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1. Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53‐deficient myeloma cells

Author

Romane Durand, Céline Bellanger, Géraldine Descamps, Christelle Dousset, Sophie Maïga, Jennifer Derrien, Laura Thirouard, Louise Bouard, Hélène Asnagli, Philip Beer, Andrew Parker, Patricia Gomez‐Bougie, Marie‐Claire Devilder, Philippe Moreau, Cyrille Touzeau, Agnès Moreau‐Aubry, David Chiron, and Catherine Pellat‐Deceunynck

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract In multiple myeloma, as in B‐cell malignancies, mono‐ and especially bi‐allelic TP53 gene inactivation is a high‐risk factor for treatment resistance, and there are currently no therapies specifically targeting p53 deficiency. In this study, we evaluated if the loss of cell cycle control in p53‐deficient myeloma cells would confer a metabolically actionable vulnerability. We show that CTP synthase 1 (CTPS1), which encodes a CTP synthesis rate‐limiting enzyme essential for DNA and RNA synthesis in lymphoid cells, is overexpressed in samples from myeloma patients displaying a high proliferation rate (high MKI67 expression) or a low p53 score (synonymous with TP53 deletion and/or mutation). This overexpression of CTPS1 was associated with reduced survival in two cohorts. Using scRNA‐seq analysis in 24 patient samples, we further demonstrate that myeloma cells in the S or G2/M phase display high CTPS1 expression. Pharmacological inhibition of CTPS1 by STP‐B induced cell cycle arrest in early S phase in isogenic NCI‐H929 or XG7 TP53+/+, TP53−/−, and TP53R175H/R175H cells and in a TP53−/R123STOP patient sample. The functional annotation of transcriptional changes in 10 STP‐B‐treated myeloma cell lines revealed a decrease in protein translation and confirmed the blockade of cells into the S phase. The pharmacological inhibition of ATR, which governs the intrinsic S/G2 checkpoint, in STP‐B‐induced S‐phase arrested cells synergistically induced cell death in TP53+/+, TP53−/−, and TP53R175H/R175H isogenic cell lines (Bliss score >15). This combination induced replicative stress and caspase‐mediated cell death and was highly effective in resistant/refractory patient samples with TP53 deletion and/or mutation and in TP53−/− NCI‐H929 xenografted NOD‐scid IL2Rgamma mice. Our in vitro, ex vivo, and in vivo data provide the rationale for combined CTPS1 and ATR inhibition for the treatment of p53‐deficient patients.

Published
2024
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2. Comparative efficacy and safety of stiripentol, cannabidiol and fenfluramine as first‐line add‐on therapies for seizures in Dravet syndrome: A network meta‐analysis

Author

Renzo Guerrini, Catherine Chiron, Delphine Vandame, Warren Linley, and Toby Toward

Subjects
cannabidiol, Dravet syndrome, fenfluramine, network meta‐analysis, stiripentol, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Objectives Stiripentol, fenfluramine, and cannabidiol are licensed add‐on therapies to treat seizures in Dravet Syndrome (DS). There are no direct or indirect comparisons assessing their full licensed dose regimens, across different jurisdictions, as first‐line add‐on therapies in DS. Methods We conducted a systematic review and frequentist network meta‐analysis (NMA) of randomized controlled trial (RCT) data for licensed add‐on DS therapies. We compared the proportions of patients experiencing: reductions from baseline in monthly convulsive seizure frequency (MCSF) of ≥50% (clinically meaningful), ≥75% (profound), and 100% (seizure‐free); serious adverse events (SAEs); discontinuations due to AEs. Results We identified relevant data from two placebo‐controlled RCTs for each drug. Stiripentol 50 mg/kg/day and fenfluramine 0.7 mg/kg/day had similar efficacy in achieving ≥50% (clinically meaningful) and ≥75% (profound) reductions from baseline in MCSF (absolute risk difference [RD] for stiripentol versus fenfluramine 1% [95% confidence interval: −20% to 22%; p = 0.93] and 6% [−15% to 27%; p = 0.59], respectively), and both were statistically superior (p

Published
2024
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3. Pitfalls of using video‐EEG for a trial endpoint in children aged

Author

Ali Bozorg, Cynthia Beller, Lori Jensen, Alexis Arzimanoglou, Catherine Chiron, Dennis Dlugos, John Gaitanis, James W. Wheless, and Carrie McClung

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Objective Double‐blind, randomized, and placebo‐controlled trial SP0967 (NCT02477839/2013‐000717‐20) did not demonstrate superior efficacy of lacosamide versus placebo in patients aged ≥1 month to

Published
2024
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4. Immunomodulatory properties of CD38 antibodies and their effect on anticancer efficacy in multiple myeloma

Author

Kamlesh Bisht, Taro Fukao, Marielle Chiron, Paul Richardson, Djordje Atanackovic, Eduardo Chini, Wee Joo Chng, Helgi Van De Velde, and Fabio Malavasi

Subjects
adenosine, bone marrow niche, CD38 antibodies, daratumumab, immunomodulation, isatuximab, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background CD38 has been established as an important therapeutic target for multiple myeloma (MM), for which two CD38 antibodies are currently approved—daratumumab and isatuximab. CD38 is an ectoenzyme that degrades NAD and its precursors and is involved in the production of adenosine and other metabolites. Aim Among the various mechanisms by which CD38 antibodies can induce MM cell death is immunomodulation, including multiple pathways for CD38‐mediated T‐cell activation. Patients who respond to anti‐CD38 targeting treatment experience more marked changes in T‐cell expansion, activity, and clonality than nonresponders. Implications Resistance mechanisms that undermine the immunomodulatory effects of CD38‐targeting therapies can be tumor intrinsic, such as the downregulation of CD38 surface expression and expression of complement inhibitor proteins, and immune microenvironment‐related, such as changes to the natural killer (NK) cell numbers and function in the bone marrow niche. There are numerous strategies to overcome this resistance, which include identifying and targeting other therapeutic targets involved in, for example, adenosine production, the activation of NK cells or monocytes through immunomodulatory drugs and their combination with elotuzumab, or with bispecific T‐cell engagers.

