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1. PnP-Flow: Plug-and-Play Image Restoration with Flow Matching

Author: Martin, Ségolène, Gagneux, Anne, Hagemann, Paul, and Steidl, Gabriele
Subjects: Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract: In this paper, we introduce Plug-and-Play (PnP) Flow Matching, an algorithm for solving imaging inverse problems. PnP methods leverage the strength of pre-trained denoisers, often deep neural networks, by integrating them in optimization schemes. While they achieve state-of-the-art performance on various inverse problems in imaging, PnP approaches face inherent limitations on more generative tasks like inpainting. On the other hand, generative models such as Flow Matching pushed the boundary in image sampling yet lack a clear method for efficient use in image restoration. We propose to combine the PnP framework with Flow Matching (FM) by defining a time-dependent denoiser using a pre-trained FM model. Our algorithm alternates between gradient descent steps on the data-fidelity term, reprojections onto the learned FM path, and denoising. Notably, our method is computationally efficient and memory-friendly, as it avoids backpropagation through ODEs and trace computations. We evaluate its performance on denoising, super-resolution, deblurring, and inpainting tasks, demonstrating superior results compared to existing PnP algorithms and Flow Matching based state-of-the-art methods.
Published: 2024

2. Optimizing Communication on HPV Vaccination to Parents of 11- to 14-Year-Old Adolescents in France: A Discrete Choice Experiment

Author: Chyderiotis, Sandra, Sicsic, Jonathan, Gagneux-Brunon, Amandine, Raude, Jocelyn, Barret, Anne-Sophie, Bruel, Sébastien, Gauchet, Aurélie, Le Duc Banaszuk, Anne-Sophie, Michel, Morgane, Giraudeau, Bruno, Thilly, Nathalie, and Mueller, Judith E.
Published: 2024
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3. Bacterial diversity dominates variable macrophage responses of tuberculosis patients in Tanzania

Author: Hiza, Hellen, Zwyer, Michaela, Hella, Jerry, Arbués, Ainhoa, Sasamalo, Mohamed, Borrell, Sonia, Xu, Zhi Ming, Ross, Amanda, Brites, Daniela, Fellay, Jacques, Reither, Klaus, Gagneux, Sébastien, and Portevin, Damien
Published: 2024
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4. Barriers and facilitators to the HPV vaccine: a multicenter qualitative study of French general practitioners

Author: Tron, Arthur, Schlegel, Vincent, Pinot, Juliette, BRUEL, Sébastien, Ecollan, Marie, Bel, Josselin Le, Rossignol, Louise, Gauchet, Aurélie, Gagneux-Brunon, Amandine, Mueller, Judith, Banaszuk, Anne-Sophie, Thilly, Nathalie, Gilberg, Serge, and Partouche, Henri
Published: 2024
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5. Bedaquiline resistance in patients with drug-resistant tuberculosis in Cape Town, South Africa: a retrospective longitudinal cohort study

Author: Derendinger, Brigitta, Dippenaar, Anzaan, de Vos, Margaretha, Huo, Stella, Alberts, Rencia, Tadokera, Rebecca, Limberis, Jason, Sirgel, Frik, Dolby, Tania, Spies, Claudia, Reuter, Anja, Folkerts, Megan, Allender, Christopher, Lemmer, Darrin, Van Rie, Annelies, Gagneux, Sebastien, Rigouts, Leen, Riele, Julian te, Dheda, Keertan, Engelthaler, David M, Warren, Robin, Metcalfe, John, Cox, Helen, and Theron, Grant
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Biological Sciences, Tuberculosis, Genetics, Rare Diseases, Prevention, Antimicrobial Resistance, Infectious Diseases, Orphan Drug, Clinical Research, Human Genome, HIV/AIDS, Biotechnology, Patient Safety, Evaluation of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, 6.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Aetiology, Infection, Good Health and Well Being, Adult, Humans, Adolescent, Antitubercular Agents, South Africa, Mycobacterium tuberculosis, Retrospective Studies, Microbial Sensitivity Tests, Longitudinal Studies, Reinfection, Tuberculosis, Multidrug-Resistant, Microbiology, Immunology, Medical microbiology
Abstract: BackgroundBedaquiline is a life-saving tuberculosis drug undergoing global scale-up. People at risk of weak tuberculosis drug regimens are a priority for novel drug access despite the potential source of Mycobacterium tuberculosis-resistant strains. We aimed to characterise bedaquiline resistance in individuals who had sustained culture positivity during bedaquiline-based treatment.MethodsWe did a retrospective longitudinal cohort study of adults (aged ≥18 years) with culture-positive pulmonary tuberculosis who received at least 4 months of a bedaquiline-containing regimen from 12 drug-resistant tuberculosis treatment facilities in Cape Town, South Africa, between Jan 20, 2016, and Nov 20, 2017. Sputum was programmatically collected at baseline (ie, before bedaquiline initiation) and each month to monitor treatment response per the national algorithm. The last available isolate from the sputum collected at or after 4 months of bedaquiline was designated the follow-up isolate. Phenotypic drug susceptibility testing for bedaquiline was done on baseline and follow-up isolates in MGIT960 media (WHO-recommended critical concentration of 1 μg/mL). Targeted deep sequencing for Rv0678, atpE, and pepQ, as well as whole-genome sequencing were also done.FindingsIn total, 40 (31%) of 129 patients from an estimated pool were eligible for this study. Overall, three (8%) of 38 patients assessable by phenotypic drug susceptibility testing for bedaquiline had primary resistance, 18 (47%) gained resistance (acquired or reinfection), and 17 (45%) were susceptible at both baseline and follow-up. Several Rv0678 and pepQ single-nucleotide polymorphisms and indels were associated with resistance. Although variants occurred in Rv0676c and Rv1979c, these variants were not associated with resistance. Targeted deep sequencing detected low-level variants undetected by whole-genome sequencing; however, none were in genes without variants already detected by whole-genome sequencing. Patients with baseline fluoroquinolone resistance, clofazimine exposure, and four or less effective drugs were more likely to have bedaquiline-resistant gain. Resistance gain was primarily due to acquisition; however, some reinfection by resistant strains occurred.InterpretationBedaquiline-resistance gain, for which we identified risk factors, was common in these programmatically treated patients with sustained culture positivity. Our study highlights risks associated with implementing life-saving new drugs and shows evidence of bedaquiline-resistance transmission. Routine drug susceptibility testing should urgently accompany scale-up of new drugs; however, rapid drug susceptibility testing for bedaquiline remains challenging given the diversity of variants observed.FundingDoris Duke Charitable Foundation, US National Institute of Allergy and Infectious Diseases, South African Medical Research Council, National Research Foundation, Research Foundation Flanders, Stellenbosch University Faculty of Medicine Health Sciences, South African National Research Foundation, Swiss National Science Foundation, and Wellcome Trust.
Published: 2023

6. Sociodemographic determinants of HPV vaccine awareness, uptake, and intention among parents of adolescents in France 2021-22

Author: Alexia F. Rivera, Josée M. Dussault, Damien Oudin Doglioni, Sandra Chyderiotis, Jonathan Sicsic, Anne-Sophie Barret, Jocelyn Raude, Aurélie Gauchet, Amandine Gagneux-Brunon, Sébastien Bruel, Morgane Michel, Anne-Sophie Le Duc-Banaszuk, Nathalie Thilly, and Judith E. Mueller
Subjects: HPV, human papillomavirus vaccine, awareness, uptake, intention, social determinants, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract: Human Papillomavirus (HPV) vaccine coverage was
Published: 2024
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7. Long Covid: a global health issue – a prospective, cohort study set in four continents

Author: Synne Jenum, Renaud Tamisier, Clark D Russell, Rachel Evans, Piero Valentini, Sylvain Diamantis, Dominique Deplanque, Jordi Rello, Agnes Meybeck, Maxime Hentzien, Clotilde Allavena, André Cabié, Firouzé Bani-Sadr, Patrick Rossignol, Lionel Piroth, Mathieu Blot, Marie-Pierre Debray, François Angoulvant, Marc Leone, Ewen M Harrison, Maria Zambon, Michael Edelstein, Florentia Kaguelidou, Marc Lambert, Olivier Lairez, Tom Solomon, Carrol Gamble, Laura Marsh, Christiana Kartsonaki, Natalie Wright, Behzad Nadjm, Srinivas Murthy, Gail Carson, Jake Dunning, Laura Merson, Peter Horby, Timothy M Uyeki, Piero Olliaro, Guillermo Maestro de la Calle, Stephen R Knight, Thomas M Drake, Marlene Murris, Aurore Bousquet, Kenneth A McLean, Hugues Cordel, Marc Fabre, Laurence Bouillet, Katrina Hann, Xavier Duval, James Lee, Christian Rabaud, Paul Klenerman, Jean-Christophe Lucet, Jean-François Timsit, Jennifer Lee, David J Lowe, Nicolas Terzi, Saad Nseir, Gwenhaël Colin, Steve Webb, Kalynn Kennon, Caroline Mudara, Diana Hernández, Yazdan Yazdanpanah, Jean-François Payen, Samreen Ijaz, Joanne McPeake, Meera Chand, Catherine A Shaw, Cameron J Fairfield, Bruno Levy, Eric D'ortenzio, Pierre Delobel, Tiphaine Goulenok, Bronner P Gonçalves, Arnaud Scherpereel, Danilo Buonsenso, Mark G Pritchard, Susanne Dudman, Adrien Auvet, Caterina Caminiti, Debby Bogaert, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Merce Jourdain, Sue Smith, Jia Wei, Antoine Khalil, Clément Le Bihan, Nathalie Pansu, Vincent Le Moing, Victor Fomin, Christophe Fraser, Daniel Munblit, William Greenhalf, François-Xavier Lescure, Nicolas Carlier, Saye Khoo, Annemarie B Docherty, Christopher A Green, Riinu Pius, Louise Sigfrid, Sophie Halpin, Clare Jackson, Antonia Ho, Malcolm G Semple, Andrew Dagens, Carlo Palmieri, Lance Turtle, Zeno Bisoffi, Thomas Flament, Julie Mankikian, Romain Basmaci, Peter Openshaw, Rob Fowler, Tom Fletcher, Adrien Lemaignen, Pierre Tattevin, Christelle Delmas, Hélène Espérou, Claire Lévy-Marchal, Olivier Picone, Jeanne Sibiude, Cecile Yelnik, Michelle Girvan, Piero L Olliaro, Beatrice Alex, Benjamin Bach, Wendy S Barclay, Graham S Cooke, Ana da Silva Filipe, Alexander J Mentzer, Alison M Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, William A Paxton, Georgios Pollakis, David L Robertson, Vanessa Sancho-Shimizu, Janet T Scott, Shiranee Sriskandan, David Stuart, Charlotte Summers, Emma C Thomson, Ryan S Thwaites, Lance C W Turtle, Hayley Hardwick, Wilna Oosthuyzen, Fiona Griffiths, Jo Dalton, Egle Saviciute, Stephanie Roberts, Janet Harrison, Marie Connor, Gary Leeming, Ross Hendry, Victoria Shaw, Jade Ghosn, Lucille Blumberg, Nicolas Benech, Odile Launay, Yoan Lavie-Badie, Minh Le, Elise Artaud-Macari, Muge Cevik, Nicola Latronico, Mylène Maillet, Didier Laureillard, Ben Morton, Claire Hastie, Nicholas Sedillot, Anne-Sophie Boureau, Laurent Abel, Guillaume Martin-Blondel, Valérie Garrait, Isabelle Delacroix, Andrea Cortegiani, Jean-Benoît Arlet, Raphaël Borie, Kévin Bouiller, Vincent Langlois, Mélanie Roriz, Vincent Dubée, John H Amuasi, Madiha Hashmi, Edwin Jesudason, Jan Cato Holter, Anders Benjamin Kildal, Luis Felipe Reyes, Anna Beltrame, Sulaiman Lakoh, Stéphanie Fry, Lynsey Goodwin, Laurent Plantier, Anna Casey, Denis Malvy, Nina Jamieson, François Dubos, Jean-Sébastien Hulot, Paola Rodari, Frank Bloos, Cécile Tromeur, Paul Loubet, Marina Esposito-Farèse, France Mentré, Valérie Gaborieau, Cécile Goujard, Vincent Thibault, Adam Ali, Sadie Kelly, Fernando A Bozza, Bertrand Dussol, Marion Schneider, Marielle Buisson, Yves Levy, Carine Roy, Walter Picard, Olivier Sanchez, Nazir Lone, Antoine Kimmoun, Roberto Roncon-Albuquerque, Nathan Peiffer-Smadja, Julien Poissy, Lila Bouadma, Bruno Lina, Maude Bouscambert, Alexandre Gaymard, Gilles Peytavin, Jeremie Guedj, Claire Andrejak, Cedric Laouenan, Anissa Chair, Samira Laribi, Marie-Capucine Tellier, Sandrine Couffin-Cadiergues, Ventzislava Petrov-Sanchez, Alpha Diallo, Sarah Tubiana, Patrick Imbert, Emmanuelle Mercier, Waasila Jassat, Arsene Kpangon, Dominique Luton, Simone Piva, Sophie Mahy, Pierre-Adrien Bolze, Sarah Moore, Raphael Favory, Andrea Angheben, Andrea Rossanese, Matthew Hall, Johann Auchabie, Christophe Rapp, Vincent Peigne, Fredrik Müller, Christl A Donnelly, François Goehringer, Elodie Curlier, Catherine Chirouze, Vegard Skogen, Stéphane Jaureguiberry, Laurent Bitker, Hodane Yonis, Laurent Mandelbrot, Jérémie Pasquier, Bato Hammarström, Thushan de Silva, Polina Bugaeva, Julie Chas, Dario Sinatti, Arne Søraas, Murray Wham, Sara Clohisey, Seán Keating, Thibault Chiarabini, Agnes Sommet, Hugues Aumaître, Charlotte Charpentier, Sylvie LeGac, Sarah E McDonald, Jeanne Truong, Anne-Hélène Boivin, Mariachiara Ippolito, Ellen Pauley, Diane Descamps, Sérgio Gaião, Stéphane Lasry, Amanda Rojek, Charlotte Salmon Gandonniere, Sebastien Preau, Benoit Thill, Karine Faure, Denis Garot, Grégory Corvaisier, Elsa Nyamankolly, Merete Ellingjord-Dale, Eva Geraud, Barbara Wanjiru Citarella, Kévin Alexandre, Nathalie Allou, Séverine Ansart, Laurène Azemar, Cecile Azoulay, Delphine Bachelet, Claudine Badr, Valeria Balan, Marie Bartoli, Joaquín Baruch, Jules Bauer, Alexandra Bedossa, Husna Begum, Marine Beluze, Delphine Bergeaud, Giulia Bertoli, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Krishna Bhavsar, Laetitia Bodenes, Isabela Bolaños, Olivier Bouchaud, Sabelline Bouchez, Camile Bouisse, Marielle Boyer-Besseyre, Axelle Braconnier, Ingrid G Bustos, Denis Butnaru, Eder Caceres, Cyril Cadoz, Valentine Campana, Pauline Caraux-Paz, Thierry Carmoi, Marie-Christine Carret, Maire-Laure Casanova, Guylaine Castor-Alexandre, François-Xavier Catherine, Minerva Cervantes-Gonzalez, Catherine Chakveatze, Jean-Marc Chapplain, Antoine Cheret, Bernard Cholley, Marie-Charlotte Chopin, Roxane Courtois, Stéphanie Cousse, Alexa Debard, Nathalie DeCastro, Romain Decours, Eve Defous, Karen Delavigne, Elisa Demonchy, Emmanuelle Denis, Mathilde Desvallées, Kévin Didier, Jean-Luc Diehl, Vincent Dinot, Fara Diop, Alphonsine Diouf, Félix Djossou, Céline Dorival, Nathalie Dournon, Murray Dryden, Alexandre Ducancelle, Paul Dunand, Brigitte Elharrar, Philippine Eloy, Isabelle Enderle, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Manuel Etienne, Isabelle Fabre, François-Xavier Ferrand, Eglantine Ferrand Devouge, Nicolas Ferriere, Céline Ficko, Erwan Fourn, Rostane Gaci, Jean-Charles Gagnard, Esteban Garcia-Gallo, Tristan Gigante, Guillermo Giordano, Valérie Gissot, Petr Glybochko, Marie Gominet, Isabelle Gorenne, Laure Goubert, Pascal Granier, Segolène Greffe, Martin Guego, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Thomas Guimard, Ali Hachemi, Nadir Hadri, Rebecca Hamidfar, Lars Heggelund, Rupert Higgins, Hikombo Hitoto, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Margaux Isnard, Danielle Jaafar, Salma Jaafoura, Julien Jabot, Florence Jego, Cédric Joseph, Ouifiya Kafif, Sabina Kali, Younes Kerroumi, Marie Lachatre, Marie Lacoste, Marie Lagrange, Fabrice Laine, Antonio Lalueza, Marie Langelot-Richard, Delphine Lariviere, Andy Law, Laurent Lefebvre, Bénédicte Lefebvre, Benjamin Lefèvre, Jean-Daniel Lelievre, Véronique Lemee, Anthony Lemeur, Quentin Lepiller, Olivier Lesens, Mathieu Lesouhaitier, Geoffrey Liegeon, Guillaume Lingas, Sylvie Lion-Daolio, Marine Livrozet, Bouchra Loufti, Guillame Louis, Liem Luong, Moïse Machado, Gabriel Macheda, Rafael Mahieu, Thomas Maitre, Victoria Manda, Aldric Manuel, Samuel Markowicz, Martin Martinot, Mathieu Mattei, Laurence Maulin, Thierry Mazzoni, Cécile Mear-Passard, Antoine Merckx, Mayka Mergeay-Fabre, Vanina Meysonnier, Mehdi Mezidi, Isabelle Michelet, Lucia Moro, Julien Moyet, Jimmy Mullaert, Nadège Neant, Nikita Nekliudov, Anthony Nghi, Duc Nguyen, Nadia Ouamara, Rachida Ouissa, Eric Oziol, Justine Pages Maïder Pagadoy, Aurélie Papadopoulos, Bruno Pastene, Christelle Paul, Florent Peelman, Daniel Perez, Thomas Perpoint, Vincent Pestre, Ryadh Pokeerbux, Diane Ponscarme, Marie Rafiq, Blandine Rammaert, Stanislas Rebaudet, Sarah Redl, Anne-Sophie Resseguier, Matthieu Revest, Laurent Richier, Patrick Rispal, Karine Risso, Olivier Robineau, Manuel Rosa-Calatrava, Benoît Roze, Hélène Salvator, Pierre-François Sandrine, Benjamine Sarton, Eric Senneville, Albert Sotto, Sarah Stabler, Andrey Svistunov, Coralie Tardivon, François Téoulé, Olivier Terrier, Simon-Djamel Thiberville, Peter S Timashev, Noémie Tissot, Tiffany Trouillon, Christelle Tual, Noémie Vanel, Charline Vauchy, Aurélie Veislinger, Fanny Vuotto, Aurélie Wiedemann, Marion Zabbe, David Zucman, Silvio Hamacher, Ekaterina Pazukhina, Allegra Chatterjee, Kyle Gomez, Matteo Puntoni, Oksana Kruglova, Yock Ping Chow, Yash Doshi, Sara Isabel Duque Vallejo, Elsa D Ibáñez-Prada, Yuli V Fuentes, Margaret E O'Hara, Tigist Menkir, Amal Abrous, Younes Ait Tamlihat, Aliya Mohammed Alameen, Marta Alessi, Kazali Enagnon Alidjnou, Jean Baptiste Assie, Eyvind W Axelsen, John Kenneth Baillie, José Luis Bernal Sobrino, Sonja Hjellegjerde Brunvoll, Roar Bævre-Jensen, Jose Andres Calvache, Léo Chenard, Juan Luis Cruz Bermúdez, Jaime Cruz Rojo, Charlene Da Silveira, John Arne Dahl, Etienne De Montmollin, Cristina De Rose, Fernanda Dias Da Silva, Thomas Drake, Amiel A Dror, Anne Margarita Dyrhol-Riise, Linn Margrete Eggesbø, Mohammed El Sanharawi, William Finlayson, Aline-Marie Florence, Linda Gail Skeie, Noelia García Barrio, Anatoliy Gavrylov, Louis Gerbaud Morlaes, Yanay Gorelik, Mette Stausland Istre, Silje Bakken Jørgensen, Karl Trygve Kalleberg, Beathe Kiland Granerud, Eyrun Floerecke Kjetland Kjetland, Gry Kloumann Bekken, Galyna Kutsyna, Nadhem Lafhej, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Hervé Le Nagard, Sophie Letrou, Wei Shen Lim, Andreas Lind, Carlos Lumbreras Bermejo, Miles Lunn, Olga Martynenko, Roberta Meta, Lina Morales Cely, Clara Mouton Perrot, Alamin Mustafa, Karl Erik Müller, Ebrahim Ndure, Anders Benteson Nygaard, Claudia Milena Orozco-Chamorro, Paul Otiku, Miguel Pedrera Jiménez, Frank Olav Pettersen, Chiara Piubelli, Víctor Quirós González, Else Quist-Paulsen, Dag Henrik Reikvam, Antonia Ricchiuto, Aleksander Rygh Holten, Nadia Saidani, Pablo Serrano Balazote, Nassima Si Mohammed, Lene Bergendal Solberg, Edouard Soum, Elisabetta Spinuzza, Trude Steinsvik, Birgitte Stiksrud, Mathew Thorpe, Vadim Tieroshyn, Kristian Tonby, Anders Tveita, Sylvie Van Der Werf, Paul Henri Wicky, Ibrahim Richard Bangura, Leonardo Bastos, Daniel Cassaglia, Barbara Citarella, Sarah Duque, Anne Margarita Dyrhol Riise, Annelies Gillesen, Bronner P Goncalvez, Margareta O’Hara, Lars Hegelund, Aquiles Henriquez Trujillo, Elsa D Ibañez, Jane Ireson, Oksana Krugalova, Sam Lissaeur, Sinnadurai Manohan, Prasan K Panda, Daniel R Plotkin, Liliana Resende, Sergio Ruiz Saltana, Steffi Ryckaert, Girish Sindhwani Pulm, and Caroline Vika
Subjects: Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract: Introduction A proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs).Methods A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to
Published: 2024
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8. Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania.

