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1. Evaluating the Impact of EnteraGam In People With COVID-19 (PICNIC)

Author: Lemus Buhils, SL and Clinical Research Unit, IMIM (Hospital del Mar Medical Research Institute)
Published: 2023

2. How come scientists uncritically adopt and embody Thomson’s bibliographic impact factor?

Author: Universidad de Alicante. Departamento de Enfermería Comunitaria, Medicina Preventiva y Salud Pública e Historia de la Ciencia, Instituto Municipal de Investigación Médica (IMIM-Hospital del Mar), Porta Serra, Miquel, Álvarez-Dardet, Carlos, Universidad de Alicante. Departamento de Enfermería Comunitaria, Medicina Preventiva y Salud Pública e Historia de la Ciencia, Instituto Municipal de Investigación Médica (IMIM-Hospital del Mar), Porta Serra, Miquel, and Álvarez-Dardet, Carlos
Abstract: The bibliographic impact factor (BIF) of Thomson Scientific is sometimes not a valid scientometric indicator for a number of reasons. One major reason is the strong influence of the number of “source items” or “articles” for each journal that the company chooses each year as BIF’s denominator. The irresistible fascination with (and picturesque uses of) a construct as scientifically weak as BIF are simple reminders that scientists are embedded in and embody culture.
Published: 2008

3. Patient-centered care in Coronary Heart Disease: what do you want to measure? A systematic review of reviews on patient-reported outcome measures

Author: Yolanda Pardo, Olatz Garin, Cristina Oriol, Víctor Zamora, Aida Ribera, Montserrat Ferrer, Institut Català de la Salut, [Pardo Y] CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Health Services Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. [Garin O, Zamora V, Ferrer M] CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Health Services Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. [Oriol C] Unitat de Suport a la Recerca Metropolitana Nord, Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Mataró, Spain. [Ribera A] CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca de Malalties Cardiovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cor - Malalties - Tractament, Atenció centrada en el pacient, Health Care (Public Health)::Delivery of Health Care::Comprehensive Health Care::Primary Health Care::Patient-Centered Care [PUBLIC HEALTH], Patient-reported outcomes, Health-related quality of life, Symptoms scale, Public Health, Environmental and Occupational Health, Cardiovascular Diseases::Heart Diseases::Myocardial Ischemia::Coronary Disease [DISEASES], Coronary Heart Disease, Functional status, enfermedades cardiovasculares::enfermedades cardíacas::isquemia miocárdica::enfermedad coronaria [ENFERMEDADES], atención a la salud (salud pública)::prestación sanitaria::atención integral de salud::atención primaria de la salud::atención centrada en el paciente [SALUD PÚBLICA]
Abstract: Coronary heart disease; Health-related quality of life; Patient-reported outcomes Malaltia coronària; Qualitat de vida relacionada amb la salut; Resultats informats pel pacient Enfermedad coronaria; Calidad de vida relacionada con la salud; Resultados informados por el paciente Background The number of published articles on Patient-Reported Outcomes Measures (PROMs) in Coronary Heart Disease (CHD), a leading cause of disability-adjusted life years lost worldwide, has been growing in the last decades. The aim of this study was to identify all the disease-specific PROMs developed for or used in CHD and summarize their characteristics (regardless of the construct), to facilitate the selection of the most adequate one for each purpose. Methods A systematic review of reviews was conducted in MEDLINE, Scopus, and the Cochrane Database of Systematic Reviews. PROQOLID and BiblioPRO libraries were also checked. PROMs were classified by construct and information was extracted from different sources regarding their main characteristics such as aim, number of items, specific dimensions, original language, and metric properties that have been assessed. Results After title and abstract screening of 1224 articles, 114 publications were included for full text review. Finally, we identified 56 PROMs: 12 symptoms scales, 3 measuring functional status, 21 measuring Health-Related Quality of Life (HRQL), and 20 focused on other constructs. Three of the symptoms scales were specifically designed for a study (no metric properties evaluated), and only five have been included in a published study in the last decade. Regarding functional status, reliability and validity have been assessed for Duke Activity Index and Seattle Angina Questionnaire, which present multiple language versions. For HRQL, most of the PROMs included physical, emotional, and social domains. Responsiveness has only been evaluated for 10 out the 21 HRQL PROMs identified. Other constructs included psychological aspects, self-efficacy, attitudes, perceptions, threats and expectations about the treatment, knowledge, adjustment, or limitation for work, social support, or self-care. Conclusions There is a wide variety of instruments to assess the patients’ perspective in CHD, covering several constructs. This is the first systematic review of specific PROMs for CHD including all constructs. It has practical significance, as it summarizes relevant information that may help clinicians, researchers, and other healthcare stakeholders to choose the most adequate instrument for promoting shared decision making in a trend towards value-based healthcare. This study was supported by grants from the Instituto de Salud Carlos III FEDER: Fondo Europeo de Desarrollo Regional (grant number PI16/00130); Generalitat de Catalunya, Spain (grant number and 2017 SGR 452); and the Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBER of Epidemiology and Public Health). The funders of the study had no role in the study design and conduct, data collection, management, analysis, or interpretation; they also had no role in the preparation, writing, reviewing, and submission of this manuscript.
Published: 2023

4. Palbociclib Rechallenge for Hormone Receptor-Positive/HER-Negative Advanced Breast Cancer: Findings from the Phase II BioPER Trial

Author: Joan Albanell, José Manuel Pérez-García, Miguel Gil-Gil, Giuseppe Curigliano, Manuel Ruíz-Borrego, Laura Comerma, Joan Gibert, Meritxell Bellet, Begoña Bermejo, Lourdes Calvo, Juan de la Haba, Enrique Espinosa, Alessandro Marco Minisini, Vanesa Quiroga, Ana Santaballa Bertran, Leonardo Mina, Beatriz Bellosillo, Federico Rojo, Silvia Menéndez, Miguel Sampayo-Cordero, Crina Popa, Andrea Malfettone, Javier Cortés, Antonio Llombart-Cussac, Institut Català de la Salut, [Albanell J] Medical Oncology Department, Hospital del Mar, Barcelona, Spain. Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Centro de Investigacion Biomédica en Red de Oncología (CIBERONC-ISCIII), Madrid, Spain. Universitat Pompeu Fabra, Barcelona, Spain. GEICAM, Spain. [Pérez-García JM] International Breast Cancer Center (IBCC), Quironsalud Group, Barcelona, Spain. Medica Scientia Innovation Research (MEDSIR), Barcelona, Spain and Ridgewood, New Jersey. [Gil-Gil M] GEICAM, Spain. Catalan Institute of Oncology, Breast Cancer Unit, Medical Oncology Department, IDIBELL, Barcelona, Spain. [Curigliano G] Istituto Europeo di Oncologia, IRCCS, Milano, Italy. University of Milano, Department of Oncology and Hemato-Oncology, Milano, Italy. [Ruíz-Borrego M] GEICAM, Spain. Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Comerma L] Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Pathology Department, Hospital del Mar, Barcelona, Spain. [Bellet M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, Receptor, ErbB-2, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Medicaments antineoplàstics - Ús terapèutic, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Breast Neoplasms, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Piperazines, Càncer de mama, Mama --Tumors, Breast cancer, Clinical trials, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Quimioteràpia, Antineoplastic Combined Chemotherapy Protocols, Humans, Càncer, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Biochemical markers, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Oncology, Mama - Càncer - Tractament, Marcadors bioquímics, Female, Protocols clínics, Assaigs clínics
Abstract: Hormone receptor; Advanced breast cancer Càncer de mama avançat; Receptor hormonal Cáncer de mama avanzado; Receptor hormonal Purpose: To assess the efficacy and exploratory biomarkers of continuing palbociclib plus endocrine therapy (ET) beyond progression on prior palbociclib-based regimen in patients with hormone receptor–positive/HER2-negative (HR+/HER2−) advanced breast cancer (ABC). Patients and Methods: The multicenter, open-label, phase II BioPER trial included women who had experienced a progressive disease (PD) after having achieved clinical benefit on the immediately prior palbociclib plus ET regimen. Palbociclib (125 mg, 100 mg, or 75 mg daily orally for 3 weeks and 1 week off as per prior palbociclib-based regimen) plus ET of physician's choice were administered in 4-week cycles until PD or unacceptable toxicity. Coprimary endpoints were clinical benefit rate (CBR) and percentage of tumors with baseline loss of retinoblastoma (Rb) protein expression. Additional endpoints included safety and biomarker analysis. Results: Among 33 patients enrolled, CBR was 34.4% [95% confidence interval (CI), 18.6–53.2; P < 0.001] and 13.0% of tumors (95% CI, 5.2–27.5) showed loss of Rb protein expression, meeting both coprimary endpoints. Median progression-free survival was 2.6 months (95% CI, 1.8–6.7). No new safety signals were reported. A signature that included baseline mediators of therapeutic resistance to palbociclib and ET (low Rb score, high cyclin E1 score, ESR1 mutation) was independently associated with shorter median progression-free survival (HR, 22.0; 95% CI, 1.71–282.9; P = 0.018). Conclusions: Maintaining palbociclib after progression on prior palbociclib-based regimen seems to be a reasonable, investigational approach for selected patients. A composite biomarker signature predicts a subset of patients who may not derive a greater benefit from palbociclib rechallenge, warranting further validation in larger randomized controlled trials. This work was supported by Pfizer. The authors would like to thank the patients, their caregivers, and their families for participating in this study and all investigators and site personnel. The BioPER study was conceived and designed by Medica Scientia Innovation Research (MEDSIR) in collaboration with Pfizer Inc., which funded the study and provided palbociclib. J. Albanell acknowledges CIBERONC CB16/12/00241, PI21/00002, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union, Generalitat de Catalunya (2017 SGR 507).
Published: 2022

5. Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients

Author: Ana Gutiérrez, Pedro Zapater, Elena Ricart, María González-Vivó, Jordi Gordillo, David Olivares, Isabel Vera, Míriam Mañosa, Javier P. Gisbert, Mariam Aguas, Eugenia Sánchez-Rodríguez, Maia Bosca-Watts, Viviana Laredo, Blau Camps, Ignacio Marín-Jiménez, Yamile Zabana, María Dolores Martín-Arranz, Roser Muñoz, Mercè Navarro, Eva Sierra, Lucía Madero, Milagros Vela, José Lázaro Pérez-Calle, Empar Sainz, Xavier Calvet, Lara Arias, Victor Morales, Fernando Bermejo, Luis Fernández-Salazar, Manuel Van Domselaar, Luisa De Castro, Cristina Rodríguez, Carmen Muñoz-Villafranca, Rufo Lorente, Montserrat Rivero, Eva Iglesias, Belén Herreros, David Busquets, Joan Riera, María Pilar Martínez-Montiel, Marta Roldón, Oscar Roncero, Esther Hinojosa, Mónica Sierra, Jesús Barrio, Ruth De Francisco, José Huguet, Olga Merino, Daniel Carpio, Daniel Ginard, Fernando Muñoz, Marta Piqueras, Pedro Almela, Federico Argüelles-Arias, Guillermo Alcaín, Luis Bujanda, Noemí Manceñido, Alfredo J. Lucendo, Pilar Varela, Iago Rodríguez-Lago, Laura Ramos, Laura Sempere, Eva Sesé, Manuel Barreiro-de Acosta, Eugeni Domènech, Rubén Francés, [Gutiérrez A] Servicio Medicina Digestiva, Hospital General Universitario Alicante, Alicante, Spain. IIS Isabial, Hospital General Universitario Alicante, Alicante, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. [Zapater P] IIS Isabial, Hospital General Universitario Alicante, Alicante, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Unidad Farmacología Clínica, Hospital General Universitario Alicante, Alicante, Spain. Instituto IDIBE, Universidad Miguel Hernández, San Juan de Alicante, Spain. [Ricart E] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Servicio de Medicina Digestiva Hospital Clínic, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain.[González-Vivó M] Servicio Medicina Digestiva, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. [Gordillo J] Servicio Patología Digestiva, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain. [Olivares D] Servicio Medicina Digestiva, Hospital Universitario Clínico San Carlos, Madrid, Spain. [Piqueras M] Servicio Medicina Digestiva, Hospital de Terrassa, Consorci Sanitari de Terrassa, Barcelona, Spain, Consorci Sanitari de Terrassa, [Gutiérrez A] Servicio Medicina Digestiva, Hospital General Universitario Alicante, Alicante, Spain. IIS Isabial, Hospital General Universitario Alicante, Alicante, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. [Zapater P] IIS Isabial, Hospital General Universitario Alicante, Alicante, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Unidad Farmacología Clínica, Hospital General Universitario Alicante, Alicante, Spain. Instituto IDIBE, Universidad Miguel Hernández, San Juan de Alicante, Spain. [Ricart E] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Servicio de Medicina Digestiva Hospital Clínic, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain. [González-Vivó M] Servicio Medicina Digestiva, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. [Gordillo J] Servicio Patología Digestiva, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain. [Olivares D] Servicio Medicina Digestiva, Hospital Universitario Clínico San Carlos, Madrid, Spain. [Morales V] Servicio Medicina Digestiva, Hospital General de Granollers, Granollers, Spain, and Hospital General de Granollers
Subjects: Digestive System Diseases::Gastrointestinal Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Crohn Disease [DISEASES], Medicine (General), phenotype, Digestive System Diseases::Gastrointestinal Diseases::Gastroenteritis::Inflammatory Bowel Diseases::Crohn Disease [DISEASES], General Medicine, immigrant, Inflammatory bowel diseases, Crohn, Malaltia de, Malalties inflamatòries intestinals, enfermedades del sistema digestivo::enfermedades gastrointestinales::gastroenteritis::enfermedad inflamatoria intestinal::enfermedad de Crohn [ENFERMEDADES], Fenotip, enfermedades del sistema digestivo::enfermedades gastrointestinales::gastroenteritis::enfermedad inflamatoria intestinal [ENFERMEDADES], Digestive System Diseases::Gastrointestinal Diseases::Digestive System Diseases::Gastrointestinal Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Colitis, Ulcerative [DISEASES], Crohn's disease, R5-920, Colitis ulcerosa, inflammatory bowel disease, Immigrants, enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedad inflamatoria intestinal::colitis ulcerosa [ENFERMEDADES], Persons::Emigrants and Immigrants [NAMED GROUPS], biologics, Intestins - Inflamació, Digestive System Diseases::Gastrointestinal Diseases::Gastroenteritis::Inflammatory Bowel Diseases [DISEASES], personas::emigrantes e inmigrantes [DENOMINACIONES DE GRUPOS], ulcerative colitis
Abstract: BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain.MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients.ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92–2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0–1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses.ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.
Published: 2022

6. Measurement properties of the EQ-5D-Y administered through a smartphone app in children with asthma: a longitudinal questionnaire study

Author: Mayoral, Karina, Garin, Olatz, Lizano-Barrantes, Catalina, Pont, Angels, Caballero-Rabasco, Araceli M, Praena-Crespo, Manuel, Valdesoiro-Navarrete, Laura, Guerra, María Teresa, Castillo, José Antonio, Mir, Inés de, Tato, Eva, Alonso, Jordi, Serra-Sutton, Vicky, Pardo, Yolanda, Ferrer, Montse, ARCA Group, Universidad de Sevilla. Departamento de Farmacología, Instituto de Salud Carlos III, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Institut Català de la Salut, [Mayoral K] Health Service Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona Biomedical Research Park, Barcelona, Spain. Departament de Pediatria, Obstetrícia i Ginecologia, Departament de Medicina Preventiva, Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBER en Epidemiología y Salud Pública, CIBERESP, Madrid, Spain. [Garin O] Health Service Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona Biomedical Research Park, Barcelona, Spain. CIBER en Epidemiología y Salud Pública, CIBERESP, Madrid, Spain. Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain. [Lizano-Barrantes C] Health Service Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona Biomedical Research Park, Barcelona, Spain. Department of Pharmaceutical Care and Clinical Pharmacy, Faculty of Pharmacy, Universidad de Costa Rica, San José, Costa Rica. Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain. [Pont A] Health Service Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona Biomedical Research Park, Barcelona, Spain. CIBER en Epidemiología y Salud Pública, CIBERESP, Madrid, Spain. [Caballero-Rabasco AM] Paediatric Pulmonology and Allergy Unit, Paediatric Department, Hospital Del Mar, Barcelona, Spain. Departament de Pediatria, Obstetrícia i Ginecologia, Departament de Medicina Preventiva, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Praena-Crespo M] Centro de Salud La Candelaria. Servicio Andaluz de Salud, Sevilla, Spain. Grupo de Vías Respiratorias de La Asociación Española de Pediatras de Atención Primaria (AEPAP), Madrid, Spain.[Mir I] Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Aplicacions mòbils, Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Qüestionaris, Validity, Surveys and Questionnaires, Humans, Prospective Studies, Child, Asma, Public Health, Environmental and Occupational Health, Reproducibility of Results, técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Responsiveness, Respiratory Tract Diseases::Bronchial Diseases::Asthma [DISEASES], General Medicine, Smartphone app, Ciencias de la información::metodologías computacionales::soporte lógico (informática)::aplicaciones en aparatos electrónicos portátiles [CIENCIA DE LA INFORMACIÓN], Reliability, Information Science::Computing Methodologies::Software::Mobile Applications [INFORMATION SCIENCE], Mobile Applications, Asthma, Health-Related Quality of Life, enfermedades respiratorias::enfermedades bronquiales::asma [ENFERMEDADES], Quality of Life, EQ-5D-Y
Abstract: Calidad de vida relacionada con la salud; Asma; Aplicación para teléfonos inteligentes Qualitat de vida relacionada amb la salut; Asma; Aplicació per a telèfons intel·ligents Health-related quality of life; Asthma; Smartphone app Background Asthma impacts children’s physical, emotional, and psychosocial Health-Related Quality of Life (HRQL). The EQ-5D-Y is a generic econometric instrument developed to measure HRQL in children. Objective Evaluation of feasibility, validity, reliability, and responsiveness of EQ-5D-Y descriptive system and utility index to allow the assessment of HRQL in children with asthma, aged 8–11 years (self-response version) or under 8 years old (proxy-response version). Methods We used data from baseline to 10 months of follow-up of an observational, prospective study of children with persistent asthma recruited by pediatricians in Spain (2018–2020). HRQL instruments were administered through a smartphone application: ARCA app. The EQ-5D-Y is composed of a 5-dimension descriptive system, a utility index ranging from 1 to − 0.5392, and a general health visual analogue scale (EQ-VAS). The Pediatric Asthma Impact Scale (PROMIS-PAIS) includes 8 items, providing a raw score. Construct validity hypotheses were stated a priori, and evaluated following two approaches, multitrait–multimethod matrix and known groups’ comparisons. Reliability and responsiveness subsamples were defined by stability or change in EQ-VAS and the Asthma Control Questionnaire (ACQ), to estimate the intraclass correlation coefficient (ICC) and the magnitude of change over time. Results The EQ-5D-Y was completed at baseline for 119 children (81 self-responded and 38 through proxy response), with a mean age of 9.1 (1.7) years. Mean (SD) of the EQ-5D-Y utility index was 0.93 (0.11), with ceiling and floor effects of 60.3% and 0%, respectively. Multitrait–multimethod matrix confirmed the associations previously hypothesized for the EQ-5D-Y utility index [moderate with PROMIS-PAIS (0.38) and weak with ACQ (0.28)], and for the EQ-5D-Y dimension “problems doing usual activities” [moderate with the ACQ item (0.35) and weak with the PROMIS-PAIS item (0.17)]. Statistically significant differences were found in the EQ-5D-Y between groups defined by asthma control, reliever inhalers use, and second-hand smoke exposure, with mostly moderate effect sizes (0.45–0.75). The ICC of the EQ-5D-Y utility index in the stable subsamples was high (0.81 and 0.79); and responsiveness subsamples presented a moderate to large magnitude of change (0.68 and 0.78), though without statistical significance. Conclusions These results support the use of the EQ-5D-Y as a feasible, valid, and reliable instrument for evaluating HRQL in children with persistent asthma. Further studies are needed on the responsiveness of the EQ-5D-Y in this population. Financial support for this study was provided through grants by the Instituto de Salud Carlos III FEDER: Fondo Europeo de Desarrollo Regional (PI15/00449 and FI16/00071), University of Costa Rica (OAICE-85-2019), and Generalitat de Catalunya (2017 SGR 452). The funding agreements ensure the authors’ independence in designing the study, interpreting the data, and writing and publishing the report.
Published: 2022

7. Air Pollution and Surrounding Greenness in Relation to Ischemic Stroke: A Population-Based Cohort Study

Author: Uxue Lazcano, Sergio Olmos, Cathryn Tonne, Carles Milà, Carla Avellaneda-Gómez, Albert Ambros, Jaume Roquer, Rosa Maria Vivanco-Hidalgo, Antonia Valentin, [Avellaneda-Gómez C] Neurology Department, IMIM-Hospital del Mar, Barcelona, Spain. Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. Complex Hospitalari Moisès Broggi, Consorci Sanitari Integral, Barcelona, Spain. [Vivanco-Hidalgo RM] Neurology Department, IMIM-Hospital del Mar, Barcelona, Spain. Agència de Qualitat i Avaluació Sanitàries de Catalunya (AQUAS), Departament de Salut, Generalitat de Catalunya, Barcelona, Spain. [Olmos S, Valentin A, Milà C, Ambros A, Tonne C] ISGlobal, Barcelona, Spain. CIBER epidemiología y salud pública (CIBERESP), Madrid, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. [Lazcano U] Agència de Qualitat i Avaluació Sanitàries de Catalunya (AQUAS), Departament de Salut, Generalitat de Catalunya, Barcelona, Spain. [] ISGlobal, Barcelona, Spain. CIBER epidemiología y salud pública (CIBERESP), Madrid, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. [Roquer J] Neurology Department, IMIM-Hospital del Mar, Barcelona, Spain. Universitat Autònoma de Barcelona (UAB), Barcelona, Spain, and Departament de Salut
Subjects: Isquèmia cerebral, History, Adolescent, Polymers and Plastics, Population, Stroke incidence, Air pollution, enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos cerebrovasculares::accidente cerebrovascular [ENFERMEDADES], Lower risk, medicine.disease_cause, Industrial and Manufacturing Engineering, Cohort Studies, Black carbon, Air Pollution, Environmental Health Surveillance::Environmental Health::Environmental Monitoring::Air Monitoring::Air Pollution::Air Pollutants [HEALTH SURVEILLANCE], Environmental health, medicine, Humans, GE1-350, Business and International Management, Transient ischemic attack, education, Air quality index, Ischemic Stroke, General Environmental Science, Nitrogen dioxide, Green space, Air Pollutants, education.field_of_study, Proportional hazards model, business.industry, Incidence (epidemiology), vigilancia en salud ambiental::salud ambiental::monitorización del ambiente::monitorización del aire::contaminación del aire::contaminantes atmosféricos [VIGILANCIA SANITARIA], Environmental Exposure, Aire - Contaminació, Environmental sciences, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Stroke [DISEASES], Cohort, Residence, Particulate matter, business
Abstract: Background: Evidence for the association between environmental exposures and ischemic stroke (IS) is limited and inconsistent. We aimed to assess the relationship between long-term exposure to air pollutants, residential surrounding greenness, and incident IS, and to identify population subgroups particularly vulnerable to these exposures. Methods: We used data from administrative health registries of the public healthcare system in Catalonia, Spain to construct a cohort of individuals aged 18 years and older without a previous stroke diagnosis at 1 st January, 2016 (n=3 521 274). We collected data on sociodemographic characteristics and cerebrovascular risk factors, and derived exposure at the participant’s residence to ambient levels of fine particulate matter (PM 2.5 ), black carbon (BC), nitrogen dioxide (NO 2 ), and Normalized Difference Vegetation Index (NDVI) in 300m buffer as an indicator of greenness. The primary outcome was IS diagnosis at any point during the follow-up. We used Cox proportional hazards models to estimate associations between environmental exposures and incident IS and stratified analyses to investigate effect modification. Findings: Between 1 st January, 2016 and 31st December, 2017, 10 865 individuals were admitted to public hospitals with an IS diagnosis. Individuals with a high residential exposure to air pollution were at greater risk of IS: HR 1·04 (95% CI:0·99-1·10) per 5µg/m 3 of PM 2.5 ; HR 1·05 (95% CI:1·00-1·10) per 1µg/m 3 of BC; HR 1·04 (95% CI:1·03-1·06) per 10µg/m 3 of NO 2 . Conversely, those individuals with higher residential surrounding green space (NDVI), had lower risk of IS (HR 0·84; CI 95%:0·7-1·0). There was no evidence of effect modification by individual characteristics. Interpretation: Higher incidence of IS was observed in relation to long-term exposures to PM 2.5 , BC and NO 2 in a region that meets European health-based air quality standards. Residential surrounding greenness was associated with lower incidence of IS.Funding: Spanish Ministries of Health, Science and Innovation and Economy and Competitiveness. Funding: The study was funded by the Spanish Ministry of Economy through the Carlos III Health Institute (ISCIII-FIS-FEDER-ERDF, PI18/00056). This project was also funded in part by the following sources: INVICTUS PLUS. FEDER, RD16/0019/0002 and the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018- 000806-S). Carla Avellaneda-Gomez was funded by a Rio Hortega fellowship (CM18/00040) awarded by the Spanish Ministry of Science and Innovation. Cathryn Tonne is funded by a Ramon y Cajal fellowship (RYC-2015-17402) awarded by the Spanish Ministry of Economy and Competitiveness. Declaration of Interest: None to declare. Ethical Approval: We received approval from our local ethics committee (code 2018/7917/I).
Published: 2021
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8. Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air ® App