Published
2023
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5. First demographic insights reveal high extinction risk of an endemic raptor species: the Reunion harrier

Author

Rémi Fay, Pierrick Ferret, Damien Chiron, Michael Schaub, and Steve Augiron

Subjects
Circus maillardi, extinction, fledging success, hatching success, population growth rate, population viability, Biology (General), QH301-705.5, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract

Gathering demographic information on rare species is critical to understanding their population dynamics and implementing efficient conservation measures. Using integrated models, we jointly analyzed multiple data sets, including capture–recapture, GPS tracking and nest monitoring data collected over the last 10 years, to provide the first demographic insights for one of the world's rarest raptors, the endemic Reunion harrier Circus maillardi. We estimated key demographic rates including annual survival and breeding parameters (clutch size, hatching and fledging success), and used population projection models to assess population growth rate and quasi‐extinction risk. In order to guide future conservation actions for the population, we evaluated the effects of different management scenarios that improve survival, fecundity, or both, on population growth and quasi‐extinction risk. Comparison of the estimated annual survival (juvenile and subadult survival: 0.66; adult survival: 0.71) and breeding parameters (clutch size: 2.3; hatching success: 0.45; fledging success: 0.83) with those of other harrier species suggests that adult survival and breeding parameters of Reunion harriers are low. A small data set collected 40 years ago suggests that the probability of an egg producing a fledgling was higher and has declined to the current low level. The population models project that the Reunion harrier population is declining and faces a high risk of quasi‐extinction in the next 40 years. Only management measures that simultaneously improve adult survival and fecundity could lead to a recovery of the population. These alarming results call for immediate conservation action aimed at rapidly improving the demographic rates.

Published
2023
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7. Sensory characterization of the perceived quality of East African Highland Cooking Bananas (Matooke)

Author

Khakasa, Elizabeth, Muyanja, Charles, Mugabi, Robert, Bugaud, Christophe, Forestier-Chiron, Nelly, Uwimana, Brigitte, Arinaitwe, Ivan Kabiita, Nowakunda, Kephas, Khakasa, Elizabeth, Muyanja, Charles, Mugabi, Robert, Bugaud, Christophe, Forestier-Chiron, Nelly, Uwimana, Brigitte, Arinaitwe, Ivan Kabiita, and Nowakunda, Kephas

Abstract

Background: In recent years, it has become increasingly evident that banana projects in Uganda needed to incorporate consumer preferences into the breeding pipelines to increase the acceptability of new cultivars. A trained panel used quantitative descriptive analysis (QDA) as a tool to assess the sensory characteristics of thirty-two cooking bananas (Matooke). The aim was to investigate which characteristics best-described matooke for consumer acceptability. Results: Fourteen descriptors were generated. The preferred attributes of matooke were high intensity of yellow colour, homogeneous distribution of yellow colour, good matooke aroma, highly moldable by touch, moist and smooth in the mouth. ANOVA revealed significant differences in the yellowness, homogeneity of the colour, firmness, moistness, smoothness, matooke aroma, hardness, and moldability across the genotypes (p<0.05). PCA showed strong positive correlations between yellowness and homogeneity of the colour (R=0.92). Smoothness in the mouth and moldability by touch were strongly and positively correlated (R=0.88). Firmness in the mouth was well predicted by hardness by touch (R2=0.85). The matooke samples were ranked into two sensory clusters by agglomerative hierarchical clustering (AHC). Conclusion: The study showed attribute terms that could be used to describe matooke, and also revealed that QDA may be used as a tool during the assessment and selection of new cooking banana hybrids to identify relevant sensory attributes because of its ability to discriminate among the banana hybrids.

Published
2024

8. Urban intensity gradients shape community structure, life‐history traits and performance in a multitrophic system

Author

Casanelles‐Abella, Joan, primary, Pellissier, Loïc, additional, Aleixo, Cristiana, additional, Orti, Marta Alós, additional, Chiron, François, additional, Deguines, Nicolas, additional, Laanisto, Lauri, additional, Myczko, Łukasz, additional, Müller, Stefanie, additional, Niinemets, Ülo, additional, Pinho, Pedro, additional, Samson, Roeland, additional, Tryjanowski, Piotr, additional, Villarroya‐Villalba, Lucía, additional, and Moretti, Marco, additional

Published
2024
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13. Geometric morphometric analysis reveals age-related differences in the distal femur of Europeans

Author

Etienne Cavaignac, Frederic Savall, Elodie Chantalat, Marie Faruch, Nicolas Reina, Philippe Chiron, and Norbert Telmon

Subjects
Distal femur dimorphism, Principal component analysis, Procrustes analysis, Geometric morphometric analysis, Biological anthropology, Orthopedic surgery, RD701-811
Abstract

Abstract Background Few studies have looked into age-related variations in femur shape. We hypothesized that three-dimensional (3D) geometric morphometric analysis of the distal femur would reveal age-related differences. The purpose of this study was to show that differences in distal femur shape related to age could be identified, visualized, and quantified using three-dimensional (3D) geometric morphometric analysis. Methods Geometric morphometric analysis was carried out on CT scans of the distal femur of 256 subjects living in the south of France. Ten landmarks were defined on 3D reconstructions of the distal femur. Both traditional metric and geometric morphometric analyses were carried out on these bone reconstructions. These analyses were used to identify trends in bone shape in various age-based subgroups (60). Results Only the average bone shape of the

Published
2017
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14. Three-dimensional geometric morphometric analysis reveals ethnic dimorphism in the shape of the femur

Author

Etienne Cavaignac, Ke Li, Marie Faruch, Frederic Savall, Philippe Chiron, W. Huang, and Norbert Telmon

Subjects
Distal femur dimorphism, Principal component analysis, Procrustes analysis, Geometric morphometric analysis, Biological anthropology, Orthopedic surgery, RD701-811
Abstract