Author: Zwyer, Michaela, Rutaihwa, Liliana, Windels, Etthel, Hella, Jerry, Menardo, Fabrizio, Sasamalo, Mohamed, Sommer, Gregor, Schmülling, Lena, Borrell, Sonia, Reinhard, Miriam, Dötsch, Anna, Hiza, Hellen, Stritt, Christoph, Sikalengo, George, Fenner, Lukas, De Jong, Bouke, Kato-Maeda, Midori, Jugheli, Levan, Ernst, Joel, Niemann, Stefan, Jeljeli, Leila, Ballif, Marie, Egger, Matthias, Rakotosamimanana, Niaina, Yeboah-Manu, Dorothy, Asare, Prince, Malla, Bijaya, Dou, Horng, Zetola, Nicolas, Wilkinson, Robert, Cox, Helen, Carter, E, Gnokoro, Joachim, Yotebieng, Marcel, Gotuzzo, Eduardo, Abimiku, Alashle, Avihingsanon, Anchalee, Xu, Zhi, Fellay, Jacques, Portevin, Damien, Reither, Klaus, Stadler, Tanja, Gagneux, Sebastien, and Brites, Daniela
Subjects: Humans, Mycobacterium tuberculosis, Tanzania, Tuberculosis, Genotype, Virulence
Abstract: In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data. We show that the TB epidemic in Dar es Salaam is dominated by multiple MTBC genotypes introduced to Tanzania from different parts of the world during the last 300 years. The most common MTBC genotypes deriving from these introductions exhibited differences in transmission rates and in the duration of the infectious period, but little differences in overall fitness, as measured by the effective reproductive number. Moreover, measures of disease severity and bacterial load indicated no differences in virulence between these genotypes during active TB. Instead, the combination of an early introduction and a high transmission rate accounted for the high prevalence of L3.1.1, the most dominant MTBC genotype in this setting. Yet, a longer co-existence with the host population did not always result in a higher transmission rate, suggesting that distinct life-history traits have evolved in the different MTBC genotypes. Taken together, our results point to bacterial factors as important determinants of the TB epidemic in Dar es Salaam.
Published: 2023

