo models.
January 30, 2019: Bioorganic & Medicinal Chemistry Letters
https://read.qxmd.com/read/30761390/elimination-of-epidemic-meningitis-in-the-african-region-progress-and-challenges-2010-2016
#2
Amadou Fall, André Fouda Bita, Clement Lingani, Mamoudou Djingarey, Carole Tevi-Benissan, Marie-Pierre Preziosi, Olivier Ronveaux, R Mihigo, J Okeibunor, Bartholomew Dicky Akanmori
Background: Epidemics of meningococcal disease constitute a major public health challenge in Africa, affecting mostly the 24 countries of the meningitis belt. These epidemics led to a call for a call for a safe, effective and affordable conjugate vaccine against the major serogroup responsible for recent epidemics by leaders of the region. Objective: This paper documents experiences with efforts at eliminating epidemic meningitis in the African Region. Method: The meningoccocal serogroup A conjugate vaccine was developed, licensed and offered to more than 235 million people through mass vaccination campaigns in 16 countries since 2010...
July 2, 2018: Journal of immunological sciences
https://read.qxmd.com/read/30761132/repurposing-of-drugs-as-novel-influenza-inhibitors-from-clinical-gene-expression-infection-signatures
#3
Andrés Pizzorno, Olivier Terrier, Claire Nicolas de Lamballerie, Thomas Julien, Blandine Padey, Aurélien Traversier, Magali Roche, Marie-Eve Hamelin, Chantal Rhéaume, Séverine Croze, Vanessa Escuret, Julien Poissy, Bruno Lina, Catherine Legras-Lachuer, Julien Textoris, Guy Boivin, Manuel Rosa-Calatrava
Influenza virus infections remain a major and recurrent public health burden. The intrinsic ever-evolving nature of this virus, the suboptimal efficacy of current influenza inactivated vaccines, as well as the emergence of resistance against a limited antiviral arsenal, highlight the critical need for novel therapeutic approaches. In this context, the aim of this study was to develop and validate an innovative strategy for drug repurposing as host-targeted inhibitors of influenza viruses and the rapid evaluation of the most promising candidates in Phase II clinical trials...
2019: Frontiers in Immunology
https://read.qxmd.com/read/30720091/efficacy-of-aflibercept-with-folfox-and-maintenance-with-fluoropyrimidine-as-first%C3%A2-line-therapy-for-metastatic-colorectal-cancer-gercor-velvet-phase-ii-study
#4
Benoist Chibaudel, Jean-Baptiste Bachet, Thierry André, Dominique Auby, Jérôme Desramé, Gaël Deplanque, Cédric Lecaille, Christophe Louvet, Christophe Tournigand, Valérie Lebrun-Ly, Jérôme Dauba, Gérard Lledo, Marie-Line Garcia, Olivier Dubreuil, Nabil Baba Hamed, Aurélia Meurisse, Annette K Larsen, Annemilaï Tijeras-Raballand, Franck Bonnetain, Aimery De Gramont
Aflibercept in combination with 5‑fluorouracil (5‑FU)/irinotecan improves overall survival in the second‑line therapy of patients with metastatic colorectal cancer (mCRC). In this study, we evaluated the effects of aflibercept in first‑line therapy with FOLFOX followed by maintenance with fluoropyrimidine. VELVET was a prospective, single‑arm multicenter phase II study (completed). Patients with previously untreated, unresectable, evaluable or measurable mCRC, with an age ≥18 years, and an ECOG performance status of 0‑2 received 6 cycles of modified FOLFOX7 (5‑FU/folinic acid and oxaliplatin) with aflibercept at 4 mg/kg every 2 weeks followed by maintenance therapy with fluoropyrimidine with aflibercept until disease progression or limiting toxicity...