Abstract Background Ethnic dimorphism in the distal femur has never been studied in a three-dimensional analysis focused on shape instead of size. Yet, this dimorphism has direct implications in orthopedic surgery and in anthropology. The goal of this study was to show that differences in distal femur shape related to ethnic dimorphism could be identified, visualized, and quantified using 3D geometric morphometric analysis. Methods CT scans of the distal femur were taken from 482 patients who were free of any bone-related pathology: 240 patients were European (E) and 242 were Asian (A). Ten osteometric landmarks based on standard bone landmarks used in anthropometry were placed on these scans. Geometric morphometric analysis, principal component analysis (PCA), canonical variates analysis (CVA), and other discriminant analyses (Goodall’s F-test and Mahalanobis distance) were performed. A cross-validation analysis was carried out to determine the percentage of cases in which the ethnicity was correctly estimated. Results The shape of the E and A distal femur differed significantly (Goodall’s F = 94.43, P

Published
2017
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15. <scp>Anti‐CD38</scp> monoclonal antibody interference with blood compatibility testing: Differentiating isatuximab and daratumumab via functional epitope mapping

Author

Btissam Chami, Makoto Okuda, Morvarid Moayeri, France Pirenne, Yoko Hidaka, Ashok Nambiar, Zhili Song, Olivier Bedel, Bailin Zhang, Joern Hopke, Gejing Deng, Chen Zhu, Sandrine Macé, Marielle Chiron, Francisco Adrian, Taro Fukao, Frank G. Basile, and Thomas Martin

Subjects
Mice, Neuroblastoma, Epitopes, Immunology, Animals, Antibodies, Monoclonal, Immunology and Allergy, Antineoplastic Agents, Hematology, Multiple Myeloma, ADP-ribosyl Cyclase 1, Epitope Mapping
Abstract

There are two FDA-approved anti-CD38 monoclonal antibodies for treatment of multiple myeloma: isatuximab and daratumumab. Owing to expression of CD38 on reagent red blood cells (RBCs), these antibodies interfere with indirect antiglobulin tests (IATs). We sought to understand differences in such interference by performing binding experiments.In vitro experiments to compare the binding to RBCs of isatuximab and daratumumab alone or in the presence of a mouse anti-human CD38 antibody (HB-7 or AT13/5) or a nicotinamide adenine dinucleotide-analog CD38 inhibitor were performed and quantified by flow cytometry, imaging, mass spectrometry, surface plasmon resonance, and LigandTracer technologies. Serologic testing was performed on plasma samples spiked with isatuximab or daratumumab.CD38 expressed on RBCs can be directly bound by daratumumab, whereas isatuximab requires a co-factor, such as HB-7, AT13/5, or a CD38 inhibitor, suggesting that the isatuximab epitope on RBCs is masked in vitro. Daratumumab samples more frequently showed interference and had stronger reactions than isatuximab samples. Dithiothreitol treatment was equally effective in mitigating the interference caused by either drug.Both isatuximab and daratumumab interfere with IATs but at different magnitudes, reflecting distinct binding to CD38 on RBCs. From the binding studies, we conclude that the isatuximab epitope on RBCs is masked in vitro and binding requires a certain CD38 conformation or co-factor. This circumstance may explain why interference is seen only in a subset of patients receiving isatuximab when compared with interference seen in most patients on daratumumab therapy.

Published
2022
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17. Mechanical approach for the evaluation of the crispiness of food granular products

Author

Boudina, Imen, Delalonde, Michèle, Koegel, Laurène, Maraval, Isabelle, Forestier-Chiron, Nelly, Domingo, Romain, Ricci, Julien, Sharkawi, Tahmer, Rondet, Eric, Boudina, Imen, Delalonde, Michèle, Koegel, Laurène, Maraval, Isabelle, Forestier-Chiron, Nelly, Domingo, Romain, Ricci, Julien, Sharkawi, Tahmer, and Rondet, Eric

Abstract

Crispiness of food products is a key parameter for consumer acceptance. Available methods to evaluate this attribute are subjective and have limitations. They are particularly difficult to implement when granular products are considered. The present study aims to provide a physical characterization of the crispiness of food granular products (gari and grinded corn flakes) based on the compression cycle modeling and the determination of the Py (yield pressure) parameter of the Heckel model. High Py values attributed to the brittle behavior, are indicative of product crispiness. Furthermore, Py parameter showed sensitivity to the plasticizing effect of water. This developed physical method was validated through sensory analysis and acoustic measurements which are both considered as reference methods for crispiness evaluation. The brittle/plastic behavior attributed to crispy/non crispy products respectively was confirmed through image analysis using X-ray microcomputed tomography. The latter made it possible to distinguish the brittle from the plastic behavior through the particle size distribution evolution. This work suggests that the Py value is a relevant indicator for the crispiness evaluation of granular products. This physical characterization is expected to contribute in food engineering as an alternative method for granular products crispiness in a simpler and a more objective way.

Published
2023

18. Density of predating Asian hornets at hives disturbs the 3D flight performance of honey bees and decreases predation success

Author

Poidatz, Juliette, Chiron, Guillaume, Kennedy, Peter J., Osborne, Juliet L., Requier, Fabrice, Poidatz, Juliette, Chiron, Guillaume, Kennedy, Peter J., Osborne, Juliet L., and Requier, Fabrice

Abstract

Automated 3D image-based tracking systems are new and promising devices to investigate the foraging behavior of flying animals with great accuracy and precision. 3D analyses can provide accurate assessments of flight performance in regard to speed, curvature, and hovering. However, there have been few applications of this technology in ecology, particularly for insects. We used this technology to analyze the behavioral interactions between the Western honey bee Apis mellifera and its invasive predator the Asian hornet, Vespa velutina nigrithorax. We investigated whether predation success could be affected by flight speed, flight curvature, and hovering of the Asian hornet and honey bees in front of one beehive. We recorded a total of 603,259 flight trajectories and 5175 predator–prey flight interactions leading to 126 successful predation events, representing 2.4% predation success. Flight speeds of hornets in front of hive entrances were much lower than that of their bee prey; in contrast to hovering capacity, while curvature range overlapped between the two species. There were large differences in speed, curvature, and hovering between the exit and entrance flights of honey bees. Interestingly, we found hornet density affected flight performance of both honey bees and hornets. Higher hornet density led to a decrease in the speed of honey bees leaving the hive, and an increase in the speed of honey bees entering the hive, together with more curved flight trajectories. These effects suggest some predator avoidance behavior by the bees. Higher honey bee flight curvature resulted in lower hornet predation success. Results showed an increase in predation success when hornet number increased up to 8 individuals, above which predation success decreased, likely due to competition among predators. Although based on a single colony, this study reveals interesting outcomes derived from the use of automated 3D tracking to derive accurate measures of individual behavior and be