Author: Bédard, Annabelle, Antó, Josep, Fonseca, Joao, Arnavielhe, Sylvie, Bachert, Claus, Bedbrook, Anna, Bindslev-Jensen, Carsten, Bosnic-Anticevich, Sinthia, Cardona, Victoria, Cruz, Alvaro, Fokkens, Wytske, Garcia-Aymerich, Judith, Hellings, Peter, Ivancevich, Juan, Klimek, Ludger, Kuna, Piotr, Kvedariene, Violeta, Larenas-Linnemann, Désirée, Melen, Erik, Monti, Ricardo, Mösges, Ralf, Mullol, Joaquim, Papadopoulos, Nikos, Pham-Thi, Nhan, Samolinski, Boleslaw, V Tomazic, Peter, Toppila-Salmi, Sanna, Ventura, Maria Teresa, Yorgancioglu, Arzu, Bousquet, Jean, Pfaar, Oliver, Basagana, Xavier, Bosnic‐Anticevich, Sinthia, Pham‐Thi, Nhân, Hellings, PW, Aberer, W., Agache, I., Akdis, Ca, Akdis, M., Aliberti, MR, Almeida, R., Amat, F., Angles, R, Annesi‐Maesano, I, Ansotegui, IJ, Anto, JM, Arnavielle, S, Asayag, E, Asarnoj, A, Arshad, H, Avolio, F, Bacci, E, Baiardini, I, Barbara, C, Barbagallo, M., Baroni, I, Barreto, BA, Basagaña, X., Bateman, ED, Bedolla‐Barajas, M, Bewick, M., Beghé, B., Bel, EH, Bergmann, KC, Bennoor, KS, Benson, M, Bertorello, L, Białoszewski, AZ, Bieber, T., Bialek, S, Bindslev‐Jensen, Carsten, Bjermer, L., Blain, H., Blasi, F., Blua, A, Bochenska Marciniak, M, Bogus‐Buczynska, I, Boner, AL, Bonini, M., Bonini, S., Bosnic‐Anticevich, CS, Bosse, I., Bouchard, J., Boulet, LP, Bourret, R., Bousquet, Pj, Braido, F, Briedis, V, Brightling, CE, Brozek, J, Bucca, C, Buhl, R, Buonaiuto, R, Panaitescu, C, Burguete Cabañas, MT, Burte, E., Bush, A, Caballero‐Fonseca, F, Caillaud, D., Caimmi, D., Calderon, MA, Camargos, PAM, Camuzat, T., Canfora, G, Canonica, Gw, Carlsen, KH, Carreiro‐Martins, P, Carriazo, AM, Carr, W, Cartier, C., Casale, T., Castellano, G, Cecchi, L, Cepeda, AM, Chavannes, NH, Chen, Y., Chiron, R., Chivato, T, Chkhartishvili, E, Chuchalin, AG, Chung, KF, Ciaravolo, MM, Ciceran, A, Cingi, C, Ciprandi, G, Carvalho Coehlo, AC, Colas, L, Colgan, E, Coll, J, Conforti, D, Constantinidis, J, de Sousa, J Correia, Cortés‐Grimaldo, RM, Corti, F, 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J, Hernández, L, Hourihane, JO’B, Huerta‐Villalobos, YR, Humbert, M., Iaccarino, G., Illario, M, Ispayeva, Z, Ivancevich, JC, Jares, EJ, Jassem, E, Johnston, Sl, Joos, G, Jung, KS, Just, J., Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, AF, Karjalainen, J, Kardas, P, Keil, T, Keith, PK, Khaitov, M, Khaltaev, N, Kleine‐Tebbe, J, Kowalski, Ml, Kuitunen, M, Kull, I., Kupczyk, M, Krzych‐Fałta, E, Lacwik, P, Larenas‐Linnemann, Désirée, Laune, D., Lauri, D, Lavrut, J, Le, LTT, Lessa, M, Levato, G, Li, J., Lieberman, P, Lipiec, A, Lipworth, B, Lodrup Carlsen, KC, Louis, R, Lourenço, O, Luna‐Pech, JA, Magnan, A., Mahboub, B, Maier, D., Mair, A, Majer, I, Malva, J, Mandajieva, E, Manning, P, De Manuel Keenoy, E, Marshall, GD, Masjedi, MR, Maspero, JF, Mathieu‐Dupas, E, Matta Campos, JJ, Matos, AL, Maurer, M, Mavale‐Manuel, S, Mayora, O, Meco, C, Medina‐Avalos, MA, Melo‐Gomes, E, Meltzer, EO, Menditto, E., Miculinic, N, Mihaltan, F., Milenkovic, B, Moda, G, Mogica‐Martinez, MD, Mohammad, Y, 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S, Wallace, D, Wang, DY, Waserman, S., Werfel, T, Westman, M, Wickman, M., Williams, DM, Williams, S, Wilson, N, Wright, J, Wroczynski, P, Yakovliev, P, Yawn, BP, Yiallouros, PK, Yusuf, OM, Zar, HJ, Zhang, L., Zhong, N, Zernotti, ME, Zhanat, I, Zidarn, M, Zuberbier, T., Zubrinich, C, Zurkuhlen, A, Mercier, Jacques, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto = University of Porto, KYomed INNOV, Ghent University Hospital, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Odense University Hospital [Odense, Denmark], Woolcock Institute of Medical Research [Sydney], The University of Sydney, Vall d'Hebron University Hospital [Barcelona], ProAR - FMB, Federal University of Bahia School of Medicine, European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), University Hospitals Leuven [Leuven], Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], Division of Internal Medicine, Asthma and Allergy, Medical University of Łódź (MUL)-Barlicki University Hospital, Vilnius University [Vilnius], Clínica de Alergia- Asma y Pediatría, Hospital Medica Sur, Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Astrid Lindgren Children's Hospital, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP), Medical University of Warsaw - Poland, Department of Pulmonology, Manisa Celal Bayar University, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Department of Allergy and Clinical Immunology, Faculty of Medicine-Transylvania University, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Department Engineering Quimica (ICEMS), Aix Marseille Université (AMU), Istituto Nazionale di Fisica Nucleare, sezione di Bari (INFN, sezione di Bari), Istituto Nazionale di Fisica Nucleare (INFN), iQ4U consultants Ltd, Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton-School of Medicine, Department of Respiratory Medicine and Allergy, Department of Pathophysiology and Transplantation, Università degli Studi di Milano = University of Milan (UNIMI), Istituto di Geoscienze e Georisorse, Pavia, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II = Università degli studi di Napoli Federico II, CHU Montpellier, Laboratoire National Henri Becquerel (LNHB), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Département d'instrumentation Numérique (DIN (CEA-LIST)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique (LOBIP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Région Languedoc-Roussillon-Midi-Pyrénées, University of South Florida [Tampa] (USF), Chinese academy of sciences Sanya, Centres de Ressources et de Compétences de la Mucoviscidose [Montpellier] (CRCM [Montpellier]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-Service des Maladies Respiratoires, Laboratoire de Génie Informatique et d'Ingénierie de Production (LGI2P), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Department of Paediatrics, UCB Pharma, Colombes, CHU Strasbourg, Università degli Studi di Salerno = University of Salerno (UNISA), Hôpital Foch [Suresnes], Service de pneumologie [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Informatique, Image, Intelligence Artificielle (I3A), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-IMT - MINES ALES (IMT - MINES ALES), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Center for Allergy and Immunology Research [Tbilisi], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Center for Turbulence Research [Stanford] (CTR), Stanford University, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The Institute of Environmental Medicine [Stockholm] (IMM), Karolinska Institutet [Stockholm], Sysdiag-Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic (SysDiag ), BIO-RAD-Centre National de la Recherche Scientifique (CNRS), Équipe de Recherche en Textes, Informatique, Multilinguisme (ERTIM), Institut National des Langues et Civilisations Orientales (Inalco), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Biomax Informatics AG, 'Federico II' University of Naples Medical School, Pneumology Department, Marius Nasta Institute of Pneumology, Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Johns Hopkins University School of Medicine [Baltimore], CARSAT-LR, Montpellier, Dept. of Electronic Engineering, Chubu University, Institute for Solid State Physics, The University of Tokyo (UTokyo), Respiratory Medicine, Laboratoire de physique et chimie des nano-objets (LPCNO), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, University of Cyprus [Nicosia] (UCY), Son Pisa Primary Care Centre, IB-Salut Balearic Health Service, Department of Computer Science [Haifa], University of Haifa [Haifa], University of Edinburgh, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Réseau National de Surveillance Aérobiologique (RNSA), CIRCE, Ctr Res Energy Resources & Consumpt, Zaragoza 50018, Spain, University of Turku, Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), ASA (Advanced Solution Accelerator) (Data management : Développement Back-Office, hébergement…), 34830 Jacou, Consiglio nazionale delle ricerche, Instituto di fisiologia clinica, McMaster University [Hamilton, Ontario], Department of Molecular Medicine and Surgery, UMR CNRS 8179, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), University Hospital of Cologne [Cologne], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), ISGlobal, Barcelona, Spain, Universitat Pompeu Fabra (UPF), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, IMIM (Hospital del Mar Research Institute), Barcelona, Spain, CINTESIS, Center for Research in Health Technology and Information Systems, Faculdade de Medicina da Universidade do Porto, Porto, Portugal, Medida, Lda Porto, Porto, Portugal, KYomed INNOV, Montpellier, France, Upper Airways Research Laboratory, ENT Dept, Ghent University Hospital, Ghent, Belgium, MACVIA-France, Montpellier, France, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense Research Center for Anaphylaxis (ORCA), Odense, Denmark, Woolcock Institute of Medical Research, University of Sydney and Woolcock Emphysema Centre and Sydney Local Health District, Glebe, NSW, Australia, Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron & ARADyAL Research Network, Barcelona, Spain, ProAR – Nucleo de Excelencia em Asma, Federal University of Bahia, Brasil and WHO GARD Planning Group, Salvador, Brazil, Department of Otorhinolaryngology, Amsterdam University Medical Centres, AMC, Amsterdam, Netherlands, Euforea, Brussels, Belgium, Department of Otorhinolaryngology, University Hospitals Leuven, Leuven, Belgium, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, Servicio de Alergia e Immunologia, Clinica Santa Isabel, Buenos Aires, Argentina, Center for Rhinology and Allergology, Wiesbaden, Germany, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland, Department of Pathology, Faculty of Medicine, Institute of Biomedical Sciences, Vilnius University, Vilnius, Lithuania, Clinic of Chest diseases and Allergology, Faculty of Medicine, Institute of Clinical Medicine, Vilnius, Lithuania, Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico, Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Allergy and Clinical Immunology Unit, Department of Medical Sciences, University of Torino & Mauriziano Hospital, Torino, Italy, Institute of Medical Statistics, and Computational Biology, Medical Faculty, University of Cologne, Cologne, Germany, CRI-Clinical Research International-Ltd, Hamburg, Germany, Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic, University of Barcelona, Barcelona, Spain, Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Division of Infection, Immunity & Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, United Kingdom, Allergy Department, Pasteur Institute, Paris, France, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland, Department of General ORL, H&NS, Medical University of Graz, Graz, Austria, Skin and Allergy Hospital, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland, Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, Italy, Department of Pulmonary Diseases, Faculty of Medicine, Celal Bayar University, Manisa, Turkey, University Hospital, Montpellier, France, INSERM U 1168, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, Villejuif, France, UMR-S 1168, Université Versailles St-Quentin-en-Yvelines, Versailles, France, Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin Institute of Health, Berlin, Germany, Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Phillipps-Universität, Marburg, Germany, Universidade do Porto, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Pasteur [Paris], University of Milan, University of Naples Federico II-CNR, Rome, Italy and Department of Medicine, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Università degli Studi di Salerno (UNISA), CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, University of Helsinki, Service d'Allergologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), University of Cyprus [Nicosia], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bedard, A., Anto, J. M., Fonseca, J. A., Arnavielhe, S., Bachert, C., Bedbrook, A., Bindslev-Jensen, C., Bosnic-Anticevich, S., Cardona, V., Cruz, A. A., Fokkens, W. J., Garcia-Aymerich, J., Hellings, P. W., Ivancevich, J. C., Klimek, L., Kuna, P., Kvedariene, V., Larenas-Linnemann, D., Melen, E., Monti, R., Mosges, R., Mullol, J., Papadopoulos, N. G., Pham-Thi, N., Samolinski, B., Tomazic, P. V., Toppila-Salmi, S., Ventura, M. T., Yorgancioglu, A., Bousquet, J., Pfaar, O., Basagana, X., Aberer, W., Agache, I., Akdis, C. A., Akdis, M., Aliberti, M. R., Almeida, R., Amat, F., Angles, R., Annesi-Maesano, I., Ansotegui, I. J., Arnavielle, S., Asayag, E., Asarnoj, A., Arshad, H., Avolio, F., Bacci, E., Baiardini, I., Barbara, C., Barbagallo, M., Baroni, I., Barreto, B. A., Bateman, E. D., Bedolla-Barajas, M., Bewick, M., Beghe, B., Bel, E. H., Bergmann, K. C., Bennoor, K. S., Benson, M., Bertorello, L., Bialoszewski, A. Z., Bieber, T., Bialek, S., Bjermer, L., Blain, H., Blasi, F., Blua, A., Bochenska Marciniak, M., Bogus-Buczynska, I., Boner, A. L., Bonini, M., Bonini, S., Bosse, I., Bouchard, J., Boulet, L. P., Bourret, R., Bousquet, P. J., Braido, F., Briedis, V., Brightling, C. E., Brozek, J., Bucca, C., Buhl, R., Buonaiuto, R., Panaitescu, C., Burguete Cabanas, M. T., Burte, E., Bush, A., Caballero-Fonseca, F., Caillaud, D., Caimmi, D., Calderon, M. A., Camargos, P. A. M., Camuzat, T., Canfora, G., Canonica, G. W., Carlsen, K. H., Carreiro-Martins, P., Carriazo, A. M., Carr, W., Cartier, C., Casale, T., Castellano, G., Cecchi, L., Cepeda, A. M., Chavannes, N. H., Chen, Y., Chiron, R., Chivato, T., Chkhartishvili, E., Chuchalin, A. G., Chung, K. F., Ciaravolo, M. M., Ciceran, A., Cingi, C., Ciprandi, G., Carvalho Coehlo, A. C., Colas, L., Colgan, E., Coll, J., Conforti, D., Constantinidis, J., Correia de Sousa, J., Cortes-Grimaldo, R. M., Corti, F., Costa, E., Costa-Dominguez, M. C., Courbis, A. L., Cox, L., Crescenzo, M., Custovic, A., Czarlewski, W., Dahlen, S. E., D'Amato, G., Dario, C., da Silva, J., Dauvilliers, Y., Darsow, U., De Blay, F., De Carlo, G., Dedeu, T., de Fatima Emerson, M., De Feo, G., De Vries, G., De Martino, B., Motta Rubini, N. P., Deleanu, D., Denburg, J. A., Devillier, P., Di Capua Ercolano, S., Di Carluccio, N., Didier, A., Dokic, D., Dominguez-Silva, M. G., Douagui, H., Dray, G., Dubakiene, R., Durham, S. R., Du Toit, G., Dykewicz, M. S., El-Gamal, Y., Eklund, P., Eller, E., Emuzyte, R., Farrell, J., Farsi, A., Ferreira de Mello, J., Ferrero, J., Fink-Wagner, A., Fiocchi, A., Fontaine, J. F., Forti, S., Fuentes-Perez, J. M., Galvez-Romero, J. L., Gamkrelidze, A., Garcia-Cobas, C. Y., Garcia-Cruz, M. H., Gemicioglu, B., Genova, S., Christoff, G., Gereda, J. E., Gerth van Wijk, R., Gomez, R. M., Gomez-Vera, J., Gonzalez Diaz, S., Gotua, M., Grisle, I., Guidacci, M., Guldemond, N. A., Gutter, Z., Guzman, M. A., Haahtela, T., Hajjam, J., Hernandez, L., Hourihane, J. O. '. B., Huerta-Villalobos, Y. R., Humbert, M., Iaccarino, G., Illario, M., Ispayeva, Z., Jares, E. J., Jassem, E., Johnston, S. L., Joos, G., Jung, K. S., Just, J., Jutel, M., Kaidashev, I., Kalayci, O., Kalyoncu, A. F., Karjalainen, J., Kardas, P., Keil, T., Keith, P. K., Khaitov, M., Khaltaev, N., Kleine-Tebbe, J., Kowalski, M. L., Kuitunen, M., Kull, I., Kupczyk, M., Krzych-Falta, E., Lacwik, P., Laune, D., Lauri, D., Lavrut, J., Le, L. T. T., Lessa, M., Levato, G., Li, J., Lieberman, P., Lipiec, A., Lipworth, B., Lodrup Carlsen, K. C., Louis, R., Lourenco, O., Luna-Pech, J. A., Magnan, A., Mahboub, B., Maier, D., Mair, A., Majer, I., Malva, J., Mandajieva, E., Manning, P., De Manuel Keenoy, E., Marshall, G. D., Masjedi, M. R., Maspero, J. F., Mathieu-Dupas, E., Matta Campos, J. J., Matos, A. L., Maurer, M., Mavale-Manuel, S., Mayora, O., Meco, C., Medina-Avalos, M. A., Melo-Gomes, E., Meltzer, E. O., Menditto, E., Mercier, J., Miculinic, N., Mihaltan, F., Milenkovic, B., Moda, G., Mogica-Martinez, M. D., Mohammad, Y., Momas, I., Montefort, S., Mora Bogado, D., Morais-Almeida, M., Morato-Castro, F. F., Mota-Pinto, A., Moura Santo, P., Munter, L., Muraro, A., Murray, R., Naclerio, R., Nadif, R., Nalin, M., Napoli, L., Namazova-Baranova, L., Neffen, H., Niedeberger, V., Nekam, K., Neou, A., Nieto, A., Nogueira-Silva, L., Nogues, M., Novellino, E., Nyembue, T. D., O'Hehir, R. E., Odzhakova, C., Ohta, K., Okamoto, Y., Okubo, K., Onorato, G. L., Ortega Cisneros, M., Ouedraogo, S., Pali-Scholl, I., Palkonen, S., Panzner, P., Park, H. S., Papi, A., Passalacqua, G., Paulino, E., Pawankar, R., Pedersen, S., Pepin, J. L., Pereira, A. M., Persico, M., Phillips, J., Picard, R., Pigearias, B., Pin, I., Pitsios, C., Plavec, D., Pohl, W., Popov, T. A., Portejoie, F., Potter, P., Pozzi, A. C., Price, D., Prokopakis, E. P., Puy, R., Pugin, B., Pulido Ross, R. E., Przemecka, M., Rabe, K. F., Raciborski, F., Rajabian-Soderlund, R., Reitsma, S., Ribeirinho, I., Rimmer, J., Rivero-Yeverino, D., Rizzo, J. A., Rizzo, M. C., Robalo-Cordeiro, C., Rodenas, F., Rodo, X., Rodriguez Gonzalez, M., Rodriguez-Manas, L., Rolland, C., Rodrigues Valle, S., Roman Rodriguez, M., Romano, A., Rodriguez-Zagal, E., Rolla, G., Roller-Wirnsberger, R. E., Romano, M., Rosado-Pinto, J., Rosario, N., Rottem, M., Ryan, D., Sagara, H., Salimaki, J., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G. K., Schunemann, H. J., Scichilone, N., Schmid-Grendelmeier, P., Sarquis Serpa, F., Shamai, S., Sheikh, A., Sierra, M., Simons, F. E. R., Siroux, V., Sisul, J. C., Skrindo, I., Sole, D., Somekh, D., Sondermann, M., Sooronbaev, T., Sova, M., Sorensen, M., Sorlini, M., Spranger, O., Stellato, C., Stelmach, R., Stukas, R., Sunyer, J., Strozek, J., Szylling, A., Tebyrica, J. N., Thibaudon, M., To, T., Todo-Bom, A., Trama, U., Triggiani, M., Suppli Ulrik, C., Urrutia-Pereira, M., Valenta, R., Valero, A., Valiulis, A., Valovirta, E., van Eerd, M., van Ganse, E., van Hage, M., Vandenplas, O., Vezzani, G., Vasankari, T., Vatrella, A., Verissimo, M. T., Viart, F., Viegi, G., Vicheva, D., Vontetsianos, T., Wagenmann, M., Walker, S., Wallace, D., Wang, D. Y., Waserman, S., Werfel, T., Westman, M., Wickman, M., Williams, D. M., Williams, S., Wilson, N., Wright, J., Wroczynski, P., Yakovliev, P., Yawn, B. P., Yiallouros, P. K., Yusuf, O. M., Zar, H. J., Zhang, L., Zhong, N., Zernotti, M. E., Zhanat, I., Zidarn, M., Zuberbier, T., Zubrinich, C., Zurkuhlen, A., HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Universidade do Porto [Porto], Kyomed, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Universitat Pompeu Fabra [Barcelona], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service des Maladies Respiratoires, Hôpital Arnaud de Villeneuve-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Dermatology [Graz, Austria], Medical University Graz, University of Zürich [Zürich] (UZH), National Institute for Nuclear Physics (INFN), Institut Jean Lamour (IJL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), University of South Florida (USF), University of Salerno (UNISA), CHU Toulouse [Toulouse]-Hôpital Larrey, Institut Mines-Télécom [Paris] (IMT), Center for Turbulence Research (CTR), Stanford University [Stanford], Service d'allergologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), The University of Tokyo, Sondra, CentraleSupélec, Université Paris-Saclay (SONDRA), ONERA-CentraleSupélec-Université Paris-Saclay, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche sur les Systèmes Atomiques et Moléculaires Complexes (IRSAMC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), RNSA, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ear, Nose and Throat, AII - Inflammatory diseases, Pulmonology, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bedard A., Anto J.M., Fonseca J.A., Arnavielhe S., Bachert C., Bedbrook A., Bindslev-Jensen C., Bosnic-Anticevich S., Cardona V., Cruz A.A., Fokkens W.J., Garcia-Aymerich J., Hellings P.W., Ivancevich J.C., Klimek L., Kuna P., Kvedariene V., Larenas-Linnemann D., Melen E., Monti R., Mosges R., Mullol J., Papadopoulos N.G., Pham-Thi N., Samolinski B., Tomazic P.V., Toppila-Salmi S., Ventura M.T., Yorgancioglu A., Bousquet J., Pfaar O., Basagana X., Aberer W., Agache I., Akdis C.A., Akdis M., Aliberti M.R., Almeida R., Amat F., Angles R., Annesi-Maesano I., Ansotegui I.J., Arnavielle S., Asayag E., Asarnoj A., Arshad H., Avolio F., Bacci E., Baiardini I., Barbara C., Barbagallo M., Baroni I., Barreto B.A., Bateman E.D., Bedolla-Barajas M., Bewick M., Beghe B., Bel E.H., Bergmann K.C., Bennoor K.S., Benson M., Bertorello L., Bialoszewski A.Z., Bieber T., Bialek S., Bjermer L., Blain H., Blasi F., Blua A., Bochenska Marciniak M., Bogus-Buczynska I., Boner A.L., Bonini M., Bonini S., Bosse I., Bouchard J., Boulet L.P., Bourret R., Bousquet P.J., Braido F., Briedis V., Brightling C.E., Brozek J., Bucca C., Buhl R., Buonaiuto R., Panaitescu C., Burguete Cabanas M.T., Burte E., Bush A., Caballero-Fonseca F., Caillaud D., Caimmi D., Calderon M.A., Camargos P.A.M., Camuzat T., Canfora G., Canonica G.W., Carlsen K.H., Carreiro-Martins P., Carriazo A.M., Carr W., Cartier C., Casale T., Castellano G., Cecchi L., Cepeda A.M., Chavannes N.H., Chen Y., Chiron R., Chivato T., Chkhartishvili E., Chuchalin A.G., Chung K.F., Ciaravolo M.M., Ciceran A., Cingi C., Ciprandi G., Carvalho Coehlo A.C., Colas L., Colgan E., Coll J., Conforti D., Constantinidis J., Correia de Sousa J., Cortes-Grimaldo R.M., Corti F., Costa E., Costa-Dominguez M.C., Courbis A.L., Cox L., Crescenzo M., Custovic A., Czarlewski W., Dahlen S.E., D'Amato G., Dario C., da Silva J., Dauvilliers Y., Darsow U., De Blay F., De Carlo G., Dedeu T., de Fatima Emerson M., De Feo G., De Vries G., De Martino B., Motta Rubini N.P., Deleanu D., Denburg J.A., Devillier P., Di Capua Ercolano S., Di Carluccio N., Didier A., Dokic D., Dominguez-Silva M.G., Douagui H., Dray G., Dubakiene R., Durham S.R., Du Toit G., Dykewicz M.S., El-Gamal Y., Eklund P., Eller E., Emuzyte R., Farrell J., Farsi A., Ferreira de Mello J., Ferrero J., Fink-Wagner A., Fiocchi A., Fontaine J.F., Forti S., Fuentes-Perez J.M., Galvez-Romero J.L., Gamkrelidze A., Garcia-Cobas C.Y., Garcia-Cruz M.H., Gemicioglu B., Genova S., Christoff G., Gereda J.E., Gerth van Wijk R., Gomez R.M., Gomez-Vera J., Gonzalez Diaz S., Gotua M., Grisle I., Guidacci M., Guldemond N.A., Gutter Z., Guzman M.A., Haahtela T., Hajjam J., Hernandez L., Hourihane J.O.'.B., Huerta-Villalobos Y.R., Humbert M., Iaccarino G., Illario M., Ispayeva Z., Jares E.J., Jassem E., Johnston S.L., Joos G., Jung K.S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu A.F., Karjalainen J., Kardas P., Keil T., Keith P.K., Khaitov M., Khaltaev N., Kleine-Tebbe J., Kowalski M.L., Kuitunen M., Kull I., Kupczyk M., Krzych-Falta E., Lacwik P., Laune D., Lauri D., Lavrut J., Le L.T.T., Lessa M., Levato G., Li J., Lieberman P., Lipiec A., Lipworth B., Lodrup Carlsen K.C., Louis R., Lourenco O., Luna-Pech J.A., Magnan A., Mahboub B., Maier D., Mair A., Majer I., Malva J., Mandajieva E., Manning P., De Manuel Keenoy E., Marshall G.D., Masjedi M.R., Maspero J.F., Mathieu-Dupas E., Matta Campos J.J., Matos A.L., Maurer M., Mavale-Manuel S., Mayora O., Meco C., Medina-Avalos M.A., Melo-Gomes E., Meltzer E.O., Menditto E., Mercier J., Miculinic N., Mihaltan F., Milenkovic B., Moda G., Mogica-Martinez M.D., Mohammad Y., Momas I., Montefort S., Mora Bogado D., Morais-Almeida M., Morato-Castro F.F., Mota-Pinto A., Moura Santo P., Munter L., Muraro A., Murray R., Naclerio R., Nadif R., Nalin M., Napoli L., Namazova-Baranova L., Neffen H., Niedeberger V., Nekam K., Neou A., Nieto A., Nogueira-Silva L., Nogues M., Novellino E., Nyembue T.D., O'Hehir R.E., Odzhakova C., Ohta K., Okamoto Y., Okubo K., Onorato G.L., Ortega Cisneros M., Ouedraogo S., Pali-Scholl I., Palkonen S., Panzner P., Park H.S., Papi A., Passalacqua G., Paulino E., Pawankar R., Pedersen S., Pepin J.L., Pereira A.M., Persico M., Phillips J., Picard R., Pigearias B., Pin I., Pitsios C., Plavec D., Pohl W., Popov T.A., Portejoie F., Potter P., Pozzi A.C., Price D., Prokopakis E.P., Puy R., Pugin B., Pulido Ross R.E., Przemecka M., Rabe K.F., Raciborski F., Rajabian-Soderlund R., Reitsma S., Ribeirinho I., Rimmer J., Rivero-Yeverino D., Rizzo J.A., Rizzo M.C., Robalo-Cordeiro C., Rodenas F., Rodo X., Rodriguez Gonzalez M., Rodriguez-Manas L., Rolland C., Rodrigues Valle S., Roman Rodriguez M., Romano A., Rodriguez-Zagal E., Rolla G., Roller-Wirnsberger R.E., Romano M., Rosado-Pinto J., Rosario N., Rottem M., Ryan D., Sagara H., Salimaki J., Sanchez-Borges M., Sastre-Dominguez J., Scadding G.K., Schunemann H.J., Scichilone N., Schmid-Grendelmeier P., Sarquis Serpa F., Shamai S., Sheikh A., Sierra M., Simons F.E.R., Siroux V., Sisul J.C., Skrindo I., Sole D., Somekh D., Sondermann M., Sooronbaev T., Sova M., Sorensen M., Sorlini M., Spranger O., Stellato C., Stelmach R., Stukas R., Sunyer J., Strozek J., Szylling A., Tebyrica J.N., Thibaudon M., To T., Todo-Bom A., Trama U., Triggiani M., Suppli Ulrik C., Urrutia-Pereira M., Valenta R., Valero A., Valiulis A., Valovirta E., van Eerd M., van Ganse E., van Hage M., Vandenplas O., Vezzani G., Vasankari T., Vatrella A., Verissimo M.T., Viart F., Viegi G., Vicheva D., Vontetsianos T., Wagenmann M., Walker S., Wallace D., Wang D.Y., Waserman S., Werfel T., Westman M., Wickman M., Williams D.M., Williams S., Wilson N., Wright J., Wroczynski P., Yakovliev P., Yawn B.P., Yiallouros P.K., Yusuf O.M., Zar H.J., Zhang L., Zhong N., Zernotti M.E., Zhanat I., Zidarn M., Zuberbier T., Zubrinich C., and Zurkuhlen A.
Subjects: 0301 basic medicine, SYMPTOMS, Smart phone, Allergy, Escala visual analógica, INNOVATION, [SDV]Life Sciences [q-bio], Medical and Health Sciences, Correlation, visual analogue scale, 0302 clinical medicine, Quality of life, Visual analogue scale, QUALITY-OF-LIFE, Màscares, Immunology and Allergy, score, Nose, Rinitis, Rhinitis, PRODUCTIVITY COSTS, asthma, MASK, rhinitis, Score, Explained variation, Response Variability, Mobile Applications, ALLERGIC RHINITIS, rhiniti, medicine.anatomical_structure, TRIALS, Rinite, 1107 Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Smartphone, medicine.medical_specialty, MASK study group, Immunology, MACVIA-ARIA, 03 medical and health sciences, Allergic, medicine, Humans, TECHNOLOGY, IMMUNOTHERAPY, Asma, Asthma, business.industry, Rhinitis, Allergic, medicine.disease, RHINOCONJUNCTIVITIS, 030104 developmental biology, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, Physical therapy, Clinical Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. Methods: All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. Results: A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. Conclusions: VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies. © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Published: 2020
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9. Exploring Renal Changes after Bariatric Surgery in Patients with Severe Obesity

Author: Anna Oliveras, Susana Vázquez, María José Soler, Isabel Galceran, Xavier Duran, Albert Goday, David Benaiges, Marta Crespo, Julio Pascual, Marta Riera, Institut Català de la Salut, [Oliveras A] Nephrology Department, Hospital Universitari del Mar, Barcelona, Spain. IMIM, Hospital del Mar Medical Research Institute, Barcelona, Spain. Department of Experimental and Health Sciences, Area of Medicine, Universitat Pompeu Fabra, Barcelona, Spain. Red de Investigación Renal (REDINREN), Instituto Carlos III-FEDER, Madrid, Spain. [Vázquez S, Galceran I] Nephrology Department, Hospital Universitari del Mar, Barcelona, Spain. IMIM, Hospital del Mar Medical Research Institute, Barcelona, Spain. [Soler MJ] Grup de Recerca en Nefrologia i Trasplantament Renal, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Duran X] IMIM, Hospital del Mar Medical Research Institute, Barcelona, Spain. [Goday A] IMIM, Hospital del Mar Medical Research Institute, Barcelona, Spain. Endocrinology Department, Hospital Universitari del Mar, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Bariatric surgery, Glucose metabolism, Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [DISEASES], Hyperfiltration, diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Otros calificadores::Otros calificadores::/cirugía [Otros calificadores], General Medicine, Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Other subheadings::Other subheadings::/surgery [Other subheadings], intervenciones quirúrgicas::cirugía bariátrica [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Obesitat - Cirurgia, Avaluació de resultats (Assistència sanitària), enfermedades nutricionales y metabólicas::trastornos nutricionales::hipernutrición::obesidad [ENFERMEDADES], Medicine, Albuminuria, Surgical Procedures, Operative::Bariatric Surgery [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Renin-angiotensin axis, bariatric surgery, hyperfiltration, albuminuria, renin-angiotensin axis, aldosterone, glucose metabolism, Aldosterone
Abstract: Albuminuria; Aldosterone; Glucose metabolism Albuminuria; Aldosterona; Metabolismo de la glucosa Albuminúria; Aldosterona; Metabolisme de la glucosa Obesity-related hyperfiltration leads to an increased glomerular filtration rate (GFR) and hyperalbuminuria. These changes are reversible after bariatric surgery (BS). We aimed to explore obesity-related renal changes post-BS and to seek potential mechanisms. Sixty-two individuals with severe obesity were prospectively examined before and 3, 6 and 12 months post-BS. Anthropometric and laboratory data, 24 h-blood pressure, renin-angiotensin-aldosterone system (RAS) components, adipokines and inflammatory markers were determined. Both estimated GFR (eGFR) and albuminuria decreased from the baseline at all follow-up times (p-for-trend
Published: 2022
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10. Regions of homozygosity confer a worse prognostic impact in myelodysplastic syndrome with normal karyotype

Author: Mar Mallo, Heinz Tuechler, Leonor Arenillas, Sophie Raynaud, Thomas Cluzeau, Lee‐Yung Shih, Chiang Tung‐Liang, Christina Ganster, Katayoon Shirneshan, Detlef Haase, Martí Mascaró, Laura Palomo, José Cervera, Esperanza Such, Nicola Trim, Sally Jeffries, Emma Ridgway, Giovanni Marconi, Giovanni Martinelli, Francesc Solé, Institut Català de la Salut, [Mallo M] MDS Research Group, Institut de Recerca Contra la Leucèmia Josep Carreras (IJC), ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. Microarrays Unit, Institut de Recerca Contra la Leucèmia Josep Carreras (IJC), ICO-Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. [Tuechler H] Boltzmann Institute for Leukaemia Research and Hematology, Vienna, Austria. [Arenillas L] Hematological Cytology Laboratory, Pathology Department, Hospital del Mar, GRETNHE, IMIM (Hospital del Mar Research Institute), Barcelona, Spain. [Raynaud S, Cluzeau T] Hematology Department, Cote d’Azur University, CHU of Nice, Nice, France. [Shih LY] Division of Hematology, Chang Gung Memorial Hospital-Linkuo, Chang Gung University, Taoyuan City, Taiwan. [Palomo L] Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Síndromes mielodisplàsiques - Aspectes genètics, Síndromes mielodisplàsiques - Prognosi, Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myelodysplastic Syndromes [DISEASES], enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::síndromes mielodisplásicos [ENFERMEDADES], General Medicine, Diagnosis::Prognosis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], diagnóstico::pronóstico [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]
Abstract: Chromosome; Cytogenetics; Myelodysplastic syndromes Cromosoma; Citogenética; Síndromes mielodisplásicos Cromosoma; Citogenètica; Síndromes mielodisplàsics Half of the myelodysplastic syndromes (MDS) have normal karyotype by conventional banding analysis. The percentage of true normal karyotype cases can be reduced by 20–30% with the complementary application of genomic microarrays. We here present a multicenter collaborative study of 163 MDS cases with a normal karyotype (≥10 metaphases) at diagnosis. All cases were analyzed with the ThermoFisher® microarray (either SNP 6.0 or CytoScan HD) for the identification of both copy number alteration(CNA) and regions of homozygosity (ROH). Our series supports that 25 Mb cut-off as having the most prognostic impact, even after adjustment by IPSS-R. This study highlights the importance of microarrays in MDS patients, to detect CNAs and especially to detect acquired ROH which has demonstrated a high prognostic impact. 2017 SGR288 (GRC) and CERCA Programme/Generalitat de Catalunya. Fundació Internacional Josep Carreras; Italy Ministry of Health.
Published: 2023
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11. Rates and Predictors of Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections According to Different Management Strategies: A Multinational Cohort Study—The ARTHR-IS Study Group

Author: Reinaldo, Espíndola, Venanzio, Vella, Natividad, Benito, Isabel, Mur, Sara, Tedeschi, Eleonora, Zamparini, Johannes G E, Hendriks, Luisa, Sorlí, Oscar, Murillo, Laura, Soldevila, Mathew, Scarborough, Claire, Scarborough, Jan, Kluytmans, Mateo Carlo, Ferrari, Mathias W, Pletz, Iain, Mcnamara, Rosa, Escudero-Sanchez, Cedric, Arvieux, Cecile, Batailler, Frédéric-Antoine, Dauchy, Wai-Yan, Liu, Jaime, Lora-Tamayo, Julia, Praena, Andrew, Ustianowski, Elisa, Cinconze, Michele, Pellegrini, Fabio, Bagnoli, Jesús, Rodríguez-Baño, Maria Dolores, Del Toro, Gabriella, Lindergard, Hospital Universitario Virgen Macarena [Séville], GlaxoSmithKline [Siena, Italy] (GSK), Hospital de la Santa Creu i Sant Pau, University of Bologna/Università di Bologna, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Department of Orthopaedic Surgery and Trauma, Maxima MC, parent, IMIM-Hospital del Mar, Generalitat de Catalunya, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), John Radcliffe Hospital [Oxford University Hospital], Amphia Ziekenhuis = Amphia Hospital [Breda, The Netherlands] (AZ=AH), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Jena University Hospital [Jena], Norfolk and Norwich University Hospital, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406 ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Catharina Hospital, Hospital Universitario HM Sanchinarro [Madrid, Spain], Hospital Universitario Virgen del Rocío [Sevilla], North Manchester General Hospital, This work was supported by the Innovative Medicines Initiative Joint Undertaking (grant agreement No. 115523), COMBACTE-NET consortium (European Union FP7/2007–2013 and GlaxoSmithKline Biologicals SA, as EFPIA partner). European Development Regional Fund ‘‘A way to achieve Europe’’, Operative Program Intelligence Growth 2014-2020. The study sponsor is also funding the journal’s Rapid Service Fee., European Project: 115523,EC:FP7:SP1-JTI,IMI-JU-06-2012,COMBACTE(2013), European Commission, GlaxoSmithKline, European Federation of Pharmaceutical Industries and Associations, Red Española de Investigación en Patología Infecciosa, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Espíndola, Reinaldo, Vella, Venanzio, Benito, Natividad, Mur, Isabel, Tedeschi, Sara, Zamparini, Eleonora, Hendriks, Johannes G E, Sorlí, Luisa, Murillo, Oscar, Soldevila, Laura, Scarborough, Mathew, Scarborough, Claire, Kluytmans, Jan, Ferrari, Mateo Carlo, Pletz, Mathias W, Mcnamara, Iain, Escudero-Sanchez, Rosa, Arvieux, Cedric, Batailler, Cecile, Dauchy, Frédéric-Antoine, Liu, Wai-Yan, Lora-Tamayo, Jaime, Praena, Julia, Ustianowski, Andrew, Cinconze, Elisa, Pellegrini, Michele, Bagnoli, Fabio, Rodríguez-Baño, Jesú, and Del Toro, Maria Dolores
Subjects: STAPHYLOCOCCUSAUREUS, Microbiology (medical), Staphylococcus aureus, Prosthetic joint infection, Infectious Diseases, Functional failure, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clinical failure, Outcome
Abstract: [Introduction] Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome., [Methods] A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016. The outcome variable was TF, including related mortality, clinical failure and functional loss both after the initial surgical procedure and after all procedures at 18 months. Predictors of TF were identified by logistic regression. Landmark analysis was used to avoid immortal time bias with rifampicin when debridement, antibiotics and implant retention (DAIR) was performed., [Results] One hundred twenty cases of SA-PJI were included. TF rates after the first and all surgical procedures performed were 32.8% and 24.2%, respectively. After all procedures, functional loss was 6.0% for DAIR and 17.2% for prosthesis removal. Variables independently associated with TF for the first procedure were Charlson ≥ 2, haemoglobin 30 kg/m2 and delay of DAIR, while rifampicin use was protective. For all procedures, the variables associated with TF were haemoglobin, [Conclusions] TF remains common in SA-PJI. Functional loss accounted for a substantial proportion of treatment failures, particularly after prosthesis removal. Use of rifampicin after DAIR was associated with a protective effect. Among the risk factors identified, anaemia and obesity have not frequently been reported in previous studies., [Trial registration] This study is registered at clinicaltrials.gov, registration no. NCT03826108., This work was supported by the Innovative Medicines Initiative Joint Undertaking (grant agreement No. 115523), COMBACTE-NET consortium (European Union FP7/2007–2013 and GlaxoSmithKline Biologicals SA, as EFPIA partner). R.E, L.S, O. M, R. E-S, J. L–T, J. P, J. R-B and MD. del T are members of the Spanish Network for Research in Infectious Diseases (REIPI), supported by Plan Nacional de I + D + i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001; 0002; 0005; 0009; 0011; 0015), co‐ financed by European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligence Growth 2014‐2020.
Published: 2022
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12. Antitumor activity of the PI3K δ-sparing inhibitor MEN1611 in PIK3CA mutated, trastuzumab-resistant HER2 + breast cancer

Author: Alessio Fiascarelli, Giuseppe Merlino, Stefania Capano, Simone Talucci, Diego Bisignano, Alessandro Bressan, Daniela Bellarosa, Corrado Carrisi, Alessandro Paoli, Mario Bigioni, Patrizia Tunici, Clelia Irrissuto, Massimiliano Salerno, Joaquin Arribas, Elisa de Stanchina, Maurizio Scaltriti, Monica Binaschi, Institut Català de la Salut, [Fiascarelli A, Merlino G, Capano S, Talucci S, Bisignano D, Bressan A] Menarini Group, Preclinical and Translational Sciences, Menarini Ricerche SpA, Pomezia, Rome, Italy. [Arribas J] Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Preclinical and Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer, Monforte de Lemos, Madrid, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Oncology, acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas [COMPUESTOS QUÍMICOS Y DROGAS], Otros calificadores::/uso terapéutico [Otros calificadores], Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Mama - Càncer - Tractament, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Other subheadings::/therapeutic use [Other subheadings], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors [CHEMICALS AND DRUGS], Proteïnes quinases - Inhibidors - Ús terapèutic
Abstract: Purpose Dysregulation of the PI3K pathway is one of the most common events in breast cancer. Here we investigate the activity of the PI3K inhibitor MEN1611 at both molecular and phenotypic levels by dissecting and comparing its profile and efficacy in HER2 + breast cancer models with other PI3K inhibitors. Methods Models with different genetic backgrounds were used to investigate the pharmacological profile of MEN1611 against other PI3K inhibitors. In vitro studies evaluated cell viability, PI3K signaling, and cell death upon treatment with MEN1611. In vivo efficacy of the compound was investigated in cell line- and patient-derived xenografts models. Results Consistent with its biochemical selectivity, MEN1611 demonstrated lower cytotoxic activity in a p110δ-driven cellular model when compared to taselisib, and higher cytotoxic activity in the p110β-driven cellular model when compared to alpelisib. Moreover, MEN1611 selectively decreased the p110α protein levels in PIK3CA mutated breast cancer cells in a concentration- and proteasome-dependent manner. In vivo, MEN1611 monotherapy showed significant and durable antitumor activity in several trastuzumab-resistant PIK3CA-mutant HER2 + PDX models. The combination of trastuzumab and MEN1611 significantly improved the efficacy compared to single agent treatment. Conclusions The profile of MEN1611 and its antitumoral activity suggest an improved profile as compared to pan-inhibitors, which are limited by a less than ideal safety profile, and isoform selective molecules, which may potentially promote development of resistance mechanisms. The compelling antitumor activity in combination with trastuzumab in HER2 + trastuzumab-resistant, PIK3CA mutated breast cancer models is at the basis of the ongoing B-Precise clinical trial (NCT03767335).
Published: 2023

13. Targeting HER2-AXL heterodimerization to overcome resistance to HER2 blockade in breast cancer

Author: Anna Adam-Artigues, Enrique J. Arenas, Alex Martínez-Sabadell, Fara Brasó-Maristany, Raimundo Cervera, Eduardo Tormo, Cristina Hernando, María Teresa Martínez, Juan Carbonell-Asins, Soraya Simón, Jesús Poveda, Santiago Moragón, Sandra Zazo, Débora Martínez, Ana Rovira, Octavio Burgués, Federico Rojo, Joan Albanell, Begoña Bermejo, Ana Lluch, Aleix Prat, Joaquín Arribas, Pilar Eroles, Juan Miguel Cejalvo, Institut Català de la Salut, [Adam-Artigues A, Cervera R] INCLIVA Biomedical Research Institute, Valencia, Spain. [Arenas EJ] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Center for Biomedical Network Research on Cancer (CIBERONC), Madrid, Spain. [Martínez-Sabadell A] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Brasó-Maristany F] August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain. Department of Medical Oncology, Hospital Clinic de Barcelona, Barcelona, Spain. [Tormo E] INCLIVA Biomedical Research Institute, Valencia, Spain. Center for Biomedical Network Research on Cancer (CIBERONC), Madrid, Spain. [Arribas J] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Center for Biomedical Network Research on Cancer (CIBERONC), Madrid, Spain. Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos [FENÓMENOS Y PROCESOS], neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasm [PHENOMENA AND PROCESSES], Multidisciplinary, Receptor, ErbB-2, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Breast Neoplasms, Trastuzumab, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Càncer de mama, Càncer--Tractament, Phosphatidylinositol 3-Kinases, Breast cancer, Drug Resistance, Neoplasm, Cell Line, Tumor, Drug resistance, Mama - Càncer - Tractament, Mama--Càncer, Humans, Female, Tumors, Resistència als medicaments
Abstract: Breast cancer; Heterodimerization Cáncer de mama; Heterodimerización Càncer de mama; Heterodimerització Anti-HER2 therapies have markedly improved prognosis of HER2-positive breast cancer. However, different mechanisms play a role in treatment resistance. Here, we identified AXL overexpression as an essential mechanism of trastuzumab resistance. AXL orchestrates epithelial-to-mesenchymal transition and heterodimerizes with HER2, leading to activation of PI3K/AKT and MAPK pathways in a ligand-independent manner. Genetic depletion and pharmacological inhibition of AXL restored trastuzumab response in vitro and in vivo. AXL inhibitor plus trastuzumab achieved complete regression in trastuzumab-resistant patient-derived xenograft models. Moreover, AXL expression in HER2-positive primary tumors was able to predict prognosis. Data from the PAMELA trial showed a change in AXL expression during neoadjuvant dual HER2 blockade, supporting its role in resistance. Therefore, our study highlights the importance of targeting AXL in combination with anti-HER2 drugs across HER2-amplified breast cancer patients with high AXL expression. Furthermore, it unveils the potential value of AXL as a druggable prognostic biomarker in HER2-positive breast cancer. A.A.-A., E.J.A., and F.B.-M. were supported by Asociación Española contra el Cáncer AECC (PRDVA18013LLUC to A.A.-A., POSTD211413AREN to E.J.A., and AECC_Postdoctoral17-1062 to F.B.-M.). A.M.-S. was funded by the Spanish Government (PFIS FI20/00188). J.Ar. is supported by Breast Cancer Research Foundation (BCRF-20-08), Instituto de Salud Carlos III Project reference number AC15/00062, and the EC under the framework of the ERA-NET TRANSCAN-2 initiative cofinanced by FEDER, Instituto de Salud Carlos III (CB16/12/00449 and PI19/01181), and Asociación Española Contra el Cáncer (AECC). A.P. was supported by Instituto de Salud Carlos III—PI19/01846, Breast Cancer Now—2018NOVPCC1294. P.E. and A.L. were funded by Instituto de Salud Carlos III and cofinanced by FEDER (PI18/01219 to P.E. and CB16/12/00481 to A.L.). J.M.C. was funded by Sociedad Española de Oncología Médica (Rio Hortega-SEOM) and Compromiso ADAMED.
Published: 2023