February 1, 2019: International Journal of Oncology
https://read.qxmd.com/read/30712918/type-2-diabetes-mellitus-and-osteoarthritis
#5
REVIEW
Nicola Veronese, Cyrus Cooper, Jean-Yves Reginster, Marc Hochberg, Jaime Branco, Olivier Bruyère, Roland Chapurlat, Nasser Al-Daghri, Elaine Dennison, Gabriel Herrero-Beaumont, Jean-François Kaux, Emmanuel Maheu, René Rizzoli, Roland Roth, Lucio C Rovati, Daniel Uebelhart, Mila Vlaskovska, André Scheen
OBJECTIVES: Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are common diseases that frequently co-exist, along with overweight/obesity. While the mechanical impact of excess body weight on joints may explain lower limb OA, we sought to explore whether T2DM is linked to OA outside of excess weight and whether T2DM may play a role in OA pathophysiology. The consequence of T2DM on OA outcomes is a question of research interest. METHODS: We conducted a critical review of the literature to explore the association between T2DM and OA, whether any association is site-specific for OA, and whether the presence of T2DM impacts on OA outcomes...
January 11, 2019: Seminars in Arthritis and Rheumatism
https://read.qxmd.com/read/30675804/local-pulmonary-drug-delivery-in-the-preterm-rabbit-feasibility-and-efficacy-of-daily-intratracheal-injections
#6
Thomas Salaets, Andre Gie, Julio Jimenez, Margo Aertgeerts, Olivier Gheysens, Greetje Vande Velde, Michel Koole, Xabi Murgia, Costanza Casiraghi, Francesca Ricci, Fabrizio Salomone, Gino Villetti, Karel Allegaert, Jan Deprest, Jaan Toelen
Recent clinical trials in newborns have successfully used surfactant as a drug carrier for an active compound, in order to minimize systemic exposure. To investigate the translational potential of surfactant-compound mixtures and other local therapeutics, a relevant animal model is required where intratracheal (IT) administration for maximal local deposition is technically possible and well tolerated. Preterm rabbit pups (born at 28 days of gestation) were exposed to either hyperoxia or normoxia and randomized to receive daily IT surfactant, daily IT saline or no injections for 7 days...
January 24, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/30664011/central-venous-to-arterial-pco2-difference-arteriovenous-oxygen-content-and-outcome-after-adult-cardiac-surgery-with-cardiopulmonary-bypass-a-prospective-observational-study
#7
Mouhamed D Moussa, Arthur Durand, Guillaume Leroy, Liu Vincent, Antoine Lamer, Guillaume Gantois, Olivier Joulin, Slimane Ait-Ouarab, Delphine Deblauwe, Brandt Caroline, Christophe Decoene, André Vincentelli, Benoit Vallet, Julien Labreuche, Eric Kipnis, Emmanuel Robin
BACKGROUND: Rapid identification and treatment of tissue hypoxia reaching anaerobiosis (dysoxia) may reduce organ failure and the occurrence of major postoperative complications (MPC) after cardiac surgery. The predictive ability of PCO2-based dysoxia biomarkers, central venous-to-arterial PCO2 difference (ΔPCO2) and ΔPCO2 to arteriovenous oxygen content difference ratio, is poorly studied in this setting. OBJECTIVES: We evaluated the ability of PCO2-based tissue dysoxia biomarkers, blood lactate concentration and central venous oxygen saturation measured 2 h after admission to the ICU as predictors of MPC...