Published
2023

24. Sensory characterization of the perceived quality of East African highland cooking bananas ( <scp> matooke </scp> )

Author

Elizabeth Khakasa, Charles Muyanja, Robert Mugabi, Christophe Bugaud, Nelly Forestier‐Chiron, Brigitte Uwimana, Ivan Kabiita Arinaitwe, and Kephas Nowakunda

Subjects
S01 - Nutrition humaine - Considérations générales, Nutrition and Dietetics, Sélection, Qualité des aliments, Comportement du consommateur, Banane plantain, F30 - Génétique et amélioration des plantes, Propriété organoleptique, Analyse quantitative, Analyse organoleptique, Préférence alimentaire, Q04 - Composition des produits alimentaires, Agronomy and Crop Science, Food Science, Biotechnology
Abstract

Background: In recent years, it has become increasingly evident that banana projects in Uganda needed to incorporate consumer preferences into the breeding pipelines to increase the acceptability of new cultivars. A trained panel used quantitative descriptive analysis (QDA) as a tool to assess the sensory characteristics of thirty-two cooking bananas (Matooke). The aim was to investigate which characteristics best-described matooke for consumer acceptability. Results: Fourteen descriptors were generated. The preferred attributes of matooke were high intensity of yellow colour, homogeneous distribution of yellow colour, good matooke aroma, highly moldable by touch, moist and smooth in the mouth. ANOVA revealed significant differences in the yellowness, homogeneity of the colour, firmness, moistness, smoothness, matooke aroma, hardness, and moldability across the genotypes (p

Published
2023
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27. An innovative ethosuximide granule formulation designed for pediatric use: Comparative pharmacokinetics, safety, tolerability, and palatability profile versus reference syrup

Author

Diezi, Léonore, primary, Dao, Kim, additional, Jullien, Vincent, additional, Roussel‐Maupetit, Caroline, additional, Burton, Ingrid, additional, André, Pascal, additional, Bardinet, Carine, additional, Rothuizen, Laura E., additional, Chtioui, Haithem, additional, Manso‐Silvan, Maria A., additional, Guittet, Catherine, additional, Brunner‐Ferber, Françoise, additional, Vandenhende, Francois, additional, Chiron, Catherine, additional, Granier, Luc‐André, additional, and Buclin, Thierry, additional

Published
2022
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28. Anti‐CD38 monoclonal antibody interference with blood compatibility testing: Differentiating isatuximab and daratumumab via functional epitope mapping

Author

Chami, Btissam, primary, Okuda, Makoto, additional, Moayeri, Morvarid, additional, Pirenne, France, additional, Hidaka, Yoko, additional, Nambiar, Ashok, additional, Song, Zhili, additional, Bedel, Olivier, additional, Zhang, Bailin, additional, Hopke, Joern, additional, Deng, Gejing, additional, Zhu, Chen, additional, Macé, Sandrine, additional, Chiron, Marielle, additional, Adrian, Francisco, additional, Fukao, Taro, additional, Basile, Frank G., additional, and Martin, Thomas, additional

Published
2022
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29. GluN2C selective inhibition is a target to develop new antiepileptic compounds

Author

Gataullina, Svetlana, primary, Galvani, Gilles, additional, Touchet, Sabrina, additional, Nous, Caroline, additional, Lemaire, Éric, additional, Laschet, Jacques, additional, Chiron, Catherine, additional, Dulac, Olivier, additional, Dossi, Elena, additional, Brion, Jean‐Daniel, additional, Messaoudi, Samir, additional, Alami, Mouad, additional, and Huberfeld, Gilles, additional

Published
2022
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31. Wild bee larval food composition in five European cities

Author

Casanelles‐Abella, Joan, primary, Keller, Alexander, additional, Müller, Stefanie, additional, Aleixo, Cristiana, additional, Alós‐Orti, Marta, additional, Chiron, François, additional, Laanisto, Lauri, additional, Myczko, Łukasz, additional, Pinho, Pedro, additional, Samson, Roeland, additional, Tryjanowski, Piotr, additional, Van Mensel, Anskje, additional, Villarroya‐Villalba, Lucía, additional, Pellissier, Loïc, additional, and Moretti, Marco, additional

