Author: "Medical University of Gdańsk" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Medical University of Gdańsk"' showing total 5,066 results

Start Over Author "Medical University of Gdańsk"

5,066 results on '"Medical University of Gdańsk"'

1. Assessment of Patients With Drug-resistant Temporal Lobe Epilepsy With EEG Extended With Intra-auricular Electrodes

Author: NaoX Technologies, Warsaw Medical University Clinical Center, Departments and Clinics of Emergency Medicine of the Medical University of Gdańsk, and Przemyslaw Kunert, Professor Dr. Hab.
Published: 2024

2. Refined treatment response criteria for indolent systemic mastocytosis proposed by the ECNM-AIM consortium

Author: National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Medical University of Gdańsk, Austrian Science Fund, Pyatilova, Polina, Akin, Cem, Álvarez-Twose, Iván, Arock, Michel, Bonadonna, Patrizia, Brockow, Knut, Butterfield, Joseph H., Broesby-Olsen, Sigurd, Carter, Melody C., Castells, Mariana, George, Tracy I., Gotlib, Jason, Greiner, Georg, Gulen, Theo, Hartmann, Karin, Hermine, Olivier, Horny, Hans-Peter, Jawhar, Mohamad, Lange, Magdalena, Lyons, Jonathan J., Maurer, Marcus, Metcalfe, Dean D., Nedoszytko, Boguslaw, Niedoszytko, Marek, Orfao, Alberto, Reiter, Andreas, Schwaab, Juliana, Sotlar, Karl, Sperr, Wolfgang R., Triggiani, Massimo, Valent, Peter, Siebenhaar, Frank, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Medical University of Gdańsk, Austrian Science Fund, Pyatilova, Polina, Akin, Cem, Álvarez-Twose, Iván, Arock, Michel, Bonadonna, Patrizia, Brockow, Knut, Butterfield, Joseph H., Broesby-Olsen, Sigurd, Carter, Melody C., Castells, Mariana, George, Tracy I., Gotlib, Jason, Greiner, Georg, Gulen, Theo, Hartmann, Karin, Hermine, Olivier, Horny, Hans-Peter, Jawhar, Mohamad, Lange, Magdalena, Lyons, Jonathan J., Maurer, Marcus, Metcalfe, Dean D., Nedoszytko, Boguslaw, Niedoszytko, Marek, Orfao, Alberto, Reiter, Andreas, Schwaab, Juliana, Sotlar, Karl, Sperr, Wolfgang R., Triggiani, Massimo, Valent, Peter, and Siebenhaar, Frank
Abstract: Indolent systemic mastocytosis (ISM) has a favorable prognosis and normal life expectancy. However, many patients suffer from mast cell (MC) mediator-related symptoms, which significantly affect quality of life (QoL). Cutaneous, gastrointestinal, and neurological complaints, musculoskeletal pain, and the presence of skin lesions, anaphylaxis, and osteoporosis are the main symptoms and signs in ISM and must be assessed in all patients before and during treatment. Validated mastocytosis-specific patient-reported outcome measures (PROMs) should be used for this purpose. Serum tryptase and KIT D816V allele burden are recommended as secondary outcome parameters, noting that they do not reflect the severity of signs, symptoms, and related QoL impairment, but indirectly express MC burden. Changes from baseline of 90%, 60%, and 30% indicate complete response >90%, major response 60% to 90%, partial response 30% to 60%, and no response <30% to treatment. To conclude, we recommend the use of PROMs as primary outcome parameters to define treatment response in patients with ISM in clinical trials and in everyday clinical practice.
Published: 2022

3. Partial Least Square and Hierarchical Clustering in ADMET Modeling: Prediction of Blood – Brain Barrier Permeation of α-Adrenergic and Imidazoline Receptor Ligands