January 16, 2019: European Journal of Anaesthesiology
https://read.qxmd.com/read/30662951/global-patterns-and-drivers-of-ecosystem-functioning-in-rivers-and-riparian-zones
#8
Scott D Tiegs, David M Costello, Mark W Isken, Guy Woodward, Peter B McIntyre, Mark O Gessner, Eric Chauvet, Natalie A Griffiths, Alex S Flecker, Vicenç Acuña, Ricardo Albariño, Daniel C Allen, Cecilia Alonso, Patricio Andino, Clay Arango, Jukka Aroviita, Marcus V M Barbosa, Leon A Barmuta, Colden V Baxter, Thomas D C Bell, Brent Bellinger, Luz Boyero, Lee E Brown, Andreas Bruder, Denise A Bruesewitz, Francis J Burdon, Marcos Callisto, Cristina Canhoto, Krista A Capps, María M Castillo, Joanne Clapcott, Fanny Colas, Checo Colón-Gaud, Julien Cornut, Verónica Crespo-Pérez, Wyatt F Cross, Joseph M Culp, Michael Danger, Olivier Dangles, Elvira de Eyto, Alison M Derry, Veronica Díaz Villanueva, Michael M Douglas, Arturo Elosegi, Andrea C Encalada, Sally Entrekin, Rodrigo Espinosa, Diana Ethaiya, Verónica Ferreira, Carmen Ferriol, Kyla M Flanagan, Tadeusz Fleituch, Jennifer J Follstad Shah, André Frainer Barbosa, Nikolai Friberg, Paul C Frost, Erica A Garcia, Liliana García Lago, Pavel Ernesto García Soto, Sudeep Ghate, Darren P Giling, Alan Gilmer, José Francisco Gonçalves, Rosario Karina Gonzales, Manuel A S Graça, Mike Grace, Hans-Peter Grossart, François Guérold, Vlad Gulis, Luiz U Hepp, Scott Higgins, Takuo Hishi, Joseph Huddart, John Hudson, Samantha Imberger, Carlos Iñiguez-Armijos, Tomoya Iwata, David J Janetski, Eleanor Jennings, Andrea E Kirkwood, Aaron A Koning, Sarian Kosten, Kevin A Kuehn, Hjalmar Laudon, Peter R Leavitt, Aurea L Lemes da Silva, Shawn J Leroux, Carri J LeRoy, Peter J Lisi, Richard MacKenzie, Amy M Marcarelli, Frank O Masese, Brendan G McKie, Adriana Oliveira Medeiros, Kristian Meissner, Marko Miliša, Shailendra Mishra, Yo Miyake, Ashley Moerke, Shorok Mombrikotb, Rob Mooney, Tim Moulton, Timo Muotka, Junjiro N Negishi, Vinicius Neres-Lima, Mika L Nieminen, Jorge Nimptsch, Jakub Ondruch, Riku Paavola, Isabel Pardo, Christopher J Patrick, Edwin T H M Peeters, Jesus Pozo, Catherine Pringle, Aaron Prussian, Estefania Quenta, Antonio Quesada, Brian Reid, John S Richardson, Anna Rigosi, José Rincón, Geta Rîşnoveanu, Christopher T Robinson, Lorena Rodríguez-Gallego, Todd V Royer, James A Rusak, Anna C Santamans, Géza B Selmeczy, Gelas Simiyu, Agnija Skuja, Jerzy Smykla, Kandikere R Sridhar, Ryan Sponseller, Aaron Stoler, Christopher M Swan, David Szlag, Franco Teixeira-de Mello, Jonathan D Tonkin, Sari Uusheimo, Allison M Veach, Sirje Vilbaste, Lena B M Vought, Chiao-Ping Wang, Jackson R Webster, Paul B Wilson, Stefan Woelfl, Marguerite A Xenopoulos, Adam G Yates, Chihiro Yoshimura, Catherine M Yule, Yixin X Zhang, Jacob A Zwart
River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes...