Published
2022
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32. 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, Costa, E, Costa‐Dominguez, MC, Courbis, AL, Cox, L, Crescenzo, M, Cruz, AA, Custovic, A., Czarlewski, W., Dahlen, Se, D’Amato, G, Dario, C, Da Silva, J., Dauvilliers, Y., Darsow, U, De Blay, F., De Carlo, G, Dedeu, T, de Fátima Emerson, M, De Feo, G., De Vries, G, De Martino, B, Motta Rubini, NP, Deleanu, D, Denburg, JA, devillier, P., Di Capua Ercolano, S, Di Carluccio, N, Didier, A., Dokic, D, Dominguez‐Silva, MG, Douagui, H, Dray, G., Dubakiene, R, Durham, Sr, Du Toit, G, Dykewicz, MS, El‐Gamal, Y, Eklund, P, Eller, E, Emuzyte, R., Farrell, J, Farsi, A, de Mello, J Ferreira, Ferrero, J, Fink‐Wagner, A, Fiocchi, A, Fokkens, WJ, Fonseca, JA, Fontaine, Jf, Forti, S, Fuentes‐Perez, JM, Gálvez‐Romero, JL, Gamkrelidze, A, Garcia‐Aymerich, Judith, García‐Cobas, CY, Garcia‐Cruz, MH, Gemicioğlu, B, Genova, S, Christoff, G, Gereda, JE, Van Wijk, R Gerth, Gomez, RM, Gómez‐Vera, J, González Diaz, S, Gotua, M., Grisle, I, Guidacci, M, Guldemond, NA, Gutter, Z, Guzmán, MA, Haahtela, T., Hajjam, 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, Momas, I., Montefort, S, Mora Bogado, D, Morais‐Almeida, M, Morato‐Castro, FF, Mota‐Pinto, A, Moura Santo, P, Münter, 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, TD, O’Hehir, RE, Odzhakova, C, Ohta, K., Okamoto, Y., Okubo, K, Onorato, GL, Ortega Cisneros, M, Ouédraogo, S., Pali‐Schöll, I, Palkonen, S, Panzner, P, Papadopoulos, NG, Park, HS, Papi, A., Passalacqua, G, Paulino, E, Pawankar, R, Pedersen, S, Pépin, JL, Pereira, AM, Persico, M, PHILLIPS, J, Picard, R., Pigearias, B, Pin, I., Pitsios, C., Plavec, D, Pohl, W, Popov, TA, Portejoie, F., Potter, P, Pozzi, AC, Price, D, Prokopakis, EP, Puy, R, Pugin, B, Pulido Ross, RE, Przemecka, M, Rabe, KF, Raciborski, F, Rajabian‐Soderlund, R, Reitsma, S, Ribeirinho, I, Rimmer, J, Rivero‐Yeverino, D, Rizzo, JA, Rizzo, MC, Robalo‐Cordeiro, C, Rodenas, F, Rodo, X, Rodriguez Gonzalez, M, Rodriguez‐Mañas, L, Rolland, C, Rodrigues Valle, S, Roman Rodriguez, M., Romano, A, Rodriguez‐Zagal, E, Rolla, G, Roller‐Wirnsberger, RE, Romano, M, Rosado‐Pinto, J, Rosario, N., Rottem, M, Ryan, D, Sagara, H, Salimäki, J, Sanchez‐Borges, M, Sastre‐Dominguez, J, Scadding, GK, Schunemann, HJ, Scichilone, N, Schmid‐Grendelmeier, P, Sarquis Serpa, F, Shamai, S., Sheikh, A., Sierra, M, Simons, FER, Siroux, V., Sisul, JC, Skrindo, I, Solé, 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, Tebyriçá, JN, Thibaudon, M., To, T., Todo‐Bom, A, Tomazic, PV, Toppila‐Salmi, Sanna, 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, Ventura, MT, Vezzani, G, Vasankari, T, Vatrella, A., Verissimo, MT, Viart, F., Viegi, G., Vicheva, D, Vontetsianos, T, Wagenmann, M, Walker, 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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33. How wild bees find a way in European cities: Pollen metabarcoding unravels multiple feeding strategies and their effects on distribution patterns in four wild bee species

Author

Pedro Pinho, Nicolas Deguines, Stefanie Müller, Loïc Pellissier, Marta Alós Ortí, Anskje Van Mensel, Piotr Tryjanowski, Roeland Samson, Alexander Keller, François Chiron, Tiit Hallikma, Cristiana Aleixo, Joan Casanelles-Abella, Marco Moretti, Lauri Laanisto, Repositório da Universidade de Lisboa, Swiss Federal Institute for Forest, Snow and Landscape Research WSL, Institute of Terrestrial Ecosystems (ITES), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Department of Evolutionary Biology and Environmental Studies, Universität Zürich [Zürich] = University of Zurich (UZH), Ludwig-Maximilians-Universität München (LMU), Centre for Ecology - Evolution and Environmental Changes (cE3c), Universidade de Lisboa (ULISBOA), Institute of Agricultural and Environmental Sciences (IAES), Estonian University of Life Sciences (EMU), Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Ecologie, Evolution, Symbiose (EES), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), University of Antwerp (UA), Poznan University of Life Sciences (Uniwersytet Przyrodniczy w Poznaniu) (PULS), and ANR-16-EBI3-0012,BIOVEINS,Connectivity of green and blue infrastructures: living veins for biodiverse and healthy cities(2016)

Subjects
0106 biological sciences, Distribution (economics), urbanization, Biology, medicine.disease_cause, 010603 evolutionary biology, 01 natural sciences, urban biodiversity, 03 medical and health sciences, remote sensing, feeding behaviour, trap-nests, Urbanization, Pollen, medicine, species distribution models, 030304 developmental biology, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, 0303 health sciences, Ecology, business.industry, fungi, cavity-nesting bees, food and beverages, Remote sensing (archaeology), business
Abstract

1. Urban ecosystems can sustain populations of wild bees, partly because of their rich native and exotic floral resources. A better understanding of the urban bee diet, particularly at the larval stage, is necessary to understand biotic interactions and feeding behaviour in urban ecosystems, and to promote bees by improving the management of urban floral resources. 2. We investigated the larval diet and distribution patterns of four solitary wild bee species with different diet specialization (i.e. Chelostoma florisomne, Osmia bicornis, Osmia cornuta and Hylaeus communis) along urban intensity gradients in five European cities (Antwerp, Paris, Poznan, Tartu and Zurich) using two complementary analyses. Specifically, using trap-nests and pollen metabarcoding techniques, we characterized the species' larval diet, assessed diet consistency across cities and modelled the distribution of wild bees using species distribution models (SDMs). 3. Our results demonstrate that urban wild bees display different successful strategies to exploit existing urban floral resources: not only broad generalism (i.e. H. communis) but also intermediate generalism, with some degree of diet conservatism at the plant family or genus level (i.e. O. cornuta and O. bicornis), or even strict specialization on widely available urban pollen hosts (i.e. C. florisomne). Furthermore, we detected important diet variation in H. communis, with a switch from an herbaceous pollen diet to a tree pollen diet with increasing urban intensity. 4. Species distribution modelling indicated that wild bee distribution ranges inside urban ecosystems ultimately depend on their degree of specialization, and that broader diets result in less sensitivity to urban intensity. 5. Policy implications. Satisfying larval dietary requirements is critical to preserving and enhancing wild bee distributions within urban gradients. For high to intermediate levels of feeding specialization, we found considerable consistency in the preferred plant families or genera across the studied cities, which could be generalized to other cities where these bees occur. Identifying larval floral preferences (e.g. using pollen metabarcoding) could be helpful for identifying key plant taxa and traits for bee survival and for improving strategies to develop bee-friendly cities., Journal of Applied Ecology, 59 (2), ISSN:0021-8901, ISSN:1365-2664