14. Human metastatic cholangiocarcinoma patient-derived xenografts and tumoroids for preclinical drug evaluation

Author: Queralt Serra-Camprubí, Helena Verdaguer, Winona Oliveros, Núria Lupión-Garcia, Alba Llop-Guevara, Cristina Molina, Maria Vila-Casadesús, Anthony Turpin, Cindy Neuzillet, Joan Frigola, Jessica Querol, Mariana Yáñez-Bartolomé, Florian Castet, Carles Fabregat-Franco, Carmen Escudero-Iriarte, Marta Escorihuela, Enrique J. Arenas, Cristina Bernadó-Morales, Noemí Haro, Francis J. Giles, Óscar J. Pozo, Josep M. Miquel, Paolo G. Nuciforo, Ana Vivancos, Marta Melé, Violeta Serra, Joaquín Arribas, Josep Tabernero, Sandra Peiró, Teresa Macarulla, Tian V. Tian, Institut Català de la Salut, [Serra-Camprubí Q, Lupión-Garcia N, Llop-Guevara A, Molina C, Querol J, Yáñez-Bartolomé M, Escudero-Iriarte C, Escorihuela M, Arenas EJ, Bernadó-Morales C, Miquel JM, Nuciforo PG, Serra V, Peiró S, Tian TV] Preclinical and Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Verdaguer H, Castet F, Fabregat-Franco C, Tabernero J, Macarulla T] Preclinical and Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Gastrointestinal and Endocrine Tumor Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Oliveros W] Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona, Spain. [Vila-Casadesús M, Vivancos A] Cancer Genomics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Frigola J] Clinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Arribas J] Preclinical and Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigacion Biomédica en Red de Cáncer, Monforte de Lemos, Madrid, Spain. Department of Medicine and Life Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain. Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, and Barcelona Supercomputing Center
Subjects: Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC], neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma::colangiocarcinoma [ENFERMEDADES], Cancer Research, Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Cholangiocarcinoma [DISEASES], Metastatic Cholangiocarcinoma, Conductes biliars - Càncer - Tractament, Conductes biliars -- Tumors, Drug response, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias del tracto biliar::neoplasias de los conductos biliares [ENFERMEDADES], Investigative Techniques::Drug Development::Drug Evaluation, Preclinical [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], técnicas de investigación::desarrollo de medicamentos::evaluación preclínica de medicamentos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Biliary Tract Neoplasms::Bile Duct Neoplasms [DISEASES], Oncology, Statistical analysis, Simulació per ordinador, Medicaments - Assaigs clínics, Pathogenic mutations, Càncer, Genètica, Cancer
Abstract: Cholangiocarcinoma (CCA) is usually diagnosed at advanced stages, with limited therapeutic options. Preclinical models focused on unresectable metastatic CCA are necessary to develop rational treatments. Pathogenic mutations in IDH1/2, ARID1A/B, BAP1, and BRCA1/2 have been identified in 30\\%–50\\% of patients with CCA. Several types of tumor cells harboring these mutations exhibit homologous recombination deficiency (HRD) phenotype with enhanced sensitivity to PARP inhibitors (PARPi). However, PARPi treatment has not yet been tested for effectiveness in patient-derived models of advanced CCA.We have established a collection of patient-derived xenografts from patients with unresectable metastatic CCA (CCA\_PDX). The CCA\_PDXs were characterized at both histopathologic and genomic levels. We optimized a protocol to generate CCA tumoroids from CCA\_PDXs. We tested the effects of PARPis in both CCA tumoroids and CCA\_PDXs. Finally, we used the RAD51 assay to evaluate the HRD status of CCA tissues.This collection of CCA\_PDXs recapitulates the histopathologic and molecular features of their original tumors. PARPi treatments inhibited the growth of CCA tumoroids and CCA\_PDXs with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1. In line with these findings, only CCA\_PDX and CCA patient biopsy samples with mutations of BRCA2 showed RAD51 scores compatible with HRD.Our results suggest that patients with advanced CCA with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1, are likely to benefit from PARPi therapy. This collection of CCA\_PDXs provides new opportunities for evaluating drug response and prioritizing clinical trials. The authors would like to thank the patients and their families for their support. This work was supported by grants from the Fundaci o Marat o TV3 awarded to T. Macarulla, M. Mel e, and S. Peir o; BeiGene research grant awarded toT. Macarulla and S. Peir o; AECC (INVES20036TIAN), Ram on y Cajal investigator program (RYC2020-029098-I), Proyecto de IþDþi (PID2019-108008RJ-I00), and FERO Foundation grant awarded to T.V. Tian; Proyecto de Investigaci on en Salud from the Instituto de Salud Carlos III (ISCIII) (PI20/00898) awarded to T. Macarulla; FIS/FEDER from the Instituto de Salud Carlos III (ISCIII) (PI12/01250; CP08/00223; PI16/00253 and CB16/12/00449) awarded to S. Peir o; and Ram on y Cajal investigator program (RYC-2017-22249) awarded to M. Mel e. Q. Serra-Camprubí is a recipient of the Ph.D. fellowship from La Caixa Foundation (LCF/PR/PR12/51070001). A. LlopGuevara was supported by the AECC (INVES20095LLOP) and V. Serra by the ISCIII (CPII19/00033). E.J. Arenas was funded by the AECC (POSTD211413AREN).J. Arribas is funded by the Instituto de Salud Carlos III (AC15/00062, CB16/12/00449, and PI22/00001). This publication is based upon the work of COST Action CA18122, European Cholangiocarcinoma Network, supported by the COST (European Cooperation in Science and Technology, www.cost.eu), a funding agency for research and innovation networks. The authors would like to thank Dr. V.A. Raker for manuscript editing and Drs. N. Herranz and J. Mateo for scientific discussions. The authors acknowledge the infrastructure and support of the FERO Foundation, La Caixa Foundation, and the Cellex Foundation. Peer Reviewed "Article signat per 31 autors/es: Queralt Serra-Camprubí; Helena Verdaguer; Winona Oliveros; Núria Lupión-Garcia; Núria Lupión-Garcia;Alba Llop-Guevara; Cristina Molina; Maria Vila-Casadesús; Anthony Turpin; Cindy Neuzillet; Joan Frigola; Jessica Querol; Mariana Yáñez-Bartolomé; Florian Castet; Carles Fabregat-Franco; Carmen Escudero-Iriarte; Marta Escorihuela; Enrique J. Arenas; Cristina Bernadó-Morales; Noemí Haro; Francis J. Giles; Óscar J. Pozo; Josep M. Miquel ; Paolo G. Nuciforo; Ana Vivancos; Marta Melé; Violeta Serra ; Joaquín Arribas; Josep Tabernero; Sandra Peiró; Teresa Macarulla; Tian V. Tian"
Published: 2022

15. High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer

Author: Stefan Michiels, Cristina Saura, Cristina Viaplana, Marta Palafox, Abel Gonzalez-Perez, Alejandra Bruna, Paolo Nuciforo, Marta Guzman, Arribas Joaquín, Meritxell Bellet, Alicia García-Sanz, Violeta Serra, Faye Su, Olga Rodriguez, Nuria Lopez-Bigas, Analia Azaro, Monica Arnedos, Javier Hernández-Losa, Maurizio Scaltriti, Mafalda Oliveira, Laia Monserrat, Marta Capelán, Maria Teresa Herrera-Abreu, Carlos Caldas, Guillermo Villacampa, Leonardo Mina, Judit Grueso, Chandra S. Verma, Srinivasaraghavan Kannan, Robert Clarke, Nusaibah Ibrahimi, R. Dienstmann, Andreu Ódena, Nicholas C. Turner, Fara Brasó-Maristany, Aleix Prat, Mònica Sánchez-Guixé, Kui Lin, Gonzalez-Perez, Abel [0000-0002-8582-4660], Oliveira, Mafalda [0000-0001-9152-8799], Ibrahimi, Nusaibah [0000-0003-4537-0323], Kannan, Srinivasaraghavan [0000-0002-9539-5249], Sánchez-Guixé, Mònica [0000-0002-9430-4413], Hernández, Javier [0000-0003-1526-3201], Clarke, Robert B [0000-0001-5407-3123], Caldas, Carlos [0000-0003-3547-1489], Arribas, Joaquín [0000-0002-0504-0664], Michiels, Stefan [0000-0002-6963-2968], Turner, Nicholas C [0000-0001-8937-0873], Prat, Aleix [0000-0003-2377-540X], Nuciforo, Paolo [0000-0003-1380-0990], Lopez-Bigas, Nuria [0000-0003-4925-8988], Scaltriti, Maurizio [0000-0002-5522-1447], Saura, Cristina [0000-0001-8296-5065], Serra, Violeta [0000-0001-6620-1065], Apollo - University of Cambridge Repository, Institut Català de la Salut, [Palafox M, Monserrat L, Òdena A, Sánchez-Guixé M, Rodríguez O, Guzmán M, Grueso J] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Bellet M, Bellet M, Capelán M, Azaro A, Saura C] Breast Cancer and Melanoma Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Villacampa G, Viaplana C, Dienstmann R] Oncology Data Science Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Gonzalez-Perez A] Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain. Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Spain. [Hernández J] Grup de Recerca de Patologia Molecular Translacional, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Arribas J] CIBERONC, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Growth Factors Laboratory, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. [Nuciforo P] Molecular Oncology Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Serra V] Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. CIBERONC, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: endocrine system, Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasm [PHENOMENA AND PROCESSES], endocrine system diseases, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Ubiquitin-Protein Ligases, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], General Physics and Astronomy, Antineoplastic Agents, Breast Neoplasms, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Predictive markers, Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors [CHEMICALS AND DRUGS], General Biochemistry, Genetics and Molecular Biology, Càncer de mama, Phosphatidylinositol 3-Kinases, Text mining, Breast cancer, Er breast cancer, Medicine, Humans, Cancer models, neoplasms, Protein Kinase Inhibitors, Resistència als medicaments, fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos [FENÓMENOS Y PROCESOS], neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Multidisciplinary, Manchester Cancer Research Centre, acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas [COMPUESTOS QUÍMICOS Y DROGAS], business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Inhibitor resistance, Cyclin-Dependent Kinase 4, General Chemistry, Cyclin-Dependent Kinase 6, Proteïnes quinases - Inhibidors, Retinoblastoma Binding Proteins, Receptors, Estrogen, Drug Resistance, Neoplasm, Drug resistance, Mama - Càncer - Tractament, Cancer research, Female, business, Biomarkers
Abstract: CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n = 89). We also identified heterozygous RB1 loss as biomarker of acquired resistance and poor clinical outcome. Combination of the CDK4/6 inhibitor ribociclib with the PI3K inhibitor alpelisib showed antitumor activity in estrogen receptor-positive non-basal-like breast cancer patient-derived xenografts, independently of PIK3CA, ESR1 or RB1 mutation, also in drug de-escalation experiments or omitting endocrine therapy. Our results offer insights into predicting primary/acquired resistance to CDK4/6 inhibitors and post-progression therapeutic strategies. This study has been supported by the Susan G. Komen Foundation (CCR15330331) and by the Catalan Agency AGAUR (2017 SGR 540) [to V.S.]. V.S. received funds from the Instituto de Salud Carlos III: grants PI13/01714, CP14/00228, MV15/00041, CPII19/00033 and PI20/00892. M.P. received a Juan de la Cierva Grant from the Ministerio de Economía y Competitividad (FJCI-2015-25412), L.Mo. a grant from FI-AGAUR (2019 FI_B 01199), F.B-M. a grant from the Fundación Científica Asociación Española Contra el Cáncer (AECC_Postdoctoral17-1062) and M.S-G, a Marie Slodowska-Curie Innovative Training Networks PhD fellowship (H2020-MSCA-ITN-2015_675392). This work was supported by Breast Cancer Research Foundation (BCRF-19-08), Instituto de Salud Carlos III Project Reference number AC15/00062 and the EC under the framework of the ERA-NET TRANSCAN-2 initiative co-financed by FEDER, Instituto de Salud Carlos III (CB16/12/00449 and PI19/01181) and Asociación Española Contra el Cáncer (to J.A.). R.B.C. laboratory is supported by Breast Cancer Now (grant numbers: MAN-Q1 and MAN-Q2), NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007) and EdiREX Horizon 2020 grant No.731105. The xenograft program in the C.C. laboratory is supported by Cancer Research UK and also received funding from an EU H2020 Network of Excellence (EuroCAN). This work has been supported by NIH grants P30 CA008748 and RO1CA190642-01, the CDMRP grant BC171535P1, and the Breast Cancer Research Foundation [to M.S.]. A.P. received funds from Instituto de Salud Carlos III—PI16/00904 and PI19/01846, Breast Cancer Now—2018NOVPCC1294, Breast Cancer Research Foundation-AACR Career Development Awards for Translational Breast Cancer Research 19-20-26-PRAT, Fundació La Marató TV3 201935-30, the European Union’s Horizon 2020 research and innovation program H2020-SC1-BHC-2018-2020. IRB Barcelona is a recipient of a Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Economy and Competitiveness (MINECO; Government of Spain) and is supported by CERCA (Generalitat de Catalunya). C. S. Verma reports grants from MSD International and grants from Ipsen outside the submitted work.
Published: 2022
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16. Early-life respiratory tract infections and the risk of school-age lower lung function and asthma

Author: van Meel, Evelien R, Mensink-Bout, Sara M, den Dekker, Herman T, Ahluwalia, Tarunveer S, Annesi-Maesano, Isabella, Arshad, Syed Hasan, Baïz, Nour, Barros, Henrique, von Berg, Andrea, Bisgaard, Hans, Bønnelykke, Klaus, Carlsson, Christian J, Casas, Maribel, Chatzi, Leda, Chevrier, Cecile, Dalmeijer, Geertje, Dezateux, Carol, Duchen, Karel, Eggesbø, Merete, van der Ent, Cornelis, Fantini, Maria, Flexeder, Claudia, Frey, Urs, Forastiere, Fransesco, Gehring, Ulrike, Gori, Davide, Granell, Raquel, Griffiths, Lucy J, Inskip, Hazel, Jerzynska, Joanna, Karvonen, Anne M, Keil, Thomas, Kelleher, Cecily, Kogevinas, Manolis, Koppen, Gudrun, Kuehni, Claudia E, Lambrechts, Nathalie, Lau, Susanne, Lehmann, Irina, Ludvigsson, Johnny, Magnus, Maria Christine, Mélen, Erik, Mehegan, John, Mommers, Monique, Nybo Andersen, Anne-Marie, Nystad, Wenche, Pedersen, Eva S L, Pekkanen, Juha, Peltola, Ville, Pike, Katharine C, Pinot de Moira, Angela, Pizzi, Costanza, Polanska, Kinga, Popovic, Maja, Porta, Daniela, Roberts, Graham, Santos, Ana Cristina, Schultz, Erica S, Standl, Marie, Sunyer, Jordi, Thijs, Carel, Toivonen, Laura, Uphoff, Eleonora, Usemann, Jakob, Vafeidi, Marina, Wright, John, de Jongste, Johan C, Jaddoe, Vincent W V, Duijts, Liesbeth, IRAS OH Epidemiology Chemical Agents, Salvy-Córdoba, Nathalie, The Generation R Study Group, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Herlev and Gentofte Hospital, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), St Mary's Hospital [London], University Hospital Southampton NHS Foundation Trust, Departamento de Ciências da Saúde Pública e Forenses e Educação Médica [Porto, Portugal], Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto-Universidade do Porto = University of Porto, ISPUP-EPIUnit, University of Porto Medical School and Institute of Public Health, Marien-Hospital Wesel gGmbH, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), University of Southern California (USC), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Barts & The London School of Medicine and Dentistry, Linköping university hospital, Norwegian Institute of Public Health [Oslo] (NIPH), Alma Mater Studiorum University of Bologna (UNIBO), Helmholtz Zentrum München = German Research Center for Environmental Health, University Children’s Hospital Basel = Hôpital pédiatrique universitaire des deux Bâle [Bâle, Suisse] (UKBB), Lazio Regional Health Service [Rome], Institute for Risk Assessment Sciences [Utrecht, The Netherlands] (IRAS), Utrecht University [Utrecht], MRC Integrative Epidemiology Unit [Bristol, Royaume-Uni] (MRC IEU), University of Bristol [Bristol], Swansea University Medical School [Swansea, Royaume-Uni], Swansea University, University of Southampton, Nofer Institute of Occupational Medicine (NIOM), Finnish Institute for Health and Welfare [Helsinki, Finland] (FIHW), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Würzburg = Universität Würzburg, Bavarian Health and Food Safety Authority, School of Public Health, Physiotherapy and Sports Science [Dublin, Irlande], University College Dublin [Dublin] (UCD), National School of Public Health [Athens], IMIM-Hospital del Mar, Generalitat de Catalunya, Flemish Institute for Technological Research (VITO), Institute of Social and Preventive Medicine [Bern] (ISPM), Universität Bern [Bern] (UNIBE), Bern University Hospital [Berne] (Inselspital), Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Sach's Children's Hospital [Stockholm], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Copenhagen = Københavns Universitet (UCPH), TKK Helsinki University of Technology (TKK), Turku University Hospital (TYKS), Bristol Royal Hospital for Children, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Medical Sciences [Turin, Italy] (DMS), Università degli studi di Torino = University of Turin (UNITO), The David Hide Asthma and Allergy Research Centre, St Mary's Hospital-University Hospital Southampton NHS Foundation Trust, Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK, University of Crete [Heraklion] (UOC), Epidemiologie, RS: CAPHRI - R5 - Optimising Patient Care, Pediatrics, Epidemiology, IRAS OH Epidemiology Chemical Agents, and Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR)
Subjects: Pulmonary and Respiratory Medicine, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Vital Capacity, Infant, 610 Medicine & health, ALSPAC, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Asthma, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 360 Social problems & social services, Child, Preschool, Forced Expiratory Volume, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Humans, Prospective Studies, Child, Preschool, Lung, Respiratory Tract Infections
Abstract: Background: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. Methods: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. Results: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. Conclusions: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections. A comprehensive list of grant funding is available on the ALSPAC website (www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). BAMSE: BAMSE was funded by the Swedish Research Council, the Swedish Heart Lung Foundation, ALF Region Stockholm and SFO Epidemiology Karolinska Institutet. E. Mélen is supported by a European Research Council grant (TRIBAL, 757919). BiB (Born in Bradford): BiB is only possible because of the enthusiasm and commitment of the children and parents in BiB. We are grateful to all the participants, practitioners and researchers who have made BiB happen. The BiB study presents independent research commissioned by the National Institute for Health Research Collaboration for Applied Health Research and Care (NIHR CLAHRC) and the Programme Grants for Applied Research funding scheme (RP-PG-0407-10044). Core support for BiB is also provided by the Wellcome Trust (WT101597MA). BILD: This study was funded by the Swiss National Science Foundation (320030_163311). CoNER: Funds were obtained from the special programme (Programmi speciali – Art.12 bis, comma 6 D.lgs.229/99 Sanitaria e della Vigilanza sugli Enti) funded by the Italian Ministry of Health. Approval for the study was obtained from the Ethics Committee of the S. Orsola-Malpighi Teaching Hospital in April 2004 (52/2004/U/Tess). COPSAC 2000 and COPSAC 2010: All funding received by COPSAC is listed on www.copsac.com. The Lundbeck Foundation (R16-A1694), Ministry of Health (903516), Danish Council for Strategic Research (0603-00280B) and Capital Region Research Foundation have provided core support to the COPSAC research centre. We express our deepest gratitude to the children and families of the COPSAC 2000 and COPSAC 2010 cohort studies for all their support and commitment. We acknowledge and appreciate the unique efforts of the COPSAC research team. DNBC (Danish National Birth Cohort): The authors would like to thank the participants, the first Principal Investigator of DNBC, Jørn Olsen, the scientific managerial team and DNBC secretariat for being, establishing, developing and consolidating the DNBC. The DNBC was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, Pharmacy Foundation, Egmont Foundation, March of Dimes Birth Defects Foundation, Health Foundation and other minor grants. The DNBC Biobank has been supported by the Novo Nordisk Foundation and Lundbeck Foundation. Follow-up of mothers and children has been supported by the Danish Medical Research Council (SSVF 0646, 271-08-0839/06-066023, O602-01042B, 0602-02738B), Lundbeck Foundation (195/04, R100-A9193), Innovation Fund Denmark 0603-00294B (09-067124), Nordea Foundation (02-2013-2014), Aarhus Ideas (AU R9-A959-13-S804), University of Copenhagen Strategic Grant (IFSV 2012) and Danish Council for Independent Research (DFF-4183-00594, DFF-4183-00152). A. Pinot de Moira is funded by a Lundbeck Foundation grant (R264-2017-3099). EDEN: We thank the EDEN mother–child cohort study group (I. Annesi-Maesano, J.Y. Bernard, J. Botton, M.A. Charles, P. Dargent-Molina, B. de Lauzon-Guillain, P. Ducimetière, M. de Agostini, B. Foliguet, A. Forhan, X. Fritel, A. Germa, V. Goua, R. Hankard, B. Heude, M. Kaminski, B. Larroque†, N. Lelong, J. Lepeule, G. Magnin, L. Marchand, C. Nabet, F. Pierre, R. Slama, M.J. Saurel-Cubizolles, M. Schweitzer and O. Thiebaugeorges). We thank all funding sources for the EDEN study (not allocated for the present study but for the cohort): Foundation for Medical Research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 programme), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, MeDALL projects), Diabetes National Research Program (in collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l'Education Nationale complementary health insurance (MGEN), French national agency for food security, and French speaking association for the study of diabetes and metabolism (ALFEDIAM). The funding source had no involvement in the conception of the present study. FLEHS: This study was conducted within the framework of the Flemish Centre of Expertise on Environment and Health, funded by the Dept of the Environment of the Flemish Government, Flemish Agency of Care and Health, and Flemish Dept of Economy, Science and Innovation. GASPII: The GASPII cohort was funded by the Italian Ministry of Health (2001), the research leading to these results has received funding from the European Community's Seventh Framework Program under grant agreement 261357 (MeDALL). Generation R: This study was funded by Erasmus MC Rotterdam, Erasmus University Rotterdam and the Netherlands Organisation for Health Research and Development. V.W.V. Jaddoe received a grant from the European Research Council (ERC-2014-CoG-648916). L. Duijts received funding from cofunded ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 (696295; 2017), the Netherlands Organisation for Health Research and Development (ZonMw; 529051014; 2017), Science Foundation Ireland (SFI/16/ERA-HDHL/3360), and European Union (ALPHABET project). The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206, 2016; EUCAN-Connect 824989; ATHLETE, 874583). The researchers are independent from the funders. The study sponsors had no role in the study design, data analysis, interpretation of data or writing of this report. Generation XXI: Generation XXI was supported by the European Regional Development Fund (ERDF) through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology (FCT), Portuguese Ministry of Science, Technology and Higher Education, and by the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UIDB/04750/2020), Administração Regional de Saúde Norte (Regional Dept of Ministry of Health) and Fundação Calouste Gulbenkian. A.C. Santos is founded by FCT Investigator contracts IF/01060/2015. GINI: The GINIplus study was mainly supported for the first 3 years by the Federal Ministry for Education, Science, Research and Technology (interventional arm) and Helmholtz Zentrum München (former GSF) (observational arm). The 4- and 6-year follow-up examinations of the GINIplus study were covered from the respective budgets of the five study centres (Helmholtz Zentrum München (former GSF), Research Institute at Marien-Hospital, Wesel, LMU Munich, TU Munich and from 6 years onwards also from IUF – Leibniz Research Institute for Environmental Medicine at the University of Düsseldorf). HUMIS: We thank all mothers for participating in the HUMIS study. HUMIS was funded by a grant from the Norwegian Research Council (226402). The HUMIS study was approved by the Norwegian Data Inspectorate (2002/1398) and by the Regional Ethics Committee for Medical Research in Norway (S-02122), and the specific use in the current study was approved by the Ethics Committee as well (2010/1259/REK sør-øst). INMA: Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI09/00090, FIS-PI18/01142 including FEDER funds), CIBERESP, Dept of Health of the Basque Government (2013111089) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia and Beasain). Menorca: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; 97/0588; 00/0021-2, PI061756; PS0901958, PI14/00677 including FEDER funds), CIBERESP, Beca de la IV convocatoria de Ayudas a la Investigación en Enfemerdades Neurodegeneratives de La Caixa, and EC contract QLK4-CT-200-00263. Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 including FEDER funds), Generalitat de Catalunya-CIRIT 1999SGR 00241 and Fundació La marató de TV3 (090430). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. M. Casas holds a Miguel Servet fellowship (CP16/00128) funded by Instituto de Salud Carlos III and cofunded by the European Social Fund “Investing in your future”. Valencia: This study was funded by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663; Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, UGP-15-249), and Alicia Koplowitz Foundation 2017. Isle of Wight: This study was funded by grants from the National Institutes of Health USA (R01HL082925), Asthma UK (364), Isle of Wight NHS Trust and the British Medical Association. KOALA: The collection of data relevant for this study was funded by grants from the Netherlands Organisation for Health Research and Development (ZonMw; 2100.0090) and the Netherlands Asthma Foundation (3.2.03.48, 3.2.07.022). The researchers are independent from the funders. The funders had no role in the study design, data analysis, interpretation of data or writing of this report. We thank the children and parents for their participation in the KOALA study. LRC (Leicestershire Respiratory Cohorts): This study was funded by grants from the Swiss National Science Foundation (SNF: 320030-182628, 320030-162820, 3233-069348, 3200-069349) and Asthma UK 07/048. Lifeways Cross-Generation Cohort Study: This study was funded by the Health Research Board, Ireland, and the Irish Dept of Health and Children's Health Promotion Policy Unit. LISA: The LISA study was mainly supported by grants from the Federal Ministry for Education, Science, Research and Technology and in addition from Helmholtz Zentrum München (former GSF), Helmholtz Centre for Environmental Research – UFZ, Leipzig, Research Institute at Marien-Hospital Bad Honnef for the first 2 years. The 4-, 6-, 10- and 15-year follow-up examinations of the LISA study were covered from the respective budgets of the involved partners (Helmholtz Zentrum München (former GSF), Helmholtz Centre for Environmental Research – UFZ, Leipzig, Research Institute at Marien-Hospital Wesel, Pediatric Practice, Bad Honnef, IUF – Leibniz Research Institute for Environmental Medicine at the University of Düsseldorf) and in addition by a grant from the Federal Ministry for Environment (IUF Düsseldorf, FKZ 20462296). Further, the 15-year follow-up examination of the LISA study was supported by the Commission of the European Communities, the Seventh Framework Program: MeDALL project. This project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (949906). LucKi: LucKi is supported by Child and Youth Health Care Zuyderland, Public Health Service South Limburg and Maastricht University. We thank all parents and children for their participation in LucKi. LUKAS: This study was funded by research grants from the Academy of Finland (139021, 287675, 296814, 296817, 308254); Juho Vainio Foundation; EVO/VTR funding; Päivikki and Sakari Sohlberg Foundation; Farmers’ Social Insurance Institution (Mela); Finnish Cultural Foundation; Foundation for Pediatric Research; European Union QLK4-CT-2001-00250; and Finnish Institute for Health and Welfare, Finland. MAS-90: This study was funded by grants from the German Federal Ministry of Education and Research (MBMF; 07015633m 07ALE27, 01EE9405/5, 01EE9406) and the German Research Foundation (DFG; KE1462/2-1). Millennium Cohort Study: This study was funded by the Economic and Social Research Council and a consortium of UK government funders. We are grateful to the participating families and the Centre for Longitudinal Studies (CLS), UCL Institute of Education, for the use of these data and to the UK Data Service for making them available. However, neither CLS nor the UK Data Service bear any responsibility for the analysis or interpretation of these data. This work was supported by the Welcome Trust (187389/B/08/Z). MoBa: The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this ongoing cohort study. This research was supported by the Research Council of Norway through its Centres of Excellence funding scheme (262700). NINFEA: The authors are grateful to all the participants of the NINFEA cohort. The NINFEA study was partially funded by the Compagnia San Paolo Foundation. This research was partially funded by the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206). PELAGIE: We are grateful to the families who participated and continue to participate in the study. The cohort is supported by INSERM and received funding from the French National Research Agency, Fondation de France, French Agency for Food, Environmental and Occupational Health & Safety, National Institute for Public Health Surveillance (InVS), French Ministry of Labour, and French Ministry of Ecology. PIAMA: This study was funded by the Netherlands Organisation of Health Research and Development, Netherlands Organisation for Scientific Research, Netherlands Asthma Fund, Netherlands Ministry of Spatial Planning, Housing and the Environment, and Netherlands Ministry of Health, Welfare and Sport. REPRO_PL: This study was funded by the National Science Center Poland (DEC-2014/15/B/N27/00998). Rhea: This study was funded by the European Union Social Fund and the Hellenic Ministry of Health (“Program of prevention and early diagnosis of obesity and neurodevelopment disorders in preschool age children in the prefecture of Heraklion, Crete, Greece”; MIS 349580, NSRF 2007–2013). Additional funding from the National Institute of Environmental Health Sciences (NIEHS) supported L. Chatzi (R01ES030691, R01ES029944, R01ES030364, R21ES029681, R21ES028903, P30ES007048). STEPS: This study was funded by the University of Turku, Abo Akademi University, Turku University Hospital, Academy of Finland (123571, 140251, 277535) and Foundation for Pediatric Research Finland. SWS: This study was funded by the Medical Research Council, British Heart Foundation, Arthritis Research UK, Food Standards Agency, NIHR Southampton Biomedical Research Centre and the European Union's Seventh Framework Programme (FP7/2007–2013), project EarlyNutrition (289346), and the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206). WHISTLER: The WHISTLER birth cohort was supported with a grant from the Netherlands Organisation for Health Research and Development (2001-1-1322) and by an unrestricted grant from GlaxoSmithKline Netherlands. GlaxoSmithKline had no role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the report for publication. WHISTLER-Cardio was supported with an unrestricted strategic grant from the University Medical Center Utrecht (UMCU).
Published: 2022
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17. Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Author: Amare, Azmeraw T., Schubert, Klaus Oliver, Hou, Liping, Clark, Scott R., Papiol, Sergi, Cearns, Micah, Heilbronner, Urs, Degenhardt, Franziska, Tekola-Ayele, Fasil, Hsu, Yi Hsiang, Shekhtman, Tatyana, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M., Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Dayer, Alexandre, Del Zompo, Maria, DePaulo, J. Raymond, Étain, Bruno, Jamain, Stephane, Falkai, Peter, Forstner, Andreas J., Frisen, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jiménez, Esther, Kahn, Jean Pierre, Kassem, Layla, Kuo, Po Hsiu, Kato, Tadafumi, Kelsoe, John R., Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Tortorella, Alfonso, Manchia, Mirko, Martinsson, Lina, McCarthy, Michael J., McElroy, Susan L., Colom, Francesc, Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nöthen, Markus M., Novák, Tomas, O’Donovan, Claire, Ozaki, Norio, Ösby, Urban, Pfennig, Andrea, Potash, James B., Reif, Andreas, Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F.M., Bacanu, Silviu Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Binder, Elisabeth B., Blackwood, Douglas H.R., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane varregaard, Clarke, Toni Kim, Coleman, Jonathan R.I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Hickie, Ian B., Homuth, Georg, Horn, Carsten, Hottenga, Jouke Jan, Hougaard, David M., Ising, Marcus, Jansen, Rick, Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O’Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C.B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Dannlowski, Udo, de Geus, E. J.C., Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O’Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., Reininghaus, Eva, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Schofield, Peter R., Schweizer, Barbara W., Severino, Giovanni, Shilling, Paul D., Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M., Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Maj, Mario, Turecki, Gustavo, Vieta, Eduard, Veeh, Julia, Wright, Adam, Zandi, Peter P., Mitchell, Philip B., Bauer, Michael, Alda, Martin, McMahon, Francis J., APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Human genetics, APH - Digital Health, APH - Methodology, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Complex Trait Genetics, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Jamain, Stéphane, University of Adelaide, South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), Mental Health Services [Adelaide, SA, Australia], National Institute of Mental Health (NIMH), Ludwig Maximilian University [Munich] (LMU), Georg-August-University = Georg-August-Universität Göttingen, Institut für Genetik - Universität Bonn / Institute of Genetics - University of Bonn, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Harvard Medical School [Boston] (HMS), Harvard School of Public Health, University of California [San Diego] (UC San Diego), University of California (UC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Dokkyo Medical University, Università degli Studi di Cagliari = University of Cagliari (UniCa), Universitat Autònoma de Barcelona (UAB), Centro de Investigación Biomédica en Red de Salud Mental [Barcelona, Spain] (CIBERSAM), Hospital Sant Joan de Déu [Barcelona], Geneva University Hospital (HUG), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Karl-Franzens-Universität Graz, Mayo Clinic [Rochester], McGill University Health Center [Montreal] (MUHC), National Taiwan University [Taiwan] (NTU), University Hospital Basel [Basel], Poznan University of Medical Sciences [Poland] (PUMS), Johns Hopkins University (JHU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Basel (Unibas), Neuroscience Research Australia [Sydney, NSW, Australia] (NRA), University of New South Wales [Sydney] (UNSW), Psychiatrie de l'enfant et de l'adolescent [CH C. Perrens, Bordeaux], SECOP - centre hospitalier Charles Perrens, Dalhousie University [Halifax], 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry [Bucharest, Romania], Mood Disorders Center of Ottawa (MDCO), University of Ottawa [Ottawa], Osaka University [Osaka], Graduate School of Medicine [Osaka], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Psychiatrie et Psychologie Clinique de Liaison [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Psychothérapique de Nancy (CPN), National Institutes of Health [Bethesda] (NIH), Environmental Molecular Biology Laboratory (RIKEN), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Goethe-University Frankfurt am Main, Landesklinikum Neunkirchen (LK Neunkirchen), Hokkaido University Graduate School of Medicine [Sapporo, Japan], Sahlgrenska Academy at University of Gothenburg [Göteborg], Research Service VA San Diego Healthcare System, Università degli Studi di Perugia = University of Perugia (UNIPG), University of Cincinnati (UC), IMIM-Hospital del Mar, Generalitat de Catalunya, Max Planck Institute of Experimental Medicine [Göttingen] (MPI), Max-Planck-Gesellschaft, University of Salerno (UNISA), University of the Study of Campania Luigi Vanvitelli, National Institute of Mental Health [Klecany, Czech Republic] (NIMH), Nagoya University Graduate School of Medicine [Japon], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Medical University Graz, Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Sigmund Freud University (SFU), Douglas Mental Health University Institute [Montréal], University of Heidelberg, Medical Faculty, Black Dog Institute [Sydney, Australia], Johns Hopkins Bloomberg School of Public Health [Baltimore], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, The Florey Institute of Neuroscience and Mental Health [Parkville, VIC, Australie], University of Melbourne, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium: Naomi R Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M Byrne, Abdel Abdellaoui, Mark J Adams, Esben Agerbo, Tracy M Air, Till F M Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T F Beekman, Tim B Bigdeli, Elisabeth B Binder, Douglas H R Blackwood, Julien Bryois, Henriette N Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Varregaard Christensen, Toni-Kim Clarke, Jonathan R I Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E Crawford, Gail Davies, Ian J Deary, Franziska Degenhardt, Eske M Derks, Nese Direk, Conor V Dolan, Erin C Dunn, Thalia C Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K Finucane, Andreas J Forstner, Josef Frank, Héléna A Gaspar, Michael Gill, Fernando S Goes, Scott D Gordon, Jakob Grove, Lynsey S Hall, Christine Søholm Hansen, Thomas F Hansen, Stefan Herms, Ian B Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M Hougaard, Marcus Ising, Rick Jansen, Eric Jorgenson, James A Knowles, Isaac S Kohane, Julia Kraft, Warren W Kretzschmar, Jesper Krogh, Zoltán Kutalik, Yihan Li, Penelope A Lind, Donald J MacIntyre, Dean F MacKinnon, Robert M Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E Medland, Divya Mehta, Christel M Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M Mondimore, Grant W Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G Nivard, Dale R Nyholt, Paul F O'Reilly, Hogni Oskarsson, Michael J Owen, Jodie N Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E Peterson, Erik Pettersson, Wouter J Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A Quiroz, Per Qvist, John P Rice, Brien P Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C Schulte, Ling Shen, Jianxin Shi, Stanley I Shyn, Engilbert Sigurdsson, Grant C B Sinnamon, Johannes H Smit, Daniel J Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A Thomson, Thorgeir E Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M van Hemert, Alexander Viktorin, Peter M Visscher, Yunpeng Wang, Bradley T Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H Witt, Yang Wu, Hualin S Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T Baune, Klaus Berger, Dorret I Boomsma, Sven Cichon, Udo Dannlowski, E J C de Geus, J Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J Grabe, Steven P Hamilton, Caroline Hayward, Andrew C Heath, Kenneth S Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S Li, Susanne Lucae, Pamela A F Madden, Patrik K Magnusson, Nicholas G Martin, Andrew M McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M Nöthen, Michael C O'Donovan, Sara A Paciga, Nancy L Pedersen, Brenda W J H Penninx, Roy H Perlis, David J Porteous, James B Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G Schulze, Jordan W Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M Weissman, Thomas Werge, Cathryn M Lewis, Douglas F Levinson, Gerome Breen, Anders D Børglum, Patrick F Sullivan., Epidemiology, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Georg-August-University [Göttingen], University of California, Universita degli Studi di Cagliari [Cagliari], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Graz, Università degli Studi di Perugia (UNIPG), University of Münster, Karl-Franzens-Universität [Graz, Autriche], Amare, A. T., Schubert, K. O., Hou, L., Clark, S. R., Papiol, S., Cearns, M., Heilbronner, U., Degenhardt, F., Tekola-Ayele, F., Hsu, Y. -H., Shekhtman, T., Adli, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J. -M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., Brichant-Petitjean, C., Cervantes, P., Chen, H. -C., Chillotti, C., Cichon, S., Cruceanu, C., Czerski, P. M., Dalkner, N., Dayer, A., Del Zompo, M., Depaulo, J. R., Etain, B., Jamain, S., Falkai, P., Forstner, A. J., Frisen, L., Frye, M. A., Fullerton, J. M., Gard, S., Garnham, J. S., Goes, F. S., Grigoroiu-Serbanescu, M., Grof, P., Hashimoto, R., Hauser, J., Herms, S., Hoffmann, P., Hofmann, A., Jimenez, E., Kahn, J. -P., Kassem, L., Kuo, P. -H., Kato, T., Kelsoe, J. R., Kittel-Schneider, S., Kliwicki, S., Konig, B., Kusumi, I., Laje, G., Landen, M., Lavebratt, C., Leboyer, M., Leckband, S. G., Tortorella, A., Manchia, M., Martinsson, L., Mccarthy, M. J., Mcelroy, S. L., Colom, F., Mitjans, M., Mondimore, F. M., Monteleone, P., Nievergelt, C. M., Nothen, M. M., Novak, T., O'Donovan, C., Ozaki, N., Osby, U., Pfennig, A., Potash, J. B., Reif, A., Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Adams, M. J., Agerbo, E., Air, T. M., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bigdeli, T. B., Binder, E. B., Blackwood, D. H. R., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Castelao, E., Christensen, J., Clarke, T. -K., Coleman, J. R. I., Colodro-Conde, L., Couvy-Duchesne, B., Craddock, N., Crawford, G. E., Davies, G., Deary, I. J., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Kiadeh, F. F. H., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Gordon, S. D., Grove, J., Hall, L. S., Hansen, C. S., Hansen, T. F., Hickie, I. B., Homuth, G., Horn, C., Hottenga, J. -J., Hougaard, D. M., Ising, M., Jansen, R., Jorgenson, E., Knowles, J. A., Kohane, I. S., Kraft, J., Kretzschmar, W. W., Krogh, J., Kutalik, Z., Li, Y., Lind, P. A., Macintyre, D. J., Mackinnon, D. F., Maier, R. M., Maier, W., Marchini, J., Mbarek, H., Mcgrath, P., Mcguffin, P., Medland, S. E., Mehta, D., Middeldorp, C. M., Mihailov, E., Milaneschi, Y., Milani, L., Montgomery, G. W., Mostafavi, S., Mullins, N., Nauck, M., Ng, B., Nivard, M. G., Nyholt, D. R., O'Reilly, P. F., Oskarsson, H., Owen, M. J., Painter, J. N., Pedersen, C. B., Pedersen, M. G., Peterson, R. E., Pettersson, E., Peyrot, W. J., Pistis, G., Posthuma, D., Quiroz, J. A., Qvist, P., Rice, J. P., Riley, B. P., Rivera, M., Mirza, S. S., Schoevers, R., Schulte, E. C., Shen, L., Shi, J., Shyn, S. I., Sigurdsson, E., Sinnamon, G. C. B., Smit, J. H., Smith, D. J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K. E., Teismann, H., Teumer, A., Thompson, W., Thomson, P. A., Thorgeirsson, T. E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A. G., Umbricht, D., Van der Auwera, S., van Hemert, A. M., Viktorin, A., Visscher, P. M., Wang, Y., Webb, B. T., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Witt, S. H., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Baune, B. T., Berger, K., Boomsma, D. I., Dannlowski, U., de Geus, E. J. C., Domenici, E., Domschke, K., Esko, T., Grabe, H. J., Hamilton, S. P., Hayward, C., Heath, A. C., Kendler, K. S., Kloiber, S., Lewis, G., Li, Q. S., Lucae, S., Madden, P. A. F., Magnusson, P. K., Martin, N. G., Mcintosh, A. M., Metspalu, A., Mors, O., Mortensen, P. B., Muller-Myhsok, B., Nordentoft, M., O'Donovan, M. C., Paciga, S. A., Pedersen, N. L., Penninx, B. W. J. H., Perlis, R. H., Porteous, D. J., Preisig, M., Rietschel, M., Schaefer, C., Schulze, T. G., Smoller, J. W., Stefansson, K., Tiemeier, H., Uher, R., Volzke, H., Weissman, M. M., Werge, T., Lewis, C. M., Levinson, D. F., Breen, G., Borglum, A. D., Sullivan, P. F., Reininghaus, E., Rouleau, G. A., Rybakowski, J. K., Schalling, M., Schofield, P. R., Schweizer, B. W., Severino, G., Shilling, P. D., Shimoda, K., Simhandl, C., Slaney, C. M., Squassina, A., Stamm, T., Stopkova, P., Maj, M., Turecki, G., Vieta, E., Veeh, J., Wright, A., Zandi, P. P., Mitchell, P. B., Bauer, M., Alda, M., Mcmahon, F. J., and Adult Psychiatry
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Lithium (medication), [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Genome-wide association study, Logistic regression, THERAPY, ddc:616.89, 0302 clinical medicine, Medicine, Major depression, PREDICTORS, Depression (differential diagnoses), RISK, Depression, Psychiatry and Mental health, Quartile, Cohort, AUGMENTATION, medicine.drug, POLARITY, medicine.medical_specialty, GENETICS, Bipolar disorder, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Lithium, PROPHYLACTIC LITHIUM, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Internal medicine, Humans, ddc:610, AGENTS, Molecular Biology, Genetic association, Depressive Disorder, Major, business.industry, medicine.disease, EFFICACY, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, PHARMACOLOGICAL-TREATMENTS, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: © 2020, The Author(s), under exclusive licence to Springer Nature Limited.Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.
Published: 2021
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18. Metabolic Messengers: endocannabinoids