January 2019: Science Advances
https://read.qxmd.com/read/30660595/natural-history-treatment-and-long-term-follow-up-of-patients-with-multiple-endocrine-neoplasia-type-2b-an-international-multicentre-retrospective-study
#9
Frederic Castinetti, Steven G Waguespack, Andreas Machens, Shinya Uchino, Kornelia Lazaar, Gabriella Sanso, Tobias Else, Sarka Dvorakova, Xiao Ping Qi, Rossella Elisei, Ana Luisa Maia, John Glod, Delmar Muniz Lourenço, Nuria Valdes, Jes Mathiesen, Nelson Wohllk, Tushar R Bandgar, Delphine Drui, Marta Korbonits, Maralyn R Druce, Caroline Brain, Tom Kurzawinski, Atila Patocs, Maria Joao Bugalho, Andre Lacroix, Philippe Caron, Patricia Fainstein-Day, Francoise Borson Chazot, Marc Klein, Thera P Links, Claudio Letizia, Laura Fugazzola, Olivier Chabre, Letizia Canu, Regis Cohen, Antoine Tabarin, Anita Spehar Uroic, Dominique Maiter, Sandrine Laboureau, Caterina Mian, Mariola Peczkowska, Frederic Sebag, Thierry Brue, Delphine Mirebeau-Prunier, Laurence Leclerc, Birke Bausch, Amandine Berdelou, Akihiro Sukurai, Petr Vlcek, Jolanta Krajewska, Marta Barontini, Carla Vaz Ferreira Vargas, Laura Valerio, Lucieli Ceolin, Srivandana Akshintala, Ana Hoff, Christian Godballe, Barbara Jarzab, Camilo Jimenez, Charis Eng, Tsuneo Imai, Martin Schlumberger, Elizabeth Grubbs, Henning Dralle, Hartmut P Neumann, Eric Baudin
BACKGROUND: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. METHODS: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions...
January 16, 2019: Lancet Diabetes & Endocrinology
https://read.qxmd.com/read/30658935/pet-adapted-treatment-for-newly-diagnosed-advanced-hodgkin-lymphoma-ahl2011-a-randomised-multicentre-non-inferiority-phase-3-study
#10
René-Olivier Casasnovas, Reda Bouabdallah, Pauline Brice, Julien Lazarovici, Hervé Ghesquieres, Aspasia Stamatoullas, Jehan Dupuis, Anne-Claire Gac, Thomas Gastinne, Bertrand Joly, Krimo Bouabdallah, Emmanuelle Nicolas-Virelizier, Pierre Feugier, Franck Morschhauser, Richard Delarue, Hassan Farhat, Philippe Quittet, Alina Berriolo-Riedinger, Adrian Tempescul, Véronique Edeline, Hervé Maisonneuve, Luc-Matthieu Fornecker, Thierry Lamy, Alain Delmer, Peggy Dartigues, Laurent Martin, Marc André, Nicolas Mounier, Alexandra Traverse-Glehen, Michel Meignan
BACKGROUND: Increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated ) improves progression-free survival in patients with advanced Hodgkin lymphoma compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), but is associated with increased risks of haematological toxicity, secondary myelodysplasia or leukaemia, and infertility. We investigated whether PET monitoring during treatment could allow dose de-escalation by switching regimen (BEACOPPescalated to ABVD) in early responders without loss of disease control compared with standard treatment without PET monitoring...