Author: Nikolic, Katarina; Faculty of Pharmacy, University of Belgrade, Filipic, Slavica; Faculty of Pharmacy, University of Belgrade, Smoliński, Adam; Central Mining Institute, Department of Energy Saving and Air Protection, Plac Gwarków 1, 40-166 Katowice, Kaliszan, Roman; Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gen. J. Hellera 107, 80-416 Gdańsk, Agbaba, Danica; Faculty of Pharmacy, University of Belgrade, Nikolic, Katarina; Faculty of Pharmacy, University of Belgrade, Filipic, Slavica; Faculty of Pharmacy, University of Belgrade, Smoliński, Adam; Central Mining Institute, Department of Energy Saving and Air Protection, Plac Gwarków 1, 40-166 Katowice, Kaliszan, Roman; Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gen. J. Hellera 107, 80-416 Gdańsk, and Agbaba, Danica; Faculty of Pharmacy, University of Belgrade
Abstract: PURPOSE. Rate of brain penetration (logPS), brain/plasma equilibration rate (logPS-brain), and extent of blood-brain barrier permeation (logBB) of 29 α-adrenergic and imidazoline-receptors ligands were examined in Quantitative-Structure-Property Relationship (QSPR) study. METHODS. Experimentally determined chromatographic retention data (logKw at pH 4.4, slope (S) at pH 4.4, logKw at pH 7.4, slope (S) at pH 7.4, logKw at pH 9.1, and slope (S) at pH 9.1) and capillary electrophoresis migration parameters (μeff at pH 4.4, μeff at pH 7.4, and μeff at pH 9.1), together with calculated molecular descriptors, were used as independent variables in the QSPR study by use of partial least square (PLS) methodology. RESULTS. Predictive potential of the formed QSPR models, QSPR(logPS), QSPR(logPS-brain), QSPR(logBB), was confirmed by cross- and external validation. Hydrophilicity (Hy) and H-indices (H7m) were selected as significant parameters negatively correlated with both logPS and logPS-brain, while topological polar surface area (TPSA(NO)) was chosen as molecular descriptor negatively correlated with both logPS and logBB. The principal component analysis (PCA) and hierarchical clustering analysis (HCA) were applied to cluster examined drugs based on their chromatographic, electrophoretic and molecular properties. Significant positive correlations were obtained between the slope (S) at pH 7.4 and logBB in A/B cluster and between the logKw at pH 9.1 and logPS in C/D cluster. CONCLUSIONS. Results of the QSPR, clustering and correlation studies could be used as novel tool for evaluation of blood-brain barrier permeation of related α-adrenergic/imidazoline receptor ligands.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.PURPOSE. Rate of brain penetration (logPS), brain/plasma equilibration rate (logPS-brain), and extent of blood-brain barrier permeation (logBB) of 29 α-adrene

4. Variation of the clinical spectrum and genotype-phenotype associations in Coenzyme Q10 deficiency associated glomerulopathy