9. Bacterial diversity dominates variable macrophage responses of tuberculosis patients in Tanzania

Author: Hellen Hiza, Michaela Zwyer, Jerry Hella, Ainhoa Arbués, Mohamed Sasamalo, Sonia Borrell, Zhi Ming Xu, Amanda Ross, Daniela Brites, Jacques Fellay, Klaus Reither, Sébastien Gagneux, and Damien Portevin
Subjects: Mycobacterium tuberculosis complex, Macrophage, Patient, Infection, Cytokine, Tanzania, Medicine, Science
Abstract: Abstract The Mycobacterium tuberculosis complex (MTBC) comprises nine human-adapted lineages that differ in their geographical distribution. Local adaptation of specific MTBC genotypes to the respective human host population has been invoked in this context. We aimed to assess if bacterial genetics governs MTBC pathogenesis or if local co-adaptation translates into differential susceptibility of human macrophages to infection by different MTBC genotypes. We generated macrophages from cryopreserved blood mononuclear cells of Tanzanian tuberculosis patients, from which the infecting MTBC strains had previously been phylogenetically characterized. We infected these macrophages ex vivo with a phylogenetically similar MTBC strain (“matched infection”) or with strains representative of other MTBC lineages (“mismatched infection”). We found that L1 infections resulted in a significantly lower bacterial burden and that the intra-cellular replication rate of L2 strains was significantly higher compared the other MTBC lineages, irrespective of the MTBC lineage originally infecting the patients. Moreover, L4-infected macrophages released significantly greater amounts of TNF-α, IL-6, IL-10, MIP-1β, and IL-1β compared to macrophages infected by all other strains. While our results revealed no measurable effect of local adaptation, they further highlight the strong impact of MTBC phylogenetic diversity on the variable outcome of the host–pathogen interaction in human tuberculosis.
Published: 2024
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10. Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Author: Astrid Marchal, Elizabeth T. Cirulli, Iva Neveux, Evangelos Bellos, Ryan S. Thwaites, Kelly M. Schiabor Barrett, Yu Zhang, Ivana Nemes-Bokun, Mariya Kalinova, Andrew Catchpole, Stuart G. Tangye, András N. Spaan, Justin B. Lack, Jade Ghosn, Charles Burdet, Guy Gorochov, Florence Tubach, Pierre Hausfater, Clifton L. Dalgard, Shen-Ying Zhang, Qian Zhang, Christopher Chiu, Jacques Fellay, Joseph J. Grzymski, Vanessa Sancho-Shimizu, Laurent Abel, Jean-Laurent Casanova, Aurélie Cobat, Alexandre Bolze, Alessandro Aiuti, Saleh Al-Muhsen, Fahd Al-Mulla, Ali Amara, Mark S. Anderson, Evangelos Andreakos, Andrés A. Arias, Lisa M. Arkin, Hagit Baris Feldman, Paul Bastard, Alexandre Belot, Catherine M. Biggs, Dusan Bogunovic, Anastasiia Bondarenko, Alessandro Borghesi, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Manish J. Butte, Giorgio Casari, John Christodoulou, Roger Colobran, Antonio Condino-Neto, Stefan N. Constantinescu, Megan A. Cooper, Murkesh Desai, Beth A. Drolet, Xavier Duval, Jamila El Baghdadi, Philippine Eloy, Sara Espinosa-Padilla, Carlos Flores, José Luis Franco, Antoine Froidure, Peter K. Gregersen, Bodo Grimbacher, Filomeen Haerynck, David Hagin, Rabih Halwani, Lennart Hammarström, James R. Heath, Elena W.Y. Hsieh, Eystein Husebye, Kohsuke Imai, Yuval Itan, Emmanuelle Jouanguy, Elżbieta Kaja, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davood Mansouri, László Maródi, France Mentré, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine H. Mogensen, Tomohiro Morio, Lisa F.P. Ng, Luigi D. Notarangelo, Antonio Novelli, Giuseppe Novelli, Cliona O'Farrelly, Satoshi Okada, Keisuke Okamoto, Tayfun Ozcelik, Qiang Pan-Hammarström, Jean W. Pape, Rebeca Perez de Diego, Jordi Perez-Tur, David S. Perlin, Graziano Pesole, Anna M. Planas, Carolina Prando, Aurora Pujol, Anne Puel, Lluis Quintana-Murci, Sathishkumar Ramaswamy, Laurent Renia, Igor Resnick, Carlos Rodríguez-Gallego, Anna Sediva, Mikko R.J. Seppänen, Mohammad Shahrooei, Anna Shcherbina, Ondrej Slaby, Andrew L. Snow, Pere Soler-Palacín, Vassili Soumelis, Ivan Tancevski, Ahmad Abou Tayoun, Şehime Gülsün Temel, Christian Thorball, Pierre Tiberghien, Sophie Trouillet-Assant, Stuart E. Turvey, K. M. Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Donald C. Vinh, Horst von Bernuth, Joost Wauters, Mayana Zatz, Pawel Zawadzki, Serge Bureau, Yannick Vacher, Anne Gysembergh-Houal, Lauren Demerville, Abla Benleulmi-Chaachoua, Sebastien Abad, Radhiya Abassi, Abdelrafie Abdellaoui, Abdelkrim Abdelmalek, Hendy Abdoul, Helene Abergel, Fariza Abeud, Sophie Abgrall, Noemie Abisror, Marylise Adechian, Nordine Aderdour, Hakeem Farid Admane, Frederic Adnet, Sara Afritt, Helene Agostini, Claire Aguilar, Sophie Agut, Tommaso Francesco Aiello, Marc Ait Kaci, Hafid Ait Oufella, Gokula Ajeenthiravasan, Virginie Alauzy, Fanny Alby-Laurent, Lucie Allard, Marie-Alexandra Alyanakian, Blanca Amador Borrero, Sabrina Amam, Lucile Amrouche, Marc Andronikof, Dany Anglicheau, Nadia Anguel, Djillali Annane, Mohammed Aounzou, Caroline Aparicio, Gladys Aratus, Jean-Benoit Arlet, Jeremy Arzoine, Elisabeth Aslangul, Mona Assefi, Adeline Aubry, Laetitia Audiffred, Etienne Audureau, Christelle Nathalie Auger, Jean-Charles Auregan, Celine Awotar, Sonia Ayllon Milla, Delphine Azan, Laurene Azemar, Billal Azzouguen, Marwa Bachir Elrufaai, Aïda Badsi, Prissile Bakouboula, Coline Balcerowiak, Fanta Balde, Elodie Baldivia, Eliane-Flore Bangamingo, Amandine Baptiste, Fanny Baran-Marszak, Caroline Barau, Nathalie Barget, Flore Baronnet, Romain Barthelemy, Jean-Luc Baudel, Camille Baudry, Elodie Baudry, Laurent Beaugerie, Adel Belamri, Nicolas Belaube, Rhida Belilita, Pierre Bellassen, Rawan Belmokhtar, Isabel Beltran, Ruben Benainous, Mourad Benallaoua, Robert Benamouzig, Amélie Benbara, Jaouad Benhida, Anis Benkhelouf, Jihene Benlagha, Chahinez Benmostafa, Skander Benothmane, Miassa Bentifraouine, Laurence Berard, Quentin Bernier, Enora Berti, Astrid Bertier, Laure Berton, Simon Bessis, Alexandra Beurton, Celine Bianco, Clara Bianquis, Frank Bidar, Philippe Blanche, Clarisse Blayau, Alexandre Bleibtreu, Emmanuelle Blin, Coralie Bloch-Queyrat, Marie-Christophe Boissier, Diane Bollens, Marion Bolzoni, Rudy pierre Bompard, Nicolas Bonnet, Justine Bonnouvrier, Shirmonecrystal Botha, Wissam Boucenna, Fatiha Bouchama, Olivier Bouchaud, Hanane Bouchghoul, Taoueslylia Boudjebla, Noel Boudjema, Catherine Bouffard, Adrien Bougle, Meriem Bouguerra, Leila Bouras, Agnes Bourcier, Anne Bourgarit Durand, Anne Bourrier, Fabrice Bouscarat, Diane Bouvry, Nesrine Bouziri, Ons Bouzrara, Sarah Bribier, Delphine Brugier, Melanie Brunel, Eida Bui, Anne Buisson, Iryna Bukreyeva, Côme Bureau, Jacques Cadranel, Johann Cailhol, Ruxandra Calin, Clara Campos Vega, Pauline Canavaggio, Marta Cancella, Delphine Cantin, Albert Cao, Lionel Carbillon, Nicolas Carlier, Clementine Cassard, Guylaine Castor, Marion Cauchy, Olivier Cha, Benjamin Chaigne, Salima Challal, Karine Champion, Patrick Chariot, Julie Chas, Simon Chauveau, Anthony Chauvin, Clement Chauvin, Nathalie Chavarot, Kamélia Chebbout, Mustapha Cherai, Ilaria Cherubini, Amelie Chevalier, Thibault Chiarabini, Thierry Chinet, Richard Chocron, Pascaline Choinier, Juliette Chommeloux, Christophe Choquet, Laure Choupeaux, Benjamin Chousterman, Dragosmarius Ciocan, Ada Clarke, Gaëlle Clavere, Florian Clavier, Karine Clement, Sebastien Clerc, Yves Cohen, Fleur Cohen, Adrien Cohen, Audrey Coilly, Hester Colboc, Pauline Colin, Magalie Collet, Chloé Comarmond, Emeline Combacon, Alain Combes, Celine Comparon, Jean-Michel Constantin, Hugues Cordel, Anne-Gael Cordier, Adrien Costantini, Nathalie Costedoat Chalumeau, Camille Couffignal, Doriane Coupeau, Alain Creange, Yannie Cuvillier Lamarre, Charlène Da Silveira, Sandrine Dautheville Guibal El Kayani, Nathalie De Castro, Yann De Rycke, Lucie Del Pozo, Quentin Delannoy, Mathieu Delay, Robin Deleris, Juliette Delforge, Laëtitia Delphine, Noemie Demare, Sophie Demeret, Alexandre Demoule, Aurore Deniau, François Depret, Sophie Derolez, Ouda Derradji, Nawal Derridj, Vincent Descamps, Lydia Deschamps, Celine Desconclois, Cyrielle Desnos, Karine Desongins, Robin Dhote, Benjamin Diallo, Morgane Didier, Myriam Diemer, Stephane Diez, Juliette Djadi-Prat, Fatima-Zohra Djamouri Monnory, Siham Djebara, Naoual Djebra, Minette Djietcheu, Hadjer Djillali, Nouara Djouadi, Severine Donneger, Catarina Dos Santos, Nathalie Dournon, Martin Dres, Laura Droctove, Marie Drogrey, Margot Dropy, Elodie Drouet, Valérie Dubosq, Evelyne Dubreucq, Estelle Dubus, Boris Duchemann, Thibault Duchenoy, Emmanuel Dudoignon, Romain Dufau, Florence Dumas, Clara Duran, Emmanuelle Duron, Antoine Durrbach, Claudine Duvivier, Nathan Ebstein, Jihane El Khalifa, Alexandre Elabbadi, Caroline Elie, Gabriel Ernotte, Anne Esling, Martin Etienne, Xavier Eyer, Muriel Sarah Fartoukh, Takoua Fayali, Marion Fermaut, Arianna Fiorentino, Souha Fliss, Marie-Céline Fournier, Benjamin Fournier, Hélène Francois, Olivia Freynet, Yvann Frigout, Isaure Fromont, Axelle Fuentes, Thomas Furet, Joris Galand, Marc Garnier, Agnes Gaubert, Stéphane Gaudry, Samuel Gaugain, Damien Gauthier, Maxime Gautier, Sophie Georgin-Lavialle, Daniela Geromin, Mohamed Ghalayini, Bijan Ghaleh, Myriam Ghezal, Aude Gibelin, Linda Gimeno, Benoit Girard, Bénédicte Giroux Leprieur, Doryan Gomes, Elisabete Gomes-Pires, Anne Gouge, Amel Gouja, Helene Goulet, Sylvain Goupil, Jeanne Goupil De Bouille, Julien Gras, Segolene Greffe, Lamiae Grimaldi, Paul Guedeney, Bertrand Guidet, Matthias Guillo, Mariechristelle Gulczynski, Tassadit Hadjam, Didier Haguenauer, Soumeya Hammal, Nadjib Hammoudi, Olivier Hanon, Anarole Harrois, Coraline Hautem, Guillaume Hekimian, Nicholas Heming, Olivier Hermine, Sylvie Ho, Marie Houllier, Benjamin Huot, Tessa Huscenot, Wafa Ibn Saied, Ghilas Ikherbane, Meriem Imarazene, Patrick Ingiliz, Lina Iratni, Stephane Jaureguiberry, Jean-Francois Jean-Marc, Deleena Jeyarajasingham, Pauline Jouany, Veronique Jouis, Clement Jourdaine, Ouifiya Kafif, Rim Kallala, Sandrine Katsahian, Lilit Kelesyan, Vixra Keo, Flora Ketz, Warda Khamis, Enfel Khelili, Mehdi Khellaf, Christy Gaëlla Kotokpo Youkou, Ilias Kounis, Gaelle Kpalma, Jessica Krause, Vincent Labbe, Karine Lacombe, Jean-Marc Lacorte, Anne Gaelle Lafont, Emmanuel Lafont, Lynda Lagha, Lionel Lamhaut, Aymeric Lancelot, Cecilia Landman, Fanny Lanternier, Cecile Larcheveque, Caroline Lascoux Combe, Ludovic Lassel, Benjamin Laverdant, Christophe Lavergne, Jean-Rémi Lavillegrand, Pompilia Lazureanu, Loïc Le Guennec, Lamia Leberre, Claire Leblanc, Marion Leboyer, Francois Lecomte, Marine Lecorre, Romain Leenhardt, Marylou Lefebvre, Bénédicte Lefebvre, Paul Legendre, Anne Leger, Laurence Legros, Justyna Legrosse, Sébastien Lehuunghia, Julien Lemarec, Jeremie Leporrier-Ext, Manon Lesein, Hubert Lesur, Vincent Levy, Albert Levy, Edwige Lopes, Amanda Lopes, Vanessa Lopez, Julien Lopinto, Olivier Lortholary, Badr Louadah, Bénédicte Loze, Marie-Laure Lucas, Axelle Lucasamichi, Liem Binh Luong, Arouna Magazimama-Ext, David Maingret, Lakhdar Mameri, Philippe Manivet, Cylia Mansouri, Estelle Marcault, Jonathan Marey, Nathalie Marin, Clémence Marois, Olivier Martin, Lou Martineau, Cannelle Martinez-Lopez, Pierre Martyniuck, Pauline Mary De Farcy, Nessrine Marzouk, Rafik Masmoudi, Alexandre Mebazaa, Frédéric Mechai, Fabio Mecozzi, Chamseddine Mediouni, Bruno Megarbane, Mohamed Meghadecha, Élodie Mejean, Arsene Mekinian, Nour Mekki Abdelhadi, Rania Mekni, Thinhinan Sabrina Meliti, Breno Melo Lima, Paris Meng, Soraya Merbah, Fadhila Messani, Yasmine Messaoudi, Baboo-Irwinsingh Mewasing, Lydia Meziane, Carole Michelot-Burger, Françoise Mignot, Fadi Hillary Minka, Makoto Miyara, Pierre Moine, Jean-Michel Molina, Anaïs Montegnies-Boulet, Alexandra Monti, Claire Montlahuc, Anne-Lise Montout, Alexandre Moores, Caroline Morbieu, Helene Mortelette, Stéphane Mouly, Rosita Muzaffar, Cherifa Iness Nacerddine, Marine Nadal, Hajer Nadif, Kladoum Nassarmadji, Pierre Natella, Sandrine Ndingamondze, Stefan Neraal, Caroline Nguyen, Bao N'Guyen, Isabelle Nion Larmurier, Luc Nlomenyengue, Nicolas Noel, Hilario Nunes, Edris Omar, Zineb Ouazene, Elise Ouedraogo, Wassila Ouelaa, Anissa Oukhedouma, Yasmina Ould Amara, Herve Oya, Johanna Oziel, Thomas Padilla, Elena Paillaud, Solenne Paiva, Beatrice Parfait, Perrine Parize, Christophe Parizot, Antoine Parrot, Arthur Pavot, Laetitia Peaudecerf, Frédéric Pene, Marion Pepin, Julie Pernet, Claire Pernin, Mylène Petit, Olivier Peyrony, Marie-Pierre Pietri, Olivia Pietri, Marc Pineton De Chambrun, Michelle Pinson, Claire Pintado, Valentine Piquard, Christine Pires, Benjamin Planquette, Sandrine Poirier, Anne-Laure Pomel, Stéphanie Pons, Diane Ponscarme, Annegaelle Pourcelot, Valérie Pourcher, Anne Pouvaret, Florian Prever, Miresta Previlon, Margot Prevost, Marie-Julie Provoost, Cyril Quemeneur, Cédric Rafat, Agathe Rami, Brigitte Ranque, Maurice Raphael, Jean Herle Raphalen, Anna Rastoin, Mathieu Raux, Amani Rebai, Michael Reby, Alexis Regent, Asma Regrag, Matthieu Resche-Rigon, Quentin Ressaire, Christian Richard, Mariecaroline Richard, Maxence Robert, Benjamin Rohaut, Camille Rolland-Debord, Jacques Ropers, Anne-Marie Roque-Afonso, Charlotte Rosso, Mélanie Rousseaux, Nabila Rousseaux, Swasti Roux, Lorène Roux, Claire Rouzaud, Antoine Rozes, Emma Rubenstein, Jean-Marc Sabate, Sheila Sabet, Sophie-Caroline Sacleux, Nathalie Saidenberg Kermanach, Faouzi Saliba, Dominique Salmon, Laurent Savale, Guillaume Savary, Rebecca Sberro, Anne Scemla, Frederic Schlemmer, Mathieu Schwartz, Saïd Sedfi, Samia Sefir-Kribel, Philippe Seksik, Pierre Sellier, Agathe Selves, Nicole Sembach, Luca Semerano, Marie-Victoire Senat, Damien Sene, Alexandra Serris, Lucile Sese, Naima Sghiouar, Johanna Sigaux, Martin Siguier, Johanne Silvain, Noémie Simon, Tabassome Simon, Lina Innes Skandri, Miassa Slimani, Aurélie Snauwaert, Harry Sokol, Heithem Soliman, Nisrine Soltani, Benjamin Soyer, Gabriel Steg, Lydia Suarez, Tali-Anne Szwebel, Kossi Taffame, Yacine Tandjaoui-Lambiotte, Claire Tantet, Mariagrazia Tateo, Igor Theodose, Pierre clement Thiebaud, Caroline Thomas, Kelly Tiercelet, Julie Tisserand, Carole Tomczak, Krystel Torelino, Fatima Touam-Ext, Lilia Toumi, Gustave Toury, Mireille Toy-Miou, Olivia Tran Dinh Thanh Lien, Alexy Trandinh, Jean-Marc Treluyer, Baptiste Trinque, Jennifer Truchot, Sarah Tubiana, Simone Tunesi, Matthieu Turpin, Agathe Turpin, Tomas Urbina, Rafael Usubillaga Narvaez, Yurdagul Uzunhan, Prabakar Vaittinadaayar, Arnaud Valent, Maelle Valentian, Nadia Valin, Hélène Vallet, Marina Vaz, Miguel-Alejandro Vazquezibarra, Benoit Vedie, Laetitia Velly, Celine Verstuyft, Cedric Viallette, Eric Vicaut, Dorothee Vignes, Damien Vimpere, Myriam Virlouvet, Guillaume Voiriot, Lena Voisot, Emmanuel Weiss, Nicolas Weiss, Anaïs Winchenne, Youri Yordanov, Lara Zafrani, Mohamad Zaidan, Wissem Zaidi, Cathia Zak, Aida Zarhrate-Ghoul, Ouassila Zatout, Suzanne Zeino, Michel Zeitouni, Naïma Zemirli, Lorene Zerah, Ounsa Zia, Marianne Ziol, Oceane Zolario, Julien Zuber, Claire Andrejak, François Angoulvant, Delphine Bachelet, Marie Bartoli, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, Lila Bouadma, Sabelline Bouchez, Maude Bouscambert, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chirouze, Alexandra Coelho, Sandrine Couffin-Cadiergues, Eric d’Ortenzio, Marie-Pierre Debray, Laurene Deconinck, Dominique Deplanque, Diane Descamps, Mathilde Desvallée, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Brigitte Elharrar, Vincent Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Eglantine Ferrand Devouge, Nathalie Gault, Alexandre Gaymard, Tristan Gigante, Morgane Gilg, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Ikram Houas, Jean-Sébastien Hulot, Salma Jaafoura, Florentia Kaguelidou, Sabrina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Sophie Letrou, Yves Levy, Bruno Lina, Guillaume Lingas, Jean-Christophe Lucet, Denis Malvy, Marina Mambert, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Duc Nguyen, Marion Noret, Saad Nseir, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadja, Thomas Perpoint, Ventzislava Petrov-Sanchez, Gilles Peytavin, Huong Pham, Olivier Picone, Oriane Puéchal, Christian Rabaud, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Richa Su, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Christelle Tual, Sylvie Van Der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanah, Loubna Alavoine, Charlotte Charpentier, Aline Dechanet, Jean-Luc Ecobichon, Wahiba Frezouls, Nadhira Houhou, Jonathan Lehacaut, Pauline Manchon, Mariama Nouroudine, Caroline Quintin, Michael Thy, Sylvie van der Werf, Valérie Vignali, Abir Chahine, Nawal Waucquier, Maria-Claire Migaud, Félix Djossou, Mayka Mergeay-Fabre, Aude Lucarelli, Magalie Demar, Léa Bruneau, Patrick Gérardin, Adrien Maillot, Christine Payet, Bruno Laviolle, Fabrice Laine, Christophe Paris, Mireille Desille-Dugast, Julie Fouchard, Thierry Pistone, Pauline Perreau, Valérie Gissot, Carole L.E. Goas, Samatha Montagne, Lucie Richard, Kévin Bouiller, Maxime Desmarets, Alexandre Meunier, Marilou Bourgeon, Benjamin Lefévre, Hélène Jeulin, Karine Legrand, Sandra Lomazzi, Bernard Tardy, Amandine Gagneux-Brunon, Frédérique Bertholon, Elisabeth Botelho-Nevers, Christelle Kouakam, Leturque Nicolas, Layidé Roufai, Karine Amat, Hélène Espérou, Samia Hendou, Giuseppe Foti, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Giacomo Bellani, Jorge Abad, Giulia Accordino, Micol Angelini, Sergio Aguilera-Albesa, Aina Aguiló-Cucurull, Esra Akyüz Özkan, Ilad Alavi Darazam, Jonathan Antonio Roblero Albisures, Juan C. Aldave, Miquel Alfonso Ramos, Taj Ali Khan, Anna Aliberti, Seyed Alireza Nadji, Gulsum Alkan, Suzan A. AlKhater, Jerome Allardet-Servent, Luis M. Allende, Rebeca Alonso-Arias, Mohammed S. Alshahrani, Laia Alsina, Zahir Amoura, Arnau Antolí, Romain Arrestier, Mélodie Aubart, Teresa Auguet, Iryna Avramenko, Gökhan Aytekin, Axelle Azot, Seiamak Bahram, Fanny Bajolle, Fausto Baldanti, Aurélie Baldolli, Maite Ballester, Benoit Barrou, Federica Barzaghi, Sabrina Basso, Gulsum Iclal Bayhan, Liliana Bezrodnik, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blázquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Elisabeth Botdhlo-Nevers, Aurore Bousquet, David Boutolleau, Claire Bouvattier, Oksana Boyarchuk, Juliette Bravais, M. Luisa Briones, Marie-Eve Brunner, Raffaele Bruno, Maria Rita P. Bueno, Huda Bukhari, Jacinta Bustamante, Juan José Cáceres Agra, Ruggero Capra, Raphael Carapito, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Irene Cassaniti, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Jale Bengi Celik, Alessandro Ceschi, Martin Chalumeau, Bruno Charbit, Cécile Boulanger, Père Clavé, Bonaventura Clotet, Anna Codina, Cloé Comarmond, Patrizia Comoli, Angelo G. Corsico, Taner Coşkuner, Aleksandar Cvetkovski, Cyril Cyrus, David Dalmau, François Danion, David Ross Darley, Vincent Das, Nicolas Dauby, Stéphane Dauger, Paul De Munte, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Isabelle Desguerre, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Elena Domínguez-Garrido, Clément Dubost, Olov Ekwall, Şefika Elmas Bozdemir, Marwa H. Elnagdy, Melike Emiroglu, Akifumi Endo, Emine Hafize Erdeniz, Selma Erol Aytekin, Maria Pilar Etxart Lasa, Romain Euvrard, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Ricard Ferrer, Jose Ferreres, Bruno Francois, Victoria Fumadó, Kitty S.C. Fung, Francesca Fusco, Alenka Gagro, Blanca Garcia Solis, Pierre Garçon, Pascale Gaussem, Zeynep Gayretli, Juana Gil-Herrera, Laurent Gilardin, Audrey Giraud Gatineau, Mònica Girona-Alarcón, Karen Alejandra Cifuentes Godínez, Jean-Christophe Goffard, Nacho Gonzales, Luis I. Gonzalez-Granado, Rafaela González-Montelongo, Antoine Guerder, Belgin Gülhan, Victor Daniel Gumucio, Leif Gunnar Hanitsch, Jan Gunst, Marta Gut, Jérôme Hadjadj, Selda Hancerli, Tetyana Hariyan, Nevin Hatipoglu, Deniz Heppekcan, Elisa Hernandez-Brito, Po-ki Ho, María Soledad Holanda-Peña, Juan P. Horcajada, Sami Hraiech, Linda Humbert, Ivan F.N. Hung, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Marie-Thérèse Jimeno, Iolanda Jordan, Saliha Kanık-Yüksek, Yalcin Kara, Aydın Karahan, Adem Karbuz, Kadriye Kart Yasar, Ozgur Kasapcopur, Kenichi Kashimada, Sevgi Keles, Yasemin Kendir Demirkol, Yasutoshi Kido, Can Kizil, Ahmet Osman Kılıç, Adam Klocperk, Antonia Koutsoukou, Zbigniew J. Król, Hatem Ksouri, Paul Kuentz, Arthur M.C. Kwan, Yat Wah M. Kwan, Janette S.Y. Kwok, Jean-Christophe Lagier, David S.Y. Lam, Vicky Lampropoulou, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Daniele Lilleri, Edson Jose Adrian Bolanos Lima, Agnes Linglart, Eduardo López-Collazo, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Kwok-Cheung Lung, Charles-Edouard Luyt, David C. Lye, Cinthia Magnone, Enrico Marchioni, Carola Marioli, Majid Marjani, Laura Marques, Jesus Marquez Pereira, Andrea Martín-Nalda, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Carmen Mata-Martínez, Alexis Mathian, Larissa R.B. Matos, Gail V. Matthews, Julien Mayaux, Raquel McLaughlin-Garcia, Philippe Meersseman, Jean-Louis Mège, Armand Mekontso-Dessap, Isabelle Melki, Federica Meloni, Jean-François Meritet, Paolo Merlani, Özge Metin Akcan, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Matthieu Million, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Yoko Mizoguchi, Bhavi P. Modi, Francesco Mojoli, Elsa Moncomble, Abián Montesdeoca Melián, Antonio Morales Martinez, Francisco Morandeira, Pierre-Emmanuel Morange, Clémence Mordacq, Guillaume Morelle, Stéphane J. Mouly, Adrián Muñoz-Barrera, Cyril Nafati, Shintaro Nagashima, Yu Nakagama, Bénédicte Neven, João Farela Neves, Yuk-Yung Ng, Hubert Nielly, Yeray Novoa Medina, Esmeralda Nuñez Cuadros, Semsi Nur Karabela, J. Gonzalo Ocejo-Vinyals, Mehdi Oualha, Amani Ouedrani, Tayfun Özçelik, Aslinur Ozkaya-Parlakay, Michele Pagani, Maria Papadaki, Philippe Parola, Tiffany Pascreau, Stéphane Paul, Estela Paz-Artal, Sigifredo Pedraza, Nancy Carolina González Pellecer, Silvia Pellegrini, Rebeca Pérez de Diego, Xosé Luis Pérez-Fernández, Aurélien Philippe, Quentin Philippot, Adrien Picod, Marc Pineton de Chambrun, Antonio Piralla, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Garyphallia Poulakou, Marie S. Pouletty, Persia Pourshahnazari, Jia Li Qiu-Chen, Paul Quentric, Thomas Rambaud, Didier Raoult, Violette Raoult, Anne-Sophie Rebillat, Claire Redin, Léa Resmini, Pilar Ricart, Jean-Christophe Richard, Raúl Rigo-Bonnin, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora-Blanch, Mathieu P. 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Tavernier, Loreto Vidaur Tello, Benjamin Terrier, Guillaume Thiery, Karolina Thorn, Caroline Thumerelle, Imran Tipu, Martin Tolstrup, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Vasiliki Triantafyllia, Jesús Troya, Owen T.Y. Tsang, Liina Tserel, Eugene Y.K. Tso, Alessandra Tucci, Şadiye Kübra Tüter Öz, Matilde Valeria Ursini, Takanori Utsumi, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Valentina Velez-Santamaria, Silvia Patricia Zuniga Veliz, Mateus C. Vidigal, Sébastien Viel, Cédric Villain, Marie E. Vilaire-Meunier, Judit Villar-García, Audrey Vincent, Dimitri Van der Linden, Alla Volokha, Fanny Vuotto, Els Wauters, Alan K.L. Wu, Tak-Chiu Wu, Aysun Yahşi, Osman Yesilbas, Mehmet Yildiz, Barnaby E. Young, Ufuk Yükselmiş, Marco Zecca, Valentina Zuccaro, Jens Van Praet, Bart N. Lambrecht, Eva Van Braeckel, Cédric Bosteels, Levi Hoste, Eric Hoste, Fré Bauters, Jozefien De Clercq, Catherine Heijmans, Hans Slabbynck, Leslie Naesens, Benoit Florkin, Mary-Anne Young, Amanda Willis, Paloma Lapuente-Suanzes, Ana de Andrés-Martín, Matilda Berkell, Valerio Carelli, Alessia Fiorentino, Surbhi Malhotra, Alessandro Mattiaccio, Tommaso Pippucci, Marco Seri, Evelina Tacconelli, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Peter Bonta, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve de Bree, Sanne de Bruin, David T.P. Buis, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Mirjam Dijkstra, Dave A. Dongelmans, Romein W.G. Dujardin, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Endry H.T. Lim, Niels van Mourik, Jeaninne Nellen, Esther J. Nossent, Frederique Paulus, Edgar Peters, Dan A.I. Pina-Fuentes, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Maurits C.F. J. de Rotte, Michiel Schinkel, Marcus J. Schultz, Femke A.P. Schrauwen, Alex Schuurmans, Jaap Schuurmans, Kim Sigaloff, Marleen A. Slim, Patrick Smeele, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa M. Tsonas, Pieter R. Tuinman, Marc van der Valk, Denise P. Veelo, Carolien Volleman, Heder de Vries, Lonneke A. Vught, Michèle van Vugt, Dorien Wouters, A.H. Zwinderman, Matthijs C. Brouwer, W. Joost Wiersinga, Alexander P.J. Vlaar, Miranda F. Tompkins, Camille Alba, Daniel N. Hupalo, John Rosenberger, Gauthaman Sukumar, Matthew D. Wilkerson, Xijun Zhang, Justin Lack, Andrew J. Oler, Kerry Dobbs, Ottavia M. Delmonte, Jeffrey J. Danielson, Andrea Biondi, Laura Rachele Bettini, Mariella D’Angiò, Ilaria Beretta, Luisa Imberti, Alessandra Sottini, Virginia Quaresima, Eugenia Quiros-Roldan, Camillo Rossi, Riccardo Castagnoli, Daniela Montagna, Amelia Licari, and Gian Luigi Marseglia
Subjects: HLA, association, asymptomatic infection, COVID-19, population stratification, Genetics, QH426-470
Abstract: Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.
Published: 2024
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11. Barriers and facilitators to the HPV vaccine: a multicenter qualitative study of French general practitioners