January 15, 2019: Lancet Oncology
https://read.qxmd.com/read/30639323/complex-compound-inheritance-of-lethal-lung-developmental-disorders-due-to-disruption-of-the-tbx-fgf-pathway
#11
Justyna A Karolak, Marie Vincent, Gail Deutsch, Tomasz Gambin, Benjamin Cogné, Olivier Pichon, Francesco Vetrini, Heather C Mefford, Jennifer N Dines, Katie Golden-Grant, Katrina Dipple, Amanda S Freed, Kathleen A Leppig, Megan Dishop, David Mowat, Bruce Bennetts, Andrew J Gifford, Martin A Weber, Anna F Lee, Cornelius F Boerkoel, Tina M Bartell, Catherine Ward-Melver, Thomas Besnard, Florence Petit, Iben Bache, Zeynep Tümer, Marie Denis-Musquer, Madeleine Joubert, Jelena Martinovic, Claire Bénéteau, Arnaud Molin, Dominique Carles, Gwenaelle André, Eric Bieth, Nicolas Chassaing, Louise Devisme, Lara Chalabreysse, Laurent Pasquier, Véronique Secq, Massimiliano Don, Maria Orsaria, Chantal Missirian, Jérémie Mortreux, Damien Sanlaville, Linda Pons, Sébastien Küry, Stéphane Bézieau, Jean-Michel Liet, Nicolas Joram, Tiphaine Bihouée, Daryl A Scott, Chester W Brown, Fernando Scaglia, Anne Chun-Hui Tsai, Dorothy K Grange, John A Phillips, Jean P Pfotenhauer, Shalini N Jhangiani, Claudia G Gonzaga-Jauregui, Wendy K Chung, Galen M Schauer, Mark H Lipson, Catherine L Mercer, Arie van Haeringen, Qian Liu, Edwina Popek, Zeynep H Coban Akdemir, James R Lupski, Przemyslaw Szafranski, Bertrand Isidor, Cedric Le Caignec, Paweł Stankiewicz
Primary defects in lung branching morphogenesis, resulting in neonatal lethal pulmonary hypoplasias, are incompletely understood. To elucidate the pathogenetics of human lung development, we studied a unique collection of samples obtained from deceased individuals with clinically and histopathologically diagnosed interstitial neonatal lung disorders: acinar dysplasia (n = 14), congenital alveolar dysplasia (n = 2), and other lethal lung hypoplasias (n = 10). We identified rare heterozygous copy-number variant deletions or single-nucleotide variants (SNVs) involving TBX4 (n = 8 and n = 2, respectively) or FGF10 (n = 2 and n = 2, respectively) in 16/26 (61%) individuals...
January 2, 2019: American Journal of Human Genetics
https://read.qxmd.com/read/30639161/validation-and-refinement-of-the-clinical-staging-model-in-a-french-cohort-of-outpatient-with-schizophrenia-face-sz
#12
Godin Ophelia, Fond Guillaume, Bulzacka Ewa, Schürhoff Frank, Boyer Laurent, M Andre, Andrianarisoa Meja, Aouizerate Bruno, Berna Fabrice, Capdevielle Delphine, Chereau Isabelle, Dorey Jean-Michel, Dubertret Caroline, Dubreucq Julien, Faget Catherine, Lancon Christophe, Leignier Sylvain, Mallet Jasmina, Misdrahi David, Passerieux Christine, Rey Romain, Roux Paul, Vidailhet Pierre, Costagliola Dominique, Leboyer Marion, Llorca Pierre-Michel, Andrianarisoa Méja, Aouizerate Bruno, Berna Fabrice, Blanc Olivier, Brunel Lore, Bulzacka Ewa, Capdevielle Delphine, Chéreau-Boudet Isabelle, Chesnoy-Servanin Gabrielle, Danion Jean-Marie, D'Amato Thierry, Deloge Arnaud, Delorme Claire, Denizot Hélène, Dorey Jean-Michel, Dubertret Caroline, Dubreucq Julien, Faget Catherine, Fluttaz Cécile, Fond Guillaume, Fonteneau Sandrine, Gabayet Franck, Giraud-Baro Elisabeth, Hardy-Baylé Marie-Christine, Lacelle Delphine, Lançon Christophe, Laouamri Hakim, Leboyer Marion, Le Gloahec Tifenn, Le Strat Yann, Llorca Pierre-Michel, Mallet Jasmina, Metairie Emeline, Misdrahi David, Passerieux Christine, Peri Pauline, Pires Sylvie, Portalier Céline, Rey Romain, Roman Céline, Sebilleau Mathilde, Schandrin Aurélie, Schneider Priscille, Schurhoff Franck, Tessier Arnaud, Tronche Anne-Marie, Urbach Mathieu, Vaillant Florence, Vehier Aurélie, Vidailhet Pierre, Vilà Estelle, Yazbek Hanan, Zinetti-Bertschy Anna
OBJECTIVE: Existing staging models have not been fully validated. Thus, after classifying patients with schizophrenia according to the staging model proposed by McGorry et al. (2010), we explored the validity of this staging model and its stability after one-year of follow-up. METHOD: Using unsupervised machine-learning algorithm, we classified 770 outpatients into 5 clinical stages, the highest being the most severe. Analyses of (co)variance were performed to compare each stage in regard to socio-demographics factors, clinical characteristics, co-morbidities, ongoing treatment and neuropsychological profiles...