Published
2021
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34. How wild bees find a way in European cities: Pollen metabarcoding unravels multiple feeding strategies and their effects on distribution patterns in four wild bee species

Author

Casanelles‐Abella, Joan, primary, Müller, Stefanie, additional, Keller, Alexander, additional, Aleixo, Cristiana, additional, Alós Orti, Marta, additional, Chiron, François, additional, Deguines, Nicolas, additional, Hallikma, Tiit, additional, Laanisto, Lauri, additional, Pinho, Pedro, additional, Samson, Roeland, additional, Tryjanowski, Piotr, additional, Van Mensel, Anskje, additional, Pellissier, Loïc, additional, and Moretti, Marco, additional

Published
2021
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36. Author response for 'Whole genome copy number analysis in search of new prognostic biomarkers in first line treatment of mantle cell lymphoma. A study by the <scp>LYSA</scp> group'

Author

Marie-Hélène Delfau-Larue, Olivier Pichon, Anne Moreau, Catherine Thieblemont, Olivier Hermine, Olivier Theisen, David Chiron, Florence Magrangeas, Yannick Le Bris, Marie C. Béné, Benoit Tessoulin, S. Minvielle, E. Gyan, Steven Le Gouill, Catherine Guérin-Charbonnel, Hervé Maisonneuve, Lucie Oberic, Barbara Burroni, Catherine Pellat-Deceunynck, and Danielle Canioni

Subjects
First line treatment, Group (mathematics), medicine, Cancer research, Copy number analysis, Mantle cell lymphoma, Biology, medicine.disease, Genome
Published
2020
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37. Early and long-term electroclinical features of patients with epilepsy and PCDH19 mutation

Author

Isabelle Desguerre, Anne Sophie Arbues, Nicole Chemaly, Anna Kaminska, Rima Nabbout, Isabelle An, Emma Losito, Jean Marc Pinard, Agnès Gautier, Olivier Dulac, Catherine Chiron, and Nathalie Villeneuve

Subjects
0301 basic medicine, Psychosis, Pediatrics, medicine.medical_specialty, Adolescent, Disease, 030105 genetics & heredity, Electroencephalography, Young Adult, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Dravet syndrome, Intellectual disability, medicine, Humans, Genetic Predisposition to Disease, Child, Retrospective Studies, medicine.diagnostic_test, business.industry, Brain, Infant, Cognition, General Medicine, Cadherins, medicine.disease, Protocadherins, Phenotype, Neurology, Frontal lobe, Child, Preschool, Mutation, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Protocadherin 19 (PCDH19) mutations have been identified in epilepsy in females with mental retardation as well as patients with a "Dravet-like" phenotype. We aimed to elucidate the electroclinical phenotype associated with PCDH19 mutation, which is currently difficult to identify at onset leading to a delay in diagnosis. We retrospectively reviewed clinical and EEG data for 13 consecutive patients with PCDH19 mutations or deletions diagnosed at our centers from 2009 to 2011, and followed these patients into adolescence and adulthood. We identified a specific temporal sequence of electroclinical manifestations, identified as three main stages. During the first two years of life, previously healthy girls presented with clusters of afebrile focal seizures. Early seizures were recorded on video-EEG in 10/13 patients, and were focal (n=8) with temporo-occipital and frontal onset. Three patients with strictly stereotyped focal seizures underwent a pre-surgical work-up. Two patients started with generalized seizures, one presenting with early-onset atypical absences and the other generalized tonic-clonic seizures. During the course of the disease, from two to 10 years, seizures became fever-sensitive and continued to recur in clusters, although these were less frequent. Seizures were mainly described by eyewitnesses as generalized tonic-clonic, even though three of five seizures, recorded on EEG, showed a focal onset with fast bilateral spread. Atypical absences and fever-induced tonic-clonic seizures remained frequent in only one patient until the age of 16 years. No specific treatment or combination appeared to be more effective over another. Various degrees of cognitive or behavioural impairment were reported for all patients, but it was in the second decade that behavioural disturbances prevailed with hetero-aggressiveness and behaviour associated with frontal lobe abnormalities leading to psychosis in two. Early recognition of the above features should improve early diagnosis and long-term management of patients with epilepsy and PCDH19 mutations.

Published
2018
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38. Proposition of a Minimal Effective Dose of Vigabatrin for the Treatment of Infantile Spasms Using Pediatric and Adult Pharmacokinetic Data

Author

Christelle Rodrigues, Vincent Jullien, Paul Duhamel, Catherine Chiron, Gérard Pons, Olivier Dulac, Hugues Bienayme, Rima Nabbout, and Marwa Ounissi

Subjects
Adult, Male, Minimal effective dose, medicine.medical_specialty, Population, Urology, Biological Availability, Renal function, Models, Biological, 030226 pharmacology & pharmacy, Vigabatrin, Treatment failure, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, medicine, Humans, Pharmacology (medical), Child, education, Distribution Volume, Pharmacology, education.field_of_study, business.industry, Infant, Increased risk, Child, Preschool, 030220 oncology & carcinogenesis, Anticonvulsants, Female, business, Monte Carlo Method, Spasms, Infantile, medicine.drug
Abstract

Vigabatrin is an antiepileptic drug indicated as monotherapy in infantile spasms. However, the pharmacokinetic profile of this compound in infants and young children is still poorly understood, as is the minimal effective dose, critical information given the risk of exposure-related retinal toxicity with vigabatrin. A reasonable approach to determining this minimal dose would be to identify the lowest dose providing a low risk of exposure overlap with the 36-mg/kg dose, which is the highest dose associated with an increased risk for treatment failure, based on randomized dose-ranging data. A population pharmacokinetic model was consequently developed from 28 children (aged 0.4-5.7 years) for the active S(+)-enantiomer, using Monolix software. In parallel, a population model was developed from published adult data and scaled to children using theoretical allometry and maturation of the renal function. A one-compartment model with zero-order absorption and first-order elimination described the pediatric data. Mean population estimates (percentage interindividual variability) for the apparent clearance, apparent distribution volume, and absorption duration were 2.36 L/h (24.5%), 17 L (38%), and 0.682 hours, respectively. Apparent clearance and apparent distribution volume were related to body weight by empirical allometric equations. Monte Carlo simulations evidenced that a daily dose of 80 mg/kg should minimize exposure overlap with the 36-mg/kg dose. Similar results were obtained for the adult model scaled to children. Consequently, a minimal effective dose of 80 mg/kg/day could be considered for patients with infantile spasms.