Author: Arnau Busquets-García, Juan P. Bolaños, Giovanni Marsicano, Agencia Estatal de Investigación (España), European Commission, Ministerio de Ciencia e Innovación (España), Ministerio de Sanidad (España), Junta de Castilla y León, European Research Council, Fondation pour la Recherche Médicale, Canadian Institutes of Health Research, Région Nouvelle-Aquitaine, Agence Nationale de la Recherche (France), Busquets-Garcia, Arnau, Bolaños, Juan P., Marsicano, Giovanni, IMIM-Hospital del Mar, Generalitat de Catalunya, Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Agencia Estatal de Investigación, Conseil Régional Aquitaine, ANR-13-BSV4-0006,NeuroNutriSens,Dissection des mécanismes hypothalamiques impliqués dans la détection du statut nutritionnel et régulation de la prise alimentaire via les interactions entre mTORC1, les mélanocortines et les endocannabinoïdes.(2013), ANR-16-CE37-0010,ORUPS,Représentation sensorielle lors d'états psychotiques(2016), ANR-10-LABX-0043,BRAIN,Bordeaux Region Aquitaine Initiative for Neuroscience(2010), European Project: 260515,EC:FP7:ERC,ERC-2010-StG_20091118,ENDOFOOD(2011), and European Project: 640923,H2020,ERC-2014-PoC,CannaPreg(2015)
Subjects: Central Nervous System, Biochemical Phenomena, Glucose transport, Endocrinology, Diabetes and Metabolism, Adipose tissue, Oxygen consumption, Signal transduction, Mitogen activated protein kinase, Biochemistry, Drug degradation, Drug synthesis, Protein kinase B, Phospholipase C, Fatty liver, Physiology (medical), Internal Medicine, Homeostasis, Oxidative phosphorylation, Endocannabinoid, Protein p53, Mammalian target of rapamycin, Metabolic messenger, Messenger RNA, Brain, Glial biology, Energy metabolism, Cell Biology, Cannabis sativa, Cannabinoid 1 receptor, cAMP signaling, Metabolism, Liver, Aerobic metabolism, Neuronal physiology, Protein expression, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Rho guanine nucleotide binding protein, Endocannabinoids
Abstract: Endocannabinoid signalling is considered one of the most important modulatory systems in a whole organism. Research has yielded great insight on the mechanisms that link endocannabinoids and metabolic functions. Here, we provide a brief overview of the metabolic roles of endocannabinoids in tissue, cellular and subcellular-dependent mechanisms. In general, we point out how the central and peripheral control of body energy metabolism likely represents the main function of type-1 cannabinoid receptors. More specifically, we focus on recent advances underlying mechanisms of endocannabinoid control of cell metabolism through the modulation of the functions of specific organelles. While highlighting a historical summary and summarizing past discoveries, this short review aims at proposing future open questions for a field that does not stop surprising researchers with unexpected and exciting discoveries., We also thank all the members of A.B.-G.’s, J.P.B.’s and G.M.’s labs for useful discussions and for their invaluable support. The work of A.B.-G. is supported by: Agencia Estatal de Investigación-FEDER (RTI2018-093667-A-100); the ERC starting Grant (HighMemory, #948217); the IBRO Return Home Fellowships 2019 and the Ramon y Cajal programme (RYC-2017-21776) funded by MCIN/ AEI/10.13039/501100011033 and FSE). The work of J.P.B. is funded by the Agencia Estatal de Investigación (PID2019-105699RB-I00; PDC2021-121013-I00; RED2018‐102576‐T; MCIN/AEI/10.13039/501100011033 & European Union NextGenerationEU/PRTR), Plan Nacional de Drogas (Ministerio de Sanidad; 2020I028) and Junta de Castilla y León (CS/151P20 and Escalera de Excelencia CLU-2017-03). The work of G.M. is funded by: INSERM, European Research Council (Endofood, ERC–2010–StG–260515 and CannaPreg, ERC-2014-PoC-640923, MiCaBra, ERC-2017-AdG-786467), Fondation pour la Recherche Medicale (FRM, DRM20101220445), the Human Frontiers Science Program, Region Nouvelle Aquitaine, Agence Nationale de la Recherche (ANR, NeuroNutriSens ANR-13-BSV4-0006 and ORUPS ANR-16-CE37-0010-01 and BRAIN ANR-10-LABX-0043).
Published: 2022
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19. Study protocol comparing the ethical, psychological and socio-economic impact of personalised breast cancer screening to that of standard screening in the 'My Personal Breast Screening' (MyPeBS) randomised clinical trial

Author: Alexandra Roux, Rachel Cholerton, Jonathan Sicsic, Nora Moumjid, David P. French, Paolo Giorgi Rossi, Corinne Balleyguier, Michal Guindy, Fiona J. Gilbert, Jean-Benoit Burrion, Xavier Castells, David Ritchie, Debbie Keatley, Camille Baron, Suzette Delaloge, Sandrine de Montgolfier, Gilbert, Fiona [0000-0002-0124-9962], Apollo - University of Cambridge Repository, Apollo-University Of Cambridge Repository, Malbec, Odile, Institut de Recherche Interdisciplinaire sur les enjeux Sociaux - sciences sociales, politique, santé (IRIS), École des hautes études en sciences sociales (EHESS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Sorbonne Paris Nord, University of Manchester [Manchester], Laboratoire Interdisciplinaire de Recherche Appliquée en Economie de la Santé (LIRAES (URP_ 4470)), Université Paris Cité (UPCité), Parcours santé systémique (P2S), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Léon Bérard [Lyon], Azienda Unità Sanitaria Locale di Bologna (AUSL), Institut Gustave Roussy (IGR), Imagerie thérapeutique (radiologie interventionnelle), Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Ben-Gurion University of the Negev (BGU), University of Cambridge [UK] (CAM), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), IMIM-Hospital del Mar, Generalitat de Catalunya, European Cancer Leagues [Brussels, Belgium] (ECL), Independent Cancer Patients' Voice [London, UK] (ICPV), UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Pathologie mammaire, and Département de médecine oncologique [Gustave Roussy]
Subjects: Adult, Cancer Research, [SDV]Life Sciences [q-bio], Satisfaction, Breast Neoplasms, Middle Aged, Inequity, Risk-stratification, [SDV] Life Sciences [q-bio], Study Protocol, Oncology, Socioeconomic Factors, Genetics, Quality of Life, Humans, Mass Screening, Female, Underserved populations, Breast cancer screening, Comprehension, Psychological impact, Early Detection of Cancer, Aged, Randomized Controlled Trials as Topic
Abstract: Background: the MyPeBS study is an ongoing randomised controlled trial testing whether a risk-stratified breast cancer screening strategy is non-inferior, or eventually superior, to standard age-based screening at reducing incidence of stage 2 or more cancers. This large European Commission-funded initiative aims to include 85,000 women aged 40 to 70 years, without prior breast cancer and not previously identified at high risk in six countries (Belgium, France, Italy, Israel, Spain, UK). A specific work package within MyPeBS examines psychological, socio-economic and ethical aspects of this new screening strategy. It compares women's reported data and outcomes in both trial arms on the following issues: general anxiety, cancer-related worry, understanding of breast cancer screening strategy and information-seeking behaviour, socio-demographic and economic characteristics, quality of life, risk perception, intention to change health-related behaviours, satisfaction with the trial. Methods: at inclusion, 3-months, 1-year and 4-years, each woman participating in MyPeBS is asked to fill online questionnaires. Descriptive statistics, bivariate analyses, subgroup comparisons and analysis of variations over time will be performed with appropriate tests to assess differences between arms. Multivariate regression models will allow modelling of different patient reported data and outcomes such as comprehension of the information provided, general anxiety or cancer worry, and information seeking behaviour. In addition, a qualitative study (48 semi-structured interviews conducted in France and in the UK with women randomised in the risk-stratified arm), will help further understand participants' acceptability and comprehension of the trial, and their experience of risk assessment. Discussion: beyond the scientific and medical objectives of this clinical study, it is critical to acknowledge the consequences of such a paradigm shift for women. Indeed, introducing a risk-based screening relying on individual biological differences also implies addressing non-biological differences (e.g. social status or health literacy) from an ethical perspective, to ensure equal access to healthcare. The results of the present study will facilitate making recommendations on implementation at the end of the trial to accompany any potential change in screening strategy. MyPeBS project is funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement N°755394 and underwent a full external peer review process at this step. MyPeBS has received funding from the PHRC-K research-funding programme (17–154) for the conduct of the study in France. DPF is supported by the NIHR Biomedical Research Centre in Manchester (IS-BRC-1215–20007). FJG is supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215–20014). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. XC is supported by grants from Instituto de Salud Carlos III FEDER (PI19/00007). MyPeBS is supported by the French health insurance systems (CNAM, MSA, MGEN, CPRPSNCF) for the covering of screening exams extra-costs, and by the Malakoff Humanis social protection group through the financing of the equipment of the recruiting centres with digital tablets to inform women about the study.
Published: 2022
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20. Association Between Pulmonary Embolism and COVID‐19 in Emergency Department Patients Undergoing Computed Tomography Pulmonary Angiogram: The PEPCOV International Retrospective Study

Author: Anne Laure Feral-Pierssens, Judith Gorlicki, Pierre Géraud Claret, Ben Bloom, Mélanie Roussel, Florent Femy, A Penaloza, Alfons Aguirre, Fabien Brigant, Òscar Miró, Pierrick Le Borgne, Alessio Marra, Said Laribi, Yonathan Freund, Sébastien Beaune, Olivier Lucidarme, Emmanuel Montassier, Tahar Chouihed, Céline Occelli, Anthony Chauvin, Bárbara Lara Hernández, Jennifer Truchot, Barbara Pena, Prabakar Vaittinada Ayar, Sami Ellouze, Marine Cachanado, Nicolas Javaud, Tabassome Simon, Marie Drogrey, Service des Urgences [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Hospital Clínic de Barcelona [Catalonia, Spain], ASST Papa Giovanni XXIII [Bergamo, Italy], Université de Sherbrooke (UdeS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cliniques Universitaires Saint-Luc [Bruxelles], Université Catholique de Louvain = Catholic University of Louvain (UCL), Pontificia Universidad Católica de Chile (UC), Hôpital Ambroise Paré [AP-HP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), SAMU 93 [Bobigny], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine d'urgence [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Universidad de Alicante, IMIM-Hospital del Mar, Generalitat de Catalunya, Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Lariboisière-Fernand-Widal [APHP], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Urgences [CHU Nantes], Hôtel-Dieu de Nantes, Microbiotes, Hôtes, Antibiotiques et Résistances bactériennes (MiHAR) (MiHAR), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Pasteur [Nice] (CHU), Services des urgences [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service des Urgences [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Hopital Saint-Louis [AP-HP] (AP-HP), Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie [CHU Pitié-Salpétrière], Barts Health NHS Trust [London, UK], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Gestionnaire, Hal Sorbonne Université, Service d'Accueil des Urgences [CHU Pitié-Salpêtrière] (SAU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, and Service d'Urgences Adultes [CHU Saint-Antoine]
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Pulmonary angiogram, Tomografia, [SDV]Life Sciences [q-bio], Computed tomography, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Pandèmia de COVID-19, 2020, Embòlia pulmonar, medicine.diagnostic_test, business.industry, 030208 emergency & critical care medicine, Retrospective cohort study, General Medicine, Emergency department, medicine.disease, 3. Good health, Pulmonary embolism, [SDV] Life Sciences [q-bio], Emergency Medicine, business
Abstract: International audience; Background: There have been reports of procoagulant activity in patients with COVID-19. Whether there is an association between pulmonary embolism (PE) and COVID-19 in the emergency department (ED) is unknown. The aim of this study was to assess whether COVID-19 is associated with PE in ED patients who underwent a computed tomographic pulmonary angiogram (CTPA).Methods: A retrospective study in 26 EDs from six countries. ED patients in whom a CTPA was performed for suspected PE during a 2-month period covering the pandemic peak. The primary endpoint was the occurrence of a PE on CTPA. COVID-19 was diagnosed in the ED either on CT or reverse transcriptase-polymerase chain reaction. A multivariable binary logistic regression was built to adjust with other variables known to be associated with PE. A sensitivity analysis was performed in patients included during the pandemic period.Results: A total of 3,358 patients were included, of whom 105 were excluded because COVID-19 status was unknown, leaving 3,253 for analysis. Among them, 974 (30%) were diagnosed with COVID-19. Mean (±SD) age was 61 (±19) years and 52% were women. A PE was diagnosed on CTPA in 500 patients (15%). The risk of PE was similar between COVID-19 patients and others (15% in both groups). In the multivariable binary logistic regression model, COVID-19 was not associated with higher risk of PE (adjusted odds ratio = 0.98, 95% confidence interval = 0.76 to 1.26). There was no association when limited to patients in the pandemic period.Conclusion: In ED patients who underwent CTPA for suspected PE, COVID-19 was not associated with an increased probability of PE diagnosis. These results were also valid when limited to the pandemic period. However, these results may not apply to patients with suspected COVID-19 in general.
Published: 2020
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21. Clinical trials in pediatric ALS: a TRICALS feasibility study

Author: Tessa Kliest, Ruben P.A. Van Eijk, Ammar Al-Chalabi, Alberto Albanese, Peter M. Andersen, Maria Del Mar Amador, Geir BrÅthen, Veronique Brunaud-Danel, Lev Brylev, William Camu, Mamede De Carvalho, Cristina Cereda, Hakan Cetin, Delia Chaverri, Adriano Chiò, Philippe Corcia, Philippe Couratier, Fabiola De Marchi, Claude Desnuelle, Michael A. Van Es, JesÚs Esteban, Massimiliano Filosto, Alberto GarcÍa Redondo, Julian Grosskreutz, Clemens O. Hanemann, Trygve HolmØy, Helle HØyer, Caroline Ingre, Blaz Koritnik, Magdalena Kuzma-Kozakiewicz, Thomas Lambert, Peter N. Leigh, Christian Lunetta, Jessica Mandrioli, Christopher J. Mcdermott, Thomas Meyer, Jesus S. Mora, Susanne Petri, MÓnica Povedano, Evy Reviers, Nilo Riva, Kit C.B. Roes, Miguel Á. Rubio, FranÇois Salachas, Stayko Sarafov, Gianni SorarÙ, Zorica Stevic, Kirsten Svenstrup, Anette Torvin MØller, Martin R. Turner, Philip Van Damme, Lucie A.G. Van Leeuwen, Luis Varona, Juan F. VÁzquez Costa, Markus Weber, Orla Hardiman, Leonard H. Van Den Berg, Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Maurice Wohl Clinical Neuroscience Institut, King‘s College London, King's College Hospital (KCH), Department Neurological Sciences, Milan University, IRCCS Humanitas Clinical Institute, Rozzano, M, Umeå University, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lille, Ministry of Healthcare of Russian Federation, Department of Neurology, Montpellier CHU, Gui De Chauliac Hospital, Montpellier, Université de Lisbonne, Medizinische Universität Wien = Medical University of Vienna, Hospital Universitario La Paz, Università degli studi di Torino = University of Turin (UNITO), Centre de compétence de la Sclérose Latérale Amyotrophique [CHRU Tours] (SLA CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Epidémiologie des Maladies Chroniques en zone tropicale (EpiMaCT), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de Neurologie [CHU Limoges], CHU Limoges, Centre référent Sclérose Latérale Amyotrophique et autres maladies du motoneurone [CHU Limoges] (SLA CHU Limoges), Neurology Clinic, University Hospital 'Maggiore della Carità', Novara, Hôpital Pasteur [Nice] (CHU), Centro de Diagnóstico de Enfermedades Moleculares, Dpto. Biol. Mol. Centro de Biología Molecular-SO UAM-CSIC. Universidad Autónoma Madrid, Campus Cantoblanco, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Car, University of Brescia, Lubeck University Hospital, Peninsula Schools of Medicine and Dentistry, Plymouth University, University of Oslo (UiO), Akershus University Hospital [Lørenskog], Telemark Hospital Trust [Skien, Norway], Karolinska Institutet, Department of Neurology, Karolinska University Hospital [Stockholm], University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Departement de Neurology (MEDICAL UNIVERSITY OF WARSAW), Medical University of Warsaw - Poland, University Hospitals of North Midlands NHS Trust, Royal Stoke Hospital, Stoke-on-Trent, United Kingdom., University of Sussex, University of Modena and Reggio Emilia, Department of Biomedical Sciences, Department of Neuroscience, Academic Neurology Unit, University of Sheffield, Sant Rafael Hospital, Department of Neurology, Hannover Medical School, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, University of Barcelona, Leuven University Hospitals, Division of Neuroscience, San Raffaele Scientific Institute, San Raffaele Scientific Institute, Milan, Italy, Radboud University Medical Center [Nijmegen], IMIM-Hospital del Mar, Generalitat de Catalunya, Medical University of Sofia [Bulgarie], Université de Padoue, Institute of Neurology, Clinical Center of Serbia, University of Belgrade, Belgrade, University of Belgrade [Belgrade], University of Copenhagen = Københavns Universitet (UCPH), Aarhus University Hospital, University of Oxford, Nuffield Department of Clinical Neurosciences, Oxford, UK, University Hospitals Leuven [Leuven], Servicio de Neurología, Hospital de Cruces, Barakaldo, Vizcaya, Neurology Service, Hospital Universitario La Fe, Valencia, Cantonal Hospital St Gallen (KSSG), and Department of Neurology, The Adelaide and Meath Hospital, Trinity College Dublin
Subjects: Adult, Databases, Factual, Neurologi, GENETICS, Clinical Neurology, AMYOTROPHIC-LATERAL-SCLEROSIS, Pediatric amyotrophic lateral sclerosis, pediatric investigation plan, Databases, Prevalence, Humans, clinical trial, clinical trials, ethics, therapy, Child, Feasibility Studies, Europe, Amyotrophic Lateral Sclerosis, Factual, Science & Technology, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Neurology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Neurosciences & Neurology, Life Sciences & Biomedicine
Abstract: Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (
Published: 2022
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22. Special issue editorial: Cannabinoid signalling in the brain: New vistas

Author: Arnau Busquets‐Garcia, Miriam Melis, Luigi Bellocchio, Giovanni Marsicano, Université Paris Cité, Equipe HAL, Représentation sensorielle lors d'états psychotiques - - ORUPS2016 - ANR-16-CE37-0010 - AAPG2016 - VALID, Blanc 2013 - Dissection des mécanismes hypothalamiques impliqués dans la détection du statut nutritionnel et régulation de la prise alimentaire via les interactions entre mTORC1, les mélanocortines et les endocannabinoïdes. - - NeuroNutriSens2013 - ANR-13-BSV4-0006 - Blanc 2013 - VALID, Role du recepteur CB1 mitocondriel du tissue adipeux dans la regulation de la balance energetique - - MitoCB1-Fat2019 - ANR-19-CE14-0039 - AAPG2019 - VALID, Les récepteurs couplés aux protéines G mitochondriaux en neuroprotection - - mitoGPCR2019 - ANR-19-CE16-0025 - AAPG2019 - VALID, Bordeaux Region Aquitaine Initiative for Neuroscience - - BRAIN2010 - ANR-10-LABX-0043 - LABX - VALID, IMIM-Hospital del Mar, Generalitat de Catalunya, University of Cagliari, Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Agencia Estatal de Investigacion-FEDER, Grant/Award Number: RTI2018-093667-A-100, IBRO Return Home Fellowships 2019 and the Ramon y Cajal programme, Grant/Award Number: RYC-2017-21776, MCIN/ AEI/10.13039/501100011033 and FSE, INSERM, the European Research Council, Endofood, Grant/Award Number: ERC-2010-StG-260515, CannaPreg, Grant/Award Number: ERC-2014-PoC-640923, MiCaBra, Grant/Award Number: ERC-2017-AdG-786467, Fondation pour la Recherche Medicale (FRM), Grant/Award Number: DRM20101220445, Human Frontiers Science Program, Region Nouvelle Aquitaine, Agence Nationale de la Recherche (ANR), NeuroNutriSens, Grant/Award Number: ANR-13-BSV40006, ORUPS, Grant/Award Number: ANR-16-CE37-0010-01, MitoCB1-FAT, Grant/Award Number: ANR19-CE14-0039-01, MitoGPCR, Grant/Award Number: ANR-19-CE16-0025, BRAIN, Grant/Award Number: ANR-10-LABX-0043, ANR-16-CE37-0010,ORUPS,Représentation sensorielle lors d'états psychotiques(2016), ANR-13-BSV4-0006,NeuroNutriSens,Dissection des mécanismes hypothalamiques impliqués dans la détection du statut nutritionnel et régulation de la prise alimentaire via les interactions entre mTORC1, les mélanocortines et les endocannabinoïdes.(2013), ANR-19-CE14-0039,MitoCB1-Fat,Role du recepteur CB1 mitocondriel du tissue adipeux dans la regulation de la balance energetique(2019), ANR-19-CE16-0025,mitoGPCR,Les récepteurs couplés aux protéines G mitochondriaux en neuroprotection(2019), and ANR-10-LABX-0043,BRAIN,Bordeaux Region Aquitaine Initiative for Neuroscience(2010)
Subjects: Cannabinoids, [SCCO.NEUR]Cognitive science/Neuroscience, General Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Cannabinoid Receptor Modulators, Brain, Receptors, Cannabinoid, Endocannabinoids, Signal Transduction
Abstract: International audience; The endocannabinoid system is widely expressed both in the brain and in the periphery. This system regulates a plethora of physiological functions and is composed of cannabinoid receptors, their endogenous ligands, and the enzymes involved in their metabolic processes. In the last few years, the development of new imaging and molecular tools has demonstrated that these receptors are distributed in many cell types (e.g., neuronal or glial cells) and intracellular compartments (e.g., mitochondria). Interestingly, cellular or molecular effects are differentially mediated by cannabinoid receptors according to their specific localization in different cell-types or in different subcellular locations. Moreover, the endocannabinoid system is also expressed throughout the body where it can serve to modulate the connection between the brain and the periphery. Finally, better understanding of the cannabinoid receptors structure and pharmacology has led researchers to propose interesting and new allosteric modulators of synaptic communication. The latest advances and innovative research in the cannabinoid field will provide new insights and better approaches to improve its interesting potential therapeutic profile. This special issue intends to bring together a series of empirical papers, targeted reviews and opinions from leaders in the field that will highlight the new advances in cannabinoid research.
Published: 2022
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23. A Feasibility Study of Patients with Major Depression and Substance Use Disorders: Vortioxetine as Maintenance Treatment

Author: Ignacio Basurte-Villamor, Pablo Vega, Carlos Roncero, José Martínez-Raga, Lara Grau-López, Lourdes Aguilar, Marta Torrens, Nestor Szerman, Institut Català de la Salut, [Basurte-Villamor I] Department of Psychiatry and Behavioral Health, Clínica López Ibor, Madrid, Spain. [Vega P] Institute for Addictions, Madrid Salud, Madrid City Council, Madrid, Spain. [Roncero C, Aguilar L] Department of Psychiatry, University of Salamanca Healthcare Complex, Salamanca, Spain. Institute of Biomedicine of Salamanca, University of Salamanca, Salamanca, Spain. Psychiatric Unit, School of Medicine, University of Salamanca, Salamanca, Spain. [Martínez-Raga J] Department of Psychiatry and Clinical Psychology, University Hospital Dr. Peset and University of Valencia, Valencia, Spain. [Grau-López L] Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Centre on Mental Health, CIBERSAM, Barcelona, Spain. Grup de Recerca de Psiquiatria, Salut Mental i Addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Psiquiatria i Medicina Forense, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Torrens M] Institute of Neuropsychiatry & Addictions-Hospital del Mar, Barcelona IMIM, Hospital del Mar Medical Research Institute, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Szerman N] WADD WPA Section Dual Disorders, Mental Health and Psychiatric Institute, Gregorio Marañon University Hospital, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Real-world evidence, Neuropsychiatric Disease and Treatment, Mental Disorders::Mood Disorders::Depressive Disorder::Depressive Disorder, Major [PSYCHIATRY AND PSYCHOLOGY], Mental Disorders::Substance-Related Disorders [PSYCHIATRY AND PSYCHOLOGY], Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Psychotropic Drugs::Antidepressive Agents [CHEMICALS AND DRUGS], Otros calificadores::/uso terapéutico [Otros calificadores], trastornos mentales::trastornos relacionados con sustancias [PSIQUIATRÍA Y PSICOLOGÍA], Malalties mentals - Tractament, Depressió psíquica - Tractament, Major depressive disorder, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::fármacos del sistema nervioso central::fármacos psicotrópicos::antidepresivos [COMPUESTOS QUÍMICOS Y DROGAS], Substance use disorder, Abús de substàncies, Major dual depressive disorder, Vortioxetine, Other subheadings::/therapeutic use [Other subheadings], trastornos mentales::trastornos del humor::trastorno depresivo::trastorno depresivo mayor [PSIQUIATRÍA Y PSICOLOGÍA], Dual disorder, Antidepressius - Ús terapèutic
Abstract: Ignacio Basurte-Villamor,1 Pablo Vega,2 Carlos Roncero,3â 5 JosÃ© MartÃnez-Raga,6 Lara Grau-LÃ³pez,7â 10 Lourdes Aguilar,3â 5 Marta Torrens,11 Nestor Szerman12 1Department of Psychiatry and Behavioral Health, ClÃnica LÃ³pez Ibor, Madrid, Spain; 2Institute for Addictions, Madrid Salud, Madrid City Council, Madrid, Spain; 3Department of Psychiatry, University of Salamanca Healthcare Complex, Salamanca, Spain; 4Institute of Biomedicine of Salamanca, University of Salamanca, Salamanca, Spain; 5Psychiatric Unit, School of Medicine, University of Salamanca, Salamanca, Spain; 6Department of Psychiatry and Clinical Psychology, University Hospital Dr. Peset and University of Valencia, Valencia, Spain; 7Department of Psychiatry, Hospital Universitari Vall dâHebron, Barcelona, Spain; 8Biomedical Network Research Centre on Mental Health, CIBERSAM, Barcelona, Spain; 9Group of Psychiatry, Mental Health and Addiction, Vall dâHebron Research Institute, Barcelona, Spain; 10Department of Psychiatry and Forensic Medicine, Universitat AutÃ²noma de Barcelona, Barcelona, Spain; 11Institute of Neuropsychiatry & Addictions-Hospital del Mar, Barcelona IMIM, Hospital del Mar Medical Research Institute, Barcelona University AutÃ²noma, Barcelona, Spain; 12WADD WPA Section Dual Disorders, Mental Health and Psychiatric Institute, Gregorio MaraÃ±on University Hospital, Madrid, SpainCorrespondence: Nestor Szerman, WADD WPA Section Dual Disorders, Mental Health and Psychiatric Institute, Gregorio MaraÃ±on University Hospital, C/ Lope de Rueda 43, Madrid, 28009, Spain, Tel +34 914008690, Fax +34 915739932, Email nszermanb@gmail.comBackground: Limited studies have evaluated the effectiveness of vortioxetine in real-world settings, and none of them has involved patients with dual depression (major depressive disorder [MDD] and substance use disorder [SUD]). The objective of the study was to describe the effectiveness of vortioxetine in clinical practice and determine its effect on affective symptoms, cognitive function, quality of life, and substance use in patients with MDD and SUD.Methods: Post-authorization, retrospective, multicenter, descriptive, and observational study in 80 patients with MDD and SUD receiving a maintenance treatment with vortioxetine for six months between January 2017 and April 2021.Results: Compared with baseline, scores significantly decreased after 3 and 6 months of treatment in the Montgomery-Ãsberg Depression Rating Scale total (from 28.9 to 17.7 and 12.0), and global functional impairment of the Sheehan Disability Inventory (from 26.3 to 19.1 and 16.7). The number of correct answers in the symbol digit modalities test significantly improved during vortioxetine treatment (from 40.4 to 43.8 and 48.4). Regarding the clinical global impression scale, the score for disease severity significantly decreased from 3.8 to 3.0 and 2.4. Compared with baseline, there was a significant reduction in consumption of practically all substances, especially of alcohol, cannabis, and cocaine.Conclusion: Vortioxetine was effective in clinical practice for alleviating depressive symptoms and functional impairment, and in improving cognitive and executive functions and disease severity in patients with MDD and SUD. Moreover, the treatment with vortioxetine favored a reduction in substance use and the severity of the SUDs.Keywords: vortioxetine, major depressive disorder, substance use disorder, dual disorder, major dual depressive disorder, real-world evidence
Published: 2022

24. Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: Machine learning approach

Author: Cearns, Micah, Amare, Azmeraw, Schubert, Klaus Oliver, Thalamuthu, Anbupalam, Frank, Joseph, Streit, Fabian, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean-Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna, Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr, Dalkner, Nina, Dayer, Alexandre, Degenhardt, Franziska, Zompo, Maria Del, Depaulo, J Raymond, Étain, Bruno, Falkai, Peter, Forstner, Andreas, Frisen, Louise, Frye, Mark, Fullerton, Janice, Gard, Sébastien, Garnham, Julie, Goes, Fernando, Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Heilbronner, Urs, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Hou, Liping, Hsu, Yi-Hsiang, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan, Maj, Mario, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael, Mcelroy, Susan, Colom, Francesc, Mitjans, Marina, Mondimore, Francis, Monteleone, Palmiero, Nievergelt, Caroline, Nöthen, Markus, Novák, Tomas, O'Donovan, Claire, Ozaki, Norio, Millischer, Vincent, Papiol, Sergi, Pfennig, Andrea, Pisanu, Claudia, Potash, James, Reif, Andreas, Reininghaus, Eva, Rouleau, Guy, Rybakowski, Janusz, Schalling, Martin, Schofield, Peter, Schweizer, Barbara, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul, Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire, Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Tekola-Ayele, Fasil, Tortorella, Alfonso, Turecki, Gustavo, Veeh, Julia, Vieta, Eduard, Witt, Stephanie, Roberts, Gloria, Zandi, Peter, Alda, Martin, Bauer, Michael, Mcmahon, Francis, Mitchell, Philip, Schulze, Thomas, Rietschel, Marcella, Clark, Scott, Baune, Bernhard, Cearns, Micah, Amare, Azmeraw T, Schubert, Klaus Oliver, Thalamuthu, Anbupalam, Frank, Joseph, Streit, Fabian, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean-Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M, Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M, Dalkner, Nina, Dayer, Alexandre, Degenhardt, Franziska, Zompo, Maria Del, Depaulo, J Raymond, Étain, Bruno, Falkai, Peter, Forstner, Andreas J, Frisen, Louise, Frye, Mark A, Fullerton, Janice M, Gard, Sébastien, Garnham, Julie S, Goes, Fernando S, Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Heilbronner, Ur, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Hou, Liping, Hsu, Yi-Hsiang, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Maj, Mario, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael J, Mcelroy, Susan, Colom, Francesc, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nievergelt, Caroline M, Nöthen, Markus M, Novák, Toma, O'Donovan, Claire, Ozaki, Norio, Millischer, Vincent, Papiol, Sergi, Pfennig, Andrea, Pisanu, Claudia, Potash, James B, Reif, Andrea, Reininghaus, Eva, Rouleau, Guy A, Rybakowski, Janusz K, Schalling, Martin, Schofield, Peter R, Schweizer, Barbara W, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M, Squassina, Alessio, Stamm, Thoma, Stopkova, Pavla, Tekola-Ayele, Fasil, Tortorella, Alfonso, Turecki, Gustavo, Veeh, Julia, Vieta, Eduard, Witt, Stephanie H, Roberts, Gloria, Zandi, Peter P, Alda, Martin, Bauer, Michael, Mcmahon, Francis J, Mitchell, Philip B, Schulze, Thomas G, Rietschel, Marcella, Clark, Scott R, Baune, Bernhard T, Etain, Bruno, University of South Australia [Adelaide], South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, University Medical Center Heidelberg, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], National Institute of Mental Health (NIMH), National Institutes of Health [Bethesda] (NIH), Dokkyo Medical University, Università degli Studi di Cagliari = University of Cagliari (UniCa), University of Barcelona, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Karolinska Institute, Karolinska University Hospital [Stockholm], University of California [San Diego] (UC San Diego), University of California (UC), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Medical University of Graz, Department of Health Sciences Research [Mayo Clinic] (HSR), Mayo Clinic, McGill University Health Center [Montreal] (MUHC), National Taiwan University [Taiwan] (NTU), University of Bonn, University Hospital Basel [Basel], Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Poznan University of Medical Sciences [Poland] (PUMS), Johns Hopkins University (JHU), Ludwig Maximilian University [Munich] (LMU), University of Basel (Unibas), Karolinska Institutet [Stockholm], University of New South Wales [Sydney] (UNSW), Centre hospitalier Charles Perrens [Bordeaux], Dalhousie University [Halifax], 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry [Bucharest, Romania], Mood Disorders Center of Ottawa (MDCO), University of Ottawa [Ottawa], Osaka University [Osaka], Georg-August-University = Georg-August-Universität Göttingen, University Medical Center Göttingen (UMG), Institute of Psychiatric Phenomics and Genomics (IPPG), Ludwig-Maximilians-Universität München (LMU), Harvard School of Public Health, Harvard Medical School [Boston] (HMS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Psychothérapique de Nancy [Laxou] (CPN), Juntendo University, Frankfurt University Hospital, Landesklinikum Neunkirchen (LK Neunkirchen), Hokkaido University [Sapporo, Japan], Sahlgrenska Academy at University of Gothenburg [Göteborg], VA San Diego Healthcare System [San Diego, CA, USA] (VASDHS), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, University of Cincinnati (UC), IMIM-Hospital del Mar, Generalitat de Catalunya, Instituto de Salud Carlos III [Madrid] (ISC), Università degli Studi di Salerno = University of Salerno (UNISA), National Institute of Mental Health [Klecany, Czech Republic] (NIMH), Nagoya University, Medizinische Universität Wien = Medical University of Vienna, University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Montreal Neurological Institute and Hospital, Neuroscience Research Australia (NeuRA), Sigmund Freud University (SFU), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Università degli Studi di Perugia = University of Perugia (UNIPG), Medical Faculty [Mannheim], Universität Heidelberg [Heidelberg], Johns Hopkins Bloomberg School of Public Health [Baltimore], University Medical Center, University of Adelaide, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, University of Melbourne, and The Florey Institute of Neuroscience and Mental Health
Subjects: Psychiatry and Mental health, depressive disorder, bipolar affective disorder, outcome studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Mood stabiliser, Mood stabilisers, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, genetics, genetic, depressive disorders, bipolar affective disorders
Abstract: BackgroundResponse to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Published: 2022
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25. Prenatal exposure to mixtures of phthalates and phenols and body mass index and blood pressure in Spanish preadolescents

Author: Nuria Güil-Oumrait, German Cano-Sancho, Parisa Montazeri, Nikos Stratakis, Charline Warembourg, Maria-Jose Lopez-Espinosa, Jesús Vioque, Loreto Santa-Marina, Alba Jimeno-Romero, Rosa Ventura, Nuria Monfort, Martine Vrijheid, Maribel Casas, European Commission, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Universitat de València (UV), Universidad Miguel Hernández [Elche] (UMH), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), BIODonostia Research Institute, IMIM-Hospital del Mar, Generalitat de Catalunya, This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, PI041436, PI081151 incl. FEDER funds), CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR 2009 SGR 501, Fundació La marató de TV3 (090430), EU Commission (261357, H2020 No 874583, the ATHLETE project, and No 825712, the OBERON project). Maribel Casas holds a Miguel Servet fellowship (MS16/00128) funded by Instituto de Salud Carlos III and co-funded by European Social Fund 'Investing in your future'. We acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the 'Centro de Excelencia Severo Ochoa 2019-2023' Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. INMA-Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI13/02187 and FIS-PI18/01142 incl. FEDER funds), CIBERESP, Department of Health of the Basque Government (2015111065), and the Provincial Government of Gipuzkoa (DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). INMA-Valencia: This study was funded by Grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: ISCIII (G03/176, FIS-FEDER: PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, and PI17/00663, and Miguel Servet-FEDER MS11/00178, MS15/00025, and MSII16/00051), Generalitat Valenciana (AICO/2021/182, and FISABIO: UGP 15-230, UGP-15-244, and UGP-15-249), and Alicia Koplowitz Foundation 2017.
Subjects: Pediatric Obesity, phthalates, blood pressure (BP), Phenol, [SDV]Life Sciences [q-bio], Phthalic Acids, Bayes Theorem, Blood Pressure, phenols, benzophenone-3, Body Mass Index, parabens, Cohort Studies, Pregnancy, Prenatal Exposure Delayed Effects, Humans, body mass index (BMI), Environmental Pollutants, Female, Child, General Environmental Science
Abstract: Background: Pregnant women are simultaneously exposed to several non-persistent endocrine-disrupting chem-icals, which may influence the risk of childhood obesity and cardiovascular diseases later in life. Previous prospective studies have mostly examined single-chemical effects, with inconsistent findings. We assessed the association between prenatal exposure to phthalates and phenols, individually and as a mixture, and body mass index (BMI) and blood pressure (BP) in preadolescents. Methods: We used data from the Spanish INMA birth cohort study (n = 1,015), where the 1st and 3rd-trimester maternal urinary concentrations of eight phthalate metabolites and six phenols were quantified. At 11 years of age, we calculated BMI z-scores and measured systolic and diastolic BP. We estimated individual chemical effects with linear mixed models and joint effects of the chemical mixture with hierarchical Bayesian kernel machine regression (BKMR). Analyses were stratified by sex and by puberty status. Results: In single-exposure models, benzophenone-3 (BP3) was nonmonotonically associated with higher BMI z -score (e.g. Quartile (Q) 3: beta = 0.23 [95% CI = 0.03, 0.44] vs Q1) and higher diastolic BP (Q2: beta = 1.27 [0.00, 2.53] mmHg vs Q1). Methyl paraben (MEPA) was associated with lower systolic BP (Q4: beta =-1.67 [-3.31,-0.04] mmHg vs Q1). No consistent associations were observed for the other compounds. Results from the BKMR confirmed the single-exposure results and showed similar patterns of associations, with BP3 having the highest importance in the mixture models, especially among preadolescents who reached puberty status. No overall mixture effect was found, except for a tendency of higher BMI z-score and lower systolic BP in girls. Conclusions: Prenatal exposure to UV-filter BP3 may be associated with higher BMI and diastolic BP during preadolescence, but there is little evidence for an overall phthalate and phenol mixture effect. We thank all study participants for their generous collaboration. INMA-Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds), CIBERESP, Generalitat de CatalunyaCIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR 2009 SGR 501, Fundacio La marato de TV3 (090430), EU Commission (261357, H2020 No 874583, the ATHLETE project, and No 825712, the OBERON project). Maribel Casas holds a Miguel Servet fellowship (MS16/00128) funded by Instituto de Salud Carlos III and co-funded by European Social Fund "Investing in your future". We acknowledge support from the Spanish Ministry of Science and Innovation and the State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. INMA-Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI13/02187 and FIS-PI18/01142 incl. FEDER funds), CIBERESP, Department of Health of the Basque Government (2015111065), and the Provincial Government of Gipuzkoa (DFG15/221) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain). INMA-Valencia: This study was funded by Grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: ISCIII (G03/176; FIS-FEDER: PI11/01007, PI11/02591, PI11/02038, PI12/00610, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, and PI17/00663; Miguel Servet-FEDER MS11/00178, MS15/00025, and MSII16/00051), Generalitat Valenciana (AICO/2021/182, and FISABIO: UGP 15-230, UGP-15-244, and UGP-15-249), and Alicia Koplowitz Foundation 2017.
Published: 2022
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26. Multicenter Real-World Data of Subsequent Chemotherapy after Progression to PARP Inhibitors in a Maintenance Relapse Setting

Author: Margarita Romeo, Marta Gil-Martín, Lydia Gaba, Iris Teruel, Álvaro Taus, Claudia Fina, Maria Masvidal, Paola Murata, Julen Fernández-Plana, Alejandro Martínez, Cristina Pérez, Yolanda García, Valerie Rodriguez, Sara Cros, Marta Parera, Montserrat Zanui, Silvia Catot, Beatriz Pardo, Andrea Plaja, Anna Esteve, Maria Pilar Barretina-Ginesta, [Romeo M, Teruel I] Medical Oncology Department, Institut Català d’Oncologia Badalona, Badalona Applied Research Group in Oncology (BARGO), Institut d’Investigació Germans Trias i Pujol (IGTP), Badalona, Spain. [Gil-Martín M] Medical Oncology Department, Institut Català d’Oncologia L’Hospitalet, Hospital Duran i Reynals, IDIBELL, L’Hospitalet de LLobregat, Spain. [Gaba L] Medical Oncology Department, Hospital Clínic de Barcelona, Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain. [Taus Á] Medical Oncology Department, Hospital del Mar-CIBERONC, Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. [Fina C] Medical Oncology Department, Institut Català d’Oncologia Girona, Girona Biomedical Research Institute IdIBGi, Girona, Spain. [Cros S] Medical Oncology Department, Hospital General de Granollers, Granollers, Spain, and Hospital General de Granollers
Subjects: Cancer Research, Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES], acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de poli(ADP-ribosa) polimerasas [COMPUESTOS QUÍMICOS Y DROGAS], Càncer d'ovari, platinum rechallenge, neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES], ovarian cancer, PARP inhibitors, platinum sensitivity, mechanisms of resistance, compuestos inorgánicos::elementos::metales pesados::platino (metal) [COMPUESTOS QUÍMICOS Y DROGAS], Oncology, Ovaris - Càncer, Inhibidors enzimàtics, Ovarian cancer, Quimioteràpia, Platinum rechallenge, Chemotherapy, Inorganic Chemicals::Elements::Metals, Heavy::Platinum [CHEMICALS AND DRUGS], Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Poly(ADP-ribose) Polymerase Inhibitors [CHEMICALS AND DRUGS], Platinum sensitivity
Abstract: Simple Summary Since the irruption of PARPi in the therapeutic armamentarium for ovarian cancer, concerns regarding post-progression treatment outcomes have emerged, owing to known crossed-resistance mechanisms between PARPi and platinum. In this multicentric retrospective series of ovarian cancer patients, we evaluated chemotherapy results upon progression to maintenance with PARPi in the relapsed setting. We further selected the population of platinum-sensitive patients (according to the classical definition) retreated with platinum (n = 74). In this platinum-sensitive population, overall response rate and survival outcomes of platinum rechallenge after PARPi were similar to historical series of the prePARPi era. However, within this group, analysis according to BRCA status showed that BRCA mutant patients (n = 35) presented higher rates of progression and worse survival outcomes under subsequent platinum than BRCA wild type patients (n = 39), with statistically significant differences. This is the largest real-world data series of ovarian cancer patients treated with platinum rechallenge in the post-PARPi scenario. Background: Despite impressive progression-free survival (PFS) results from PARP inhibitors (PARPi) in ovarian cancer, concerns about their effect on post-progression treatment outcomes have recently arisen, particularly when administered in the relapsed setting. Overlapping mechanisms of resistance between PARPi and platinum have been described, and optimal therapies upon progression to PARPi are unknown. We communicate real-world data (RWD) on outcomes of subsequent chemotherapy upon progression to PARPi used as maintenance in ovarian cancer relapses, particularly focusing on platinum rechallenge, according to BRCA status. Methods: Data from high-grade serous or endometrioid ovarian cancer patients who received subsequent chemotherapy after progression to maintenance PARPi in the relapsed setting, in 16 Catalan hospitals between August 2016 and April 2021, and who were followed-up until July 2021, were included. Endpoints were overall response rate (ORR), and PFS and overall survival (OS) measured from the subsequent chemotherapy starting date. Results: 111 patients were included [46 (41.4%) presented pathological BRCA1/2 mutations, 8 (7.5%) in other homologous recombination-related genes]. Sixty-four patients (57.7%) had received two prior chemotherapy lines, including the one immediately prior to PARPi. PARPi were niraparib (n = 60, 54.1%), olaparib (n = 49, 44.1%), and rucaparib (n = 2, 1.8%). A total of 81 patients remained platinum-sensitive (PS population) after progression to PARPi (when progression-free interval [PFI] was >6 months after the last cycle of prior platinum) [median PFI 12.0 months (interquartile range, IQR, 8.8-17.1)]. Of those, 74 were treated with subsequent platinum regimens, with the following results: ORR of 41.9%, median PFS (mPFS) of 6.6 months (95% CI 6-9.2), and median OS (mOS) of 20.6 months (95% CI 13.6-28.9). Analysis of these 74 patients according to BRCA status showed that PFIs for BRCA mutant and non BRCA-mutant patients were 13.6 [IQR11.2-22.2] and 10.3 [IQR 7.4-14.9] months, respectively (p = 0.010); ORR were 40.0% versus 43.6%, respectively; Rates of progression (as best response) to subsequent platinum were 45.7% versus 17.9%, respectively (p = 0.004); mPFS and mOS were 3.5 (95% CI 2.5-8.6) versus 7.5 months (95% CI 6.5-10.1, p = 0.03), and 16.4 (95% CI 9.3-27.5) versus 24.2 months (95% CI 17.2-NR, p = 0.036), respectively. Conclusion: This is the largest series of real-world data on ovarian cancer patients retreated with platinum in the post-PARPi scenario, separately analyzing BRCA mutant and non-mutant patients, to our knowledge. In our platinum-sensitive population, rechallenge with platinum after progression upon PARPi in the 3rd or later lines for ovarian cancer relapses shows relevant ORR and similar PFS outcomes to historical series of the prePARPi era. However, BRCA mutant patients presented significantly higher rates of progression under subsequent platinum and worse survival outcomes associated with subsequent platinum than non-BRCA-mutant patients.
Published: 2022

27. Gasdermin B over-expression modulates HER2-targeted therapy resistance by inducing protective autophagy through Rab7 activation

Author: Gámez-Chiachio, Manuel, Molina-Crespo, Ángela, Ramos-Nebot, Carmen, Martinez-Val, Jeannette, Martinez, Lidia, Gassner, Katja, Llobet, Francisco J., Soriano, Mario, Hernandez, Alberto, Cordani, Marco, Bernadó Morales, Cristina, Diaz, Eva, Rojo-Sebastian, Alejandro, Triviño, Juan Carlos, Sánchez-García, Laura, Rodríguez-Barrueco, Ruth, Arribas, Joaquín V, Llobet-Navás, David, Sarrió, David, Moreno-Bueno, Gema, Universitat Autònoma de Barcelona, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, Asociación Española Contra el Cáncer, Breast Cancer Research Foundation, Ministerio de Economía y Competitividad (España), Institut Català de la Salut, [Gámez-Chiachio M, Ramos-Nebot C] Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM) Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), IdiPAZ, Madrid, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. [Molina-Crespo Á, Martinez L] Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM) Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), IdiPAZ, Madrid, Spain. [Martinez-Val J] Departamento de Zoología Genética Antropología Física, Universidad Santiago de Compostela, Lugo, Spain. [Gassner K] Mecanismos Moleculares Y Terapia Experimental en Oncologia-Programa OncobellIdibell, L’Hospitalet de Llobregat, Spain. [Bernadó-Morales C] Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Leitat Medical Department, Leitat Technological Center, Barcelona, Spain. [Arribas J] Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Programa de Investigación en Cáncer, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Proteomics, Cancer Research, fenómenos fisiológicos celulares::muerte celular::autofagia [FENÓMENOS Y PROCESOS], Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasm [PHENOMENA AND PROCESSES], Cell Physiological Phenomena::Cell Death::Autophagy [PHENOMENA AND PROCESSES], Receptor, ErbB-2, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Breast Neoplasms, HER2 breast cancer, Càncer de mama, Mice, Breast cancer, Cell Line, Tumor, Gastroesophageal tumors, Autophagy, Animals, Humans, Protective autophagy, LC3B, Zebrafish, Resistència als medicaments, Tumors, fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos [FENÓMENOS Y PROCESOS], neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Chloroquine, Lapatinib, Gasdermin B, Oncology, Drug Resistance, Neoplasm, Mort cel·lular, Anti-HER2 therapy, Drug resistance, Mama - Càncer - Tractament, Female, Neoplasm Recurrence, Local
Abstract: [Background]: Gasdermin B (GSDMB) over-expression promotes poor prognosis and aggressive behavior in HER2 breast cancer by increasing resistance to therapy. Decoding the molecular mechanism of GSDMB-mediated drug resistance is crucial to identify novel effective targeted treatments for HER2/GSDMB aggressive tumors. [Methods]: Different in vitro approaches (immunoblot, qRT-PCR, flow cytometry, proteomic analysis, immunoprecipitation, and confocal/electron microscopy) were performed in HER2 breast and gastroesophageal carcinoma cell models. Results were then validated using in vivo preclinical animal models and analyzing human breast and gastric cancer samples. [Results]: GSDMB up-regulation renders HER2 cancer cells more resistant to anti-HER2 agents by promoting protective autophagy. Accordingly, the combination of lapatinib with the autophagy inhibitor chloroquine increases the therapeutic response of GSDMB-positive cancers in vitro and in zebrafish and mice tumor xenograft in vivo models. Mechanistically, GSDMB N-terminal domain interacts with the key components of the autophagy machinery LC3B and Rab7, facilitating the Rab7 activation during pro-survival autophagy in response to anti-HER2 therapies. Finally, we validated these results in clinical samples where GSDMB/Rab7/LC3B co-expression associates significantly with relapse in HER2 breast and gastric cancers. [Conclusion]: Our findings uncover for the first time a functional link between GSDMB over-expression and protective autophagy in response to HER2-targeted therapies. GSDMB behaves like an autophagy adaptor and plays a pivotal role in modulating autophagosome maturation through Rab7 activation. Finally, our results provide a new and accessible therapeutic approach for HER2/GSDMB + cancers with adverse clinical outcome., This study has been supported by the Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación (PID2019-104644RB-I00) -GMB-, the Instituto de Salud Carlos III (CIBERONC, CB16/12/00449 -JA-, CB16/12/00231 -DLN- and CB16/12/00295 -GMB-, PI19/01181 -JA-, PI18/00795, CP17/00063 and RTI2018-095611-A-I00 -DLN- and ERA-NET TRANSCAN-2 -JA- [all partly supported by FEDER funds]) and by the AECC Scientific Foundation (FC_AECC PROYE19036MOR -GMB- and LABAE19004LLOB -DLN-). Furthermore, this work was supported by Breast Cancer Research Foundation (BCRF-19–08) -JA-. We are also grateful to the CERCA Programme (Generalitat de Catalunya) for institutional support. MGC and DS contracts are funded by CIBERONC, KG is a recipient of a PFIS fellowship (FI19/00188), RRB is recipient of a Ramón y Cajal grant (RyC-2016–19671) and DLN is recipient of a Miguel Servet grant (MS17/00063) (all partly supported by FEDER funds). We are also grateful to MD Anderson BIOBANK for providing tumor samples. The bank (reference # B.0000745) belongs to the National Registry of Biobanks coordinated by the Carlos III Health Institute.
Published: 2022

28. Priorities for research on environment, climate and health, a European perspective

Author: Drakvik, Elina, Kogevinas, Manolis, Bergman, Åke, Devouge, Anais, Barouki, Robert, Devouge, Anaïs, Sarigiannis, Denis, Destoumieux-Garzón, Delphine, Matthies-Wiesler, Franziska, Peters, Annette, Zalko, Daniel, Villanueva, Cristina, Tonne, Cathryn, Cardis, Elisabeth, Diago-Navarro, Elizabeth, Antó, Josep M., Foraster, Maria, Nieuwenhuijsen, Mark, Straif, Kurt, van Veldhoven, Karin, Belesova, Kristine, Pearce, Neil, Haines, Andy, Klánová, Jana, Šebková, Kateřina, Pokorný, Lukáš, Hilscherová, Klára, Boekhold, Sandra, Staatsen, Brigit, van der Vliet, Nina, Furman, Eeva, Paloniemi, Riikka, Rekola, Aino, Aulake, Marianne, Byers, Vivienne, Gilmer, Alan, Huss, Anke, Vermeulen, Roel, Slama, Rémy, Samson, Michel, Albin, Maria, Grönlund, Åke, Garric, Jeanne, Stockholm University, Karolinska Institutet [Stockholm], Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), HERA (Health and Environment Research Agenda) Consortium: Robert Barouki, Manolis Kogevinas, Åke Bergman, Elina Drakvik, Anaïs Devouge, Denis Sarigiannis, Delphine Destoumieux-Garzón, Franziska Matthies-Wiesler, Annette Peters, Daniel Zalko, Cristina Villanueva, Cathryn Tonne, Elisabeth Cardis, Elizabeth Diago-Navarro, Josep M Antó, Maria Foraster, Mark Nieuwenhuijsen, Kurt Straif, Karin van Veldhoven, Kristine Belesova, Neil Pearce, Andy Haines, Jana Klánová, Kateřina Šebková, Lukáš Pokorný, Klára Hilscherová, Sandra Boekhold, Brigit Staatsen, Nina van der Vliet, Eeva Furman, Riikka Paloniemi, Aino Rekola, Marianne Aulake, Vivienne Byers, Alan Gilmer, Anke Huss, Roel Vermeulen, Rémy Slama, Michel Samson, Maria Albin, Åke Grönlund, Jeanne Garric, and Modat, Anne
Subjects: Transformational change, Health, Toxicology and Mutagenesis, Climate, Impact assessment, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Climate Change, Urbanization, Public Health, Environmental and Occupational Health, Research agenda, Infrastructures, Europe, [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Humans, Chemicals, Cities, Impact Assessment, Research Agenda, Transformational Change, Ecosystem
Abstract: Climate change, urbanisation, chemical pollution and disruption of ecosystems, including biodiversity loss, affect our health and wellbeing. Research is crucial to be able to respond to the current and future challenges that are often complex and interconnected by nature. The HERA Agenda, summarised in this commentary, identifies six thematic research goals in the environment, climate and health fields. These include research to 1) reduce the effects of climate change and biodiversity loss on health and environment, 2) promote healthy lives in cities and communities, 3) eliminate harmful chemical exposures, 4) improve health impact assessment and implementation research, 5) develop infrastructures, technologies and human resources and 6) promote research on transformational change towards sustainability. Numerous specific recommendations for research topics, i.e., specific research goals, are presented under each major research goal. Several methods were used to define the priorities, including web-based surveys targeting researchers and stakeholder groups as well as a series of online and face-to-face workshops, involving hundreds of researchers and other stakeholders. The results call for an unprecedented effort to support a better understanding of the causes, interlinkages and impacts of environmental stressors on health and the environment. This will require breakdown of silos within policies, research, actors as well as in our institutional arrangements in order to enable more holistic approaches and solutions to emerge. The HERA project has developed a unique and exciting opportunity in Europe to consensuate priorities in research and strengthen research that has direct societal impact. The HERA project was funded from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 825417.
Published: 2021
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29. The EHA Research Roadmap

Author: Jaffredo, Thierry, Balduini, Alessandra, Bigas, Anna, Bernardi, Rosa, Bonnet, Dominique, Canque, Bruno, Charbord, Pierre, Cumano, Anna, Delwel, Ruud, Durand, Charles, Fibbe, Willem, Forrester, Lesley, De Franceschi, Lucia, Ghevaert, Cedric, Gjertsen, Bjørn, Gottgens, Berthold, Graf, Thomas, Heidenreich, Olaf, Hermine, Olivier, Higgs, Douglas, Kleanthous, Marina, Klump, Hannes, Kouskoff, Valerie, Krause, Daniela, Lacaud, George, Celso, Cristina Lo, Martens, Joost H.A., Méndez-Ferrer, Simón, Menendez, Pablo, Oostendorp, Robert, Philipsen, Sjaak, Porse, Bo, Raaijmakers, Marc, Robin, Catherine, Stunnenberg, Henk, Theilgaard-Mönch, Kim, Touw, Ivo, Vainchenker, William, Corrons, Joan-Lluis Vives, Yvernogeau, Laurent, Schuringa, Jan Jacob, Celso, Cristina, Martens, Joost, Schuringa, Jan, Laboratoire de Biologie du Développement [IBPS] (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Pavia = University of Pavia (UNIPV), IMIM-Hospital del Mar, Generalitat de Catalunya, Josep Carreras Leukaemia Research Institute (IJC), Instituto de Salud Carlos III [Madrid] (ISC), IRCCS San Raffaele Scientific Institute [Milan, Italie], The Francis Crick Institute [London], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Leiden University Medical Center (LUMC), Universiteit Leiden, University of Edinburgh, Università degli studi di Verona = University of Verona (UNIVR), University of Cambridge [UK] (CAM), Haukeland University Hospital, University of Bergen (UiB), Barcelona Institute of Science and Technology (BIST), Universitat Pompeu Fabra [Barcelona] (UPF), Princess Máxima Center for Pediatric Oncology [Utrecht, Netherlands], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), John Radcliffe Hospital [Oxford University Hospital], Cyprus Institute of Neurology and Genetics, Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), University of Manchester [Manchester], Goethe-Universität Frankfurt am Main, Georg-Speyer-Haus, Imperial College London, Radboud University [Nijmegen], NHSBT, Universitat de Barcelona (UB), Institució Catalana de Recerca i Estudis Avançats (ICREA), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), University of Copenhagen = Københavns Universitet (UCPH), Hubrecht Institute [Utrecht, Netherlands], University Medical Center [Utrecht]-Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Center [Utrecht], Institut Gustave Roussy (IGR), Dynamique moléculaire de la transformation hématopoïétique (Dynamo), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University Medical Center Groningen [Groningen] (UMCG), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Pavia, Laboratoire d'Innovation Thérapeutique (LIT), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Laboratoire de Biologie du Développement [Paris] (LBD), Institut Pasteur [Paris], Hubrecht Institute for Developmental Biology and Stem Cell Research, Ghevaert, Cedric [0000-0002-9251-0934], Gottgens, Berthold [0000-0001-6302-5705], Apollo - University of Cambridge Repository, and Stem Cell Aging Leukemia and Lymphoma (SALL)
Subjects: Medizin, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Bioinformatics, 03 medical and health sciences, 0302 clinical medicine, SINGLE-CELL, REVEALS, Medicine, Diseases of the blood and blood-forming organs, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, DAMAGE, 0303 health sciences, VASCULAR NICHE, business.industry, ORIGIN, Normal hematopoiesis, Hematology, 3. Good health, ddc, MODEL, 030220 oncology & carcinogenesis, Perspective, RC633-647.5, business, COMMITMENT, STEM-CELLS
Abstract: International audience; In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1–2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including 11 sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European hematology research. The 11 EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cell-based Immune Therapies; and Gene Therapy.
Published: 2021
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30. Updates on the psychological and psychiatric aspects of the Ehlers–Danlos syndromes and hypermobility spectrum disorders

Author: Silvia Rosado-Figuerola, Carolina Baeza-Velasco, Antonio Bulbena, Andrea Bulbena-Cabre, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Laboratoire de Psychopathologie et Processus de Santé (LPPS (URP_4057)), Université de Paris (UP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), IMIM-Hospital del Mar, Generalitat de Catalunya, and Universitat Autònoma de Barcelona (UAB)
Subjects: Joint Instability, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Psychiatric nosology, 03 medical and health sciences, 0302 clinical medicine, Emotional distress, Genetics, medicine, Humans, 030212 general & internal medicine, Psychiatry, Genetics (clinical), Hypermobility (travel), anxiety, Anxiety Disorders, psychiatry, 3. Good health, Ehlers danlos, Mood, Anxiety, Ehlers-Danlos Syndrome, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychological aspects, Ehlers-Danlos, medicine.symptom, Psychology, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Psychopathology
Abstract: International audience; The field of the psychiatric and psychological aspects of Ehlers-Danlos syndromes (EDS) has been understudied and neglected for many years. People with EDS are often classified as "somatizers" by untrained clinicians. However, research on the biological basis of EDS is improving our understanding of the physiology and psychopathology of the disorder. In this article, we consider the literature on the psychopathological dimensions associated with EDS as well as the EDS symptoms in psychiatric conditions since our review in 2017. Literature confirms that psychological processes (i.e., fear, emotional distress, or negative emotions) in EDS have a significant impact on the outcomes of EDS. Common systemic associations are found between anxiety disorders and EDS as well as significant correlations with neurodevelopmental, eating, mood, and sleep disorders. There is limited but increasing evidence of an association between EDS and suicidal thoughts and behaviors, which should be further explored. The broad spectrum of human anxiety and associated somatic symptoms (beyond anxiety disorders) appears to be the core of the psychopathology in EDS and therefore, detecting and assessing EDS might be a new opportunity for psychiatric nosology to develop more inclusive phenotypes like the Neuroconnective Phenotype that include both somatic and psychological manifestations.
Published: 2021
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31. Adaptation and psychometric validation of Diabetes Health Profile (DHP-18) in patients with type 2 diabetes in Quito, Ecuador: a cross-sectional study

Author: Montserrat Ferrer, Aida Ribera, Mari Carmen Bernal-Soriano, Blanca Lumbreras, Lucy Anne Parker, Jordi Alonso, Ikram Benazizi, Andrés Peralta-Chiriboga, Alfonso Alonso-Jaquete, Yolanda Pardo, Institut Català de la Salut, [Benazizi I] Department of Public Health, Universidad Miguel Hernández, Sant Joan d’Alacant, Alicante, Spain. [Bernal-Soriano MC] Department of Public Health, Universidad Miguel Hernández, Sant Joan d’Alacant, Alicante, Spain. CIBER de Epidemiología y Salud Pública (CIBER ESP), Madrid, Spain. [Pardo Y, Ferrer M] CIBER de Epidemiología y Salud Pública (CIBER ESP), Madrid, Spain. Health Services Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Ribera A] CIBER de Epidemiología y Salud Pública (CIBER ESP), Madrid, Spain. Unitat d'Epidemiologia i Recerca Cardiovascular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Peralta-Chiriboga A] Department of Public Health, Universidad Miguel Hernández, Sant Joan d’Alacant, Alicante, Spain. Instituto de Salud Pública, Pontificia Universidad Católica del Ecuador, Quito, Ecuador, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Male, Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo de la glucosa::diabetes mellitus::diabetes mellitus tipo II [ENFERMEDADES], Cross-sectional study, Intraclass correlation, Diabetes Health Profile-18, Type 2 diabetes, Linguistic validation, Diabetes mellitus, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, Other subheadings::/psychology [Other subheadings], Diabetis no-insulinodependent - Aspectes psicològics, 030212 general & internal medicine, ambiente y salud pública::salud pública::medidas epidemiológicas::demografía::estado de salud::calidad de vida [ATENCIÓN DE SALUD], 030503 health policy & services, Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2 [DISEASES], Otros calificadores::/psicología [Otros calificadores], General Medicine, Reliability, Confirmatory factor analysis, Convergent validity, Diabetes Health Profle-18, Diabetes mellitus, Quality of life, Validity, Reliability, Ecuador, Female, Ecuador, 0305 other medical science, Psychology, Qualitat de vida - Avaluació, Clinical psychology, Psychometrics, Computer applications to medicine. Medical informatics, R858-859.7, Enquestes, Validity, 03 medical and health sciences, Cronbach's alpha, medicine, Humans, Hypoglycemic Agents, Research, Public Health, Environmental and Occupational Health, Reproducibility of Results, técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], medicine.disease, Environment and Public Health::Public Health::Epidemiologic Measurements::Demography::Health Status::Quality of Life [HEALTH CARE], Cross-Sectional Studies, Diabetes Mellitus, Type 2
Abstract: Introduction The Diabetes Health Profile (DHP‐18), structured in three dimensions (psychological distress (PD), barriers to activity (BA) and disinhibited eating (DE)), assesses the psychological and behavioural burden of living with type 2 diabetes. The objectives were to adapt the DHP‐18 linguistically and culturally for use with patients with type 2 DM in Ecuador, and to evaluate its psychometric properties. Methods Participants were recruited using purposive sampling through patient clubs at primary health centres in Quito, Ecuador. The DHP-18 validation consisted in the linguistic validation made by two Ecuadorian doctors and eight patient interviews. And in the psychometric validation, where participants provided clinical and sociodemographic data and responded to the SF-12v2 health survey and the linguistically and culturally adapted version of the DHP-18. The original measurement model was evaluated with confirmatory factor analysis (CFA). Reliability was assessed through internal consistency using Cronbach’s alpha and test–retest reproducibility by administering DHP-18 in a random subgroup of the participants two weeks after (n = 75) using intraclass correlation coefficient (ICC). Convergent validity was assessed by establishing previous hypotheses of the expected correlations with the SF12v2 using Spearman’s coefficient. Results Firstly, the DHP-18 was linguistically and culturally adapted. Secondly, in the psychometric validation, we included 146 participants, 58.2% female, the mean age was 56.8 and 31% had diabetes complications. The CFA indicated a good fit to the original three factor model (χ2 (132) = 162.738, p −0.40 in two of three hypotheses). Conclusions The original three factor model showed good fit to the data. Although reliability parameters were adequate for PD and DE dimensions, the BA presented lower internal consistency and future analysis should verify the applicability and cultural equivalence of some of the items of this dimension to Ecuador.
Published: 2021
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32. Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer’s disease in adults with Down syndrome