Author: Arthur Tron, Vincent Schlegel, Juliette Pinot, Sébastien BRUEL, Marie Ecollan, Josselin Le Bel, Louise Rossignol, Aurélie Gauchet, Amandine Gagneux-Brunon, Judith Mueller, Anne-Sophie Banaszuk, Nathalie Thilly, Serge Gilberg, and Henri Partouche
Subjects: Vaccine hesitancy, Mass vaccination, Vaccination refusal, Papillomavirus infections, Primary prevention, General practice, Public aspects of medicine, RA1-1270
Abstract: Abstract Background In France, human papillomavirus (HPV) vaccination coverage is low, with 30.7% of 17-year-old girls having received a complete HPV vaccination schedule in 2020. Aim To determine the perspective and behaviors of general practitioners (GPs) regarding HPV vaccination with their patients and if a reluctance is observed. Design and setting A qualitative study based on semi-directed individual interviews was conducted between December 2019 and December 2020. A representative sample of GPs with various profiles were included in 4 French regions. Method A purposive sampling was used and interviews were continued until data saturation was reached. The analysis was based on the grounded theory. Results Twenty-six GPs aged 29–66 years were interviewed. The measures taken by the French health authorities (lowering the target age, reimbursing the vaccine, extending the target population to boys) were perceived as facilitators. The reported barriers were organizational, due to low attendance of adolescents, and relational, mainly due to parental vaccine hesitancy. Physicians had to deal with fears about the perceived risks and concerns about sexuality conveyed by HPV vaccination and linked to the socio-cultural characteristics of the families. Physicians developed strategies, including scientific knowledge mobilization, empowerment of families by promoting health through prevention, repetition of the vaccination proposals, personal experience and relationship. Different practices were identified according to three GP typologies: effective, convinced but unpersuasive, and reluctant physicians. Conclusion Based on these results, specific interventions, including communication techniques, especially for hesitant or unpersuasive physicians, are needed to enable GPs to become more effective.
Published: 2024
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12. Evolution of Human-Specific Alleles Protecting Cognitive Function of Grandmothers

Author: Saha, Sudeshna, Khan, Naazneen, Comi, Troy, Verhagen, Andrea, Sasmal, Aniruddha, Diaz, Sandra, Yu, Hai, Chen, Xi, Akey, Joshua M, Frank, Martin, Gagneux, Pascal, and Varki, Ajit
Subjects: Genetics, Human Genome, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Alleles, Amino Acids, Animals, Cognition, Grandparents, Hominidae, Humans, CD33, pathogen, sialic acids, archaic genome, molecular dynamics simulation, phylogenetic analysis, Biochemistry and Cell Biology, Evolutionary Biology
Abstract: The myelomonocytic receptor CD33 (Siglec-3) inhibits innate immune reactivity by extracellular V-set domain recognition of sialic acid (Sia)-containing "self-associated molecular patterns" (SAMPs). We earlier showed that V-set domain-deficient CD33-variant allele, protective against late-onset Alzheimer's Disease (LOAD), is derived and specific to the hominin lineage. We now report multiple hominin-specific CD33 V-set domain mutations. Due to hominin-specific, fixed loss-of-function mutation in the CMAH gene, humans lack N-glycolylneuraminic acid (Neu5Gc), the preferred Sia-ligand of ancestral CD33. Mutational analysis and molecular dynamics (MD)-simulations indicate that fixed change in amino acid 21 of hominin V-set domain and conformational changes related to His45 corrected for Neu5Gc-loss by switching to N-acetylneuraminic acid (Neu5Ac)-recognition. We show that human-specific pathogens Neisseria gonorrhoeae and Group B Streptococcus selectively bind human CD33 (huCD33) as part of immune-evasive molecular mimicry of host SAMPs and that this binding is significantly impacted by amino acid 21 modification. In addition to LOAD-protective CD33 alleles, humans harbor derived, population-universal, cognition-protective variants at several other loci. Interestingly, 11 of 13 SNPs in these human genes (including CD33) are not shared by genomes of archaic hominins: Neanderthals and Denisovans. We present a plausible evolutionary scenario to compile, correlate, and comprehend existing knowledge about huCD33-evolution and suggest that grandmothering emerged in humans.
Published: 2022

13. Diagnostic accuracy of a sequence-specific Mtb-DNA hybridization assay in urine: a case-control study including subclinical TB cases

Author: Yves Tschan, Mohamed Sasamalo, Hellen Hiza, Jacques Fellay, Sébastien Gagneux, Klaus Reither, Jerry Hella, and Damien Portevin
Subjects: tuberculosis, diagnosis, non-sputum, urine, cell-free DNA, Microbiology, QR1-502
Abstract: ABSTRACT Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains one of the deadliest infectious diseases globally. Timely diagnosis is a key step in the management of TB patients and in the prevention of further transmission events. Current diagnostic tools are limited in these regards. There is an urgent need for new accurate non-sputum-based diagnostic tools for the detection of symptomatic as well as subclinical TB. In this study, we recruited 52 symptomatic TB patients (sputum Xpert MTB/RIF positive) and 58 household contacts to assess the accuracy of a sequence-specific hybridization assay that detects the presence of Mtb cell-free DNA in urine. Using sputum Xpert MTB/RIF as a reference test, the magnetic bead-capture assay could discriminate active TB from healthy household contacts with an overall sensitivity of 72.1% [confidence interval (CI) 0.59–0.86] and specificity of 95.5% (CI 0.90–1.02) with a positive predictive value of 93.9% and negative predictive value of 78.2%. The detection of Mtb-specific DNA in urine suggested four asymptomatic TB infection cases that were confirmed in all instances either by concomitant Xpert MTB/RIF sputum testing or by follow-up investigation raising the specificity of the index test to 100%. We conclude that sequence-specific hybridization assays on urine specimens hold promise as non-invasive tests for the detection of subclinical TB.IMPORTANCEThere is an urgent need for a non-sputum-based diagnostic tool allowing sensitive and specific detection of all forms of tuberculosis (TB) infections. In that context, we performed a case-control study to assess the accuracy of a molecular detection method enabling the identification of cell-free DNA from Mycobacterium tuberculosis that is shed in the urine of tuberculosis patients. We present accuracy data that would fulfill the target product profile for a non-sputum test. In addition, recent epidemiological data suggested that up to 50% of individuals secreting live bacilli do not present with symptoms at the time of screening. We report, here, that the investigated index test could also detect instances of asymptomatic TB infections among household contacts.
Published: 2024
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14. HIV co-infection is associated with reduced Mycobacterium tuberculosis transmissibility in sub-Saharan Africa.