Published
2018
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39. Do children with Dravet syndrome continue to benefit from stiripentol for long through adulthood?

Author

Marie Hélias, Olivier Dulac, Rima Nabbout, Isabelle An, Bertrand de Toffol, Cécile Laroche, Anna Kaminska, and Catherine Chiron

Subjects
Adult, Male, 0301 basic medicine, Topiramate, Pediatrics, medicine.medical_specialty, Clobazam, Adolescent, Epilepsies, Myoclonic, Status epilepticus, Young Adult, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Dravet syndrome, Intellectual disability, Stiripentol, medicine, Humans, Longitudinal Studies, Child, Adverse effect, business.industry, Dioxolanes, medicine.disease, Treatment Outcome, 030104 developmental biology, Neurology, Disease Progression, Anticonvulsants, Drug Therapy, Combination, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Objective To evaluate continuing stiripentol treatment in adulthood in Dravet syndrome (DS). Method Longitudinal data were collected from the last visit prior to age 15 years (V15 y ) to the last visit in adulthood (Vadult ) in the 40 DS patients (32 typical, eight atypical) of a French historical cohort (Paris) of subjects who continued stiripentol from childhood or adolescence to adulthood. Results At Vadult (18-40 years, median = 23 years), all the patients were still receiving stiripentol (exposure = 3-24 years, median = 18 years), associated with clobazam (40/40), valproate (39/40), and topiramate (21/40). Between V15 y and Vadult , stiripentol was interrupted in five patients (two for adverse events) but reintroduced following seizure aggravation. Loss of appetite affected 15 of 40 patients but resolved after reducing the dose of stiripentol or valproate; no other new stiripentol-related adverse events were reported. Mean stiripentol dose was progressively decreased from 39 to 25 mg/kg/d (P = 0.0002), whereas clobazam (0.27 mg/kg/d) and valproate (14 mg/kg/d) remained stable. At Vadult , 37 of 40 patients still had generalized tonic-clonic seizures, but none still had status epilepticus (vs three at V15 y ) and only one had myoclonia. During adulthood, generalized tonic-clonic seizure frequency and duration continued to decrease (P = 0.02, P = 0.008) and 10 patients experienced seizure-free periods ≥ 1 years (up to 5 years). All patients already had intellectual disability at V15 y , but retardation was more severe at Vadult (P = 0.03). Furthermore, neurological/gait condition had declined (two patients became bedridden) and behavior had worsened (P 15 years) and the DS patients treated from adult age or stiripentol-naive subjects reported in the literature. Significance The efficacy and safety of the stiripentol/valproate/clobazam combination started at pediatric age are maintained at very long term during adulthood. Such prolonged stiripentol therapy tends to positively impact the late prognosis of epilepsy, especially when initiated before adolescence.

Published
2018
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43. Whole genome copy number analysis in search of new prognostic biomarkers in first line treatment of mantle cell lymphoma. A study by the LYSA group

Author

Le Bris, Yannick, primary, Magrangeas, Florence, additional, Moreau, Anne, additional, Chiron, David, additional, Guérin‐Charbonnel, Catherine, additional, Theisen, Olivier, additional, Pichon, Olivier, additional, Canioni, Danielle, additional, Burroni, Barbara, additional, Maisonneuve, Hervé, additional, Thieblemont, Catherine, additional, Oberic, Lucie, additional, Gyan, Emmanuel, additional, Pellat‐Deceunynck, Catherine, additional, Hermine, Olivier, additional, Delfau‐Larue, Marie‐Hélène, additional, Tessoulin, Benoît, additional, Béné, Marie‐Christine, additional, Minvielle, Stéphane, additional, and Le Gouill, Steven, additional

Published
2020
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44. Automatic differential analysis of NMR experiments in complex samples

Author

Petar Markov, Lionel Chiron, Mélanie Bourjot, Jean-Philippe Starck, Laure Margueritte, Marc-André Delsuc, and Catherine Vonthron-Sénécheau

Subjects
Signal processing, Drug discovery, Chemistry, 010401 analytical chemistry, Fingerprint (computing), Automatic processing, General Chemistry, 010402 general chemistry, 01 natural sciences, Differential analysis, 0104 chemical sciences, Liquid state, Metabolomics, General Materials Science, Biological system
Abstract

Liquid state nuclear magnetic resonance (NMR) is a powerful tool for the analysis of complex mixtures of unknown molecules. This capacity has been used in many analytical approaches: metabolomics, identification of active compounds in natural extracts, and characterization of species, and such studies require the acquisition of many diverse NMR measurements on series of samples. Although acquisition can easily be performed automatically, the number of NMR experiments involved in these studies increases very rapidly, and this data avalanche requires to resort to automatic processing and analysis. We present here a program that allows the autonomous, unsupervised processing of a large corpus of 1D, 2D, and diffusion-ordered spectroscopy experiments from a series of samples acquired in different conditions. The program provides all the signal processing steps, as well as peak-picking and bucketing of 1D and 2D spectra, the program and its components are fully available. In an experiment mimicking the search of a bioactive species in a natural extract, we use it for the automatic detection of small amounts of artemisinin added to a series of plant extracts and for the generation of the spectral fingerprint of this molecule. This program called Plasmodesma is a novel tool that should be useful to decipher complex mixtures, particularly in the discovery of biologically active natural products from plants extracts but can also in drug discovery or metabolomics studies.