Author: Kaj Blennow, Sylvain Lehmann, Nicholas J. Ashton, Jordi Pegueroles, Rafael Blesa, Maria Florencia Iulita, Alberto Lleó, Miren Altuna, Valle Camacho, Henrik Zetterberg, Maria Carmona-Iragui, Daniel Alcolea, Diana Garzón, Susana Fernández, Juan Lantero-Rodriguez, Santiago Medrano-Martorell, Juan Fortea, Jordi Clarimón, Thomas K. Karikari, Olivia Belbin, Alexandre Bejanin, Laura Videla, Sílvia Valldeneu, Bessy Benejam, Isabel Barroeta, Victor Montal, Hospital de la Santa Creu i Sant Pau, Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Universitat Autònoma de Barcelona (UAB), Sahlgrenska Academy at University of Gothenburg [Göteborg], Sahlgrenska University Hospital [Gothenburg], UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), Institute of Neurology [London], Fundació Catalana de Síndrome de Down [Barcelona], University of Gothenburg (GU), King‘s College London, IMIM-Hospital del Mar, Generalitat de Catalunya, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Herrada, Anthony
Subjects: Male, 0301 basic medicine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, General Physics and Astronomy, MESH: Cognition, Disease, Gastroenterology, Cognition, 0302 clinical medicine, Neurofilament Proteins, Medicine, Phosphorylation, MESH: Neurofilament Proteins, Cerebral Cortex, education.field_of_study, MESH: Middle Aged, Multidisciplinary, Area under the curve, Middle Aged, Alzheimer's disease, MESH: Amyloid beta-Peptides, MESH: tau Proteins, Area Under Curve, Disease Progression, Biomarker (medicine), MESH: Disease Progression, Female, medicine.symptom, Adult, medicine.medical_specialty, Down syndrome, Science, Population, tau Proteins, MESH: Atrophy, Predictive markers, Asymptomatic, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, MESH: Cross-Sectional Studies, Atrophy, Alzheimer Disease, Internal medicine, Humans, Dementia, education, MESH: Humans, Amyloid beta-Peptides, MESH: Phosphorylation, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Adult, MESH: Down Syndrome, General Chemistry, medicine.disease, MESH: Cerebral Cortex, MESH: Male, Cross-Sectional Studies, 030104 developmental biology, MESH: Biomarkers, MESH: Area Under Curve, Down Syndrome, business, MESH: Female, MESH: Alzheimer Disease, Biomarkers, 030217 neurology & neurosurgery
Abstract: Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer’s disease (AD) pathology with high accuracy in the general population. In this study, we investigated plasma p-tau181 as a biomarker of AD in individuals with Down syndrome (DS). We included 366 adults with DS (240 asymptomatic, 43 prodromal AD, 83 AD dementia) and 44 euploid cognitively normal controls. We measured plasma p-tau181 with a Single molecule array (Simoa) assay. We examined the diagnostic performance of p-tau181 for the detection of AD and the relationship with other fluid and imaging biomarkers. Plasma p-tau181 concentration showed an area under the curve of 0.80 [95% CI 0.73–0.87] and 0.92 [95% CI 0.89–0.95] for the discrimination between asymptomatic individuals versus those in the prodromal and dementia groups, respectively. Plasma p-tau181 correlated with atrophy and hypometabolism in temporoparietal regions. Our findings indicate that plasma p-tau181 concentration can be useful to detect AD in DS., Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer’s disease (AD) pathology. Here, the authors investigated whether plasma ptau181 could be a potential biomarker of AD in individuals with Down syndrome (DS) and find plasma p-tau181 can detect AD in DS adults.
Published: 2021
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33. Stratifying the humoral risk of candidates to a solid organ transplantation: a proposal of the ENGAGE working group

Author: Olivier Thaunat, Nicos Kessaris, Lionel Couzi, Oriol Bestard, Marta Crespo, Bellvitge University Hospital [Barcelona, Spain], Bellvitge Biomedical Research Institute IDIBELL [Barcelona, Spain], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], IMIM-Hospital del Mar, Generalitat de Catalunya, Hospital del Mar Medical Research Institute [Barcelona, Spain] (IMIM), Universitat Pompeu Fabra [Barcelona] (UPF), Guy's Hospital [London], King‘s College London, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Admin, Oskar
Subjects: Graft Rejection, [SDV.IMM] Life Sciences [q-bio]/Immunology, Humoral alloimmune response, Human leukocyte antigen, 030230 surgery, Binary division, Serology, 03 medical and health sciences, 0302 clinical medicine, Presensitization, HLA Antigens, Isoantibodies, Humans, Medicine, Transplantation, biology, business.industry, Graft Survival, Circulating antibodies, Organ Transplantation, Kidney Transplantation, Antibody-mediated rejection, Antibody mediated rejection, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Antibody, Solid organ transplantation, business
Abstract: International audience; Detection of circulating antibodies directed against human leukocyte antigen (HLA) molecules, which corresponds to the current definition of ‘sensitized patient’, has been shown to have a severe impact on both access to transplantation and, if the anti-HLA antibodies are specific to the selected donor, survival of the graft. However, not all donor-specific antibodies (DSA) are equally harmful to the graft and progress in the understanding of humoral memory has led to the conclusion that absence of DSA at transplantation does not rule out the possibility that the patient has a preformed cellular humoral memory against the graft (thereby defining a category of DSA-negative sensitized recipients). Technological progress has led to the generation of new assays that offer unprecedented precision in exploring the different layers (serological and cellular) of alloimmune humoral memory. Based on this recent knowledge, the EuropeaN Guidelines for the mAnagement of Graft rEcipients (ENGAGE) working group to propose an updated definition of sensitization in candidates for solid organ transplantation – one that moves away from the current binary division towards a definition based on homogenous strata with similar humoral risk.
Published: 2021
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34. Estimating sodium intake from spot urine samples at population level: a validation and application study in French adults

Author: Charlotte Verdot, Katia Castetbon, Serge Hercberg, Pilar Galan, Valérie Deschamps, Michel Vernay, Camille Lassale, Dorra Guergour, Benoît Salanave, Emmanuelle Kesse-Guyot, Patrice Faure, Elise Emeville, Observatoire Régional de la Santé de la Guadeloupe, Department of Epidemiology and Public Health, University College of London [London] (UCL), IMIM-Hospital del Mar, Generalitat de Catalunya, Ecole de Santé Publique [Université Libre de Bruxelles], Université libre de Bruxelles (ULB), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), French Ministry of Health, Sante publique France, Fondation pour la Recherche Medicale, Institut National de la Sante et de la Recherche Medicale (Inserm), Institut National de la Recherche Agronomique (INRA), Conservatoire National des Arts et Metiers (CNAM), University of Paris 13, Region Ile-de-France, Caisse nationale d'Assurance maladie des Travailleurs salaries (CnamTS), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and AUDOUX, Michèle
Subjects: Adult, Male, Time Factors, urinary sodium excretion, Population level, [SDV]Life Sciences [q-bio], Population, Medicine (miscellaneous), Urine, 030204 cardiovascular system & hematology, Santé publique, Spearman's rank correlation coefficient, Urine collection device, Excretion, 03 medical and health sciences, 0302 clinical medicine, Animal science, Humans, 030212 general & internal medicine, Salt intake, education, False Negative Reactions, Aged, Urine Specimen Collection, Mathematics, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Nutrition and Dietetics, Sodium, spot urine samples, Sodium, Dietary, predictive intersalt equation, Middle Aged, Epidémiologie, salt intake, Nutrition Surveys, Diet Records, Diet, 3. Good health, [SDV] Life Sciences [q-bio], Spot urine, Mental Recall, predictive INTERSALT equation, Female, France, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The aim of this study was to assess the validity of the predictive INTERSALT equation using spot urine samples to estimate 24-hour urinary sodium (24-hUNa) excretion and daily sodium intake among the French adult population. Among 193 French adults ("validation sample"), we assessed the validity by comparing predicted 24-hUNa excretion from spot urine and measured 24-hUNa excretion from 24-hour urine collections. Spearman correlation coefficients and Bland-Altman plots were used and we calculated calibration coefficients. In a nationally representative sample of 1,720 French adults ("application sample"), the calibrated predictive equation was then applied to the spot urine Na values to estimate 24-hUNa excretion and daily Na intake. In that sample, predicted Na intake was compared to that estimated from 24-hour dietary recalls. Results were adjusted and corrected using calibration coefficients. In the validation sample, the measured 24-hUNa excretion was on average 14% higher than the predicted 24-hUNa (+ 13% for men and + 16% for women). Correlation between measured and predicted 24-hUNa excretion was moderate (Spearman r = 0.42) and the Bland-Altman plots showed underestimation at lower excretion level and overestimation at higher level. In the application study, estimated daily salt intake was 8.0 g/day using dietary recalls, 8.1 g/day using predicted INTERSALT equation and 9.3 g/day after applying calibration coefficients calculated in the validation study. Despite overall underestimation of 24-hUNa excretion by spot urinary sodium, the use of predictive INTERSALT equation remains an acceptable alternative in monitoring global Na intake/excreted in the French population but its use is not advised at the individual level., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019
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35. MZ lymphoproliferations: shared and unique characteristics

Author: Xochelli, Aliki, Bikos, Vasilis, Polychronidou, Eleftheria, Galigalidou, Chrysi, Agathangelidis, Andreas, Charlotte, Frédéric, Moschonas, Panagiotis, Davis, Zadie, Colombo, Monica, Roumelioti, Maria, Sutton, Lesley-Ann, Groenen, Patricia, van den Brand, Michiel, Boudjoghra, Myriam, Algara, Patricia, Traverse-Glehen, Alexandra, Ferrer, Ana, Stalika, Evangelia, Karypidou, Maria, Kanellis, George, Kalpadakis, Christina, Mollejo, Manuella, Pangalis, Gerasimos, Vlamos, Panayiotis, Amini, Rose-Marie, Pospisilova, Sarka, Gonzalez, David, Ponzoni, Maurilio, Anagnostopoulos, Achilles, Giudicelli, Véronique, Lefranc, Marie-Paule, Espinet, Blanca, Panagiotidis, Panagiotis, Piris, Miguel Angel, Du, Ming-Qing, Rosenquist, Richard, Papadaki, Theodora, Belessi, Chrysoula, Ferrarini, Manlio, Oscier, David, Tzovaras, Dimitrios, Ghia, Paolo, Davi, Frederic, Hadzidimitriou, Anastasia, Stamatopoulos, Kostas, Apollo - University of Cambridge Repository, Institute of Applied Biosciences, CERTH, Thessaloniki, Greece., Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Information Technologies Institute, CERTH, Thessaloniki, Greece., Department of Informatics, Ionian University, Corfu, Greece, Division of Experimental Oncology and Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy., Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Information Technologies Institute, CERTH, Thessaloniki, Greece, Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK., Molecular Pathology, Ospedale Policlinico SanMartino, Genoa, Italy., First Department of Propaedeutic Medicine, University of Athens, Athens, Greece, Uppsala Universitet [Uppsala], Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands., Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospital Virgen de la Salud, Toledo, Spain, Department of Pathology and Hematology, Hospices Civils de Lyon (HCL), Laboratori de Citologia Hematològica i Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain, Centre for Research and Technology Hellas (CERTH), Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece, Hematopathology Department, Evangelismos Hospital, Athens, Greece., Department of Haematology, University of Crete, Heraklion, Greece., Department of Haematology, Athens Medical Center, Athens, Greece, Department of Informatics [Ionian University], Ionian University [Corfu], Department of Informatics, Ionian University, Corfu, Greece., Department of Genetics and Pathology, Uppsala University Hospital, CEITEC-Central European Institute of Technology, MasarykBrno, Czech Republic., Pathology Unit, Unit of Lymphoid Malignancies, San Raffaele H Scientific Institute, Pathology Unit, San Raffaele Scientific Institute, Milan, Italy, Laboratoire d'ImmunoGénétique Moléculaire (LIGM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoris de Citologia Hematológica/Citogenética Molecular. Servei de Patologia, GRETNHE, IMIM-Hospital del Mar, Laboratori de Citologia Hematològica i Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain., Pathology Department, IIS 'Fundacion Jimenez Diaz', Madrid, Spain, Pathology, University of Cambridge [UK] (CAM), Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK, Hematology Department, Nikea General Hospital, Piraeus, Greece, Direzione Scientifica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-IST, Genoa, Italy., Informatics & Telematics Institute (ITI), CERTH, Università Vita e Salute, San Raffaele, Milano, Italy, Division of Experimental Oncology and Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece, Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden, Xochelli, Aliki, Bikos, Vasili, Polychronidou, Eleftheria, Galigalidou, Chrysi, Agathangelidis, Andrea, Charlotte, Frédéric, Moschonas, Panagioti, Davis, Zadie, Colombo, Monica, Roumelioti, Maria, Sutton, Lesley-Ann, Groenen, Patricia, van den Brand, Michiel, Boudjoghra, Myriam, Algara, Patricia, Traverse-Glehen, Alexandra, Ferrer, Ana, Stalika, Evangelia, Karypidou, Maria, Kanellis, George, Kalpadakis, Christina, Mollejo, Manuella, Pangalis, Gerasimo, Vlamos, Panayioti, Amini, Rose-Marie, Pospisilova, Sarka, Gonzalez, David, Ponzoni, Maurilio, Anagnostopoulos, Achille, Giudicelli, Véronique, Lefranc, Marie-Paule, Espinet, Blanca, Panagiotidis, Panagioti, Piris, Miguel Angel, Du, Ming-Qing, Rosenquist, Richard, Papadaki, Theodora, Belessi, Chrysoula, Ferrarini, Manlio, Oscier, David, Tzovaras, Dimitrio, Ghia, Paolo, Davi, Frederic, Hadzidimitriou, Anastasia, and Stamatopoulos, Kostas
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Genes, Immunoglobulin, Genes, Immunoglobulin Heavy Chain, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], [SDV]Life Sciences [q-bio], Immunoglobulin Variable Region, Receptors, Antigen, B-Cell, Lymphoma, B-Cell, Marginal Zone, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Complementarity Determining Regions, marginal zone lymphoma, immunoglobulin gene, antigen, ontogeny, Marginal zone lymphoma, Mutation, Tumor Microenvironment, Humans, Gene Rearrangement, B-Lymphocyte
Abstract: Contains fulltext : 203155.pdf (Publisher’s version ) (Closed access) The B cell receptor immunoglobulin (Ig) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n = 488), i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL), as well as provisional entities (n = 76), according to the WHO classification. The most striking Ig gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different Ig gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ Ig sequence dataset with a large dataset of Ig sequences (MZ-related or not; n = 65 837) revealed four major clusters of cases sharing homologous ('public') heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia, but also rheumatoid factors and non-malignant splenic MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments. Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Published: 2019
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36. Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS)

Author: Enrique Grande, A. Loehr, Petros Grivas, Dale L. Nepert, Yohann Loriot, Sumati Gupta, Daleen Thomas, Nicholas J. Vogelzang, Min Yuen Teo, Nabil Adra, Alejo Rodriguez-Vida, Rachel L. Dusek, Simon Chowdhury, S. Srinivas, Yousef Zakharia, Andrew Simmons, Andrea Necchi, Ajjai Alva, Susan Feyerabend, Kenton Wride, Rafael Morales-Barrera, Debra H. Josephs, University of Washington [Seattle], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Passeig Vall d'Hebron [Barcelona, Spain], Memorial Sloane Kettering Cancer Center [New York], University of Iowa [Iowa City], Studienpraxis Urologie [Nürtingen, Germany], Comprehensive Cancer Centers [Las Vegas, NV, USA], MD Anderson Cancer Center [Madrid, Spain], Indiana State University, Department of Internal Medicine and Computational Medicine and Bioinformatics [Ann Arbor, MI, USA], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Human Tumor Immunobiology Unit [Fondazione IRCCS Istituto Nazionale dei Tumori, Milan], Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], IMIM-Hospital del Mar, Generalitat de Catalunya, Huntsman Cancer Institute [Salt Lake City], University of Utah, Guy's and St Thomas NHS Foundation Trust [London], Stanford University School of Medicine [CA, USA], Clovis Oncology, Inc. [Boulder, CO, USA], Malbec, Odile, Institut Català de la Salut, [Grivas P] Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA 98109, USA. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Seattle Cancer Care Alliance, Seattle, WA 98109, USA. [Loriot Y] Department of Medicine, Gustave Roussy Cancer Campus, INSERM U981, Université Paris-Saclay, 94800 Villejuif, France. [Morales-Barrera R] Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Teo MY] Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. [Zakharia Y] Division of Hematology, Oncology, and Blood and Marrow Transplant, University of Iowa and Holden Comprehensive Cancer Center, Iowa City, IA 52242, USA. [Feyerabend S] Studienpraxis Urologie, 72622 Nürtingen, Germany, Vall d'Hebron Barcelona Hospital Campus, Grivas, P., Loriot, Y., Morales-Barrera, R., Teo, M. Y., Zakharia, Y., Feyerabend, S., Vogelzang, N. J., Grande, E., Adra, N., Alva, A., Necchi, A., Rodriguez-Vida, A., Gupta, S., Josephs, D. H., Srinivas, S., Wride, K., Thomas, D., Simmons, A., Loehr, A., Dusek, R. L., Nepert, D., and Chowdhury, S.
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, Indoles, DNA Repair, [SDV]Life Sciences [q-bio], Administration, Oral, Loss of Heterozygosity, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Prostate cancer, chemistry.chemical_compound, 0302 clinical medicine, Clinical endpoint, Inhibidors enzimàtics - Ús terapèutic - Eficàcia, RC254-282, BRCA1 Protein, Bladder cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, Progression-Free Survival, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Bufeta - Càncer - Tractament, Other subheadings::Other subheadings::/administration & dosage [Other subheadings], Female, Urothelial carcinoma, medicine.symptom, Research Article, medicine.medical_specialty, Metastatic Urothelial Carcinoma, Anemia, Nausea, Urinary Bladder, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Poly(ADP-ribose) Polymerase Inhibitors, 03 medical and health sciences, Internal medicine, Genetics, medicine, Humans, Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Poly(ADP-ribose) Polymerase Inhibitors [CHEMICALS AND DRUGS], Adverse effect, Rucaparib, Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Urologic Neoplasms::Urinary Bladder Neoplasms [DISEASES], Response Evaluation Criteria in Solid Tumors, Aged, BRCA2 Protein, Genomic biomarkers, Carcinoma, Transitional Cell, Otros calificadores::Otros calificadores::/administración & dosificación [Otros calificadores], neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias urológicas::neoplasias de la vejiga [ENFERMEDADES], business.industry, acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de poli(ADP-ribosa) polimerasas [COMPUESTOS QUÍMICOS Y DROGAS], medicine.disease, PARP inhibitor, 030104 developmental biology, Urinary Bladder Neoplasms, chemistry, business, Follow-Up Studies
Abstract: BackgroundATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC).MethodsPatients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks.ResultsOf 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6–1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1–10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleteriousBRCA1orBRCA2alteration.ConclusionsRucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer.Trial registrationThis trial was registered inClinicalTrials.gov(NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017–004166-10).
Published: 2021
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37. The role of bronchoscopy in patients with SARS-CoV-2 pneumonia

Author: Iker Fernández-Navamuel, Andrés Giménez Velando, Ricardo García Luján, Albert Sánchez-Font, Alfons Torrego Fernández, Marisol Arenas-De Larriva, Ana Núñez-Ares, Javier Cosano Povedano, Rosa Cordovilla, Roberto Larrosa-Barrero, Andrés Briones-Gómez, Felipe Andreo García, Roberto Martín-DeLeon, Jose Joaquin Cebrian Gallardo, Javier Flandes, Manuel Luis Rodríguez-Perálvarez, Ricardo Aguilar-Colindres, Gorane Iturricastillo, Olga Rajas, Enrique Cases Viedma, Carmen Fernández-Arias, Manuel Nuñez Delgado, Carmen Centeno Clemente, José Franco, Blanca Urrutia Royo, Maria del Mar Valdivia Salas, Albert Rafecas Codern, Virginia Pajares Ruiz, Lorena Comeche Casanova, María Pavón-Masa, Ruth García García, Laura Nuñez García, [Arenas-De Larriva,M] Dept of Bronchoscopy and Interventional Pulmonology, Hospital Universitario Reina Sofía, IMIBIC, Córdoba, Spain. [Martín-DeLeon,R] Dept of Pulmonology, Hospital Universitario Reina Sofía, IMIBIC, Córdoba, Spain. [Urrutia Royo,B] Pulmonary Dept, Thorax Clinic Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. [Fernández-Navamuel,I, Gimenez Velando,A, Nuñez García,L] Bronchoscopy and Interventional Pulmonology Unit, Pulmonology Dept, Hospital Fundacion Jimenez Diaz, ISS-FJD, CIBERES, Madrid, Spain. [Centeno Clemente,C, Andreo García,F] Interventional Pulmonology Unit, Pulmonary Dept, Thorax Clinic Institute, Hospital Universitari Germans Trias i Pujol, UAB, IGTP, Badalona, Spain. [Rafecas Codern,A, Fernández-Arias,C, Pajares Ruiz,V, Torrego Fernández,A] Respiratory Dept, Hospital Santa Creu i Sant Pau, Barcelona, Spain. [Rajas,O] Interventional Pulmonology Unit, Pulmonology Dept, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Madrid, Spain. [Iturricastillo,G] Pulmonology Dept, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, Madrid, Spain. [Garcia Lujan,R] Dept of Interventional Pulmonology, Hospital Universitario 12 Octubre and Hospital Univesitario Quirónsalud Madrid, Madrid, Spain. [Comeche Casanova,L] Dept of Pulmonology, Hospital Universitario Quirónsalud Madrid, Madrid, Spain. [Sánchez-Font,A] Pulmonology Dept, Hospital del Mar, CIBERES, UAB, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. [Aguilar-Colindres,R] Pulmonology Dept, Hospital del Mar, CIBERES, Barcelona, Spain. [Larrosa-Barrero,R] Pulmonary Dept, Hospital Universitario Clínico San Carlos, Madrid, Spain. [García García,R, Cordovilla,R] Interventional Pulmonology Unit, Pulmonary Dept, Salamanca University Hospital, Salamanca, Spain. [Núñez-Ares,A] Interventional Pulmonology Unit, Pulmonary Dept, Albacete, Spain. [Briones-Gómez,A, Cases Viedma,E] Interventional Pulmonology Unit, Pulmonary Dept, Hospital Universitario y Politécnico La Fe, Valencia, Spain. [Franco,J] Pneumology Service, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain. [Cosano Povedano,J] Bronchoscopy and Interventional Pulmonology Unit, Pulmonology Dept, Hospital Universitario Reina Sofía, IMIBIC, Córdoba, Spain. [Rodríguez-Perálvarez,ML] Maimónides Institute of Biomedical Research of Córdoba (IMIBIC), CIBERehd, Córdoba, Spain. [Cebrian Gallardo,JJ] Dept of Pulmonology, Agencia sanitaria Costa del Sol, Marbella, Spain. [Nuñez Delgado,M] Dept of Bronchoscopy and Interventional Pulmonology, Hospital Álvaro Cunqueiro, CHUVI, Vigo, Spain. [Pavón-Masa,M] Dept of Interventional Pulmonology, Hospital Universitario Virgen Macarena, Seville, Spain. [Valdivia Salas,MDM] Dept of Interventional Pulmonology, Hospital Universitario Santa Lucía, Cartagena, Spain. [Flandes,J] Bronchoscopy and Interventional Pulmonology Unit, Pulmonology Dept, Hospital Fundación Jimenez Diaz, ISS-FJD, CIBERES, Madrid, Spain., and The present study was funded by the Spanish Society of Pulmonology and Thoracic Surgery: extraordinary grant PII 2020 for research in COVID-19.
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Moco, medicine.medical_treatment, Check Tags::Male [Medical Subject Headings], Broncoscopía, medicine.disease_cause, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Respiratory System::Bronchoscopy [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Respiratory Therapy::Respiration, Artificial [Medical Subject Headings], Bronchoscopies, law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 03 medical and health sciences, Hyperaemia, 0302 clinical medicine, Bronchoscopy, law, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Statistical::Logistic Models [Medical Subject Headings], Internal medicine, Neumonía, medicine, 030212 general & internal medicine, Anatomy::Fluids and Secretions::Bodily Secretions::Mucus [Medical Subject Headings], Mechanical ventilation, medicine.diagnostic_test, business.industry, SARS-CoV-2, COVID-19, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality [Medical Subject Headings], Pneumonia, medicine.disease, Intensive care unit, Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings], Mucus, 030228 respiratory system, Superinfection, Cohort, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Medicine, Original Article, medicine.symptom, business
Abstract: BackgroundThe role of bronchoscopy in coronavirus disease 2019 (COVID-19) is a matter of debate.Patients and methodsThis observational multicentre study aimed to analyse the prognostic impact of bronchoscopic findings in a consecutive cohort of patients with suspected or confirmed COVID-19. Patients were enrolled at 17 hospitals from February to June 2020. Predictors of in-hospital mortality were assessed by multivariate logistic regression.ResultsA total of 1027 bronchoscopies were performed in 515 patients (age 61.5±11.2 years; 73% men), stratified into a clinical suspicion cohort (n=30) and a COVID-19 confirmed cohort (n=485). In the clinical suspicion cohort, the diagnostic yield was 36.7%. In the COVID-19 confirmed cohort, bronchoscopies were predominantly performed in the intensive care unit (n=961; 96.4%) and major indications were: difficult mechanical ventilation (43.7%), mucus plugs (39%) and persistence of radiological infiltrates (23.4%). 147 bronchoscopies were performed to rule out superinfection, and diagnostic yield was 42.9%. There were abnormalities in 91.6% of bronchoscopies, the most frequent being mucus secretions (82.4%), haematic secretions (17.7%), mucus plugs (17.6%), and diffuse mucosal hyperaemia (11.4%). The independent predictors of in-hospital mortality were: older age (OR 1.06; pConclusionBronchoscopy may be indicated in carefully selected patients with COVID-19 to rule out superinfection and solve complications related to mechanical ventilation. The presence of haematic secretions in the distal bronchial tract may be considered a poor prognostic feature in COVID-19.
Published: 2021

38. The clinical effectiveness of using a predictive algorithm to guide antidepressant treatment in primary care (PReDicT): an open-label, randomised controlled trial

Author: Richard Morriss, Michael Stäblein, Matilde Elices, Victor Perez Sola, Michael Browning, Philip Gorwood, Boliang Guo, Elisabetta Scanferla, Catherine J. Harmer, Andreas Reif, Henricus G. Ruhé, Colin T. Dourish, Judit Simon, Gerard R Dawson, Anne G. Lever, Jürgen Deckert, Dick J. Veltman, Guy M. Goodwin, Rebecca Dias, Anneke van Schaik, Andreas Menke, Amy C. Bilderbeck, J Kingslake, P1vital Ltd [Wallingford, UK] (Howbery Park), Department of Psychiatry [Oxford] (POWIC), University of Oxford-The Warneford Hospital, Warneford Hospital [Oxford, UK] (WH), University Hospital of Würzburg, University of Oxford, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, University of Nottingham, UK (UON), Goethe-University Frankfurt am Main, Radboud University [Nijmegen], Amsterdam Public Health Research Institute [The Netherlands], Medizinische Universität Wien = Medical University of Vienna, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), IMIM-Hospital del Mar, Generalitat de Catalunya, Amsterdam UMC - Amsterdam University Medical Center, Medical Park Chiemseeblick [Bernau-Felden, Germany], UFR d'études psychanalytiques (ED150 - Paris Diderot), Université Paris Diderot - Paris 7 (UPD7), Martinez Rico, Clara, University of Oxford [Oxford]-The Warneford Hospital, University of Oxford [Oxford], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Radboud university [Nijmegen], Amsterdam UMC, Psychiatry, APH - Mental Health, Anatomy and neurosciences, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: MEDLINE, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Human behaviour, medicine, Humans, Depression (differential diagnoses), Pharmacology, Response rate (survey), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Primary Health Care, business.industry, Depression, Cognition, Odds ratio, Anxiety Disorders, Antidepressive Agents, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Treatment Outcome, Anxiety, Antidepressant, medicine.symptom, business, Algorithm, 030217 neurology & neurosurgery, Algorithms, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Depressed patients often do not respond to the first antidepressant prescribed, resulting in sequential trials of different medications. Personalised medicine offers a means of reducing this delay; however, the clinical effectiveness of personalised approaches to antidepressant treatment has not previously been tested. We assessed the clinical effectiveness of using a predictive algorithm, based on behavioural tests of affective cognition and subjective symptoms, to guide antidepressant treatment. We conducted a multicentre, open-label, randomised controlled trial in 913 medication-free depressed patients. Patients were randomly assigned to have their antidepressant treatment guided by a predictive algorithm or treatment as usual (TaU). The primary outcome was the response of depression symptoms, defined as a 50% or greater reduction in baseline score of the QIDS-SR-16 scale, at week 8. Additional prespecified outcomes included symptoms of anxiety at week 8, and symptoms of depression and functional outcome at weeks 8, 24 and 48. The response rate of depressive symptoms at week 8 in the PReDicT (55.9%) and TaU (51.8%) arms did not differ significantly (odds ratio: 1.18 (95% CI: 0.89-1.56), P = 0.25). However, there was a significantly greater reduction of anxiety in week 8 and a greater improvement in functional outcome at week 24 in the PReDicT arm. Use of the PReDicT test did not increase the rate of response to antidepressant treatment estimated by depressive symptoms but did improve symptoms of anxiety at week 8 and functional outcome at week 24. Our findings indicate that personalisation of antidepressant treatment may improve outcomes in depressed patients. This project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 696802.
Published: 2021
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39. Cumulative Occupational Exposures and Lung Function Decline in Two Large General Population Cohorts

Author: Josep M. Antó, Deborah Jarvis, Roberto Bono, Simona Villani, Dennis Nowak, Hayat Bentouhami, Jan Paul Zock, Bénédicte Leynaert, Theodore Lytras, Kjell Torén, Isabel Urrutia, Joachim Heinrich, Bertil Forsberg, Isabelle Pin, Joost Weyler, Chantal Raherison Semjen, Jesús Martínez-Moratalla, Vivi Schlünssen, Giulia Squillacioti, Dirk Keidel, Nicole Probst-Hensch, Øistein Svanes, Torben Sigsgaard, Rain Jõgi, Pascal Demoly, Mathias Holm, Paul D. Blanc, Antonio Pereira Vega, John Watkins, Mario Olivieri, Amar Mehta, Anne-Elie Carsin, Anna Beckmeyer-Borowko, David Vernez, Thorarinn Gislason, Dan Norbäck, Roel Vermeulen, José Antonio Gullón, Manolis Kogevinas, Geza Benke, A. Sonia Buist, Hans Kromhout, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Swiss Tropical and Public Health Institute [Basel], University of Basel (Unibas), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Utrecht University [Utrecht], University of Antwerp (UA), Klinikum der Universitat Munchen, Ludwig-Maximilians-Universität München (LMU), German Center for Lung Research, Galdakao Hospital, Complejo Hospitalario Universitario de Albacete, Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Hospital Juan Ramón Jiménez, Cancer environnement (EPICENE ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine aiguë spécialisée, CHU Grenoble-Hôpital Michallon, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Università degli Studi di Pavia = University of Pavia (UNIPV), Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], University of Bergen (UiB), Sahlgrenska University Hospital [Gothenburg], Umeå University, Uppsala University, University of Copenhagen = Københavns Universitet (UCPH), Université de Lausanne = University of Lausanne (UNIL), Monash University [Melbourne], Tartu University Hospital [Tartu, Estonia], Sahlgrenska Academy at University of Gothenburg [Göteborg], Aarhus University [Aarhus], Università degli studi di Verona = University of Verona (UNIVR), University of California [San Francisco] (UC San Francisco), University of California (UC), Cardiff University, Università degli studi di Torino = University of Turin (UNITO), Oregon Health and Science University [Portland] (OHSU), Imperial College London, and Herrada, Anthony
Subjects: longitudinal studies, lung function, occupational disease, occupational exposure, spirometry, Vital Capacity, Spirometry, Lung function, Occupational Exposure, Occupational Disease, Longitudinal studies, VENTILATORY FUNCTION, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Occupational Exposure, Cohort Studies, 0302 clinical medicine, Forced Expiratory Volume, Medicine, 030212 general & internal medicine, Lung, MESH: Cohort Studies, Original Research, RISK, education.field_of_study, medicine.diagnostic_test, WORKERS, Occupational Diseases, SWISS, Occupational exposure, BURDEN, Adult, MESH: Occupational Diseases, Pulmonary and Respiratory Medicine, MESH: Bayes Theorem, Population, AMERICAN THORACIC SOCIETY, Occupational disease, MEDLINE, MESH: Forced Expiratory Volume, OBSTRUCTIVE PULMONARY-DISEASE, 03 medical and health sciences, Environmental health, Humans, COPD, MESH: Lung, education, MESH: Humans, business.industry, Bayes Theorem, MESH: Adult, AIR-POLLUTION, MESH: Vital Capacity, medicine.disease, respiratory tract diseases, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Human medicine, business, FOLLOW-UP
Abstract: International audience; Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.
Published: 2021
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40. Altered brain responses to specific negative emotions in schizophrenia