Author: Etthel M Windels, Eddie M Wampande, Moses L Joloba, W Henry Boom, Galo A Goig, Helen Cox, Jerry Hella, Sonia Borrell, Sebastien Gagneux, Daniela Brites, and Tanja Stadler
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract: Persons living with HIV are known to be at increased risk of developing tuberculosis (TB) disease upon infection with Mycobacterium tuberculosis (Mtb). However, it has remained unclear how HIV co-infection affects subsequent Mtb transmission from these patients. Here, we customized a Bayesian phylodynamic framework to estimate the effects of HIV co-infection on the Mtb transmission dynamics from sequence data. We applied our model to four Mtb genomic datasets collected in sub-Saharan African countries with a generalized HIV epidemic. Our results confirm that HIV co-infection is a strong risk factor for developing active TB. Additionally, we demonstrate that HIV co-infection is associated with a reduced effective reproductive number for TB. Stratifying the population by CD4+ T-cell count yielded similar results, suggesting that, in this context, CD4+ T-cell count is not a better predictor of Mtb transmissibility than HIV infection status alone. Together, our genome-based analyses complement observational household contact studies, and more firmly establish the negative association between HIV co-infection and Mtb transmissibility.
Published: 2024
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15. Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Author: Barbara Wanjiru Citarella, Christiana Kartsonaki, Elsa D. Ibáñez-Prada, Bronner P. Gonçalves, Joaquin Baruch, Martina Escher, Mark G. Pritchard, Jia Wei, Fred Philippy, Andrew Dagens, Matthew Hall, James Lee, Demetrios James Kutsogiannis, Evert-Jan Wils, Marília Andreia Fernandes, Bharath Kumar Tirupakuzhi Vijayaraghavan, Prasan Kumar Panda, Ignacio Martin-Loeches, Shinichiro Ohshimo, Arie Zainul Fatoni, Peter Horby, Jake Dunning, Jordi Rello, Laura Merson, Amanda Rojek, Michel Vaillant, Piero Olliaro, Luis Felipe Reyes, S.A. Moharam, Sabriya Abdalasalam, Alaa Abdalfattah Abdalhadi, Naana Reyam Abdalla, Walaa Abdalla, Almthani Hamza Abdalrheem, Ashraf Abdalsalam, Saedah Abdeewi, Esraa Hassan Abdelgaum, Mohamed Abdelhalim, Mohammed Abdelkabir, Israa Abdelrahman, Sheryl Ann Abdukahil, Lamees Adil Abdulbaqi, Salaheddin Abdulhamid, Widyan Abdulhamid, Nurul Najmee Abdulkadir, Eman Abdulwahed, Rawad Abdunabi, Ryuzo Abe, Laurent Abel, Ahmed Mohammed Abodina, Amal Abrous, Lara Absil, Kamal Abu Jabal, Nashat Abu Salah, Abdurraouf Abusalama, Tareg Abdallah Abuzaid, Subhash Acharya, Andrew Acker, Elisabeth Adam, Safia Adem, Manuella Ademnou, Francisca Adewhajah, Diana Adrião, Anthony Afum-Adjei Awuah, Melvin Agbogbatey, Saleh Al Ageel, Aya Mustafa Ahmed, Musaab Mohammed Ahmed, Shakeel Ahmed, Zainab Ahmed Alaraji, Abdulrahman Ahmed Elhefnawy Enan, Reham Abdelhamid Ahmed Khalil, Ali Mostafa Ahmed Mohamed Abdelaziz, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Aisha, Bugila Aisha, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Chika Akwani, Eman Al Qasim, Ahmed Alajeeli, Ahmed Alali, Razi Alalqam, Aliya Mohammed Alameen, Mohammed Al-Aquily, Zinah A. Alaraji, Khalid Albakry, Safa Albatni, Angela Alberti, Osama Aldabbourosama, Tala Al-dabbous, Amer Aldhalia, Abdulkarim Aldoukali, Senthilkumar Alegesan, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Asil Alflite, Huda Alfoudri, Qamrah Alhadad, Hoda Salem Alhaddad, Maali Khalid Mohamed Abdalla Alhasan, Ahmad Nabil Alhouri, Hasan Alhouri, Adam Ali, Imran Ali, Maha TagElser Mohammed Ali, Syed Ali Abbas, Yomna Ali Abdelghafar, Naseem Ali Sheikh, Kazali Enagnon Alidjnou, Mahmoud Aljadi, Sarah Aljamal, Mohammed Alkahlout, Akram Alkaseek, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Lana Almasri, Abdulrahman Almjersah, Raja Ahmed Alqandouz, Walaa Alrfaea, Moayad Alrifaee, Rawan Alsaadi, Yousef Al-Saba'a, Entisar Alshareea, Eslam Alshenawy, Aneela Altaf, João Melo Alves, João Alves, Rita Alves, Joana Alves Cabrita, Maria Amaral, Amro Essam Amer, Nur Amira, Amos Amoako Adusei, John Amuasi, Roberto Andini, Claire Andrejak, Andrea Angheben, François Angoulvant, Sophia Ankrah, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Elizabeth A. Ashley, Muhammad Ashraf, Muhammad Sheharyar Ashraf, Abir Ben Ashur, Franklin Asiedu-Bekoe, Namra Asif, Mohammad Asim, Grace Assi, Jean Baptiste Assie, Amirul Asyraf, Fouda Atangana, Ahmed Atia, Minahel Atif, Asia Atif Abdelrhman Abdallahrs, Anika Atique, Moad Atlowly, AM Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Abdelmalek Awad Ali Mohammed, Eyvind W. Axelsen, Ared Ayad, Ahmed Ayman Hassan Helmi, Laurène Azemar, Mohammed Azizeldin, Cecile Azoulay, Hakeem Babatunde, Benjamin Bach, Delphine Bachelet, Claudine Badr, Roar Bævre-Jensen, Nadia Baig, John Kenneth Baillie, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Hibah Bileid Bakeer, Ashraf Bakri, Andriy Bal, Mohanaprasanth Balakrishnan, Irene Bandoh, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S. Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Cleide Barrigoto, Marie Bartoli, Joaquín Baruch, Romain Basmaci, Muhammad Fadhli Hassin Basri, AbdAlkarim Batool, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Abigail Beane, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Lamis Berdeweel, Delphine Bergeaud, Hazel Bergin, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Isabella Bianchi, Claudia Bianco, Sandra Bichoka, Farah Nadiah Bidin, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, Muhannud Binnawara, Zeno Bisoffi, Patrick Biston, Laurent Bitker, Mustapha Bittaye, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Debby Bogaert, Anne-Hélène Boivin, Ariel Bolanga, Isabela Bolaños, Pierre-Adrien Bolze, François Bompart, Aurelius Bonifasius, Joe Bonney, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Latsaniphone Bountthasavong, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Marielle Boyer-Besseyre, Maria Boylan, Fernando Augusto Bozza, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Dorothy Breen, Patrick Breen, David Brewster, Kathy Brickell, Tessa Broadley, Helen Brotherton, Alex Browne, Nicolas Brozzi, Sonja Hjellegjerde Brunvoll, Marjolein Brusse-Keizer, Petra Bryda, Nina Buchtele, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Donald Buri, Aidan Burrell, Ingrid G. Bustos, Denis Butnaru, André Cabie, Susana Cabral, Joana Cabrita, Eder Caceres, Cyril Cadoz, Rui Caetano Garcês, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Janice Caoili, Pauline Caraux-Paz, Sheila Cárcel, Filipa Cardoso, Filipe Cardoso, Nelson Cardoso, Sofia Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Gail Carson, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Masaneh Ceesay, Shelby Cerkovnik, Minerva Cervantes-Gonzalez, Muge Cevik, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Jean-Marc Chapplain, Charlotte Charpentier, Julie Chas, Muhammad Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Léo Chenard, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Danoy Chommanam, Marie-Charlotte Chopin, Yock Ping Chow, Ting Soo Chow, Nathaniel Christy, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Rolando Claure-Del Granado, Sara Clohisey, Cassidy Codan, Caitriona Cody, Jennifer Coles, Megan Coles, Gwenhaël Colin, Michael Collins, Pamela Combs, Jennifer Connolly, Marie Connor, Anne Conrad, Elaine Conway, Graham S. Cooke, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Juthaporn Cowan, Rachel Cregan, Gloria Crowl, Jonathan Crump, Claudina Cruz, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, John Arne Dahl, Darren Dahly, Umberto D'Alessandro, Peter Daley, Zaina Dalloul, Heidi Dalton, Jo Dalton, Seamus Daly, Juliana Damas, Joycelyn Dame, Cammandji Damien, Nick Daneman, Jorge Dantas, Frédérick D'Aragon, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Bianca DeBenedictis, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Romain Decours, Eve Defous, Isabelle Delacroix, Alexandre Delamou, Eric Delaveuve, Karen Delavigne, Nathalie M. Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhangar, Alpha Diallo, Souleymane Taran Diallo, Sylvain Diamantis, André Dias, Fernanda Dias Da Silva, Rodrigo Diaz, Juan Jose Diaz, Priscila Diaz, Bakary K. Dibba, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Cedric Djadda, Félix Djossou, Annemarie B. Docherty, Helen Doherty, Arjen M. Dondorp, Christl A. Donnelly, Yoann Donohue, Sean Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, Yash Doshi, Phouvieng Douangdala, James Joshua Douglas, Renee Douma, Nathalie Dournon, Joanne Downey, Mark Downing, Thomas Drake, Aoife Driscoll, Ibrahim Kwaku Duah, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Audrey Dubot-Pérès, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, III, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Ada Ebo, Marco Echeverria-Villalobos, Michael Edelstein, Siobhan Egan, Linn Margrete Eggesbø, Khadeja Ehzaz, Carla Eira, Mohammed El Sanharawi, Marwan El Sayed, Mohammed Elabid, Mohamed Bashir Elagili, Subbarao Elapavaluru, Mohammad Elbahnasawy, Sohail Elboshra, Brigitte Elharrar, Jacobien Ellerbroek, Merete Ellingjord-Dale, Hamida ELMagrahi, Mohammad Muatasm Elmubark, Loubna Elotmani, Lauren Eloundou, Philippine Eloy, Basma Elshaikhy, Tarek Elshazly, Wafa Elsokni, Aml Ahmed Eltayeb, Iqbal Elyazar, Zarief Kamel Emad, Hussein Embarek, Isabelle Enderle, Tomoyuki Endo, Gervais Eneli, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Haneen Esaadi, Mariano Esperatti, Hélène Esperou, Catarina Espírito Santo, Marina Esposito-Farese, Rachel Essaka, Lorinda Essuman, João Estevão, Manuel Etienne, Anna Greti Everding, Mirjam Evers, Isabelle Fabre, Marc Fabre, Ismaila Fadera, Asgad Osman Abdalla Fadlalla, Amna Faheem, Arabella Fahy, Cameron J. Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Mohamed Fathi, Salem Fatima, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Jorge Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Benigno Ferreira, Isabel Ferreira, Bernardo Ferreira, Sílvia Ferreira, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Thomas Flament, Tom Fletcher, Aline-Marie Florence, Letizia Lucia Florio, Brigid Flynn, Deirdre Flynn, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Karen Forrest, Simon Forsyth, Denise Foster, Giuseppe Foti, Berline Fotso, Erwan Fourn, Robert A. Fowler, Marianne Fraher, Diego Franch-Llasat, Christophe Fraser, John F. Fraser, Marcela Vieira Freire, Ana Freitas Ribeiro, Craig French, Caren Friedrich, Ricardo Fritz, Stéphanie Fry, Nora Fuentes, Masahiro Fukuda, G. Argin, Valérie Gaborieau, Rostane Gaci, Massimo Gagliardi, Jean-Charles Gagnard, Amandine Gagneux-Brunon, Abdou Gai, Sérgio Gaião, Linda Gail Skeie, Adham Mohamed Galal Mohamed Ramadan, Phil Gallagher, Carrol Gamble, Yasmin Gani, Arthur Garan, Rebekha Garcia, Julia Garcia-Diaz, Esteban Garcia-Gallo, Navya Garimella, Denis Garot, Valérie Garrait, Basanta Gauli, Anatoliy Gavrylov, Alexandre Gaymard, Johannes Gebauer, Eva Geraud, Louis Gerbaud Morlaes, Nuno Germano, Malak Ghemmeid, Praveen Kumar Ghisulal, Jade Ghosn, Marco Giani, Tristan Gigante, Elaine Gilroy, Guillermo Giordano, Michelle Girvan, Valérie Gissot, Gezy Giwangkancana, Daniel Glikman, Petr Glybochko, Eric Gnall, Geraldine Goco, François Goehringer, Siri Goepel, Jean-Christophe Goffard, Jin Yi Goh, Brigitta Golács, Jonathan Golob, Kyle Gomez, Joan Gómez-Junyent, Marie Gominet, Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Lorenzo Grazioli, Christopher A. Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Fassou Mathias Grovogui, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Ali Hachemi, Abdurrahman Haddud, Nadir Hadri, Wael Hafez, Fakhir Raza Haidri, Fatima Mhd Rida Hajij, Sheeba Hakak, Adam Hall, Sophie Halpin, Shaher Hamdan, Abdelhafeez Hamdi, Jawad Hameed, Ansley Hamer, Raph L. Hamers, Rebecca Hamidfar, Bato Hammarström, Naomi Hammond, Terese Hammond, Lim Yuen Han, Matly Hanan, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M. Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Sulieman Hasan, Mohammad Ali Nabil Hasan, Mohd Shahnaz Hasan, Junaid Hashmi, Madiha Hashmi, Amoni Hassan, Ebtisam Hassanin, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ahmed Helmi, Ross Hendry, Martina Hennessy, Aquiles Rodrigo Henriquez-Trujillo, Maxime Hentzien, Diana Hernandez, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhlin Higgins, Rupert Higgins, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Antonia Ho, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Ikram Houas, Mabrouka Houderi, Catherine L. Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Abby Hurd, Iqbal Hussain, Aliae Mohamed Hussein, Mahmood Hussein, Fatima Ibrahim, Bashir Ibran, Samreen Ijaz, M. Arfan Ikram, Carlos Cañada Illana, Patrick Imbert, Muhammad Imran Ansari, Rana Imran Sikander, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Mariachiara Ippolito, Vera Irawany, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Mette Stausland Istre, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Hamza Jaber, Julien Jabot, Clare Jackson, Abubacarr Jagne, Stéphane Jaureguiberry, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth Noemí Jorge García, Silje Bakken Jørgensen, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Anna Jung, Hanna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Karl Trygve Kalleberg, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Armand Saloun Kamano, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Kavita Kamineni, Darshana Hewa Kandamby, Kong Yeow Kang, Darakhshan Kanwal, Dyah Kanyawati, Mohamed Karghul, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Kevin Katz, Christy Kay, Lamees Kayyali, Seán Keating, Pulak Kedia, Andrea Kelly, Aoife Kelly, Claire Kelly, Niamh Kelly, Sadie Kelly, Yvelynne Kelly, Maeve Kelsey, Kalynn Kennon, Sommay Keomany, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Shams Khail, Sarah Khaled, Imrana Khalid, Antoine Khalil, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Krish Kherajani, Michelle E. Kho, Denisa Khoo, Ryan Khoo, Saye Khoo, Muhammad Nasir Khoso, Amin Khuwaja, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Nobuya Kitamura, Eyrun Floerecke Kjetland Kjetland, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R. Knight, Robin Kobbe, Paa Kobina Forson, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Franklina Korkor Abebrese, Volkan Korten, Stephanie Kouba, Mohamed Lamine Kourouma, Karifa Kourouma, Arsène Kpangon, Karolina Krawczyk, Ali Kredan, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Anneli Krund, Pei Xuan Kuan, Ashok Kumar, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Ama Kwakyewaa Bedu-Addo, Sylvie Kwedi, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G. Laffey, Nadhem Lafhej, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Youssef Latifeh, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Cassie Lawrence, Teresa Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Ema Leal, Marta Leal Santos, Biing Horng Lee, Heng Gee Lee, Su Hwan Lee, Jennifer Lee, Todd C. Lee, Yi Lin Lee, Gary Leeming, Bénédicte Lefebvre, Laurent Lefebvre, Benjamin Lefèvre, Sylvie LeGac, Merili-Helen Lehiste, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Tanel Lepik, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Andrew Letizia, Sophie Letrou, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Kah Chuan Lim, Wei Shen Lim, Chantre Lima, Bruno Lina, Lim Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Anthony L. Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos M. Luna, Olguta Lungu, Miles Lunn, Liem Luong, Nestor Luque, Dominique Luton, Olavi Maasikas, Moïse Machado, Sara Machado, Gabriel Macheda, Mustafa Magzoub, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S. Maier, Oumou Maiga Ascofare, Mylène Maillet, Thomas Maitre, Nimisha Abdul Majeed, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Veronika Maráczi, Ceila Maria Sant′Ana Malaque, Flávio Marino, Samuel Markowicz, Ana Marques, Catherine Marquis, Laura Marsh, Brian Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Alessandra Martinelli, F. Eduardo Martinez, Martin Martinot, Alejandro Martín-Quiros, Ana Martins, João Martins, Nuno Martins, Caroline Martins Rego, Gennaro Martucci, Olga Martynenko, Eva Miranda Marwali, Marsilla Marzukie, David Maslove, Sabina Mason, Sobia Masood, Fatma Masoud, Moise Massoma, Palmer Masumbe, Mohd Basri Mat Nor, Moshe Matan, Henrique Mateus Fernandes, Meghena Mathew, Christina Mathew, Mathieu Mattei, Laurence Maulin, Juergen May, Javier Maynar, Mayfong Mayxay, Thierry Mazzoni, Lisa Mc Sweeney, Colin McArthur, Naina McCann, Peter McCanny, Aine McCarthy, Anne McCarthy, Colin McCloskey, Rachael McConnochie, Sherry McDermott, Sarah E. McDonald, Aine McElroy, Samuel McElwee, Natalie McEvoy, Allison McGeer, Kenneth A. McLean, Paul McNally, Bairbre McNicholas, Edel Meaney, Cécile Mear-Passard, Maggie Mechlin, Nastia Medombou, Omar Mehkri, Ferruccio Mele, Luis Melo, Kashif Ali Memon, João João Mendes, Ogechukwu Menkiti, Kusum Menon, France Mentré, Alexander J. Mentzer, Emmanuelle Mercier, Noémie Mercier, Antoine Merckx, Mayka Mergeay-Fabre, Blake Mergler, António Mesquita, Roberta Meta, Osama Metwally, Agnès Meybeck, Dan Meyer, Alison M. Meynert, Vanina Meysonnier, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Efstathia Mihelis, Vladislav Mihnovit, Duha Milad Abdullah, Jennene Miller, Hugo Miranda-Maldonado, Nor Arisah Misnan, Nik Nur Eliza Mohamed, Nouralsabah Mohamed, Tahira Jamal Mohamed, Alaa Mohamed Ads, Ahmed Reda Mohamed Elsayed Abdelhalim, Libya Mohammed, Shrouk Fawze Mohammed Mostafa, Manahil Omer Abdelrahman Mohammedahmed, Omer Abdullah Mohammedelhassan, Asma Moin, Walaa Mokhtar, Elena Molinos, Brenda Molloy, Mary Mone, Agostinho Monteiro, Claudia Montes, Giorgia Montrucchio, Sarah Moore, Shona C. Moore, Lina Morales Cely, Marwa Morgom, Lucia Moro, Catherine Motherway, Ana Motos, Hugo Mouquet, Clara Mouton Perrot, Julien Moyet, Suleiman Haitham Mualla, Mohamed Muftah, Aisha Kalsoom Mufti, Ng Yong Muh, Mo'nes Muhaisen, Dzawani Muhamad, Jimmy Mullaert, Fredrik Müller, Karl Erik Müller, Daniel Munblit, Syed Muneeb Ali, Nadeem Munir, Laveena Munshi, Aisling Murphy, Patrick Murray, Marlène Murris, Srinivas Murthy, Himed Musaab, Alamin Mustafa, Mus'ab Mustafa, Dana Mustafa, Himasha Muvindi, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Behzad Nadjm, Dave Nagpal, Alex Nagrebetsky, Blanka Nagybányai-Nagy, Herwin Nanda Boudoin, Mangala Narasimhan, Nageswaran Narayanan, Prashant Nasa, Rashid Nasim Khan, Ahmad Nasrallah, Adel Gerges Nassif Metri, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Nikita Nekliudov, Matthew Nelder, Erni Nelwan, Raul Neto, Emily Neumann, Wing Yiu Ng, Pauline Yeung Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Nerissa Niba, Alistair D. Nichol, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Nurul Faten Izzati Norharizam, Anita North, Alessandra Notari, Mahdad Noursadeghi, Adam Nowinski, Saad Nseir, Leonard Numfor, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Anders Benteson Nygaard, Fionnuala O. Brien, Annmarie O. Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Lawrence Ofori-Boadu, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Sally-Ann Ohene, João Oliveira, Larissa Oliveira, Piero L. Olliaro, Cinderella Omar Rageh Elnaggar, Alsarrah Ali Mohammed Omer, Pierre Ondobo, David S.Y. Ong, Jee Yan Ong, Wilna Oosthuyzen, Anne Opavsky, Peter Openshaw, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Jamel Ortoleva, Mohamed Osama Elsayed Soliman, Javier Osatnik, Linda O'Shea, Miriam O'Sullivan, Eman Othman, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Micheal Owusu, Ama Akyampomaa Owusu-Asare, Eric Oziol, Maïder Pagadoy, Justine Pages, Amanda Palacios, Massimo Palmarini, Giovanna Panarello, Hem Paneru, Lai Hui Pang, Mauro Panigada, Nathalie Pansu, Aurélie Papadopoulos, Rachael Parke, Melissa Parker, Jérémie Pasquier, Bruno Pastene, Fabian Patauner, Drashti Patel, Mohan Dass Pathmanathan, Luís Patrão, Patricia Patricio, Lisa Patterson, Rajyabardhan Pattnaik, Christelle Paul, Mical Paul, Jorge Paulos, William A. Paxton, Jean-François Payen, Sandra L. Peake, Kalaiarasu Peariasamy, Giles J. Peek, Florent Peelman, Nathan Peiffer-Smadja, Vincent Peigne, Mare Pejkovska, Paolo Pelosi, Ithan D. Peltan, Rui Pereira, Daniel Perez, Thomas Perpoint, Antonio Pesenti, Vincent Pestre, Lenka Petrou, Michele Petrovic, Ventzislava Petrov-Sanchez, Frank Olav Pettersen, Gilles Peytavin, Richard Odame Philips, Ooyanong Phonemixay, Soulichanya Phoutthavong, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Lionel Piroth, Ayodhia Pitaloka, Chiara Piubelli, Riinu Pius, Simone Piva, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Diego Bastos Porto, Andra-Maris Post, Douwe F. Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Viladeth Praphasiri, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Bambang Pujo Semedi, Mathew Pulicken, Peter Puplampu, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Else Quist-Paulsen, Mohammed Quraishi, Fadi Qutishat, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Abdelrahman Ragab, Mutia Rahardjani, Arslan Rahat Ullah, Ahmad Kashfi Haji Ab Rahman, Rozanah Abd Rahman, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Nagarajan Ramakrishnan, José Ramalho, Ahmad Afiq Ramli, Blandine Rammaert, Grazielle Viana Ramos, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Muhammad Osama Rehman Khalid, Dag Henrik Reikvam, Renato Reis, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Ana L. Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Chiara Robba, André Roberto, Stephanie Roberts, Charles Roberts, David L. Robertson, Olivier Robineau, Anna Roca, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Claire Roger, Pierre-Marie Roger, Roberto Roncon-Albuquerque, Jr., Mélanie Roriz, Manuel Rosa-Calatrava, Michael Rose, Dorothea Rosenberger, Andrea Rossanese, Matteo Rossetti, Patrick Rossignol, Carine Roy, Benoît Roze, Desy Rusmawatiningtyas, Clark D. Russell, Maeve Ryan, Steffi Ryckaert, Aleksander Rygh Holten, Isabela Saba, Sairah Sadaf, Musharaf Sadat, Valla Sahraei, Abdurraouf Said, Nadia Saidani, Pranya Sakiyalak, Fodé Bangaly Sako, Moamen Salah, Ali Alaa Salah Eldin Mohamed Abbas, Nawal Salahuddin, Leonardo Salazar, Jodat Saleem, Mohammed Saleh Alyasiri, Talat Ahmed Abu Salem, Gabriele Sales, Charlotte Salmon Gandonniere, Hélène Salvator, Dana Samardali, Shaden Samardali, Yehia Samir Shaaban Aly Orabi, Emely Sanchez, Olivier Sanchez, Kizy Sanchez de Oliveira, Angel Sanchez-Miralles, Vanessa Sancho-Shimizu, Gyan Sandhu, Zulfiqar Sandhu, Pierre-François Sandrine, Oana Săndulescu, Marlene Santos, Shirley Sarfo-Mensah, Bruno Sarmento Banheiro, Iam Claire E. Sarmiento, Benjamine Sarton, Ankana Satya, Sree Satyapriya, Rumaisah Satyawati, Egle Saviciute, Yen Tsen Saw, Justin Schaffer, Tjard Schermer, Arnaud Scherpereel, Marion Schneider, János Schnur, Stephan Schroll, Michael Schwameis, Gary Schwartz, Janet T. Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Malcolm G. Semple, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Ellen Shadowitz, Syamin Asyraf Shahidan, Hamza Shahla, Laila Shalabi, Haitam Shames, Anuraj Shankar, Shaikh Sharjeel, Pratima Sharma, Catherine A. Shaw, Victoria Shaw, John Robert Sheenan, Dr. Rajesh Mohan Shetty, Rohan Shetty, Mohiuddin Shiekh, Nobuaki Shime, Keiki Shimizu, Sally Shrapnel, Shubha Kalyan Shrestha, Pramesh Sundar Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Moses Siaw-Frimpong, Jeanne Sibiude, Bountoy Sibounheuang, Nidhal Siddig, Atif Siddiqui, Maqsood Ahmed Siddiqui, Louise Sigfrid, Fatoumata Sillah, Piret Sillaots, Catarina Silva, Maria Joao Silva, Rogério Silva, Benedict Sim Lim Heng, Wai Ching Sin, Dario Sinatti, Mahendra Singh, Punam Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Lene Bergendal Solberg, Joshua Solomon, Tom Solomon, Emily Somers, Agnès Sommet, Myung Jin Song, Rima Song, Tae Song, Jack Song Chia, Arne Søraas, Albert Sotto, Edouard Soum, Ana Chora Sousa, Marta Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Mamadou Saliou Sow, Alexandra Sperry, Elisabetta Spinuzza, B. P. Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Anca Streinu-Cercel, Adrian Streinu-Cercel, Geoff Strong, Ami Stuart, David Stuart, Richa Su, Decy Subekti, Gabriel Suen, Jacky Y. Suen, Prasanth Sukumar, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Atie Suwarti, Andrey Svistunov, Sarah Syahrin, Augustina Sylverken, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Fabio S. Taccone, Lysa Tagherset, Shahdattul Mawarni Taib, Sara Taleb, Cheikh Talla, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Hiroyuki Tanaka, Taku Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Yousef Tarek Kamal Mostafa, Ali Tarhabat, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Elmi Theron, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Niamh Thompson, Shaun Thompson, Emma C. Thomson, David Thomson, Mathew Thorpe, Surain Raaj Thanga Thurai, Ryan S. Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S. Timashev, Jean-François Timsit, Noémie Tissot, Fiona Toal, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Marta Torre, Antoni Torres, Margarida Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Aboubacar Tounkara, Michael Towers, Fodé Amara Traoré, Tony Trapani, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Alexis F. Turgeon, Jean-Marie Turmel, Lance C.W. Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, PG Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Effua Usuf, Timothy M. Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Stijn Van de Velde, Marcel van den Berge, Machteld van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Ilonka van Veen, Noémie Vanel, Henk Vanoverschelde, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Pavan Kumar Vecham, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, José Ernesto Vidal, César Vieira, Deepak Vijayan, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Manivanh Vongsouvath, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Laura Walsh, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Hassi Wesam, Sanne Wesselius, T. Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Sue Willems, Bailey Williams, Patricia J. Williams, Virginie Williams, Jessica Wittman, Calvin Wong, Xin Ci Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Lim Saio Xian, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Elizabeth Yarad, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Abdelrahman Yehia Mahmoud Abdelaal, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Touxiong Yiaye, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Gustavo E. Zabert, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, and David Zucman
Subjects: COVID-19, Non-respiratory symptoms, Respiratory symptoms, Risk factors, Mortality, Science (General), Q1-390, Social sciences (General), H1-99
Abstract: Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.
Published: 2024
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16. Health Literacy and Health Care System Confidence as Determinants of Attitudes to Vaccines in France: Representative Cross-Sectional Study