Published
2018
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45. Population pharmacokinetics of oxcarbazepine and its monohydroxy derivative in epileptic children

Author

Christelle Rodrigues, Vincent Jullien, Olivier Dulac, Gérard Pons, Catherine Chiron, Elisabeth Rey, Emmanuelle Comets, Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MHD, Population, oxcarbazepine, Reference range, Childhood epilepsy, Pharmacology, Hydroxylation, Models, Biological, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, population pharmacokinetics, medicine, Humans, Computer Simulation, Pharmacology (medical), Trough Concentration, Child, Oxcarbazepine, education, Biotransformation, education.field_of_study, Epilepsy, Maintenance dose, Chemistry, Age Factors, Carbamazepine, 3. Good health, Area Under Curve, Child, Preschool, Concomitant, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Anticonvulsants, Female, Monte Carlo Method, 030217 neurology & neurosurgery, medicine.drug
Abstract

International audience; AimsOxcarbazepine is an antiepileptic drug with an activity mostly due to its monohydroxy derivative metabolite (MHD). A parent-metabolite population pharmacokinetic model in children was developed to evaluate the consistency between the recommended paediatric doses and the reference range for trough concentration (Ctrough) of MHD (3–35 mg l–1).MethodsA total of 279 plasma samples were obtained from 31 epileptic children (age 2–12 years) after a single dose of oxcarbazepine. Concentration-time data were analysed with Monolix 4.3.2. The probability to obtain Ctrough between 3–35 mg l–1 was determined by Monte Carlo simulations for doses ranging from 10 to 90 mg kg–1 day–1.ResultsA parent-metabolite model with two compartments for oxcarbazepine and one compartment for MHD best described the data. Typical values for oxcarbazepine clearance, central and peripheral distribution volume and distribution clearance were 140 l h–1 70 kg–1, 337 l 70 kg–1, 60.7 l and 62.5 l h–1, respectively. Typical values for MHD clearance and distribution volume were 4.11 l h–1 70 kg–1 and 54.8 l 70 kg–1 respectively. Clearances and distribution volumes of oxcarbazepine and MHD were related to body weight via empirical allometric models. Enzyme-inducing antiepileptic drugs (EIAEDs) increased MHD clearance by 29.3%. Fifty-kg children without EIAEDs may need 20–30 mg kg–1 day–1 instead of the recommended target maintenance dose (30–45 mg kg–1 day–1) to obtain Ctrough within the reference range. By contrast, 10-kg children with EIAEDs would need 90 mg kg–1 day–1 instead of the maximum recommended dose of 60 mg kg–1 day–1.ConclusionThis population pharmacokinetic model of oxcarbazepine supports current dose recommendations, except for 10-kg children with concomitant EIAEDs and 50-kg children without EIAEDs.

Published
2017
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47. Functional integration changes in regional brain glucose metabolism from childhood to adulthood

Author

Frédérique Archambaud, Serge Goldman, Catherine Chiron, Kristof Baete, Koen Van Laere, Nicola Trotta, Patrick Van Bogaert, Xavier De Tiège, and Vincent Wens

Subjects
0301 basic medicine, Radiological and Ultrasound Technology, Functional integration (neurobiology), medicine.diagnostic_test, Psychophysiological Interaction, Sensory system, Cognition, Hippocampal formation, Statistical parametric mapping, Insular cortex, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, nervous system, Neurology, Positron emission tomography, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Anatomy, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract

The aim of this study was to investigate the age-related changes in resting-state neurometabolic connectivity from childhood to adulthood (6-50 years old). Fifty-four healthy adult subjects and twenty-three pseudo-healthy children underwent [(18) F]-fluorodeoxyglucose positron emission tomography at rest. Using statistical parametric mapping (SPM8), age and age squared were first used as covariate of interest to identify linear and non-linear age effects on the regional distribution of glucose metabolism throughout the brain. Then, by selecting voxels of interest (VOI) within the regions showing significant age-related metabolic changes, a psychophysiological interaction (PPI) analysis was used to search for age-induced changes in the contribution of VOIs to the metabolic activity in other brain areas. Significant linear or non-linear age-related changes in regional glucose metabolism were found in prefrontal cortices (DMPFC/ACC), cerebellar lobules, and thalamo-hippocampal areas bilaterally. Decreases were found in the contribution of thalamic, hippocampal, and cerebellar regions to DMPFC/ACC metabolic activity as well as in the contribution of hippocampi to preSMA and right IFG metabolic activities. Increases were found in the contribution of the right hippocampus to insular cortex and of the cerebellar lobule IX to superior parietal cortex metabolic activities. This study evidences significant linear or non-linear age-related changes in regional glucose metabolism of mesial prefrontal, thalamic, mesiotemporal, and cerebellar areas, associated with significant modifications in neurometabolic connectivity involving fronto-thalamic, fronto-hippocampal, and fronto-cerebellar networks. These changes in functional brain integration likely represent a metabolic correlate of age-dependent effects on sensory, motor, and high-level cognitive functional networks. Hum Brain Mapp 37:3017-3030, 2016. © 2016 Wiley Periodicals, Inc.

Published
2016
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48. INCREASED CCND1 FISH SIGNALS ARE ASSOCIATED WITH WORSE PROGNOSIS IN MANTLE CELL LYMPHOMA

Author

Hervé Maisonneuve, Y. Le Bris, Céline Bossard, Benoit Tessoulin, Marie-Christine Béné, Olivier Theisen, S. Le Gouill, Thomas Gastinne, François Subiger, Catherine Godon, David Chiron, Anne-Sophie Moreau, and Mourad Tiab

Subjects
Cancer Research, Cyclin D1, Oncology, Cancer research, medicine, %22">Fish , Mantle cell lymphoma, Hematology, General Medicine, Biology, medicine.disease
Published
2019
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49. Exploration of potential prognostic biomarkers in aflibercept plusFOLFIRIin Japanese patients with metastatic colorectal cancer

Author

Hamaguchi, Tetsuya, primary, Denda, Tadamichi, additional, Kudo, Toshihiro, additional, Sugimoto, Naotoshi, additional, Ura, Takashi, additional, Yamazaki, Kentaro, additional, Fujii, Hirofumi, additional, Kajiwara, Takeshi, additional, Nakajima, Takako Eguchi, additional, Takahashi, Shin, additional, Otsu, Satoshi, additional, Komatsu, Yoshito, additional, Nagashima, Fumio, additional, Moriwaki, Toshikazu, additional, Esaki, Taito, additional, Sato, Takeo, additional, Itabashi, Michio, additional, Oki, Eiji, additional, Sasaki, Toru, additional, Chiron, Marielle, additional, and Yoshino, Takayuki, additional

Published
2019
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