January 9, 2019: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://read.qxmd.com/read/30612698/-some-important-breakthroughs-in-oncology-and-hematology-in-2018-a-selection-by-the-editorial-board-of-bulletin-du-cancer
#13
REVIEW
Jacques-Olivier Bay, Thierry André, Christophe Caux, Serge Evrard, Antony Gonçalves, Gilles L'Allemain, Nicolas Magné, Daniel Orbach, Nicolas Penel, Manuel Rodrigues, Juliette Thariat, Antoine Thiery-Vuillemin, Marie Wislez
The editorial board of Bulletin du Cancer presents some hot topics published or presented in major oncology meetings in 2018. This selection is related to pediatric oncology and to solid and hemato-malignancies in adults, with immunotherapy approaches (checkpoints or CAR-T) as one of the major breakthroughs. Putative impacts on daily practices are discussed, in order to detail what will really change our practice.
January 3, 2019: Bulletin du Cancer
https://read.qxmd.com/read/30559449/proteasomal-degradation-of-nod2-by-nlrp12-in-monocytes-promotes-bacterial-tolerance-and-colonization-by-enteropathogens
#14
Sylvain Normand, Nadine Waldschmitt, Andreas Neerincx, Ruben Julio Martinez-Torres, Camille Chauvin, Aurélie Couturier-Maillard, Olivier Boulard, Laetitia Cobret, Fawaz Awad, Ludovic Huot, Andre Ribeiro-Ribeiro, Katja Lautz, Richard Ruez, Myriam Delacre, Clovis Bondu, Martin Guilliams, Charlotte Scott, Anthony Segal, Serge Amselem, David Hot, Sonia Karabina, Erwin Bohn, Bernhard Ryffel, Lionel F Poulin, Thomas A Kufer, Mathias Chamaillard
Mutations in the nucleotide-binding oligomerization domain protein 12 (NLRP12) cause recurrent episodes of serosal inflammation. Here we show that NLRP12 efficiently sequesters HSP90 and promotes K48-linked ubiquitination and degradation of NOD2 in response to bacterial muramyl dipeptide (MDP). This interaction is mediated by the linker-region proximal to the nucleotide-binding domain of NLRP12. Consequently, the disease-causing NLRP12 R284X mutation fails to repress MDP-induced NF-κB and subsequent activity of the JAK/STAT signaling pathway...