Author: Teresa Maristany, Carmen Natividad, Jesus J. Gomar, Raymond Salvador, Alicia Valiente-Gómez, Amalia Guerrero-Pedraza, Salvador Sarró, María Ángeles García-León, Edith Pomarol-Clotet, Francisco Portillo, Jordi Ortiz-Gil, Silvia Alonso-Lana, Pilar Salgado-Pineda, Paola Fuentes-Claramonte, Joaquim Radua, [Garcia-Leon MA, Fuentes-Claramonte P, Salgado-Pineda P] FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain. [Valiente-Gómez A] IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. [Natividad C] Hospital Mare de Déu de la Mercè, Barcelona, Spain. [Gomar JJ] Litwin-Zucker Alzheimer’s Disease Center, Feinstein Institute, Manhassett, NY, USA. [Guerrero-Pedraza A, Portillo F] Benito Menni Complex Assistencial en Salut Mental, Barcelona, Spain. [Ortiz-Gil J] Hospital General de Granollers, Granollers, Spain, and Hospital General de Granollers
Subjects: Neuroestimulació, Cognitive Neuroscience, media_common.quotation_subject, Happiness, Emotions, Computer applications to medicine. Medical informatics, R858-859.7, Stimulus (physiology), behavioral disciplines and activities, IAPS, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Tomography::Magnetic Resonance Imaging [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], mental disorders, medicine, Humans, Radiology, Nuclear Medicine and imaging, diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::tomografía::imagen por resonancia magnética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], RC346-429, Anterior cingulate cortex, media_common, Temporal cortex, Brain Mapping, técnicas de investigación::estimulación física::estimulación luminosa [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], fMRI, Brain, Regular Article, medicine.disease, Magnetic Resonance Imaging, Disgust, disciplinas y actividades conductuales::psicología del esquizofrénico [PSIQUIATRÍA Y PSICOLOGÍA], Sadness, Facial Expression, medicine.anatomical_structure, Neurology, Superior frontal gyrus, Schizophrenia, Mental Disorders::Personality Disorders::Schizotypal Personality Disorder [PSYCHIATRY AND PSYCHOLOGY], Esquizofrènia, Neurology (clinical), Neurology. Diseases of the nervous system, Psychology, Investigative Techniques::Physical Stimulation::Photic Stimulation [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Neuroscience, Imatgeria per al diagnòstic, psychological phenomena and processes, Scenic stimuli
Abstract: Highlights • Scenic stimuli might offer a better understanding of emotional processing than faces. • Emotional scenes were presented to schizophrenia patients and healthy controls. • Schizophrenia patients tend to misclassify emotional images as fear. • Schizophrenia patients hyperactivated regions involved in fear and disgust processing. • Patients’ brain response did not differ from controls in response to happy and sad scenes., Deficits in emotion processing are a core feature of schizophrenia, but their neurobiological bases are poorly understood. Previous research, mainly focused on emotional face processing and emotion recognition deficits, has shown controverted results. Furthermore, the use of faces has been questioned for not entailing an appropriate stimulus to study emotional processing. This highlights the importance of investigating emotional processing abnormalities using evocative stimuli. For the first time, we have studied the brain responses to scenic stimuli in patients with schizophrenia. We selected scenes from the IAPS that elicit fear, disgust, happiness, and sadness. Twenty-six patients with schizophrenia and thirty age-, sex- and premorbid IQ-matched healthy controls were included. Behavioral task results show that patients tended to misclassify disgust and sadness as fear. Brain responses in patients were different from controls in images eliciting disgust and fear. In response to disgust images, patients hyperactivated the right temporal cortex, which was not activated by the controls. With fear images, hyperactivation was observed in brain regions involved in fear processing, including midline regions from the medial frontal cortex to the anterior cingulate cortex, the superior frontal gyrus, inferior and superior temporal cortex, and visual areas. These results suggest that schizophrenia is characterized by hyper-responsivity to stimuli evoking high-arousal, negative emotions, and a bias towards fear in emotion recognition.
Published: 2021

41. The effect of short term exposure to outdoor air pollution on fertility

Author: Mark J. Nieuwenhuijsen, Tom Cole-Hunter, Bénédicte Jacquemin, Mireia González-Comadran, Rafael Lafuente, Miguel A. Checa, Marta Cirach, Mario Brassesco, Buenaventura Coroleu, IMIM-Hospital del Mar, Generalitat de Catalunya, École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CIBER de Epidemiología y Salud Pública (CIBERESP), University of Copenhagen = Københavns Universitet (KU), Instituto de Salud Carlos IIIInstituto de Salud Carlos IIIEuropean Commission [PI13/00454], AGAUR (Agency for Management of University and Research Grants, Generalitat de Catalunya), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and University of Copenhagen = Københavns Universitet (UCPH)
Subjects: Male, Time Factors, QH471-489, PM, [SDV]Life Sciences [q-bio], Air pollution, medicine.disease_cause, NO2, Miscarriage, Cohort Studies, 0302 clinical medicine, Endocrinology, Risk Factors, Pregnancy, 030212 general & internal medicine, Prospective cohort study, media_common, Nitrogen dioxide, ASSOCIATIONS, RISK, Air Pollutants, 030219 obstetrics & reproductive medicine, Obstetrics, Reproduction, Pregnancy Outcome, Obstetrics and Gynecology, Embryo transfer, Treatment Outcome, CARDIOVASCULAR-DISEASE, (2 5), Female, HEALTH, Infertility, Female, MAJOR ROADWAYS, Adult, medicine.medical_specialty, media_common.quotation_subject, EUROPEAN COHORTS, Reproductive medicine, Fertility, Fertilization in Vitro, PM2.5, ESCAPE, NO, PARTICULATE-MATTER, 03 medical and health sciences, PM10, LUNG-CANCER, Air Pollution, Acute exposure, medicine, Humans, business.industry, Research, Infant, Newborn, Environmental Exposure, Gynecology and obstetrics, medicine.disease, Abortion, Spontaneous, PHYSICAL-ACTIVITY, Reproductive Medicine, 13. Climate action, Spain, RG1-991, business, Particulate matter, Developmental Biology
Abstract: BackgroundThere is evidence to suggest that long term exposure to air pollution could be associated with decreased levels of fertility, although there is controversy as to how short term exposure may compromise fertility in IVF patients and what windows of exposure during the IVF process patients could be most vulnerable.MethodsThis prospective cohort study aimed to evaluate the impact of acute exposure that air pollution have on reproductive outcomes in different moments of the IVF process. Women undergoing IVF living in Barcelona were recruited. Individual air pollution exposures were modelled at their home address 15 and 3 days before embryo transfer (15D and 3D, respectively), the same day of transfer (D0), and 7 days after (D7). The pollutants modelled were: PM2.5[particulate matter (PM) ≤2.5 μm], PMcoarse(PM between 2.5 and 10μm), PM10(PM≤10 μm), PM2.5abs, and NO2and NOx. Outcomes were analyzed using multi-level regression models, with adjustment for co-pollutants and confouding factors. Two sensitivity analyses were performed. First, the model was adjusted for subacute exposure (received 15 days before ET). The second analysis was based on the first transfer performed on each patient aiming to exclude patients who failed previous transfers.ResultsOne hundred ninety-four women were recruited, contributing with data for 486 embryo transfers.Acute and subacute exposure to PMs showed a tendency in increasing miscarriage rate and reducing clinical pregnancy rate, although results were not statistically significant. The first sensitivity analysis, showed a significant risk of miscarriage for PM2.5exposure on 3D after adjusting for subacute exposure, and an increased risk of achieving no pregnancy for PM2.5, PMcoarseand PM10on 3D.The second sensitivity analysis showed a significant risk of miscarriage for PM2.5exposure on 3D, and a significant risk of achieving no pregnancy for PM2.5, PMcoarseand PM10 particularly on 3D. No association was observed for nitrogen dioxides on reproductive outcomes.ConclusionsExposure to particulate matter has a negative impact on reproductive outcomes in IVF patients. Subacute exposure seems to increase the harmful effect of the acute exposure on miscarriage and pregnancy rates. Nitrogen dioxides do not modify significantly the reproductive success.
Published: 2021
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42. Genome-wide transcriptome study in skin biopsies reveals an association of E2F4 with cadasil and cognitive impairment

Author: Israel Fernandez-Cadenas, Miquel Lledós, Ramon M. Pujol, Natalia Cullell, Jara Cárcel-Márquez, Olga Maisterra, Elena Muiño, Joan Jiménez-Balado, Cristina Gallego-Fabrega, Joan Montaner, Gemma Romeral, Jurek Krupinski, Ferran Olmos-Alpiste, Ana Rodríguez-Campello, Álvaro March, Eva Espejo, Jonathan González-Sánchez, Jaume Roquer, Caty Carrera, Nuria P. Torres-Aguila, Joan Martí-Fàbregas, University of St Andrews. School of Biology, [Muiño,E, Cullell,N, Carrera,C, Torres-Aguila,NP, Cárcel-Márquez,J, Gallego-Fabrega,C, Lledós,M, Fernández-Cadenas,I] Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l`Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Maisterra,O, Jiménez-Balado,J] Neurovascular Research Laboratory, Vall d’Hebron Institute of Research, Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. [Gallego-Fabrega,C, González-Sánchez,J] Stroke Pharmacogenomics and Genetics, Fundació MútuaTerrassa per la Docència i la Recerca, Terrassa, Spain. [González-Sánchez,J] The Manchester Metropolitan University of All Saints, Manchester, UK. [Olmos-Alpiste,F, Espejo,E, March,A, Pujol,R] Dermatology Department, Hospital del Mar-Parc de Salut Mar, Barcelona, Spain. [Rodríguez-Campello,A, Romeral,G, Roquer,J] Neurology Department, IMIM-Hospital del Mar, Barcelona, Spain. [Krupinski,J] Neurology Department, Hospital Mútua Terrassa, Terrassa, Spain. [Martí-Fàbregas,J] Neurology Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain. [Montaner,J] Biomedicine Institute of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC, University of Seville, Seville, Spain. [Montaner,J] Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain, This work was supported by a grant from the Carlos III Health Institute (PI 11/0176), Generación Project, Maestro Project, INVICTUS + network, Epigenesis Project (Marató de TV3), FEDER funds and economic donations from 'Asociación CADASIL España'. E. Muiño is supported by a Río Hortega Contract (CM18/00198) from the Carlos III Health Institute. J. Cárcel-Márquez is supported by an AGAUR Contract (agència de gestió d'ajuts universitaris i de recerca, FI_DGR 2019, grant number 2019_FI_B 00853) co-financed with Fons Social Europeu (FSE). M. Lledós is supported by a PFIS Contract (Contratos Predoctorales de Formación en Investigación en Salud) from the Carlos III Health Institute., Instituto de Salud Carlos III, Fundació La Marató de TV3, European Commission, Cadasil, Agència de Gestió d'Ajuts Universitaris i de Recerca, Institut Català de la Salut, [Muiño E, Carrera C, Torres-Aguila NP] Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Maisterra O, Jiménez-Balado J] Laboratori de Recerca Neurovascular, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Cullell N] Stroke Pharmacogenomics and Genetics Group, Institut de Recerca de l`Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Stroke Pharmacogenomics and Genetics, Fundació MútuaTerrassa per la Docència i la Recerca, Terrassa, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Atención, Male, Pathology, Endothelial cells, Ontología de genes, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genetic Research::Gene Ontology [Medical Subject Headings], Biopsy, QH301 Biology, Estudio de asociación del genoma completo, CADASIL, Transcriptomes, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::E2F Transcription Factors::E2F4 Transcription Factor [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Transcriptome, Diseases::Cardiovascular Diseases::Vascular Diseases::Cerebrovascular Disorders::Cerebral Small Vessel Diseases::CADASIL [Medical Subject Headings], Anatomy::Musculoskeletal System::Muscles::Muscle, Smooth::Muscle, Smooth, Vascular [Medical Subject Headings], Reacción en cadena de la polimerasa, Anatomy::Cells::Epithelial Cells::Endothelial Cells [Medical Subject Headings], Attention, Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Headache Disorders::Headache Disorders, Primary::Migraine Disorders [Medical Subject Headings], E2F4, Skin, Multidisciplinary, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], medicine.diagnostic_test, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Adhesion [Medical Subject Headings], Headache, Middle Aged, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome, Human [Medical Subject Headings], Polymerase chain reaction, Anatomy::Integumentary System::Skin [Medical Subject Headings], Stroke, Other subheadings::Other subheadings::/pathology [Other subheadings], Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Receptor Aggregation [Medical Subject Headings], Medicine, Biomarker (medicine), Female, Otros calificadores::Otros calificadores::/patología [Otros calificadores], Hibridación in situ, fenómenos genéticos::expresión génica::transcripción genética::fenómenos genéticos::transcriptoma [FENÓMENOS Y PROCESOS], In situ hybridization, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry, trastornos mentales::trastornos neurocognitivos::trastornos cognitivos::disfunción cognitiva [PSIQUIATRÍA Y PSICOLOGÍA], Adult, medicine.medical_specialty, Cell type, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], mRNA, Science, In silico, NDAS, Check Tags::Male [Medical Subject Headings], E2F4 Transcription Factor, QH426 Genetics, Biology, Trastorns de la cognició, Article, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Transcription, Genetic::Transcriptome [Medical Subject Headings], QH301, Executive function, Psychiatry and Psychology::Psychological Phenomena and Processes::Psychophysiology::Arousal::Attention [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cytodiagnosis::Biopsy [Medical Subject Headings], medicine, Humans, Cognitive Dysfunction, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytological Preparation Techniques::Staining and Labeling::In Situ Hybridization [Medical Subject Headings], Función ejecutiva, Persons::Persons::Age Groups::Adult [Medical Subject Headings], QH426, Mutación, ARN mensajero, Genome, Human, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies::Genome-Wide Association Study [Medical Subject Headings], Factor de transcripción E2F4, Genetic Phenomena::Gene Expression::Transcription, Genetic::Genetic Phenomena::Transcriptome [PHENOMENA AND PROCESSES], Células endoteliales, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings], Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger [Medical Subject Headings], medicine.disease, Transcriptoma, Check Tags::Female [Medical Subject Headings], Case-Control Studies, Mental Disorders::Neurocognitive Disorders::Cognition Disorders::Cognitive Dysfunction [PSYCHIATRY AND PSYCHOLOGY], Mutation, Skin biopsy, Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Executive Function [Medical Subject Headings], RC0321, Gene ontology, Dementia, Genome-Wide Association Study
Abstract: CADASIL is a small vessel disease caused by mutations in NOTCH3 that lead to an odd number of cysteines in the EGF-like repeat domain, causing protein misfolding and aggregation. The main symptoms are migraine, psychiatric disturbances, recurrent strokes and dementia, being executive function characteristically impaired. The molecular pathways altered by this receptor aggregation need to be studied further. A genome-wide transcriptome study (four cases paired with three healthy siblings) was carried out, in addition to a qRT-PCR for validation purposes (ten new cases and eight new controls). To study the expression profile by cell type of the significant mRNAs found, we performed an in situ hybridization (ISH) (nine cases and eight controls) and a research in the Single-nuclei Brain RNA-seq expression browser (SNBREB). Pathway analysis enrichment was carried out with Gene Ontology and Reactome. Neuropsychological tests were performed in five of the qRT-PCR cases. The two most significant differentially expressed mRNAs (BANP, p-value = 7.23 × 10–4 and PDCD6IP, p-value = 8.36 × 10–4) were selected for the validation study by qRT-PCR. Additionally, we selected two more mRNAs (CAMK2G, p-value = 4.52 × 10–3 and E2F4, p-value = 4.77 × 10–3) due to their association with ischemic neuronal death. E2F4 showed differential expression in the genome-wide transcriptome study and in the qRT-PCR (p = 1.23 × 10–3), and it was upregulated in CADASIL cases. Furthermore, higher E2F4 expression was associated with worse executive function (p = 2.04 × 10–2) and attention and information processing speed (IPS) (p = 8.73 × 10–2). In situ hibridization showed E2F4 expression in endothelial and vascular smooth vessel cells. In silico studies indicated that E2F4 is also expressed in brain endothelial cells. Among the most significant pathways analyzed, there was an enrichment of vascular development, cell adhesion and vesicular machinery terms and autophagy process. E2F4 is more highly expressed in the skin biopsy of CADASIL patients compared to controls, and its expression is present in endothelial cells and VSMCs. Further studies are needed to understand whether E2F4 could be useful as a biomarker, to monitor the disease or be used as a therapeutic target., This work was supported by a grant from the Carlos III Health Institute (PI 11/0176), Generación Project, Maestro Project, INVICTUS + network, Epigenesis Project (Marató de TV3), FEDER funds and economic donations from “Asociación CADASIL España”. E. Muiño is supported by a Río Hortega Contract (CM18/00198) from the Carlos III Health Institute. J. Cárcel-Márquez is supported by an AGAUR Contract (agència de gestió d'ajuts universitaris i de recerca; FI_DGR 2019, grant number 2019_FI_B 00853) co-financed with Fons Social Europeu (FSE). M. Lledós is supported by a PFIS Contract (Contratos Predoctorales de Formación en Investigación en Salud) from the Carlos III Health Institute.
Published: 2021

43. A brain atlas of axonal and synaptic delays based on modelling of cortico-cortical evoked potentials

Author: Jean-Didier, Lemaréchal, Maciej, Jedynak, Lena, Trebaul, Anthony, Boyer, François, Tadel, Manik, Bhattacharjee, Pierre, Deman, Viateur, Tuyisenge, Leila, Ayoubian, Etienne, Hugues, Blandine, Chanteloup-Forêt, Carole, Saubat, Raouf, Zouglech, Gina Catalina, Reyes Mejia, Sébastien, Tourbier, Patric, Hagmann, Claude, Adam, Carmen, Barba, Fabrice, Bartolomei, Thomas, Blauwblomme, Jonathan, Curot, François, Dubeau, Stefano, Francione, Mercedes, Garcés, Edouard, Hirsch, Elizabeth, Landré, Sinclair, Liu, Louis, Maillard, Eeva-Liisa, Metsähonkala, Ioana, Mindruta, Anca, Nica, Martin, Pail, Ana Maria, Petrescu, Sylvain, Rheims, Rodrigo, Rocamora, Andreas, Schulze-Bonhage, William, Szurhaj, Delphine, Taussig, Antonio, Valentin, Haixiang, Wang, Philippe, Kahane, Nathalie, George, Olivier, David, Elisa, Nacci, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Le Centre de Magnétoencéphalographie et d'Electroencéphalographie [CHU Pitié-Salpêtrière] (MEG-EEG), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Service de neurochirurgie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Hospital Universitario y Politécnico La Fe [Valencia, Spain], CHU Strasbourg, Centre Hospitalier Sainte Anne [Paris], Jinan University [Guangzhou], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University Emergency Hospital [Bucharest], Laboratoire Traitement du Signal et de l'Image (LTSI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), University Hospital Brno, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IMIM-Hospital del Mar, Generalitat de Catalunya, Freiburg University Medical Center, CHU Lille, Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Tsinghua University [Beijing] (THU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Firenze = University of Florence (UniFI), Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), The research leading to these results has received funding from the European Research Councilunder the European Union's Seventh Framework Programme (FP/2007-2013)/ERC GrantAgreement no. 616268 F-TRACT, the European Union’s Horizon 2020 FrameworkProgramme for Research and Innovation under Specific Grant Agreement No. 785907 and945539 (Human Brain Project SGA2 and SGA3), and from the French 'Investissementsd’avenir' programme under grant numbers ANR-11-INBS-0006 and ANR-10-IAIHU-06. PHwas supported by Swiss National Science Foundation grant #CRSII5_170873, ANR-11-INBS-0006,FLI,France Life Imaging(2011), European Project: 616268,EC:FP7:ERC,ERC-2013-CoG,F-TRACT(2014), European Project: 785907,H2020,HBP SGA2(2018), European Project: 945539,H2020,H2020-SGA-FETFLAG-HBP-2019,HBP SGA3(2020), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Gestionnaire, Hal Sorbonne Université, Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID, Functional Brain Tractography - F-TRACT - - EC:FP7:ERC2014-08-01 - 2019-07-31 - 616268 - VALID, Human Brain Project Specific Grant Agreement 2 - HBP SGA2 - - H20202018-04-01 - 2020-03-31 - 785907 - VALID, and Human Brain Project Specific Grant Agreement 3 - HBP SGA3 - - H20202020-01-01 - 2023-09-30 - 945539 - VALID
Subjects: neural mass models, 0303 health sciences, Brain Mapping, Epilepsy, cortico-cortical evoked potential, Brain, Bayes Theorem, Electric Stimulation, dynamic causal modelling, 03 medical and health sciences, 0302 clinical medicine, axonal conduction delay, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], synaptic time constant, Evoked Potentials, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (
Published: 2021
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44. Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation

Author: Arenas, Enrique J., Martínez-Sabadell, Alex, Rius Ruiz, Irene, Román Alonso, Macarena, Escorihuela, Marta, Luque, Antonio, Fajardo, Carlos Alberto, Gros, Alena, Klein, Christian, Arribas, Joaquín V, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Arenas EJ, Rius Ruiz I] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid 28029, Spain. [Martínez-Sabadell A, Román Alonso M, Escorihuela M, Luque A] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Fajardo CA, Gros A] Tumor Immunology & Immunotherapy Group, VHIO, Barcelona, Spain. [Arribas J] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid 28029, Spain. Tumor Immunology & Immunotherapy Group, VHIO, Barcelona, Spain. Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona 08003, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, Cytotoxicity, Immunologic, Receptor, ErbB-2, medicine.medical_treatment, T-Lymphocytes, General Physics and Astronomy, Cancer immunotherapy, Mice, 0302 clinical medicine, Neoplasms, Antibodies, Bispecific, Cytotoxic T cell, Otros calificadores::Otros calificadores::/inmunología [Otros calificadores], Multidisciplinary, Receptors, Chimeric Antigen, Cancer therapeutic resistance, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Signal Transduction, Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasm [PHENOMENA AND PROCESSES], T cell, Science, Down-Regulation, Biology, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, neoplasias [ENFERMEDADES], 03 medical and health sciences, Interferon-gamma, Other subheadings::Other subheadings::/immunology [Other subheadings], medicine, Animals, Humans, Resistència als medicaments, fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos [FENÓMENOS Y PROCESOS], Cancer, General Chemistry, Immunotherapy, Janus Kinase 2, medicine.disease, Chimeric antigen receptor, Neoplasms [DISEASES], 030104 developmental biology, Immunoediting, Tumor progression, Drug Resistance, Neoplasm, Cancer cell, Cancer research, Càncer - Immunoteràpia, Transcriptome
Abstract: Immunotherapy has raised high expectations in the treatment of virtually every cancer. Many current efforts are focused on ensuring the efficient delivery of active cytotoxic cells to tumors. It is assumed that, once these active cytotoxic cells are correctly engaged to cancer cells, they will unfailingly eliminate the latter, provided that inhibitory factors are in check. T cell bispecific antibodies (TCBs) and chimeric antigen receptors (CARs) offer an opportunity to test this assumption. Using TCB and CARs directed against HER2, here we show that disruption of interferon-gamma signaling confers resistance to killing by active T lymphocytes. The kinase JAK2, which transduces the signal initiated by interferon-gamma, is a component repeatedly disrupted in several independently generated resistant models. Our results unveil a seemingly widespread strategy used by cancer cells to resist clearance by redirected lymphocytes. In addition, they open the possibility that long-term inhibition of interferon-gamma signaling may impair the elimination phase of immunoediting and, thus, promote tumor progression., Several mechanisms of resistance to T cell-engaging therapies have been described for solid tumors. Here, by using T cell bispecific antibodies and chimeric antigen receptors (CAR) T cells targeting HER2, the authors show that cancer cell intrinsic disruption of interferon-gamma signalling, including downregulation of JAK2, confers resistance to T-cell mediated cytotoxicity.
Published: 2021

45. Identification of Lynch syndrome carriers among patients with small bowel adenocarcinoma

Author: Ariadna Sánchez, Luis Bujanda, Miriam Cuatrecasas, Alex Bofill, Cristina Alvarez-Urturi, Goretti Hernandez, Lara Aguilera, Sabela Carballal, Joan Llach, Cristina Herrera-Pariente, Mar Iglesias, Liseth Rivero-Sánchez, Gerhard Jung, Lorena Moreno, Teresa Ocaña, Carolina Bayarri, Maria Pellise, Antoni Castells, Sergi Castellví-Bel, Francesc Balaguer, Leticia Moreira, Institut Català de la Salut, [Sánchez A, Bofill A] Department of Gastroenterology, Hospital Clínic Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), University of Barcelona, Barcelona, Spain. [Bujanda L] Department of Gastroenterology, Biodonostia Health Research Institute, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain. [Cuatrecasas M] Department of Pathology, Hospital Clínic Barcelona, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS (Institut d’Investigacions Biomèdiques August Pi i Sunyer), University of Barcelona, Barcelona, Spain. [Alvarez-Urturi C] Department of Gastroenterology, IMIM (Hospital del Mar Medical Research Institute), Barcelona Hospital del Mar, Barcelona, Spain. [Hernandez G] Department of Gastroenterology, Hospital Universitario de Canarias, Tenerife, Spain. [Aguilera L] Servei de Gastroenterologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, Small bowel adenocarcinoma, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Rare Diseases [DISEASES], Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma [DISEASES], neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma [ENFERMEDADES], Lynch syndrome, small bowel adenocarcinoma, hereditary cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Malalties rares - Diagnòstic, Adenocarcinoma, enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::síndromes neoplásicos hereditarios::neoplasias colorrectales hereditarias sin poliposis [ENFERMEDADES], Article, digestive system diseases, Hereditary cancer, afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::enfermedades raras [ENFERMEDADES], Oncology, Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Neoplastic Syndromes, Hereditary::Colorectal Neoplasms, Hereditary Nonpolyposis [DISEASES], Malalties congènites, RC254-282
Abstract: Simple Summary Small bowel adenocarcinoma (SBA) is associated with Lynch syndrome (LS). This is the first study to evaluate the identification of LS patients based on mismatch repair deficiency (MMRd) tumor among SBA. The authors found a 21.3% prevalence of MMRd tumors and a 10.1% prevalence of LS. A germline mutation was identified in 60% of patients with a MMRd tumor. This data suggests that universal tumor MMR testing among SBA patients should be implemented for the identification of LS. Abstract Background: Small bowel adenocarcinoma (SBA) is a rare disease which can be associated with Lynch syndrome (LS). LS tumors are characterized by the presence of microsatellite instability (MSI) and/or the loss of mismatch repair (MMR) protein expression. In SBA, the frequency of MMR deficient (MMRd) tumors varies from 5% to 35%. This study aims to describe the prevalence of LS carriers among patients with MMRd small bowel adenocarcinomas. Methods: A multicenter retrospective study with identification and MMR testing of all consecutive SBA between 2004 and 2020 in a multicenter Spanish study. Demographical data, tumor characteristics, follow-up and survival information were collected. Germline testing was driven by identification of MMRd tumors. Results: A total of 94 individuals diagnosed with SBA were recruited. We observed 20 (21.3%) MMRd tumors. In 9/15 (60%) patients with MMRd tumors, a pathogenic variant was identified (three MLH1, four MSH2, one MSH6 and one PMS2). Accordingly, the prevalence of LS among all SBA cases was 10.1%. Conclusions: More than one-fifth of SBA display MMRd and in more than a half is due to LS. Our data supports the implementation of universal MMR tumor testing among SBA for the identification of LS families.
Published: 2021

46. Dynamic prediction of renal survival among deeply phenotyped kidney transplant recipients using artificial intelligence: an observational, international, multicohort study

Author: Raynaud, Marc, Aubert, Olivier, Divard, Gillian, Reese, Peter P, Kamar, Nassim, Yoo, Daniel, Chin, Chen-Shan, Bailly, Élodie, Buchler, Matthias, Ladrière, Marc, Le Quintrec, Moglie, Delahousse, Michel, Jurić, Ivana, Bašić-Jukić, Nikolina, Crespo, Marta, Silva, Helio Tedesco, Linhares, Kamilla, Ribeiro de Castro, Maria Cristina, Soler Pujol, Gervasio, Empana, Jean-Philippe, Ulloa, Camilo, Akalin, Enver, Böhmig, Georg, Huang, Edmund, Stegall, Mark D, Bentall, Andrew J, Montgomery, Robert A, Jordan, Stanley C, Oberbauer, Rainer, Segev, Dorry L, Friedewald, John J, Jouven, Xavier, Legendre, Christophe, Lefaucheur, Carmen, Loupy, Alexandre, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Pennsylvania, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Lorraine (UL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Foch [Suresnes], University of Zagreb, University Hospital Centre Zagreb, Partenaires INRAE, IMIM-Hospital del Mar, Generalitat de Catalunya, Universidade Federal de São Paulo, Universidade de São Paulo = University of São Paulo (USP), Albert Einstein College of Medicine [New York], Cedars-Sinai Medical Center, Mayo Clinic [Rochester], New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Medizinische Universität Wien = Medical University of Vienna, Johns Hopkins University School of Medicine [Baltimore], Northwestern University Feinberg School of Medicine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hopital Saint-Louis [AP-HP] (AP-HP), and Herrada, Anthony
Subjects: Male, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, MESH: Allografts, Kidney, MESH: Risk Assessment, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Kidney Transplantation, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Postoperative Complications, MESH: Postoperative Complications, MESH: Renal Insufficiency, artificial intelligence, kidney transplant, Renal Insufficiency, MESH: Middle Aged, Middle Aged, Allografts, Prognosis, MESH: Reproducibility of Results, Proteinuria, Area Under Curve, Female, Glomerular Filtration Rate, Adult, [INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI], MESH: Transplant Recipients, MESH: Bayes Theorem, Computer applications to medicine. Medical informatics, R858-859.7, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Models, Biological, Risk Assessment, MESH: Prognosis, Artificial Intelligence, MESH: Proteinuria, Humans, MESH: Artificial Intelligence, MESH: Humans, MESH: Models, Biological, Reproducibility of Results, Bayes Theorem, MESH: Adult, MESH: Kidney, Kidney Transplantation, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Transplant Recipients, MESH: Male, MESH: Glomerular Filtration Rate, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Area Under Curve, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
Abstract: Summary: Background: Kidney allograft failure is a common cause of end-stage renal disease. We aimed to develop a dynamic artificial intelligence approach to enhance risk stratification for kidney transplant recipients by generating continuously refined predictions of survival using updates of clinical data. Methods: In this observational study, we used data from adult recipients of kidney transplants from 18 academic transplant centres in Europe, the USA, and South America, and a cohort of patients from six randomised controlled trials. The development cohort comprised patients from four centres in France, with all other patients included in external validation cohorts. To build deeply phenotyped cohorts of transplant recipients, the following data were collected in the development cohort: clinical, histological, immunological variables, and repeated measurements of estimated glomerular filtration rate (eGFR) and proteinuria (measured using the proteinuria to creatininuria ratio). To develop a dynamic prediction system based on these clinical assessments and repeated measurements, we used a Bayesian joint models—an artificial intelligence approach. The prediction performances of the model were assessed via discrimination, through calculation of the area under the receiver operator curve (AUC), and calibration. This study is registered with ClinicalTrials.gov, NCT04258891. Findings: 13 608 patients were included (3774 in the development cohort and 9834 in the external validation cohorts) and contributed 89 328 patient-years of data, and 416 510 eGFR and proteinuria measurements. Bayesian joint models showed that recipient immunological profile, allograft interstitial fibrosis and tubular atrophy, allograft inflammation, and repeated measurements of eGFR and proteinuria were independent risk factors for allograft survival. The final model showed accurate calibration and very high discrimination in the development cohort (overall dynamic AUC 0·857 [95% CI 0·847–0·866]) with a persistent improvement in AUCs for each new repeated measurement (from 0·780 [0·768–0·794] to 0·926 [0·917–0·932]; p
Published: 2021
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47. Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies

Author: Bousquet, Jean, Cristol, Jean-Paul, Czarlewski, Wienczyslawa, Anto, Josep M, Martineau, Adrian, Haahtela, Tari, Fonseca, Susana C, Iaccarino, Guido, Blain, Hubert, Fiocchi, Alessandro, Canonica, G Walter, Fonseca, Joao A, Vidal, Alain, Choi, Hak-Jong, Kim, Hyun Ju, Le Moing, Vincent, Reynes, Jacques, Sheikh, Aziz, Akdis, Cezmi A, Zuberbier, Torsten, Amir Hamzah Abdul Latiff, Baharudin, Abdullah, Werner, Aberer, Nancy, Abusada, Ian, Adcock, Alejandro, Afani, Ioana, Agache, Xenofon, Aggelidis, Jenifer, Agustin, Cezmi, A Akdis, Mübeccel, Akdis, Mona, Al-Ahmad, Abou Al-Zahab Bassam, Hussam, Alburdan, Oscar, Aldrey-Palacios, Emilio Alvarez Cuesta, Hiba Alwan Salman, Ashraf, Alzaabi, Salma, Amade, Gene, Ambrocio, Rosana, Angles, Isabella, Annesi-Maesano, Ignacio, J Ansotegui, Josep, M Anto, Paula Ara Bardajo, Stefania, Arasi, Margarete, Arrais, Hasan, Arshad, Maria-Cristina, Artesani, Estrella, Asayag, Francesca, Avolio, Khuzama, Azhari, Claus, Bachert, Diego, Bagnasco, Ilaria, Baiardini, Nissera, Bajrović, Petros, Bakakos, Sergio Bakeyala Mongono, Christine, Balotro-Torres, Sergio, Barba, Cristina, Barbara, Elsa, Barbosa, Bruno, Barreto, Joan, Bartra, Xavier, Basagana, Eric, D Bateman, Lkhagvaa, Battur, Anna, Bedbrook, Martín Bedolla Barajas, Bianca, Beghé, Antra, Bekere, Elizabeth, Bel, Ali Ben Kheder, Mikael, Benson, Elena-Camelia, Berghea, Karl-Christian, Bergmann, Roberto, Bernardini, David, Bernstein, Mike, Bewick, Slawomir, Bialek, Artur, Białoszewski, Thomas, Bieber, Nils, E Billo, Maria-Beatrice, Bilo, Carsten, Bindslev-Jensen, Leif, Bjermer, Hubert, Blain, Irina, Bobolea, Malgorzata Bochenska Marciniak, Christine, Bond, Attilio, Boner, Matteo, Bonini, Sergio, Bonini, Sinthia, Bosnic-Anticevich, Isabelle, Bosse, Sofia, Botskariova, Jacques, Bouchard, Louis-Philippe, Boulet, Rodolphe, Bourret, Philippe, Bousquet, Fulvio, Braido, Andrew, Briggs, Christopher, E Brightling, Jan, Brozek, Luisa, Brussino, Roland, Buhl, Roxana, Bumbacea, Rosalva, Buquicchio, María-Teresa Burguete Cabañas, Andrew, Bush, William, W Busse, Jeroen, Buters, Fernan, Caballero-Fonseca, Moïses, A Calderon, Mario, Calvo, Paulo, Camargos, Thierry, Camuzat, R Canevari, F, Antonio, Cano, G Walter Canonica, Arnaldo, Capriles-Hulett, Luis, Caraballo, Vicky, Cardona, Kai-Hakon, Carlsen, Jonas Carmona Pirez, Jorge, Caro, Warner, Carr, Pedro, Carreiro-Martins, Fredelita, Carreon-Asuncion, Ana-Maria, Carriazo, Carme Carrion, Y Ribas, Thomas, Casale, Mary-Ann, Castor, Elizabeth, Castro, G Caviglia, A, Lorenzo, Cecchi, Alfonso Cepeda Sarabia, Maciej, Chalubinski, Ramanathan, Chandrasekharan, Yoon-Seok, Chang, Victoria, Chato-Andeza, Lida, Chatzi, Christina, Chatzidaki, Niels, H Chavannes, Claudia Chaves Loureiro, Aurora-Alejandra Chavez Garcia, Marta, Chelninska, Yuzhi, Chen, Lei, Cheng, Sharon, Chinthrajah, Tomas, Chivato, Ekaterine, Chkhartishvili, George, Christoff, Henry, Chrystyn, Derek, K Chu, Antonio, Chua, Alexander, Chuchalin, Kian Fan Chung, Alberto, Cicerán, Cemal, Cingi, Giorgio, Ciprandi, Ieva, Cirule, Ana-Carla, Coelho, Enrico, Compalati, Jannis, Constantinidis, Jaime Correia de Sousa, Elisio Manuel Costa, David, Costa, María Del Carmen Costa Domínguez, André, Coste, Cottini, M, Linda, Cox, Carlos, Crisci, Maria Angiola Crivellaro, Alvaro, A Cruz, John, Cullen, Adnan, Custovic, Biljana, Cvetkovski, Wienczyslawa, Czarlewski, Gennaro, D'Amato, Jane da Silva, Ronald, Dahl, Sven-Erik, Dahlen, Vasilis, Daniilidis, Louei Darjazini Nahhas, Ulf, Darsow, Janet, Davies, Frédéric de Blay, Giulia De Feo, Eloisa De Guia, José-Ricardo De la Torre Navarrete, Chato De Los Santos, Esteban De Manuel Keenoy, Govert De Vries, Diana, Deleanu, Pascal, Demoly, Judah, Denburg, Philippe, Devillier, Alain, Didier, Sanja Dimic Janjic, Maria, Dimou, Anh Tuan Dinh-Xuan, Ratko, Djukanovic, Maria Do Ceu Texeira, Dejan, Dokic, Margarita Gabriela Domínguez Silva, Habib, Douagui, Nikolaos, Douladiris, Maria, Doulaptsi, Gérard, Dray, Ruta, Dubakiene, Eve, Dupas, Stephen, Durham, Marzia, Duse, Mark, Dykewicz, Didier, Ebo, Natalija, Edelbaher, Thomas, Eiwegger, Patrik, Eklund, Yehia, El-Gamal, Zeinab, A El-Sayed, Shereen, S El-Sayed, Magda, El-Seify, Regina, Emuzyte, Lourdes, Enecilla, Marina, Erhola, Heidilita, Espinoza, Jesús Guillermo Espinoza Contreras, John, Farrell, Lenora, Fernandez, Paola Fimbres Jimenez, Antje Fink Wagner, Alessandro, Fiocchi, Wytske, J Fokkens, Lenia, Folletti, Joao, A Fonseca, Jean-François, Fontaine, Francesco, Forastiere, Jose Miguel Fuentes Pèrez, Emily, Gaerlan-Resureccion, Mina, Gaga, José Luis Gálvez Romero, Amiran, Gamkrelidze, Alexis, Garcia, Cecilia Yvonne García Cobas, María de la Luz Hortensia García Cruz, Valeria Garcia Ortiz, Jacques, Gayraud, Matteo, Gelardi, Bilun, Gemicioglu, Dimitra, Gennimata, Sonya, Genova, José, Gereda, Roy Gerth van Wijk, Antonio, Giuliano, René-Maximiliano, Gomez, Miguel-Ange Gonzalez Ballester, Sandra González Diaz, Maia, Gotua, Christos, Grigoreas, Ineta, Grisle, Marta, Guidacci, Nick, Guldemond, Zdenek, Gutter, Antonieta, Guzmán, Tari, Haahtela, Ramsa, Halloum, David, Halpin, Eckard, Hamelmann, Suleiman, Hammadi, Richard, Harvey, Enrico, Heffler, Joachim, Heinrich, Adnan, Hejjaoui, Birthe, Hellquist-Dahl, Luiana Hernández Velázquez, Mark, Hew, Elham, Hossny, Peter, Howarth, Martin, Hrubiško, Yunuen Rocío Huerta Villalobos, Marc, Humbert, Salina, Husain, Michael, Hyland, Guido, Iaccarino, Moustafa, Ibrahim, Nataliya, Ilina, Maddalena, Illario, Cristoforo, Incorvaia, Antonio, Infantino, Carla, Irani, Zhanat, Ispayeva, Juan Carlos Ivancevich, Edgardo Ej Jares, Deborah, Jarvis, Ewa, Jassem, Klemen, Jenko, Rubén Darío Jiméneracruz Uscanga, Sebastian, L Johnston, Guy, Joos, Maja, Jošt, Kaja, Julge, Ki-Suck, Jung, Jocelyne, Just, Marek, Jutel, Igor, Kaidashev, Omer, Kalayci, Fuat, Kalyoncu, Jeni, Kapsali, Przemyslaw, Kardas, Jussi, Karjalainen, Carmela, A Kasala, Michael, Katotomichelakis, Loreta, Kavaliukaite, Kazi, S Bennoor, Thomas, Keil, Paul, Keith, Musa, Khaitov, Nikolai, Khaltaev, You-Young, Kim, Bruce, Kirenga, Jorg, Kleine-Tebbe, Ludger, Klimek, Fanny, W Ko, Bernard Koffi N'Goran, Evangelia, Kompoti, Peter, Kopač, Gerard, Koppelman, Anja Koren Jeverica, Seppo, Koskinen, Mitja, Košnik, Tomasz, Kostka, Kosta, V Kostov, Marek, L Kowalski, Tanya, Kralimarkova, Karmen Kramer Vrščaj, Helga, Kraxner, Samo, Kreft, Vicky, Kritikos, Dmitry, Kudlay, Mikael, Kuitunen, Inger, Kull, Piotr, Kuna, Maciej, Kupczyk, Violeta, Kvedariene, Marialena, Kyriakakou, Nika, Lalek, Massimo, Landi, Stephen, Lane, Désiree, E Larenas-Linnemann, Susanne, Lau, Daniel, Laune, Jorge, Lavrut, Lan, Le, Martina, Lenzenhuber, Gualtiero, Leo, Marcus, Lessa, Michael, Levin, Jing, Li, Philip, Lieberman, Giuseppe, Liotta, Brian, Lipworth, Xuandao, Liu, Rommel, Lobo, Karin, C Lodrup Carlsen, Carlo, Lombardi, Renaud, Louis, Stelios, Loukidis, Olga, Lourenço, Jorge, A Luna Pech, Bojan, Madjar, Enrico, Maggi, Antoine, Magnan, Bassam, Mahboub, Alpana, Mair, Anke-Hilse Maitland van der Zee, Mika, Makela, Michael, Makris, Hans-Jorgen, Malling, Mariana, Mandajieva, Patrick, Manning, Manolis, Manousakis, Pavlos, Maragoudakis, Gianluigi, Marseglia, Gailen, Marshall, Mohammad Reza Masjedi, Jorge, F Máspero, Juan José Matta Campos, Marcus, Maurer, Sandra, Mavale-Manuel, Cem, Meço, Erik, Melén, Giovanni, Melioli, Elisabete, Melo-Gomes, Eli, O Meltzer, Enrica, Menditto, Andrew, Menzies-Gow, Hans, Merk, Jean-Pierre, Michel, Yann, Micheli, Neven, Miculinic, Luís, Midão, Florin, Mihaltan, Nikolaos, Mikos, Manlio, Milanese, Branislava, Milenkovic, Dimitrios, Mitsias, Bassem, Moalla, Giuliana, Moda, María Dolores Mogica Martínez, Yousser, Mohammad, Frances-Montserrat, Moharra, Mostafa, Moin, Mathieu, Molimard, Isabelle, Momas, Monique, Mommers, Alessandro, Monaco, Stephen, Montefort, Lucia-Elvira, Montenegro, Riccardo, Monti, Dory, Mora, Mario, Morais-Almeida, Ralph, Mösges, Badr Eldin Mostafa, Joaquim, Mullol, Lars, Münter, Antonella, Muraro, Ruth, Murray, Antonio, Musarra, Tihomir, Mustakov, Robert, Naclerio, Kari, C Nadeau, Rachel, Nadif, Alla, Nakonechna, Leyla, Namazova-Baranova, Gretchen, Navarro-Locsin, Hugo, Neffen, Kristof, Nekam, Angelos, Neou, Eustachio, Nettis, Daniel, Neuberger, Laurent, Nicod, Stefania, Nicola, Verena, Niederberger-Leppin, Marek, Niedoszytko, Antonio, Nieto, Ettore, Novellino, Elizabete, Nunes, Dieudonné, Nyembue, Robyn, E O'Hehir, Cvetanka, Odjakova, Ken, Ohta, Yoshitaka, Okamoto, Kimi, Okubo, Brian, Oliver, Gabrielle, L Onorato, Maria Pia Orru, Solange, Ouédraogo, Kampadilemba, Ouoba, Francisco-Javier, Padilla, Pier Luigi Paggiaro, Aris, Pagkalos, Pajno, Giovanni Battista, Gianni, Pala, P Palaniappan, S, Isabella, Pali-Schöll, Susanna, Palkonen, Stephen, Palmer, Carmen Panaitescu Bunu, Petr, Panzner, Nikos, G Papadopoulos, Vasilis, Papanikolaou, Alberto, Papi, Bojidar, Paralchev, Giannis, Paraskevopoulos, Hae-Sim, Park, Giovanni, Passalacqua, Vincenzo, Patella, Ian, Pavord, Ruby, Pawankar, Soren, Pedersen, Susete, Peleve, Simona, Pellegino, Ana, Pereira, Mariana, Pereira, Tamara, Pérez, Andrea, Perna, Diego, Peroni, Oliver, Pfaar, Nhân, Pham-Thi, Bernard, Pigearias, Isabelle, Pin, Konstantina, Piskou, Constantinos, Pitsios, Davor, Plavec, Dagmar, Poethig, Wolfgang, Pohl, Antonija Poplas Susic, Todor, A Popov, Fabienne, Portejoie, Paul, Potter, Lars, Poulsen, Alexandra, Prados-Torres, Fotis, Prarros, David, Price, Emmanuel, Prokopakis, Francesca, Puggioni, Elisa, Puig-Domenech, Robert, Puy, Klaus, Rabe, Silvia, Rabotti, Filip, Raciborski, Josephine, Ramos, Cristina, Recalcati, Marysia, T Recto, Shereen, M Reda, Frederico, S Regateiro, Norbert, Reider, Sietze, Reitsma, Susana, Repka-Ramirez, Erminia, Ridolo, Janet, Rimmer, Daniela Rivero Yeverino, José Angelo Rizzo, Carlos, Robalo-Cordeiro, Graham, Roberts, Karen, Robles, Nicolas, Roche, Mónica Rodríguez González, Eréndira Rodríguez Zagal, Giovanni, Rolla, Christine, Rolland, Regina, Roller-Wirnsberger, Miguel Roman Rodriguez, Antonino, Romano, Jan, Romantowski, Philippe, Rombaux, Joel, Romualdez, Jose, Rosado-Pinto, Nelson, Rosario, Lanny, Rosenwasser, Oliviero, Rossi, Menachem, Rottem, Philip, W Rouadi, Nikoleta, Rovina, Irma Rozman Sinur, Mauricio, Ruiz, Lucy Tania Ruiz Segura, Dermot, Ryan, Hironori, Sagara, Daiki, Sakai, Daiju, Sakurai, Wafaa, Saleh, Johanna, Salimaki, Konstantinos, Samitas, Boleslaw, Samolinski, María Guadalupe Sánchez Coronel, Mario, Sanchez-Borges, Jaime, Sanchez-Lopez, Melissa, Sansonna, Codrut, Sarafoleanu, Faradiba Sarquis Serpa, Joaquin, Sastre, Eleonora, Savi, Agne, Savonyte, Bisher, Sawaf, Glenis, K Scadding, Sophie, Scheire, Peter, Schmid-Grendelmeier, Juan Francisco Schuhl, Holger, Schunemann, Maria, Schvalbová, Jorgen, Schwarze, Nicola, Scichilone, Gianenrico, Senna, Cecilia, Sepúlveda, Elie, Serrano, Sara, Shamai, Aziz, Sheikh, Mike, Shields, Vasil, Shishkov, Nikos, Siafakas, Alexander, Simeonov, Estelle Fer Simons, Juan Carlos Sisul, Brigita, Sitkauskiene, Ingelbjorg, Skrindo, Tanja Soklič Košak, Dirceu, Solé, Martin, Sondermann, Talant, Sooronbaev, Manuel, Soto-Martinez, Manuel, Soto-Quiros, Barnaro Sousa Pinto, Milan, Sova, Michael, Soyka, Krzysztof, Specjalski, Annette, Sperl, Otto, Spranger, Sofia, Stamataki, Lina, Stefanaki, Cristiana, Stellato, Rafael, Stelmach, Timo, Strandberg, Petra, Stute, Abirami, Subramaniam, Charlotte Suppli Ulrik, Michael, Sutherland, Silvia, Sylvestre, Aikaterini, Syrigou, Luis Taborda Barata, Nadejda, Takovska, Rachel, Tan, Frances, Tan, Vincent, Tan, Ing Ping Tang, Masami, Taniguchi, Line, Tannert, Pongsakorn, Tantilipikorn, Jessica, Tattersall, Filippo, Tesi, Uta, Thieme, Carel, Thijs, Mike, Thomas, Teresa, To, Ana Maria Todo-Bom, Alkis, Togias, Peter-Valentin, Tomazic, Vesna, Tomic-Spiric, Sanna, Toppila-Salmi, Maria-José Torres Jaen, Elina, Toskala, Massimo, Triggiani, Nadja, Triller, Katja, Triller, Ioanna, Tsiligianni, Uberti, M, Ruxandra, Ulmeanu, Jure, Urbancic, Marilyn Urrutia Pereira, Martina, Vachova, Felipe, Valdés, Rudolf, Valenta, Marylin Valentin Rostan, Antonio, Valero, Arunas, Valiulis, Mina, Vallianatou, Erkka, Valovirta, Michiel Van Eerd, Eric Van Ganse, Marianne van Hage, Olivier, Vandenplas, Tuula, Vasankari, Dafina, Vassileva, Cesar Velasco Munoz, Maria Teresa Ventura, Cécilia, Vera-Munoz, Frédéric, Viart, Dilyana, Vicheva, Pakit, Vichyanond, Petra, Vidgren, Giovanni, Viegi, Claus, Vogelmeier, Leena Von Hertzen, Theodoros, Vontetsianos, Dimitris, Vourdas, Vu Tran Thien Quan, Martin, Wagenmann, Samantha, Walker, Dana, Wallace, Yun De Wang, Susan, Waserman, Katrin, Wehner, Magnus, Wickman, Sian, Williams, Dennis, Williams, Nicola, Wilson, Gary, Wong, Kent, Woo, Lucyna, Wozniak, John, Wright, Piotr, Wroczynski, Paraskevi, Xepapadaki, Plamen, Yakovliev, Masao, Yamaguchi, Kwok, Yan, Yoke Yeow Yap, Mais, Yassin, Barbara, Yawn, Panayiotis, Yiallouros, Arzu, Yorgancioglu, Shigemi, Yoshihara, Ian, Young, Osman, B Yusuf, Asghar, Zaidi, Fares, Zaitoun, Petra, Zalud, Heather, Zar, T Zedda, M, Mario, E Zernotti, Luo, Zhang, Nanshan, Zhong, Mihaela, Zidarn, Torsten, Zuberbier, Celia, Zubrinich, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Barts & The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Central Hospital [Finland] (HUCH), Departamento de Geociencias, Ambiente e Ordenamento do Territorio (DGAOT), Universidade do Porto = University of Porto, University of Naples Federico II = Università degli studi di Napoli Federico II, Euromov (EuroMov), Université de Montpellier (UM), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Center of Research in Health Technologies and Information Systems (CINTESIS), AgroParisTech, World Institute of Kimchi [Gwangju], Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Edinburgh, Universität Zürich [Zürich] = University of Zurich (UZH), Humboldt-Universität zu Berlin, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Universidade do Porto, University of Naples Federico II, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), MORNET, Dominique, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bousquet J., Cristol J.-P., Czarlewski W., Anto J.M., Martineau A., Haahtela T., Fonseca S.C., Iaccarino G., Blain H., Fiocchi A., Canonica G.W., Fonseca J.A., Vidal A., Choi H.-J., Kim H.J., Le Moing V., Reynes J., Sheikh A., Akdis C.A., Zuberbier T., Abdul Latiff A.H., Abdullah B., Aberer W., Abusada N., Adcock I., Afani A., Agache I., Aggelidis X., Agustin J., Akdis M., Al-Ahmad M., Al-Zahab Bassam A., Alburdan H., Aldrey-Palacios O., Alvarez Cuesta E., Alwan Salman H., Alzaabi A., Amade S., Ambrocio G., Angles R., Annesi-Maesano I., Ansotegui I.J., Ara Bardajo P., Arasi S., Arrais M., Arshad H., Artesani M.-C., Asayag E., Avolio F., Azhari K., Bachert C., Bagnasco D., Baiardini I., Bajrovic N., Bakakos P., Bakeyala Mongono S., Balotro-Torres C., Barba S., Barbara C., Barbosa E., Barreto B., Bartra J., Basagana X., Bateman E.D., Battur L., Bedbrook A., Bedolla Barajas M., Beghe B., Bekere A., Bel E., Ben Kheder A., Benson M., Berghea E.-C., Bergmann K.-C., Bernardini R., Bernstein D., Bewick M., Bialek S., Bialoszewski A., Bieber T., Billo N.E., Bilo M.-B., Bindslev-Jensen C., Bjermer L., Bobolea I., Bochenska Marciniak M., Bond C., Boner A., Bonini M., Bonini S., Bosnic-Anticevich S., Bosse I., Botskariova S., Bouchard J., Boulet L.-P., Bourret R., Bousquet P., Braido F., Briggs A., Brightling C.E., Brozek J., Brussino L., Buhl R., Bumbacea R., Buquicchio R., Burguete Cabanas M.-T., Bush A., Busse W.W., Buters J., Caballero-Fonseca F., Calderon M.A., Calvo M., Camargos P., Camuzat T., Canevari F., Cano A., Canonican G.W., Capriles-Hulett A., Caraballo L., Cardona V., Carlsen K.-H., Carmona Pirez J., Caro J., Carr W., Carreiro-Martins P., Carreon-Asuncion F., Carriazo A.-M., CarrionyRibas C., Casale T., Castor M.-A., Castro E., Caviglia A.G., Cecchi L., Cepeda Sarabia A., Chalubinski M., Chandrasekharan R., Chang Y.-S., Chato-Andeza V., Chatzi L., Chatzidaki C., Chavannes N.H., Chaves Loureiro C., Chavez Garcia A.-A., Chelninska M., Chen Y., Cheng L., Chinthrajah S., Chivato T., Chkhartishvili E., Christoff G., Chrystyn H., Chu D.K., Chua A., Chuchalin A., Chung K.F., Ciceran A., Cingi C., Ciprandi G., Cirule I., Coelho A.-C., Compalati E., Constantinidis J., Correia de Sousa J., Costa E.M., Costa D., del Carmen Costa Dominguez M., Coste A., Cottini M., Cox L., Crisci C., Crivellaro M.A., Cruz A.A., Cullen J., Custovic A., Cvetkovski B., D'Amato G., da Silva J., Dahl R., Dahlen S.-E., Daniilidis V., Darjazini Nahhas L., Darsow U., Davies J., de Blay F., De Feo G., De Guia E., De la Torre Navarrete J.-R., De los Santos C., De Manuel Keenoy E., De Vries G., Deleanu D., Demoly P., Denburg J., Devillier P., Didier A., Dimic Janjic S., Dimou M., Dinh-Xuan A.T., Djukanovic R., Do Ceu Texeira M., Dokic D., Dominguez Silva M.G., Douagui H., Douladiris N., Doulaptsi M., Dray G., Dubakiene R., Dupas E., Durham S., Duse M., Dykewicz M., Ebo D., Edelbaher N., Eiwegger T., Eklund P., El-Gamal Y., El-Sayed Z.A., El-Sayed S.S., El-Seify M., Emuzyte R., Enecilla L., Erhola M., Espinoza H., Espinoza Contreras J.G., Farrell J., Fernandez L., Fimbres Jimenez P., Fink Wagner A., Fokkens W.J., Folletti L., Fontaine J.-F., Forastiere F., Fuentes Perez J.M., Gaerlan-Resureccion E., Gaga M., Galvez Romero J.L., Gamkrelidze A., Garcia A., Garcia Cobas C.Y., de la Luz Hortensia Garcia Cruz M., Ortiz V.G., Gayraud J., Gelardi M., Gemicioglu B., Gennimata D., Genova S., Gereda J., Gerth van Wijk R., Giuliano A., Gomez R.-M., Gonzalez Ballester M.-A., Gonzalez Diaz S., Gotua M., Grigoreas C., Grisle I., Guidacci M., Guldemond N., Gutter Z., Guzman A., Halloum R., Halpin D., Hamelmann E., Hammadi S., Harvey R., Heffler E., Heinrich J., Hejjaoui A., Hellquist-Dahl B., Hernandez Velazquez L., Hew M., Hossny E., Howarth P., Hrubisko M., Huerta Villalobos Y.R., Humbert M., Husain S., Hyland M., Ibrahim M., Ilina N., Illario M., Incorvaia C., Infantino A., Irani C., Ispayeva Z., Ivancevich J.C., Jares E.E., Jarvis D., Jassem E., Jenko K., Jimeneracruz Uscanga R.D., Johnston S.L., Joos G., Jost M., Julge K., Jung K.-S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu F., Kapsali J., Kardas P., Karjalainen J., Kasala C.A., Katotomichelakis M., Kavaliukaite L., Bennoor K.S., Keil T., Keith P., Khaitov M., Khaltaev N., Kim Y.-Y., Kirenga B., Kleine-Tebbe J., Klimek L., Ko F.W., Koffi N'Goran B., Kompoti E., Kopac P., Koppelman G., Koren Jeverica A., Koskinen S., Kosnik M., Kostka T., Kostov K.V., Kowalski M.L., Kralimarkova T., Kramer Vrscaj K., Kraxner H., Kreft S., Kritikos V., Kudlay D., Kuitunen M., Kull I., Kuna P., Kupczyk M., Kvedariene V., Kyriakakou M., Lalek N., Landi M., Lane S., Larenas-Linnemann D.E., Lau S., Laune D., Lavrut J., Le L., Lenzenhuber M., Leo G., Lessa M., Levin M., Li J., Lieberman P., Liotta G., Lipworth B., Liu X., Lobo R., Lodrup Carlsen K.C., Lombardi C., Louis R., Loukidis S., Lourenco O., Luna Pech J.A., Madjar B., Maggi E., Magnan A., Mahboub B., Mair A., Maitland van der Zee A.-H., Makela M., Makris M., Malling H.-J., Mandajieva M., Manning P., Manousakis M., Maragoudakis P., Marseglia G., Marshall G., Masjedi M.R., Maspero J.F., Matta Campos J.J., Maurer M., Mavale-Manuel S., Meco C., Melen E., Melioli G., Melo-Gomes E., Meltzer E.O., Menditto E., Menzies-Gow A., Merk H., Michel J.-P., Micheli Y., Miculinic N., Midao L., Mihaltan F., Mikos N., Milanese M., Milenkovic B., Mitsias D., Moalla B., Moda G., Mogica Martinez M.D., Mohammad Y., Moharra F.-M., Moin M., Molimard M., Momas I., Mommers M., Monaco A., Montefort S., Montenegro L.-E., Monti R., Mora D., Morais-Almeida M., Mosges R., Mostafa B.E., Mullol J., Munter L., Muraro A., Murray R., Musarra A., Mustakov T., Naclerio R., Nadeau K.C., Nadif R., Nakonechna A., Namazova-Baranova L., Navarro-Locsin G., Neffen H., Nekam K., Neou A., Nettis E., Neuberger D., Nicod L., Nicola S., Niederberger-Leppin V., Niedoszytko M., Nieto A., Novellino E., Nunes E., Nyembue D., O'Hehir R.E., Odjakova C., Ohta K., Okamoto Y., Okubo K., Oliver B., Onorato G.L., Orru M.P., Ouedraogo S., Ouoba K., Padilla F.-J., Paggiaro P.L., Pagkalos A., Pajno G., Pala G., Palaniappan S., Pali-Scholl I., Palkonen S., Palmer S., Panaitescu Bunu C., Panzner P., Papadopoulos N.G., Papanikolaou V., Papi A., Paralchev B., Paraskevopoulos G., Park H.-S., Passalacqua G., Patella V., Pavord I., Pawankar R., Pedersen S., Peleve S., Pellegino S., Pereira A., Pereira M., Perez T., Perna A., Peroni D., Pfaar O., Pham-Thi N., Pigearias B., Pin I., Piskou K., Pitsios C., Plavec D., Poethig D., Pohl W., Poplas Susic A., Popov T.A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puggioni F., Puig-Domenech E., Puy R., Rabe K., Rabotti S., Raciborski F., Ramos J., Recalcati C., Recto M.T., Reda S.M., Regateiro F.S., Reider N., Reitsma S., Repka-Ramirez S., Ridolo E., Rimmer J., Rivero Yeverino D., Rizzo J.A., Robalo-Cordeiro C., Roberts G., Robles K., Roche N., Rodriguez Gonzalez M., Rodriguez Zagal E., Rolla G., Rolland C., Roller-Wirnsberger R., Roman Rodriguez M., Romano A., Romantowski J., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rossi O., Rottem M., Rouadi P.W., Rovina N., Rozman Sinur I., Ruiz M., Ruiz Segura L.T., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Samitas K., Samolinski B., Sanchez Coronel M.G., Sanchez-Borges M., Sanchez-Lopez J., Sansonna M., Sarafoleanu C., Sarquis Serpa F., Sastre J., Savi E., Savonyte A., Sawaf B., Scadding G.K., Scheire S., Schmid-Grendelmeier P., Schuhl J.F., Schunemann H., Schvalbova M., Schwarze J., Scichilone N., Senna G., Sepulveda C., Serrano E., Shamai S., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E.F., Sisul J.C., Sitkauskiene B., Skrindo I., Soklic Kosak T., Sole D., Sondermann M., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Pinto B.S., Sova M., Soyka M., Specjalski K., Sperl A., Spranger O., Stamataki S., Stefanaki L., Stellato C., Stelmach R., Strandberg T., Stute P., Subramaniam A., Suppli Ulrik C., Sutherland M., Sylvestre S., Syrigou A., Taborda Barata L., Takovska N., Tan R., Tan F., Tan V., Tang I.P., Taniguchi M., Tannert L., Tantilipikorn P., Tattersall J., Tesi F., Thieme U., Thijs C., Thomas M., To T., Todo-Bom A.M., Togias A., Tomazic P.-V., Tomic-Spiric V., Toppila-Salmi S., Torres Jaen M.-J., Toskala E., Triggiani M., Triller N., Triller K., Tsiligianni I., Uberti M., Ulmeanu R., Urbancic J., Urrutia Pereira M., Vachova M., Valdes F., Valenta R., Valentin Rostan M., Valero A., Valiulis A., Vallianatou M., Valovirta E., Van Eerd M., Van Ganse E., van Hage M., Vandenplas O., Vasankari T., Vassileva D., Velasco Munoz C., Ventura M.T., Vera-Munoz C., Viart F., Vicheva D., Vichyanond P., Vidgren P., Viegi G., Vogelmeier C., Von Hertzen L., Vontetsianos T., Vourdas D., Tran Thien Quan V., Wagenmann M., Walker S., Wallace D., De Wang Y., Waserman S., Wehner K., Wickman M., Williams S., Williams D., Wilson N., Wong G., Woo K., Wozniak L., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y.Y., Yassin M., Yawn B., Yiallouros P., Yorgancioglu A., Yoshihara S., Young I., Yusuf O.B., Zaidi A., Zaitoun F., Zalud P., Zar H., Zedda M.T., Zernotti M.E., Zhang L., Zhong N., and Zidarn M.
Subjects: MAPK/ERK pathway, ARIA group, Allergy, [SDV]Life Sciences [q-bio], NF-KAPPA-B, debelost, Review, Pharmacology, Resveratrol, PROTECTS, chemistry.chemical_compound, 0302 clinical medicine, RESPIRATORY SYNDROME CORONAVIRUS, ENDOPLASMIC-RETICULUM STRESS, Medicine and Health Sciences, Immunology and Allergy, Medicine, OXIDATIVE STRESS, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, 2. Zero hunger, 0303 health sciences, RESPIRATORY, INSULIN-RESISTANCE, Muscle cell proliferation, SULFORAPHANE, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SIGNALING PATHWAY, Signal transduction, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, NRF2 ACTIVATORS, MUSCLE-CELL PROLIFERATION, Immunology, 610 Medicine & health, Lung injury, Settore MED/10 - Malattie Dell'Apparato Respiratorio, ACUTE LUNG INJURY, 03 medical and health sciences, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, udc:616.9, odpornost proti inzulinu, SULFORAPHANE PROTECTS, Transcription factor, PI3K/AKT/mTOR pathway, 030304 developmental biology, Science & Technology, business.industry, SARS-CoV-2, food, medicine.disease, chemistry, hranila, SYNDROME CORONAVIRUS, business, hrana, GREEN TEA
Abstract: There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
Published: 2020
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48. Repair of G1 induced DNA double-strand breaks in S-G2/M by alternative NHEJ

Author: Loelia Babin, Caroline Demangel, Hélène Lenden-Hasse, Ludovic Deriano, Ludivine Baron, Erika Brunet, José Yélamos, Marie Bedora-Faure, Wei Yu, Chloé Lescale, Intégrité du génome, immunité et cancer - Genome integrity, Immunity and Cancer, Institut Pasteur [Paris], Genome dynamics in the immune system (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunobiologie de l'Infection - Immunobiology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), IMIM-Hospital del Mar, Generalitat de Catalunya, This project is funded by the Institut Pasteur (L.D. and C.D. labs), the Institut National du Cancer (INCa Grant # PLBIO16-181 to L.D. and E.B. labs), the Ligue Nationale Contre le Cancer (Équipe Labellisée 2019 L.D. lab and Équipe Labellisée 2017 and 2020 E.B. lab) the Cancéropôle IdF-INCa (Emergence 2016 grant to L.D. and C.D.), the Spanish Ministerio de Economía, Industria y Competitividad (Grant SAF2017-83565-R to J.Y.) as well as by the Fundación Científica de la Asociación Española Contra el Cáncer (AECC) (Grant PROYEI6018YÉLA to J.Y.)., We thank the Institut Pasteur genomics and cytometry platforms for help with sequencing and cell sorting, Frederick Alt and members of his lab for tremendous help with LAM-HTGTS experiments, Barry Sleckman for providing the RAG2-Thy1.1 complementation vector, Joy Bianchi for providing the Rag2−/− p53−/− v-Abl pro-B cell lines, Carine Giovannangeli and Anne de Cian for providing the Cas9 protein and Thomas Mercher for helpful discussions and suggestions., Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Demangel, Caroline, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Genome instability, DNA End-Joining Repair, MESH: DNA Breaks, Double-Stranded, Poly (ADP-Ribose) Polymerase-1, General Physics and Astronomy, MESH: Cell Cycle, MESH: Poly (ADP-Ribose) Polymerase-1, Genome, Càncer--Tractament, chemistry.chemical_compound, Mice, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, DNA Breaks, Double-Stranded, MESH: Animals, lcsh:Science, Double strand, Multidisciplinary, Cell Cycle, DNA repair protein XRCC4, Cell cycle, 3. Good health, Cell biology, DNA-Binding Proteins, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cell division, DNA repair, ADN--Dany, DNA recombination, Science, Double-strand DNA breaks, MESH: G1 Phase, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Targeted therapies, Animals, MESH: Mice, B cells, fungi, G1 Phase, General Chemistry, MESH: DNA End-Joining Repair, enzymes and coenzymes (carbohydrates), 030104 developmental biology, chemistry, lcsh:Q, Homologous recombination, DNA, MESH: DNA-Binding Proteins
Abstract: The alternative non-homologous end-joining (NHEJ) pathway promotes DNA double-strand break (DSB) repair in cells deficient for NHEJ or homologous recombination, suggesting that it operates at all stages of the cell cycle. Here, we use an approach in which DNA breaks can be induced in G1 cells and their repair tracked, enabling us to show that joining of DSBs is not functional in G1-arrested XRCC4-deficient cells. Cell cycle entry into S-G2/M restores DSB repair by Pol θ-dependent and PARP1-independent alternative NHEJ with repair products bearing kilo-base long DNA end resection, micro-homologies and chromosome translocations. We identify a synthetic lethal interaction between XRCC4 and Pol θ under conditions of G1 DSBs, associated with accumulation of unresolved DNA ends in S-G2/M. Collectively, our results support the conclusion that the repair of G1 DSBs progressing to S-G2/M by alternative NHEJ drives genomic instability and represent an attractive target for future DNA repair-based cancer therapies., Depending on the cell cycle stage, cells can repair their genome via different pathways. Here the authors reveal mechanistic insights into repair of double strand breaks induced during G1 in an error-prone manner by Pol θ-dependent and PARP1-independent alt NHEJ during the SG2/M phases of the cell cycle
Published: 2020
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49. Correction to: Vena cava filters in patients presenting with major bleeding during anticoagulation for venous thromboembolism

Author: Remedios Otero-Candelera, Carmine Siniscalchi, Matteo Giorgi-Pierfranceschi, Lucia Mazzolai, Egidio Imbalzano, Luis Jara-Palomares, Barbara Vitola, Christophe Vandenbriele, Laurent BERTOLETTI, Andris Skride, PEDRO RUIZ-ARTACHO, Isabelle Quere, Carme Font, María Jesús Jaras Hernández, Universitat Autònoma de Barcelona (UAB), IMIM-Hospital del Mar, Generalitat de Catalunya, Universidad Católica San Antonio de Murcia (UCAM), Hospital General Universitario Santa Lucía (Cartagena), Columbia University Medical Center (CUMC), Columbia University [New York], New York Presbyterian Hospital, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), University of Vigo [ Pontevedra], Kfar Saba and Sackler School of Medicine, Hospital Sant Joan de Déu [Barcelona], Hospital Universitario Miguel Servet, Université de Clermont-Ferrand, and Hopital Universitario Germans Trias i Pujol
Subjects: Vena cava filters, Plaintiff, medicine.medical_specialty, Statement (logic), business.industry, General surgery, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Emergency Medicine, Internal Medicine, medicine, In patient, business, Venous thromboembolism, Major bleeding
Abstract: International audience; In the original publication, part of the conflict of statement was incorrectly published as "Dr. Bikdeli reports that he was approached by lawyers on behalf of plaintiffs in litigation related to IVC filters". The correct statement should read as "Dr. Bikdeli reports that he is a consulting expert (on behalf of the plaintiff) for litigation related to a specific type of IVC filters".
Published: 2020
Full Text: View/download PDF

50. Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome

Author: Greetje Vande Velde, Neus Martínez-Abadías, Mara Dierssen, Alejandro González, Julia Albaigès, Xavier Sevillano, Rafael de la Torre, Sergi Llambrich, John M. Starbuck, Rubèn Gonzàlez, Jens Wouters, Anna Sarlé, James Sharpe, Universitat Ramon Llull. La Salle, University of Central Florida, Indiana University Robert H. McKinney School of Law, MoSAIC, Universitat de Barcelona, Barcelona Institute for Science and Technology, Universitat Pompeu Fabra, CIBERER, ICREA, European Molecular Biology Laboratory, IMIM-Hospital del Mar Medical Research Institute, and CIBERobn
Subjects: Male, Genètica -- Innovacions tecnològiques, Down syndrome, Physiology, Diseases, Catechin, Mice, Te verd, Child, Te, 61 - Medicina, Multidisciplinary, food and beverages, Skeleton (computer programming), medicine.anatomical_structure, Child, Preschool, Medicine, Female, 62 - Enginyeria. Tecnologia, Adolescent, Science, complex mixtures, Chromosomes, Article, 00 - Ciència i coneixement. Investigació. Cultura. Humanitats, medicine, Animals, Humans, Facial development, Mastication, Tea, business.industry, Plant Extracts, Infant, Translational research, Down, Síndrome de, medicine.disease, Green tea, Cromosomes, Malformacions -- Aspectes genètics, Disease Models, Animal, Face, Síndrome de Down, Dietary Supplements, Facial skeleton, Genètica -- Investigació, Down Syndrome, business, Trisomy, Chromosome 21
Abstract: Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studies. We acknowledge support from a 2016 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation IN[16]_CMA_BIO_0096 (NMA). We also acknowledge grant support from the following: CRG Awards for Collaborative Research Proposals, CRG Awards 2015-005822 (NMA, JA), Marguerite-Marie Delacroix Foundation fellowship (SL), Jerome Lejeune Foundation, #1782 (GVV, NMA), University of Central Florida start-up funds (JMS), American Association of Physical Anthropologists Professional Development Program Grant (JMS), Flemish Research Foundation (FWO) fellowship (GVV), and KU Leuven IF STG/15/024 (GVV), MINECO SAF2016-79956-R (MD), and the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013–2017’, SEV-2012-0208
Published: 2020

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