Author: Georges Khoury, Jeremy K Ward, Julien Mancini, Amandine Gagneux-Brunon, and Liem Binh Luong Nguyen
Subjects: Public aspects of medicine, RA1-1270
Abstract: BackgroundHealth literacy involves individuals’ knowledge, personal skills, and confidence to take action to evaluate and appraise health-related information and improve their health or that of their community. ObjectiveThis study aimed to analyze the association between health literacy and attitude toward vaccines, adjusted with other factors. MethodsWe used the SLAVACO Wave 3, a survey conducted in December 2021 among a sample of 2022 individuals, representative of the French adult population. We investigated factors associated with the attitude toward vaccines using respondents’ different sociodemographic data, health literacy levels, and the health care system confidence levels using a multinomial logistic regression analysis. ResultsAmong the participants, 440.4 (21.8%) were classified as “distrustful of vaccines in general,” 729.2 (36.1%) were “selectively hesitant,” and 852.4 (42.2%) were “nonhesitant.” In our model, the level of health literacy was not statistically different between the “distrustful of vaccines in general” and the “selectively hesitant” (P=.48), but it was associated with being a “nonhesitant” (adjusted odds ratio [aOR] 1.86, 95% CI 1.25-2.76). The confidence in the health care system was a strong predictor for a “nonhesitant” attitude toward vaccines (aOR 12.4, 95% CI 7.97-19.2). We found a positive correlation of 0.34 (P
Published: 2024
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17. Evaluating the Knowledge of and Behavior Toward COVID-19 and the Possibility of Isolating at a City Level: Survey Study

Author: Elise Verot, Robin Chaux, Julie Gagnaire, Paul Bonjean, Amandine Gagneux-Brunon, Philippe Berthelot, Carole Pelissier, Billal Boulamail, Franck Chauvin, Bruno Pozzetto, and Elisabeth Botelho-Nevers
Subjects: Public aspects of medicine, RA1-1270
Abstract: BackgroundMass testing campaigns were proposed in France during the first wave of the COVID-19 pandemic to detect and isolate asymptomatic individuals infected by SARS-CoV-2. During mass testing in Saint-Étienne (February 2021), we performed a survey of the general population. ObjectiveWe evaluated, on the scale of a city’s population, the literacy level about SARS-CoV-2 transmission, barrier gesture respect, and isolation acceptability or possibility in case of SARS-CoV-2 infection. MethodsWe used the validated CovQuest-CC questionnaire. Data were analyzed and correlated with volunteer characteristics and their SARS-CoV-2 screening results using multivariate analysis. ResultsIn total, 4707 participants completed the CovQuest-CC questionnaire. Multivariate analysis revealed that female sex was a determinant of a higher score of knowledge about SARS-CoV-2 transmission (adjusted β coefficient=0.14, 95% CI 0.04-0.23; corrected P=.02). Older ages of 50-59 years (adjusted β coefficient=0.25, 95% CI 0.19-0.31; corrected P
Published: 2024
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18. Perspectives of European Patient Advocacy Groups on Volunteer Registries and Vaccine Trials: VACCELERATE Survey Study

Author: Sophia Themistocleous, Christos D Argyropoulos, Paris Vogazianos, George Shiamakkides, Evgenia Noula, Andria Nearchou, Andreas Yiallouris, Charalampos Filippou, Fiona A Stewart, Markela Koniordou, Ioannis Kopsidas, Helena H Askling, Sirkka Vene, Amandine Gagneux-Brunon, Jana Baranda Prellezo, Elena Álvarez-Barco, Jon Salmanton-García, Janina Leckler, Alan J Macken, Ruth Joanna Davis, Anna Maria Azzini, Charis Armeftis, Margot Hellemans, Romina Di Marzo, Catarina Luis, Ole F Olesen, Olena Valdenmaiier, Stine Finne Jakobsen, Pontus Nauclér, Odile Launay, Patrick Mallon, Jordi Ochando, Pierre van Damme, Evelina Tacconelli, Theoklis Zaoutis, Oliver A Cornely, and Zoi Dorothea Pana
Subjects: Public aspects of medicine, RA1-1270
Abstract: BackgroundThe VACCELERATE Pan-European Scientific network aims to strengthen the foundation of vaccine trial research across Europe by following the principles of equity, inclusion, and diversity. The VACCELERATE Volunteer Registry network provides access to vaccine trial sites across the European region and supports a sustainable volunteer platform for identifying potential participants for forthcoming vaccine clinical research. ObjectiveThe aim of this study was to approach members of patient advocacy groups (PAGs) across Europe to assess their willingness to register for the VACCELERATE Volunteer Registry and their perspectives related to participating in vaccine trials. MethodsIn an effort to understand how to increase recruitment for the VACCELERATE Volunteer Registry, a standardized survey was developed in English and translated into 8 different languages (Dutch, English, French, German, Greek, Italian, Spanish, and Swedish) by the respective National Coordinator team. The online, anonymous survey was circulated, from March 2022 to May 2022, to PAGs across 10 European countries (Belgium, Cyprus, Denmark, France, Germany, Greece, Ireland, Italy, Spain, and Sweden) to share with their members. The questionnaire constituted of multiple choice and open-ended questions evaluating information regarding participants’ perceptions on participating in vaccine trials and their willingness to become involved in the VACCELERATE Volunteer Registry. ResultsIn total, 520 responses were collected and analyzed. The PAG members reported that the principal criteria influencing their decision to participate in clinical trials overall are (1) the risks involved, (2) the benefits that will be gained from their potential participation, and (3) the quality and quantity of information provided regarding the trial. The survey revealed that, out of the 520 respondents, 133 individuals across all age groups were “positive” toward registering in the VACCELERATE Volunteer Registry, with an additional 47 individuals reporting being “very positive.” Respondents from Northern European countries were 1.725 (95% CI 1.206-2.468) times more likely to be willing to participate in the VACCELERATE Volunteer Registry than respondents from Southern European countries. ConclusionsFactors discouraging participants from joining vaccine trial registries or clinical trials primarily include concerns of the safety of novel vaccines and a lack of trust in those involved in vaccine development. These outcomes aid in identifying issues and setbacks in present registries, providing the VACCELERATE network with feedback on how to potentially increase participation and enrollment in trials across Europe. Development of European health communication strategies among diverse public communities, especially via PAGs, is the key for increasing patients’ willingness to participate in clinical studies.
Published: 2024
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19. Association between SARS‐CoV‐2 viral kinetics and clinical score evolution in hospitalized patients

Author: Nadège Néant, Guillaume Lingas, Alexandre Gaymard, Drifa Belhadi, Maya Hites, Thérèse Staub, Richard Greil, Jose‐Artur Paiva, Julien Poissy, Nathan Peiffer‐Smadja, Dominique Costagliola, Yazdan Yazdanpanah, Maude Bouscambert‐Duchamp, Amandine Gagneux‐Brunon, Florence Ader, France Mentré, Florent Wallet, Charles Burdet, Jérémie Guedj, and the DisCoVeRy study group
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Abstract The role of antiviral treatment in coronavirus disease 2019 hospitalized patients is controversial. To address this question, we analyzed simultaneously nasopharyngeal viral load and the National Early Warning Score 2 (NEWS‐2) using an effect compartment model to relate viral dynamics and the evolution of clinical severity. The model is applied to 664 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020‐000936‐23) randomly assigned to either standard of care (SoC) or SoC + remdesivir. Then we use the model to simulate the impact of antiviral treatments on the time to clinical improvement, defined by a NEWS‐2 score lower than 3 (in patients with NEWS‐2
Published: 2023
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20. Psychometric validation of a 7C-model of antecedents of vaccine acceptance among healthcare workers, parents and adolescents in France

Author: Damien Oudin Doglioni, Amandine Gagneux-Brunon, Aurélie Gauchet, Sebastien Bruel, Cyril Olivier, Gérard Pellissier, Nathalie Thilly, Jonathan Sicsic, Jocelyn Raude, and Judith E. Mueller
Subjects: Medicine, Science
Abstract: Abstract Support for vaccine decision-making requires a tailored approach taking into account psychological antecedents of vaccine acceptance. We aimed at validating an extended 7C-model of antecedents in three different target population groups (healthcare workers [n = 3870], parents [n = 2002] and adolescents [n = 7118]) and two vaccinations (COVID-19, HPV) in France. We performed a secondary analysis of questionnaires collecting sociodemographic characteristics, attitudes and knowledge on vaccination, and vaccine status and intention. We used standard psychometric techniques to validate a first and second order latent structure, and evaluated their association with vaccine intentionality in three levels (refusal, indecision, acceptance). In all populations, the 7C-model yielded a very good model fit (CFI and TLI > 0.90) and, in comparison with non-nested and nested 5C-models, significantly improved the model performance (Ω2, p
Published: 2023
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21. Co‐development of a school‐based and primary care‐based multicomponent intervention to improve HPV vaccine coverage amongst French adolescents (the PrevHPV Study)

Author: Aurélie Bocquier, Sébastien Bruel, Morgane Michel, Anne‐Sophie Le Duc‐Banaszuk, Stéphanie Bonnay, Marion Branchereau, Karine Chevreul, Sandra Chyderiotis, Aurélie Gauchet, Bruno Giraudeau, Dragos‐Paul Hagiu, Judith E. Mueller, Amandine Gagneux‐Brunon, Nathalie Thilly, and PrevHPV Study Group
Subjects: co‐construction, complex Intervention, eHealth tools, human papillomavirus, motivational interview, vaccination behaviours, Medicine (General), R5-920, Public aspects of medicine, RA1-1270
Abstract: Abstract Introduction Despite various efforts to improve human papillomavirus (HPV) vaccine coverage in France, it has always been lower than in most other high‐income countries. The health authorities launched in 2018 the national PrevHPV research programme to (1) co‐develop with stakeholders and (2) evaluate the impact of a multicomponent complex intervention aimed at improving HPV vaccine coverage amongst French adolescents. Objective To describe the development process of the PrevHPV intervention using the GUIDance for rEporting of intervention Development framework as a guide. Methods To develop the intervention, we used findings from (1) published evidence on effective strategies to improve vaccination uptake and on theoretical frameworks of health behaviour change; (2) primary data on target populations' knowledge, beliefs, attitudes, preferences, behaviours and practices as well as the facilitators and barriers to HPV vaccination collected as part of the PrevHPV Programme and (3) the advice of working groups involving stakeholders in a participatory approach. We paid attention to developing an intervention that would maximise reach, adoption, implementation and maintenance in real‐world contexts. Results We co‐developed three components: (1) adolescents' and parents' education and motivation using eHealth tools (web conferences, videos, and a serious video game) and participatory learning at school; (2) general practitioners' e‐learning training on HPV using motivational interviewing techniques and provision of a decision aid tool and (3) easier access to vaccination through vaccination days organised on participating middle schools' premises to propose free of charge initiation of the HPV vaccination. Conclusion We co‐developed a multicomponent intervention that addresses a range of barriers and enablers of HPV vaccination. The next step is to build on the results of its evaluation to refine it before scaling it up if proven efficient. If so, it will add to the small number of multicomponent interventions aimed at improving HPV vaccination worldwide. Patient or Public Contribution The public (adolescents, their parents, school staff and health professionals) participated in the needs assessment using a mixed methods approach. The public was also involved in the components' development process to generate ideas about potential activities/tools, critically revise the successive versions of the tools and provide advice about the intervention practicalities, feasibility and maintenance.
Published: 2023
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22. A Genome-Focused Investigation Reveals the Emergence of a Mycobacterium tuberculosis Strain Related to Multidrug-Resistant Tuberculosis in the Amazon Region of Brazil

Author: Emilyn Costa Conceição, Johannes Loubser, Arthur Emil dos Santos Guimarães, Abhinav Sharma, Liliana Kokusanilwa Rutaihwa, Anzaan Dippenaar, Richard Steiner Salvato, Ricardo José de Paula Souza e Guimarães, Maria Cristina da Silva Lourenço, Wandyra Araújo Barros, Ninarosa Calzavara Cardoso, Robin Mark Warren, Sebastien Gagneux, Beatriz Gilda Jegerhorn Grinsztejn, Philip Noel Suffys, and Karla Valéria Batista Lima
Subjects: tuberculosis, multidrug-resistant, whole-genome sequencing, genotype emergence, MIRU-VNTR, lineage, Biology (General), QH301-705.5
Abstract: A previous study in Pará, Northern Brazil, described a strain of Mycobacterium tuberculosis with a unique genotype (SIT2517/T1) associated with multidrug-resistant tuberculosis (MDR-TB). To improve our understanding of MDR-TB transmission dynamics of these strains within this region, we performed phenotypic and genotypic drug susceptibility testing (pDST/gDST), 24-loci mycobacterial interspersed repetitive units (MIRU-VNTR) genotyping, whole-genome sequencing (WGS) and geo-epidemiology analysis. Of the 28 SIT2517/T1 isolates, 19 (67.9%) could be genotyped by 24-loci MIRU-VNTR and 15 by WGS. All belonged to sublineage 4.1.1.3, distinct from other representative Lineage 4 isolates identified in Brazil. The MDR phenotype determined by pDST was confirmed by gDST, the latter also demonstrating the presence of additional mutations conferring pre-extensively drug-resistance (pre-XDR). Discrepancies between gDST and pDST were observed for pyrazinamide and fluoroquinolones. Thirteen out of 15 isolates analyzed by WGS were clustered when applying a 12 single nucleotide polymorphisms (SNPs) cutoff. The SIT2517/T1 isolates were distributed across the metropolitan regions of Belém and Collares municipalities, showing no geographic clustering. WGS-transmission network analysis revealed a high likelihood of direct transmission and the formation of two closely linked transmission chains. This study highlights the need to implement TB genomic surveillance in the Brazilian Amazon region.
Published: 2024
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23. Mucin-mimetic glycan arrays integrating machine learning for analyzing receptor pattern recognition by influenza A viruses

Author: Lucas, Taryn M, Gupta, Chitrak, Altman, Meghan O, Sanchez, Emi, Naticchia, Matthew R, Gagneux, Pascal, Singharoy, Abhishek, and Godula, Kamil
Subjects: Chemical Sciences, Prevention, Pneumonia & Influenza, Rare Diseases, Influenza, Biotechnology, Biodefense, Infectious Diseases, Emerging Infectious Diseases, Vaccine Related, Infection, Influenza A, glycan array, hemagglutinin, machine learning, mucin, receptor pattern, Macromolecular and Materials Chemistry, Chemical sciences
Abstract: Influenza A viruses (IAVs) exploit host glycans in airway mucosa for entry and infection. Detection of changes in IAV glycan-binding phenotype can provide early indication of transmissibility and infection potential. While zoonotic viruses are monitored for mutations, the influence of host glycan presentation on viral specificity remains obscured. Here, we describe an array platform which uses synthetic mimetics of mucin glycoproteins to model how receptor presentation and density in the mucinous glycocalyx may impact IAV recognition. H1N1 and H3N2 binding in arrays of α2,3- and α2,6-sialyllactose receptors confirmed their known sialic acid-binding specificities and revealed their different sensitivities to receptor presentation. Further, the transition of H1N1 from avian to mammalian cell culture improved the ability of the virus to recognize mucin-like displays of α2,6-sialic acid receptors. Support vector machine (SVM) learning efficiently characterized this shift in binding preference and may prove useful to study viral evolution to a new host.
Published: 2021

24. Glycocalyx crowding with mucin mimetics strengthens binding of soluble and virus-associated lectins to host cell glycan receptors

Author: Honigfort, Daniel J, Altman, Meghan O, Gagneux, Pascal, and Godula, Kamil
Subjects: Rare Diseases, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Biomimetics, Cell Membrane, Epithelial Cells, Erythrocytes, Glycocalyx, Humans, Influenza A Virus, H1N1 Subtype, Lectins, Mucins, Mucous Membrane, Polysaccharides, Receptors, Cell Surface, influenza A, lectins, glycocalyx, mucin, biophysics
Abstract: Membrane-associated mucins protect epithelial cell surfaces against pathogenic threats by serving as nonproductive decoys that capture infectious agents and clear them from the cell surface and by erecting a physical barrier that restricts their access to target receptors on host cells. However, the mechanisms through which mucins function are still poorly defined because of a limited repertoire of tools available for tailoring their structure and composition in living cells with molecular precision. Using synthetic glycopolymer mimetics of mucins, we modeled the mucosal glycocalyx on red blood cells (RBCs) and evaluated its influence on lectin (SNA) and virus (H1N1) adhesion to endogenous sialic acid receptors. The glycocalyx inhibited the rate of SNA and H1N1 adhesion in a size- and density-dependent manner, consistent with the current view of mucins as providing a protective shield against pathogens. Counterintuitively, increasing the density of the mucin mimetics enhanced the retention of bound lectins and viruses. Careful characterization of SNA behavior at the RBC surface using a range of biophysical and imaging techniques revealed lectin-induced crowding and reorganization of the glycocalyx with concomitant enhancement in lectin clustering, presumably through the formation of a more extensive glycan receptor patch at the cell membrane. Our findings indicate that glycan-targeting pathogens may exploit the biophysical and biomechanical properties of mucins to overcome the mucosal glycocalyx barrier.
Published: 2021

25. Focus group study on perceptions and information needs regarding vaccines targeting the older population: a cross-country comparison in four European countries

Author: Wennekes, Manuela Dominique, Eilers, Renske, Caputo, Antonella, Gagneux-Brunon, Amandine, Gavioli, Riccardo, Nicoli, Francesco, Vokó, Zoltán, and Timen, Aura
Published: 2023
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26. Bending effects distorting axisymmetric capillary bridges. Generalized Young–Laplace equation and associated capillary forces

Author: Millet, Olivier and Gagneux, Gérard
Subjects: Distortion of capillary bridges, Mean and Gaussian curvatures impact, Generalized Young–Laplace equation, Bending effects, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract: This study proposes a theoretical contribution to the problem of the various distortions affecting axisymmetric capillary bridges, due to gravity or to bending effects linked to the Gaussian curvature. We deduce a clear hierarchization of effects between various reference configurations and put in a prominent position an exact first integral for the Young–Laplace equations, classical or generalized. These relationships are taken advantage of to obtain the theoretical expression of the varying inter-particle force, quantified effects of flexural strength. Finally, we establish a generalization of the classical “gorge method” to calculate accurately the capillary force of a profile subjected to distorsion due to bending when the gravity effects are negligible or not taken into account.
Published: 2023
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27. A direct relation between bending energy and contact angles for capillary bridges