December 17, 2018: Nature Communications
https://read.qxmd.com/read/30527956/genetic-determinants-of-risk-in-pulmonary-arterial-hypertension-international-genome-wide-association-studies-and-meta-analysis
#15
Christopher J Rhodes, Ken Batai, Marta Bleda, Matthias Haimel, Laura Southgate, Marine Germain, Michael W Pauciulo, Charaka Hadinnapola, Jurjan Aman, Barbara Girerd, Amit Arora, Jo Knight, Ken B Hanscombe, Jason H Karnes, Marika Kaakinen, Henning Gall, Anna Ulrich, Lars Harbaum, Inês Cebola, Jorge Ferrer, Katie Lutz, Emilia M Swietlik, Ferhaan Ahmad, Philippe Amouyel, Stephen L Archer, Rahul Argula, Eric D Austin, David Badesch, Sahil Bakshi, Christopher Barnett, Raymond Benza, Nitin Bhatt, Harm J Bogaard, Charles D Burger, Murali Chakinala, Colin Church, John G Coghlan, Robin Condliffe, Paul A Corris, Cesare Danesino, Stéphanie Debette, C Gregory Elliott, Jean Elwing, Melanie Eyries, Terry Fortin, Andre Franke, Robert P Frantz, Adaani Frost, Joe G N Garcia, Stefano Ghio, Hossein-Ardeschir Ghofrani, J Simon R Gibbs, John Harley, Hua He, Nicholas S Hill, Russel Hirsch, Arjan C Houweling, Luke S Howard, Dunbar Ivy, David G Kiely, James Klinger, Gabor Kovacs, Tim Lahm, Matthias Laudes, Rajiv D Machado, Robert V MacKenzie Ross, Keith Marsolo, Lisa J Martin, Shahin Moledina, David Montani, Steven D Nathan, Michael Newnham, Andrea Olschewski, Horst Olschewski, Ronald J Oudiz, Willem H Ouwehand, Andrew J Peacock, Joanna Pepke-Zaba, Zia Rehman, Ivan Robbins, Dan M Roden, Erika B Rosenzweig, Ghulam Saydain, Laura Scelsi, Robert Schilz, Werner Seeger, Christian M Shaffer, Robert W Simms, Marc Simon, Olivier Sitbon, Jay Suntharalingam, Haiyang Tang, Alexander Y Tchourbanov, Thenappan Thenappan, Fernando Torres, Mark R Toshner, Carmen M Treacy, Anton Vonk Noordegraaf, Quinten Waisfisz, Anna K Walsworth, Robert E Walter, John Wharton, R James White, Jeffrey Wilt, Stephen J Wort, Delphine Yung, Allan Lawrie, Marc Humbert, Florent Soubrier, David-Alexandre Trégouët, Inga Prokopenko, Richard Kittles, Stefan Gräf, William C Nichols, Richard C Trembath, Ankit A Desai, Nicholas W Morrell, Martin R Wilkins
BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension...
December 5, 2018: Lancet Respiratory Medicine
https://read.qxmd.com/read/30521495/loss-of-arhgef1-causes-a-human-primary-antibody-deficiency
#16
Amine Bouafia, Sébastien Lofek, Julie Bruneau, Loïc Chentout, Hicham Lamrini, Amélie Trinquand, Marie-Céline Deau, Lucie Heurtier, Véronique Meignin, Capucine Picard, Elizabeth Macintyre, Olivier Alibeu, Marc Bras, Thierry Jo Molina, Marina Cavazzana, Isabelle André-Schmutz, Anne Durandy, Alain Fischer, Eric Oksenhendler, Sven Kracker
ARHGEF1 is a RhoA-specific guanine nucleotide exchange factor expressed in hematopoietic cells. We used whole-exome sequencing to identify compound heterozygous mutations in ARHGEF1, resulting in the loss of ARHGEF1 protein expression in 2 primary antibody-deficient siblings presenting with recurrent severe respiratory tract infections and bronchiectasis. Both ARHGEF1-deficient patients showed an abnormal B cell immunophenotype, with a deficiency in marginal zone and memory B cells and an increased frequency of transitional B cells...
February 4, 2019: Journal of Clinical Investigation
https://read.qxmd.com/read/30503213/anti-nkg2a-mab-is-a-checkpoint-inhibitor-that-promotes-anti-tumor-immunity-by-unleashing-both-t-and-nk-cells
#17
Pascale André, Caroline Denis, Caroline Soulas, Clarisse Bourbon-Caillet, Julie Lopez, Thomas Arnoux, Mathieu Bléry, Cécile Bonnafous, Laurent Gauthier, Ariane Morel, Benjamin Rossi, Romain Remark, Violette Breso, Elodie Bonnet, Guillaume Habif, Sophie Guia, Ana Ines Lalanne, Caroline Hoffmann, Olivier Lantz, Jérôme Fayette, Agnès Boyer-Chammard, Robert Zerbib, Pierre Dodion, Hormas Ghadially, Maria Jure-Kunkel, Yannis Morel, Ronald Herbst, Emilie Narni-Mancinelli, Roger B Cohen, Eric Vivier
Checkpoint inhibitors have revolutionized cancer treatment. However, only a minority of patients respond to these immunotherapies. Here, we report that blocking the inhibitory NKG2A receptor enhances tumor immunity by promoting both natural killer (NK) and CD8+ T cell effector functions in mice and humans. Monalizumab, a humanized anti-NKG2A antibody, enhanced NK cell activity against various tumor cells and rescued CD8+ T cell function in combination with PD-x axis blockade. Monalizumab also stimulated NK cell activity against antibody-coated target cells...