Author: Millet, Olivier and Gagneux , Gérard
Subjects: Distortion of nonaxisymmetric capillary bridges, Mean and Gaussian curvatures impact, Euler characteristic, Generalized Young–Laplace equation, Bending effects, Fenchel’s theorem in differential geometry, Gauss–Bonnet Theorem, Geodesic curvature, Bending stress, Influence of the contact angles, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract: The didactic object of these developments on differential geometry of curves and surfaces is to present fine and convenient mathematical strategies, adapted to the study of capillary bridges. The common thread is to be able to calculate accurately in any situation the bending stress over the free surface, represented mathematically by the integral of the Gaussian curvature over the surface (called the total curvature) involved in the generalized Young–Laplace equation. We prove in particular that the resultant of the bending energy is directly linked to the wetting angles at the contact line.
Published: 2023
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28. Differential Salmonella Typhimurium intracellular replication and host cell responses in caecal and ileal organoids derived from chicken

Author: Sonia Lacroix-Lamandé, Ophélie Bernardi, Tiffany Pezier, Emilie Barilleau, Julien Burlaud-Gaillard, Anissa Gagneux, Philippe Velge, and Agnès Wiedemann
Subjects: Salmonella, chicken, intestinal segment organoid, bacterial colonization, epithelial cell responses, Veterinary medicine, SF600-1100
Abstract: Abstract Chicken infection with Salmonella Typhimurium is an important source of foodborne human diseases. Salmonella colonizes the avian intestinal tract and more particularly the caecum, without causing symptoms. This thus poses a challenge for the prevention of foodborne transmission. Until now, studies on the interaction of Salmonella with the avian gut intestine have been limited by the absence of in vitro intestinal culture models. Here, we established intestinal crypt‐derived chicken organoids to better decipher the impact of Salmonella intracellular replication on avian intestinal epithelium. Using a 3D organoid model, we observed a significantly higher replication rate of the intracellular bacteria in caecal organoids than in ileal organoids. Our model thus recreates intracellular environment, allowing Salmonella replication of avian epithelium according to the intestinal segment. Moreover, an inhibition of the cellular proliferation was observed in infected ileal and caecal organoids compared to uninfected organoids. This appears with a higher effect in ileal organoids, as well as a higher cytokine and signaling molecule response in infected ileal organoids at 3 h post-infection (hpi) than in caecal organoids that could explain the lower replication rate of Salmonella observed later at 24 hpi. To conclude, this study demonstrates that the 3D organoid is a model allowing to decipher the intracellular impact of Salmonella on the intestinal epithelium cell response and illustrates the importance of the gut segment used to purify stem cells and derive organoids to specifically study epithelial cell -Salmonella interaction.
Published: 2023
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29. Psychometric validation of a 7C-model of antecedents of vaccine acceptance among healthcare workers, parents and adolescents in France

Author: Oudin Doglioni, Damien, Gagneux-Brunon, Amandine, Gauchet, Aurélie, Bruel, Sebastien, Olivier, Cyril, Pellissier, Gérard, Thilly, Nathalie, Sicsic, Jonathan, Raude, Jocelyn, and Mueller, Judith E.
Published: 2023
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30. Differential Salmonella Typhimurium intracellular replication and host cell responses in caecal and ileal organoids derived from chicken

Author: Lacroix-Lamandé, Sonia, Bernardi, Ophélie, Pezier, Tiffany, Barilleau, Emilie, Burlaud-Gaillard, Julien, Gagneux, Anissa, Velge, Philippe, and Wiedemann, Agnès
Published: 2023
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31. Promoting HPV vaccination at school: a mixed methods study exploring knowledge, beliefs and attitudes of French school staff

Author: Bocquier, Aurélie, Branchereau, Marion, Gauchet, Aurélie, Bonnay, Stéphanie, Simon, Maïa, Ecollan, Marie, Chevreul, Karine, Mueller, Judith E., Gagneux-Brunon, Amandine, and Thilly, Nathalie
Published: 2023
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32. The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot

Author: Loiseau, Chloé, Windels, Etthel M., Gygli, Sebastian M., Jugheli, Levan, Maghradze, Nino, Brites, Daniela, Ross, Amanda, Goig, Galo, Reinhard, Miriam, Borrell, Sonia, Trauner, Andrej, Dötsch, Anna, Aspindzelashvili, Rusudan, Denes, Rebecca, Reither, Klaus, Beisel, Christian, Tukvadze, Nestani, Avaliani, Zaza, Stadler, Tanja, and Gagneux, Sebastien
Published: 2023
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33. GIV/Girdin, a non-receptor modulator for Gαi/s, regulates spatiotemporal signaling during sperm capacitation and is required for male fertility.

Author: Reynoso, Sequoyah, Castillo, Vanessa, Katkar, Gajanan Dattatray, Lopez-Sanchez, Inmaculada, Taheri, Sahar, Espinoza, Celia, Rohena, Cristina, Sahoo, Debashis, Gagneux, Pascal, and Ghosh, Pradipta
Subjects: Girdin, Sperm, cAMP, cell biology, developmental biology, human, male fertility, mouse, spermatozoa, Biochemistry and Cell Biology
Abstract: For a sperm to successfully fertilize an egg, it must first undergo capacitation in the female reproductive tract and later undergo acrosomal reaction (AR) upon encountering an egg surrounded by its vestment. How premature AR is avoided despite rapid surges in signaling cascades during capacitation remains unknown. Using a combination of conditional knockout (cKO) mice and cell-penetrating peptides, we show that GIV (CCDC88A), a guanine nucleotide-exchange modulator (GEM) for trimeric GTPases, is highly expressed in spermatocytes and is required for male fertility. GIV is rapidly phosphoregulated on key tyrosine and serine residues in human and murine spermatozoa. These phosphomodifications enable GIV-GEM to orchestrate two distinct compartmentalized signaling programs in the sperm tail and head; in the tail, GIV enhances PI3K→Akt signals, sperm motility and survival, whereas in the head it inhibits cAMP surge and premature AR. Furthermore, GIV transcripts are downregulated in the testis and semen of infertile men. These findings exemplify the spatiotemporally segregated signaling programs that support sperm capacitation and shed light on a hitherto unforeseen cause of infertility in men.
Published: 2021

34. Longitudinal antimüllerian hormone and its correlation with pubertal milestones

Author: Smith, Meghan B, Ho, Jacqueline, Ma, Lihong, Lee, Miryoung, Czerwinski, Stefan A, Glenn, Tanya L, Cool, David R, Gagneux, Pascal, Stanczyk, Frank Z, McGinnis, Lynda K, and Lindheim, Steven R
Subjects: Paediatrics, Biomedical and Clinical Sciences, Contraception/Reproduction, Pediatric, Obesity, Clinical Research, Antimüllerian hormone, menarche, pubarche, puberty, thelarche
Abstract: ObjectiveTo examine the changes in AMH levels longitudinally over time and their relationship with both body composition, particularly abdominal adiposity, and milestones of pubertal development in female children.DesignSecondary analysis of a prospective, longitudinal study.SettingUniversity affiliated research center and laboratories.PatientsEighty-nine females were examined between 1990 and 2015 to study child growth and development.InterventionsDemographic, anthropometric, growth, and pubertal milestone data with serum samples stored and subsequently analyzed for AMH.Main outcome measuresLongitudinal change in AMH and predicted AMH levels based on body composition, age, and pubertal milestones including, pubarche, thelarche, and menarche.ResultsNatural log-transformed AMH (AMHlog) levels appeared to have a nonlinear relationship with age, decreasing between 10 and 14 years of age, increasing until 16 years. A mixed effect linear model demonstrated that increased abdominal adiposity (waist/height ratio, WHtR) was significantly associated with the predicted increased AMHlog levels (β=1.37). As females progressed through the Tanner stages, the model predicted decreasing AMHlog values when adjusting for age and WHtR.ConclusionsDeclining AMH levels during puberty may not be reflective of diminished ovarian reserve as observed in adults, but may suggest a permissive role of AMH in the activation of the hypothalamic-pituitary-ovarian axis.
Published: 2021

35. The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot

Author: Chloé Loiseau, Etthel M. Windels, Sebastian M. Gygli, Levan Jugheli, Nino Maghradze, Daniela Brites, Amanda Ross, Galo Goig, Miriam Reinhard, Sonia Borrell, Andrej Trauner, Anna Dötsch, Rusudan Aspindzelashvili, Rebecca Denes, Klaus Reither, Christian Beisel, Nestani Tukvadze, Zaza Avaliani, Tanja Stadler, and Sebastien Gagneux
Subjects: Science
Abstract: Geographical hotspots with high frequency of multi-drug resistant tuberculosis (MDR-TB) have been observed in several locations, such as the country of Georgia. Here, the authors analyse genomic sequences from tuberculosis bacteria isolated from Georgia to show that the transmission fitness of MDR-TB strains is heterogeneous, and highly drug-resistant and transmissible isolates contribute to the emergence and maintenance of MDR-TB hotspots.
Published: 2023
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36. Genetic Characterization and Population Structure of Drug-Resistant Mycobacterium tuberculosis Isolated from Brazilian Patients Using Whole-Genome Sequencing

Author: Leonardo Souza Esteves, Lia Lima Gomes, Daniela Brites, Fátima Cristina Onofre Fandinho, Marcela Bhering, Márcia Aparecida da Silva Pereira, Emilyn Costa Conceição, Richard Salvato, Bianca Porphirio da Costa, Reginalda Ferreira de Melo Medeiros, Paulo Cesar de Souza Caldas, Paulo Redner, Margareth Pretti Dalcolmo, Vegard Eldholm, Sebastien Gagneux, Maria Lucia Rossetti, Afrânio Lineu Kritski, and Philip Noel Suffys
Subjects: Mycobacterium tuberculosis, drug resistance, whole-genome sequencing, genetic diversity, Brazil, novel mutations, Therapeutics. Pharmacology, RM1-950
Abstract: The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensive resistance (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides the analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definitions. Sub-lineage 4.3 (52%) was the most frequent genotype, and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected twenty novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. A cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug resistance prediction, presenting the best accuracy values for five of the nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) or genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil and the genetic and clinical data correlations and demonstrated its utility for surveillance efforts regarding the spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.
Published: 2024
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37. Author Correction: Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase

Author: Ezewudo, Matthew, Borens, Amanda, Chiner-Oms, Álvaro, Miotto, Paolo, Chindelevitch, Leonid, Starks, Angela M, Hanna, Debra, Liwski, Richard, Zignol, Matteo, Gilpin, Christopher, Niemann, Stefan, Kohl, Thomas Andreas, Warren, Robin M, Crook, Derrick, Gagneux, Sebastien, Hoffner, Sven, Rodrigues, Camilla, Comas, Iñaki, Engelthaler, David M, Alland, David, Rigouts, Leen, Lange, Christoph, Dheda, Keertan, Hasan, Rumina, McNerney, Ruth, Cirillo, Daniela M, Schito, Marco, Rodwell, Timothy C, and Posey, James
Subjects: Microbiology, Biological Sciences, Infection, Good Health and Well Being
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2020

38. Multiple Genomic Events Altering Hominin SIGLEC Biology and Innate Immunity Predated the Common Ancestor of Humans and Archaic Hominins.

Author: Khan, Naazneen, de Manuel, Marc, Peyregne, Stephane, Do, Raymond, Prufer, Kay, Marques-Bonet, Tomas, Varki, Nissi, Gagneux, Pascal, and Varki, Ajit
Subjects: CD33rSiglecs, Neanderthal/Denisovan, archaic hominin, common ancestor, evolution, great apes, hominin, sialic acid, Biochemistry and Cell Biology, Evolutionary Biology, Genetics, Developmental Biology
Abstract: Human-specific pseudogenization of the CMAH gene eliminated the mammalian sialic acid (Sia) Neu5Gc (generating an excess of its precursor Neu5Ac), thus changing ubiquitous cell surface "self-associated molecular patterns" that modulate innate immunity via engagement of CD33-related-Siglec receptors. The Alu-fusion-mediated loss-of-function of CMAH fixed ∼2-3 Ma, possibly contributing to the origins of the genus Homo. The mutation likely altered human self-associated molecular patterns, triggering multiple events, including emergence of human-adapted pathogens with strong preference for Neu5Ac recognition and/or presenting Neu5Ac-containing molecular mimics of human glycans, which can suppress immune responses via CD33-related-Siglec engagement. Human-specific alterations reported in some gene-encoding Sia-sensing proteins suggested a "hotspot" in hominin evolution. The availability of more hominid genomes including those of two extinct hominins now allows full reanalysis and evolutionary timing. Functional changes occur in 8/13 members of the human genomic cluster encoding CD33-related Siglecs, all predating the human common ancestor. Comparisons with great ape genomes indicate that these changes are unique to hominins. We found no evidence for strong selection after the Human-Neanderthal/Denisovan common ancestor, and these extinct hominin genomes include almost all major changes found in humans, indicating that these changes in hominin sialobiology predate the Neanderthal-human divergence ∼0.6 Ma. Multiple changes in this genomic cluster may also explain human-specific expression of CD33rSiglecs in unexpected locations such as amnion, placental trophoblast, pancreatic islets, ovarian fibroblasts, microglia, Natural Killer(NK) cells, and epithelia. Taken together, our data suggest that innate immune interactions with pathogens markedly altered hominin Siglec biology between 0.6 and 2 Ma, potentially affecting human evolution.
Published: 2020

39. Maximum reproductive lifespan correlates with CD33rSIGLEC gene number: Implications for NADPH oxidase‐derived reactive oxygen species in aging

Author: Khan, Naazneen, Kim, Stuart K, Gagneux, Pascal, Dugan, Laura L, and Varki, Ajit
Subjects: Biomedical and Clinical Sciences, Immunology, Aging, 1.1 Normal biological development and functioning, Underpinning research, Good Health and Well Being, Animals, Gene Dosage, Humans, Longevity, NADPH Oxidases, Neutrophils, Reactive Oxygen Species, Sialic Acid Binding Ig-like Lectin 3, Whale, Killer, CD33rSIGLEC, NADPH-oxidase, prolonged post-reproductive lifespan, reactive oxygen species, CD33rSIGLEC, Biochemistry and Cell Biology, Physiology, Medical Physiology, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medical physiology
Abstract: Humans and orcas are among the very rare species that have a prolonged post-reproductive lifespan (PRLS), during which the aging process continues. Reactive oxygen species (ROS) derived from mitochondria and from the NADPH oxidase (NOX) enzymes of innate immune cells are known to contribute to aging, with the former thought to be dominant. CD33-related-Siglecs are immune receptors that recognize self-associated-molecular-patterns and modulate NOX-derived-ROS. We herewith demonstrate a strong correlation of lifespan with CD33rSIGLEC gene number in 26 species, independent of body weight or phylogeny. The correlation is stronger when considering total CD33rSIGLEC gene number rather than those encoding inhibitory and activating subsets, suggesting that lifetime balancing of ROS is important. Combining independent lines of evidence including the short half-life and spontaneous activation of neutrophils, we calculate that even without inter-current inflammation, a major source of lifetime ROS exposure may actually be neutrophil NOX-derived. However, genomes of human supercentenarians (>110 years) do not harbor a significantly higher number of functional CD33rSIGLEC genes. Instead, lifespan correlation with CD33rSIGLEC gene number was markedly strengthened by excluding the post-reproductive lifespan of humans and orcas (R2 = 0.83; P
Published: 2020

40. Promoting HPV vaccination at school: a mixed methods study exploring knowledge, beliefs and attitudes of French school staff

Author: Aurélie Bocquier, Marion Branchereau, Aurélie Gauchet, Stéphanie Bonnay, Maïa Simon, Marie Ecollan, Karine Chevreul, Judith E. Mueller, Amandine Gagneux-Brunon, Nathalie Thilly, and the PrevHPV Study Group
Subjects: Human Papillomavirus, Vaccination, Knowledge, Attitude, Health Education, Middle school professionals, Public aspects of medicine, RA1-1270
Abstract: Abstract Background HPV vaccine coverage in France remained lower than in most other high-income countries. Within the diagnostic phase of the national PrevHPV program, we carried out a mixed methods study among school staff to assess their knowledge, beliefs and attitudes regarding HPV, HPV vaccine and vaccination in general, and regarding schools’ role in promoting HPV vaccination. Methods Middle school nurses, teachers and support staff from four French regions participated between January 2020 and May 2021. We combined: (i) quantitative data from self-administered online questionnaires (n = 301), analysed using descriptive statistics; and (ii) qualitative data from three focus groups (n = 14), thematically analysed. Results Less than half of respondents knew that HPV can cause genital warts or oral cancers and only 18% that no antiviral treatment exists. Almost 90% of the respondents knew the existence of the HPV vaccine but some misunderstood why it is recommended before the first sexual relationships and for boys; 56% doubted about its safety, especially because they think there is not enough information on this topic. Schools nurses had greater knowledge than other professionals and claimed that educating pupils about HPV was fully part of their job roles; however, they rarely address this topic due to a lack of knowledge/tools. Professionals (school nurses, teachers and support staff) who participated in the focus groups were unfavourable to offering vaccination at school because of parents’ negative reactions, lack of resources, and perceived uselessness. Conclusions These results highlight the need to improve school staff knowledge on HPV. Parents should be involved in intervention promoting HPV vaccination to prevent their potential negative reactions, as feared by school staff. Several barriers should also be addressed before organizing school vaccination programs in France.
Published: 2023
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41. Bacteremia and adrenal gland abscess due to Nocardia cyriacigeorgica: a case report and review

Author: Florian Saunier, Sylvain Grange, Josselin Rigaill, Marie-France Lutz, Amandine Gagneux-Brunon, and Elisabeth Botelho-Nevers
Subjects: Nocardia cyriacigeorgica, Nocardiosis, Adrenal gland abscess, Bacteremia, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Nocardia cyriacigeorgica is one of the most common Nocardia species found in human infections, recently reclassified. Even though Nocardia may affect all organs by hematogenous dissemination, bacteremia are uncommon. Among all possible dissemination sites, the involvement of the adrenal glands is particularly rare. Case presentation We report here a rare case of Nocardia disseminated infection with notably bacteremia and adrenal gland abscess, in a 77-years-old immunocompetent man. Adrenal gland abscess diagnosis was made by imaging (computerized tomography, magnetic resonance and positron emission tomography scan). A complete regression of all lesions including the left adrenal gland was obtained after 6 months of antibiotics. A review of literature was also performed. Conclusion Nocardia bacteremia is a rare event but blood cultures may help to improve detection of Nocardia spp. in a non-invasive way. Adrenal abscess due to Nocardia spp. is very rare with only fourteen cases reported in the literature, but it is a true cause of adrenal masses. Our report suggests that clinician should be aware of this rare location and prioritize a non-invasive diagnosis strategy.
Published: 2022
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42. How do monomorphic bacteria evolve? The Mycobacterium tuberculosis complex and the awkward population genetics of extreme clonality