November 13, 2018: Cell
https://read.qxmd.com/read/30487801/the-host-microbiota-contributes-to-early-protection-against-lung-colonization-by-mycobacterium-tuberculosis
#18
Alexia Dumas, Dan Corral, André Colom, Florence Levillain, Antonio Peixoto, Denis Hudrisier, Yannick Poquet, Olivier Neyrolles
Tuberculosis (TB), caused by the airborne bacterial pathogen Mycobacterium tuberculosis , remains a major source of morbidity and mortality worldwide. So far, the study of host-pathogen interactions in TB has mostly focused on the physiology and virulence of the pathogen, as well as, on the various innate and adaptive immune compartments of the host. Microbial organisms endogenous to our body, the so-called microbiota, interact not only with invading pathogens, but also with our immune system. Yet, the impact of the microbiota on host defense against M...
2018: Frontiers in Immunology
https://read.qxmd.com/read/30452494/association-of-primary-resistance-to-immune-checkpoint-inhibitors-in-metastatic-colorectal-cancer-with-misdiagnosis-of-microsatellite-instability-or-mismatch-repair-deficiency-status
#19
Romain Cohen, Elisabeth Hain, Olivier Buhard, Agathe Guilloux, Armelle Bardier, Rachid Kaci, Philippe Bertheau, Florence Renaud, Frédéric Bibeau, Jean-François Fléjou, Thierry André, Magali Svrcek, Alex Duval
Importance: Primary resistance to immune checkpoint inhibitors is observed in 10% to 40% of patients with metastatic colorectal cancer (mCRC) displaying microsatellite instability (MSI) or defective mismatch repair (dMMR). Objective: To investigate possible mechanisms underlying primary resistance to immune checkpoint inhibitors of mCRC displaying MSI or dMMR. Design, Setting, and Participants: This post hoc analysis of a single-center, prospective cohort included 38 patients with mCRC diagnosed as MSI or dMMR by local laboratories and entered into trials of immune checkpoint inhibitors between January 1, 2015, and December 31, 2016...
November 15, 2018: JAMA Oncology
https://read.qxmd.com/read/30428263/advancing-translational-science-for-pulmonary-ntm-infections-a-roadmap-for-research
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Shelby Daniel-Wayman, Getahun Abate, Daniel L Barber, Luiz E Bermudez, Rhea N Coler, Michael H Cynamon, Charles L Daley, Rebecca M Davidson, Thomas Dick, R Andres Floto, Emily Henkle, Steven M Holland, Mary Jackson, Richard E Lee, Eric L Nuermberger, Kenneth N Olivier, Diane J Ordway, D Rebecca Prevots, James C Sacchettini, Max Salfinger, Christopher M Sassetti, Christine F Sizemore, Kevin L Winthrop, Adrian M Zelazny
Multiple studies conducted since the mid-1990's indicate increasing prevalence of nontuberculous mycobacterial pulmonary disease (NTM PD) in North America, Europe, Asia, and Australia. This disease is often chronic, with lengthy treatment courses and a high risk of reinfection even after successful treatment. To identify critical gaps in diagnosis, treatment, and prevention of NTM PD, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on September 26, 2017, bringing together diverse experts in mycobacterial disease...
November 14, 2018: American Journal of Respiratory and Critical Care Medicine
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