Author: Stritt, Christoph and Gagneux, Sebastien
Subjects: clonality, mutation, recombination, genetic drift, natural selection, simulation, Archaeology, CC1-960, Science
Abstract: Exchange of genetic material through sexual reproduction or horizontal gene transfer is ubiquitous in nature. Among the few outliers that rarely recombine and mainly evolve by de novo mutation are a group of deadly bacterial pathogens, including the causative agents of leprosy, plague, typhoid, and tuberculosis. The interplay of evolutionary processes is poorly understood in these organisms. Population genetic methods allowing to infer mutation, recombination, genetic drift, and natural selection make strong assumptions that are difficult to reconcile with clonal reproduction and fully linked genomes consisting mainly of coding regions. In this review, we highlight the challenges of extreme clonality by discussing population genetic inference with the Mycobacterium tuberculosis complex, a group of closely related obligate bacterial pathogens of mammals. We show how uncertainties underlying quantitative models and verbal arguments affect previous conclusions about the way these organisms evolve. A question mark remains behind various quantities of applied and theoretical interest, including mutation rates, the interpretation of nonsynonymous polymorphisms, or the role of genetic bottlenecks. Looking ahead, we discuss how new tools for evolutionary simulations, going beyond the traditional Wright-Fisher framework, promise a more rigorous treatment of basic evolutionary processes in clonal bacteria.
Published: 2023
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43. Key Contributions by the Swiss Tropical and Public Health Institute Towards New and Better Drugs for Tropical Diseases

Author: Pascal Mäser, Sonja Bernhard, Reto Brun, Christian Burri, Sébastien Gagneux, Manuel W. Hetzel, Marcel Kaiser, Christian Lengeler, Gerd Pluschke, Elisabeth Reus, Matthias Rottmann, Jürg Utzinger, Louisa Warryn, Sergio Wittlin, and Jennifer Keiser
Subjects: Drug research and development, Infectious diseases of poverty, Neglected tropical diseases, Product development partnerships, Swiss TPH, Chemistry, QD1-999
Abstract: Thanks to its expertise in clinical research, epidemiology, infectious diseases, microbiology, parasitology, public health, translational research and tropical medicine, coupled with deeply rooted partnerships with institutions in low- and middle-income countries (LMICs), the Swiss Tropical and Public Health Institute (Swiss TPH) has been a key contributor in many drug research and development consortia involving academia, pharma and product development partnerships. Our know-how of the maintenance of parasites and their life-cycles in the laboratory, plus our strong ties to research centres and disease control programme managers in LMICs with access to field sites and laboratories, have enabled systems for drug efficacy testing in vitro and in vivo, clinical research, and modelling to support the experimental approaches. Thus, Swiss TPH has made fundamental contributions towards the development of new drugs – and the better use of old drugs – for neglected tropical diseases and infectious diseases of poverty, such as Buruli ulcer, Chagas disease, food-borne trematodiasis (e.g. clonorchiasis, fascioliasis and opisthorchiasis), human African trypanosomiasis, leishmaniasis, malaria, schistosomiasis, soil-transmitted helminthiasis and tuberculosis. In this article, we show case the success stories of molecules to which Swiss TPH has made a substantial contribution regarding their use as anti-infective compounds with the ultimate aim to improve people’s health and well-being.
Published: 2023
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44. Macrophage susceptibility to infection by Ghanaian Mycobacterium tuberculosis complex lineages 4 and 5 varies with self-reported ethnicity

Author: Stephen Osei-Wusu, John K. A. Tetteh, Abdul Basit Musah, Desmond Opoku Ntiamoah, Nelly Arthur, Abraham Adjei, Ainhoa Arbues, Ebenezer Addo Ofori, Kwadwo Akyea Mensah, Sutaya Elsie Afua Galevo, Abena Frema Frempong, Prince Asare, Adwoa Asante-Poku, Isaac Darko Otchere, Kwadwo Asamoah Kusi, Tobias L. Lenz, Sebastien Gagneux, Damien Portevin, and Dorothy Yeboah-Manu
Subjects: macrophage infection, Ghana, West Africa, tuberculosis, Ewe, Akan, Microbiology, QR1-502
Abstract: BackgroundThe epidemiology of Mycobacterium tuberculosis complex (MTBC) lineage 5 (L5) infections in Ghana revealed a significantly increased prevalence in Ewes compared to other self-reported ethnic groups. In that context, we sought to investigate the early phase of tuberculosis (TB) infection using ex vivo infection of macrophages derived from the blood of Ewe and Akan ethnic group volunteers with MTBC L4 and L5 strains.MethodsThe study participants consisted of 16 controls, among which self-reported Akan and Ewe ethnicity was equally represented, as well as 20 cured TB cases consisting of 11 Akans and 9 Ewes. Peripheral blood mononuclear cells were isolated from both healthy controls and cured TB cases. CD14+ monocytes were isolated and differentiated into monocyte-derived macrophages (MDMs) before infection with L4 or L5 endemic strains. The bacterial load was assessed after 2 hours (uptake) as well as 3 and 7 days post-infection.ResultsWe observed a higher capacity of MDMs from Ewes to phagocytose L4 strains (p < 0.001), translating into a higher bacillary load on day 7 (p < 0.001) compared to L5, despite the higher replication rate of L5 in Ewe MDMs (fold change: 1.4 vs. 1.2, p = 0.03) among the controls. On the contrary, within macrophages from Akans, we observed a significantly higher phagocytic uptake of L5 (p < 0.001) compared to L4, also translating into a higher load on day 7 (p = 0.04). However, the replication rate of L4 in Akan MDMs was higher than that of L5 (fold change: L4 = 1.2, L4 = 1.1, p = 0.04). Although there was no significant difference in the uptake of L4 and L5 among cured TB cases, there was a higher bacterial load of both L4 (p = 0.02) and L5 (p = 0.02) on day 7 in Ewe MDMs.ConclusionOur results suggest that host ethnicity (driven by host genetic diversity), MTBC genetic diversity, and individual TB infection history are all acting together to modulate the outcome of macrophage infections by MTBC.
Published: 2023
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45. The effect of obesity on uterine receptivity is mediated by endometrial extracellular vesicles that control human endometrial stromal cell decidualization and trophoblast invasion

Author: Laurent Galio, Laetitia Bernet, Yoann Rodriguez, Camille Fourcault, Marie‐Noëlle Dieudonné, Hélène Pinatel, Céline Henry, Valérie Sérazin, Khadija Fathallah, Anissa Gagneux, Zuzana Krupova, François Vialard, and Esther Dos Santos
Subjects: decidualization, embryo implantation, extracellular vesicle, human endometrium, obesity, proteomics, Cytology, QH573-671
Abstract: Abstract The objectives of the present study were to determine whether obesity impacts human decidualization and the endometrial control of trophoblast invasion (both of which are required for embryo implantation) and evaluate the potential involvement of endometrial extracellular vesicles (EVs) in the regulation of these physiological processes. Using primary human cell cultures, we first demonstrated that obesity is associated with significantly lower in vitro decidualization of endometrial stromal cells (ESCs). We then showed that a trophoblastic cell line's invasive ability was greater in the presence of conditioned media from cultures of ESCs from obese women. The results of functional assays indicated that supplementation of the culture medium with EVs from nonobese women can rescue (at least in part) the defect in in vitro decidualization described in ESCs from obese women. Furthermore, exposure to endometrial EVs from obese women (vs. nonobese women) was associated with significantly greater invasive activity by HTR‐8/SVneo cells. Using mass‐spectrometry‐based quantitative proteomics, we found that EVs isolated from uterine supernatants of biopsies from obese women (vs. nonobese women) presented a molecular signature focused on cell remodelling and angiogenesis. The proteomics analysis revealed two differentially expressed proteins (fibronectin and angiotensin‐converting enzyme) that might be involved specifically in the rescue of the decidualization capacity in ESCs from obese women; both of these proteins are abundantly present in endometrial EVs from nonobese women, and both are involved in the decidualization process. In conclusion, our results provided new insights into the endometrial EVs’ pivotal role in the poor uterine receptivity observed in obese women.
Published: 2023
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46. Physical activity and quality of life of people aged 50 and over living with HIV/AIDS: A cross-sectional study in a cohort in Yaounde, Cameroon

Author: Henri Olivier Tatsilong Pambou, Bertrand Tatsinkou Fossi, Amandine Gagneux-Brunon, Frederic Roche, Jessica Guyot, Elisabeth Botelho-Nevers, Caroline Dupre, Samuel Honoré Mandengue, Bienvenu Bongue, and Celine Nguefeu Nkenfou
Subjects: Aging, Quality of life and associated factors, Denial of HIV status, Sedentarity, Cameroon, Public aspects of medicine, RA1-1270
Abstract: Introduction: HIV infection has become a chronic disease. Management has shifted to the prevention and treatment of chronic diseases. Regular physical activity (PA) reduces the impact of HIV. Our objectives were to determine levels of PA, assess quality of life (QoL) and determine the degree to which Brief WHOQOLHIV domains and PA influence QoL in older PLHIV. Methods: We conducted a cross-sectional study between March 2020 and March 2021 among 136 older PLHIV at Mvog Ada District Hospital in Yaoundé. Two questionnaires were administered to assess the level of PA (Ricci and Gagnon) and the brief WHOQOL HIV. A bivariate and multivariate analyses were performed. Result: The mean age of the participants was 57.07 ± 6.7 years and the female/male ratio was 1.6. Physical inactivity was found in 56.60% of the participants; 43.40% of them felt they had a good quality of life and 65.40% had a good health status. The environmental domain and social relationship had low scores compared to the spiritual domain and the level of independence. Scores for the different domains were higher in active participants than in inactive participants; with the psychological domain more related to physical inactivity (p
Published: 2023
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47. The female reproductive tract contains multiple innate sialic acid-binding immunoglobulin-like lectins (Siglecs) that facilitate sperm survival

Author: Tecle, Eillen, Reynoso, Hector Sequoyah, Wang, Ruixuan, and Gagneux, Pascal
Subjects: Reproductive Medicine, Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Contraception/Reproduction, 1.1 Normal biological development and functioning, Underpinning research, Animals, Endometrium, Female, Immunoglobulin Fc Fragments, Male, Mice, Mice, Inbred C57BL, Neuraminidase, Neutrophil Activation, Neutrophils, Recombinant Fusion Proteins, Sialic Acid Binding Immunoglobulin-like Lectins, Sialic Acids, Spermatozoa, spermatozoa, sialic acid, reproduction, innate immunity, lectin, glycan, sialic acid-binding immunoglobulin-like lectins, Chemical Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract: A sperm that fertilizes an egg has successfully survived multiple checkpoints within the female reproductive tract, termed pre-fertilization events. The leukocytic response is a pre-fertilization event in which sperm trigger an immune response that promotes homing of circulating leukocytes to the uterine lumen to destroy most sperm. Various glycoconjugates decorate the sperm surface, including sialic acids, which are abundant at the sperm surface where they cap most glycan chains and regulate sperm migration through cervical mucus, formation of the sperm oviductal reservoir, and sperm capacitation. However, the role of sperm-associated sialic acids in the leukocytic reaction remains unknown. The cognate endogenous binding partners of sialic acids, sialic acid-binding immunoglobulin-like lectins (Siglecs) play a pivotal role in regulating many immune responses. Here we investigated whether sperm-associated sialic acids inhibit activation of neutrophils, one of the major immune cells involved in the leukocytic reaction. We used in vitro interactions between sperm and neutrophils as well as binding assays between sperm and recombinant Siglec-Fc chimeric proteins to measure interactions. Moreover, we examined whether Siglecs are expressed on human and mouse endometria, which have a role in initiating the leukocytic reaction. Surprisingly less sialylated, capacitated, sperm did not increase neutrophil activation in vitro However, we observed expression of several Siglecs on the endometrium and that these receptors interact with sialylated sperm. Our results indicate that sperm sialic acids may interact with endometrial Siglecs and that these interactions facilitate sperm survival in the face of female immunity.
Published: 2019

48. Humans and Chimpanzees Display Opposite Patterns of Diversity in Arylamine N-Acetyltransferase Genes.

Author: Vangenot, Christelle, Gagneux, Pascal, de Groot, Natasja G, Baumeyer, Adrian, Mouterde, Médéric, Crouau-Roy, Brigitte, Darlu, Pierre, Sanchez-Mazas, Alicia, Sabbagh, Audrey, and Poloni, Estella S
Subjects: Animals, Hominidae, Humans, Pan troglodytes, Arylamine N-Acetyltransferase, Genomics, Species Specificity, Haplotypes, Polymorphism, Genetic, Alleles, Multigene Family, Genome, Genetic Variation, Arylamine N-acetyltransferases, drug metabolism, great apes, multigenic family, natural selection, Polymorphism, Genetic, Genetics
Abstract: Among the many genes involved in the metabolism of therapeutic drugs, human arylamine N-acetyltransferases (NATs) genes have been extensively studied, due to their medical importance both in pharmacogenetics and disease epidemiology. One member of this small gene family, NAT2, is established as the locus of the classic human acetylation polymorphism in drug metabolism. Current hypotheses hold that selective processes favoring haplotypes conferring lower NAT2 activity have been operating in modern humans' recent history as an adaptation to local chemical and dietary environments. To shed new light on such hypotheses, we investigated the genetic diversity of the three members of the NAT gene family in seven hominid species, including modern humans, Neanderthals and Denisovans. Little polymorphism sharing was found among hominids, yet all species displayed high NAT diversity, but distributed in an opposite fashion in chimpanzees and bonobos (Pan genus) compared to modern humans, with higher diversity in Pan species at NAT1 and lower at NAT2, while the reverse is observed in humans. This pattern was also reflected in the results returned by selective neutrality tests, which suggest, in agreement with the predicted functional impact of mutations detected in non-human primates, stronger directional selection, presumably purifying selection, at NAT1 in modern humans, and at NAT2 in chimpanzees. Overall, the results point to the evolution of divergent functions of these highly homologous genes in the different primate species, possibly related to their specific chemical/dietary environment (exposome) and we hypothesize that this is likely linked to the emergence of controlled fire use in the human lineage.
Published: 2019

49. Absence of Neu5Gc and Presence of Anti-Neu5Gc Antibodies in Humans—An Evolutionary Perspective

Author: Altman, Meghan O and Gagneux, Pascal
Subjects: Microbiology, Biological Sciences, Nutrition, Clinical Research, Animals, Antibodies, Evolution, Molecular, Female, Glycocalyx, Humans, Loss of Function Mutation, Male, Mixed Function Oxygenases, Neuraminic Acids, sialic acid, Neu5Gc, Neu5Ac, xenoglycan, anti-glycan antibodies, xeno-antigen, Immunology, Medical Microbiology, Biochemistry and cell biology, Genetics
Abstract: The glycocalyx of human cells differs from that of many other mammals by the lack of the sialic acid N-glycolylneuraminic acid (Neu5Gc) and increased abundance of its precursor N-acetylneuraminic acid (Neu5Ac). Most humans also have circulating antibodies specifically targeting the non-human sialic acid Neu5Gc. Recently, several additional mammalian species have been found to also lack Neu5Gc. In all cases, loss-of-function mutations in the gene encoding the sialic acid-modifying enzyme CMAH are responsible for the drastic change in these species. Unlike other glycan antigens, Neu5Gc apparently cannot be produced by microbes, raising the question about the origin of these antibodies in humans. Dietary exposure and presentation on bacteria coating themselves with Neu5Gc from the diet are distinct possibilities. However, the majority of the non-human species that lack Neu5Gc do not consume diets rich in Neu5Gc, making it unlikely that they will have been immunized against this sialic acid. A notable exception are mustelids (ferrets, martens and their relatives) known for preying on various small mammal species rich in Neu5Gc. No studies exist on levels of anti-Neu5Gc antibodies in non-human species. Evolutionary scenarios for the repeated, independent fixation of CMAH loss-of-function mutations at various time points in the past include strong selection by parasites, especially enveloped viruses, stochastic effects of genetic drift, and directional selection via female immunity to paternal Neu5Gc. Convergent evolution of losses of the vertebrate-specific self-glycan Neu5Gc are puzzling and may represent a prominent way in which glycans become agents of evolutionary change in their own right. Such change may include the reconfiguration of innate immune lectins that use self-sialic acids as recognition patterns.
Published: 2019

50. The New Science of Practical Wisdom.

Author: Jeste, Dilip V, Lee, Ellen E, Cassidy, Charles, Caspari, Rachel, Gagneux, Pascal, Glorioso, Danielle, Miller, Bruce L, Semendeferi, Katerina, Vogler, Candace, Nusbaum, Howard, and Blazer, Dan
Subjects: Brain, Humans, Suicide, Empathy, Psychology, Social, Family, Decision Making, Aging, Genome, Human, Culture, Aged, 80 and over, Frontotemporal Dementia, Biological Evolution, Basic Behavioral and Social Science, Behavioral and Social Science, Good Health and Well Being, Clinical Sciences, History and Philosophy of Specific Fields, Philosophy, General & Internal Medicine
Abstract: Wisdom has been discussed for centuries in religious and philosophical texts. It is often viewed as a fuzzy psychological construct analogous to consciousness, stress, and resilience. This essay provides an understanding of wisdom as a scientific construct, based on empirical research starting in the 1970s. The focus is on practical rather than theoretical wisdom. While there are different conceptualizations of wisdom, it is best defined as a complex human characteristic or trait with specific components: social decision-making, emotional regulation, prosocial behavior (such as empathy and compassion), self-reflection, acceptance of uncertainty, decisiveness, and spirituality. These psychological processes involve the fronto-limbic circuitry. Wisdom is associated with positive life outcomes including better health, well-being, happiness, life satisfaction, and resilience. Wisdom tends to increase with active aging, facilitating a contribution of wise grandparents to promoting fitness of younger kin. Despite the loss of their own fertility and physical health, older adults help enhance their children's and grandchildren's well-being, health, longevity, and fertility-the "grandmother hypothesis" of wisdom. Wisdom has important implications at individual and societal levels and is a major contributor to human thriving. We need to place a greater emphasis on promoting wisdom through our educational systems from elementary to professional schools.
Published: 2019

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