Author: Stefania Drovandi, Beata S. Lipska-Ziętkiewicz, Fatih Ozaltin, Francesco Emma, Bora Gulhan, Olivia Boyer, Agnes Trautmann, Szymon Ziętkiewicz, Hong Xu, Qian Shen, Jia Rao, Korbinian M. Riedhammer, Uwe Heemann, Julia Hoefele, Sarah L. Stenton, Alexey N. Tsygin, Kar-Hui Ng, Svitlana Fomina, Elisa Benetti, Manon Aurelle, Larisa Prikhodina, Anne M. Schijvens, Mansoureh Tabatabaeifar, Maciej Jankowski, Sergey Baiko, Jianhua Mao, Chunyue Feng, Fang Deng, Caroline Rousset-Rouviere, Małgorzata Stańczyk, Irena Bałasz-Chmielewska, Marc Fila, Anne M. Durkan, Tanja Kersnik Levart, Ismail Dursun, Nasrin Esfandiar, Dorothea Haas, Anna Bjerre, Ali Anarat, Marcus R. Benz, Saeed Talebi, Nakysa Hooman, Gema Ariceta, Franz Schaefer, Lina Maria Serna Higuita, Alaleh Gheissari, Nazym Nigmatullina, Marcin Tkaczyk, Halina Borzecka, Radovan Bogdanovic, Sevgi Mir, Thomas Klopstock, Holger Prokisch, Cornelia Kornblum, Cui-Hua Liu, Shu-Zhen Sun, Yang Dong, Xiao-Wen Wang, Jiang-Wei Luan, Institut Català de la Salut, [Drovandi S] Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany. Division of Nephrology, Dialysis and Transplantation, Department of Internal Medicine, Ospedale Policlinico San Martino and University of Genoa, Genoa, Italy. Division of Nephrology, Dialysis, Transplantation, Giannina Gaslini Children's Hospital, Genoa, Italy. [Lipska-Ziętkiewicz BS] Rare Diseases Centre, Medical University of Gdańsk, Gdańsk, Poland. Department of Biology and Medical Genetics, Clinical Genetics Unit, Medical University of Gdańsk, Gdańsk, Poland. [Ozaltin F, Gulhan B] Division of Pediatric Nephrology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey. [Emma F] Department of Pediatric Subspecialties, Division of Nephrology and Dialysis, Bambino Gesù Childrens Hospital, IRCCS, Rome, Italy. [Boyer O] APHP, Necker-Enfants Malades Hospital, Pediatric Nephrology, MARHEA and SNI Reference Centers, Paris, France. Imagine Institute, Paris University, Paris, France. [Ariceta G] Servei de Nefrologia Pediàtrica, Vall d'Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: técnicas de investigación::técnicas genéticas::estudios de asociación genética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Mitochondrial Diseases, Muscle Weakness, Nephrotic Syndrome, Otros calificadores::Otros calificadores::/genética [Otros calificadores], Ubiquinone, Mitocondris - Malalties - Aspectes genètics, enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::nefrosis::síndrome nefrótico [ENFERMEDADES], Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Nephrosis::Nephrotic Syndrome [DISEASES], Nutritional and Metabolic Diseases::Metabolic Diseases::Mitochondrial Diseases [DISEASES], Ronyons - Malalties - Aspectes genètics, Coenzyme Q10, Mitochondria, Steroid-resistant Nephrotic Syndrome, Nephrology, Mutation, Other subheadings::Other subheadings::/genetics [Other subheadings], Humans, Ataxia, Steroids, Investigative Techniques::Genetic Techniques::Genetic Association Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], enfermedades nutricionales y metabólicas::enfermedades metabólicas::enfermedades mitocondriales [ENFERMEDADES], Genetic Association Studies
Abstract: Coenzyme Q10; Mitochondria; Steroid-resistant nephrotic syndrome Coenzima Q10; Mitocondrias; Síndrome nefrótico resistente a los esteroides Coenzim Q10; Mitocondris; Síndrome nefròtic resistent als esteroides Primary Coenzyme Q10 deficiency is a rare mitochondriopathy with a wide spectrum of organ involvement, including steroid-resistant nephrotic syndrome mainly associated with disease-causing variants in the genes COQ2, COQ6 or COQ8B. We performed a systematic literature review, PodoNet, mitoNET, and CCGKDD registries queries and an online survey, collecting comprehensive clinical and genetic data of 251 patients spanning 173 published (47 updated) and 78 new cases. Kidney disease was first diagnosed at median age 1.0, 1.2 and 9.8 years in individuals with disease-causing variants in COQ2, COQ6 and COQ8B, respectively. Isolated kidney involvement at diagnosis occurred in 34% of COQ2, 10.8% of COQ6 and 70.7% of COQ8B variant individuals. Classic infantile multiorgan involvement comprised 22% of the COQ2 variant cohort while 47% of them developed neurological symptoms at median age 2.7 years. The association of steroid-resistant nephrotic syndrome and sensorineural hearing loss was confirmed as the distinctive phenotype of COQ6 variants, with hearing impairment manifesting at average age three years. None of the patients with COQ8B variants, but 50% of patients with COQ2 and COQ6 variants progressed to kidney failure by age five. At adult age, kidney survival was equally poor (20-25%) across all disorders. A number of sequence variants, including putative local founder mutations, had divergent clinical presentations, in terms of onset age, kidney and non-kidney manifestations and kidney survival. Milder kidney phenotype was present in those with biallelic truncating variants within the COQ8B variant cohort. Thus, significant intra- and inter-familial phenotype variability was observed, suggesting both genetic and non-genetic modifiers of disease severity. In addition, this project has been supported by the European Reference Network for Rare Kidney Diseases (ERKNet), the PodoNet Network for Podocyte Disorders, and the German (mitoNET) and European Networks for Mitochondrial Disorders (GENOMIT). ERKNet is co-funded by the European Union within the framework of the Third Health Programme “ERN-2016 - Framework Partnership Agreement 2017-2021.” PodoNet and mitoNET/GENOMIT have received funding from the German Ministry of Education and Research, and PodoNet from the EU 7th Framework Programme (EURenOmics; grant 2012-305608) and the German Research Foundation (Scha 477/11-1). Founder effect analyses were supported by the Polish Ministry of Science and Education (2017/25/B/NZ2/00519). We would also like to thank Drs. Kei Murayama and Masaru Shimura from Chiba Children’s Hospital, Chiba, Japan, for their contribution to the clinical assessment and follow-up of 2 families. Last but not least, we gratefully acknowledge the help of Elena Levtchenko in rolling out the survey.
Published: 2022

5. Iron Insertion at the Assembly Site of the ISCU Scaffold Protein Is a Conserved Process Initiating Fe–S Cluster Biosynthesis

Author: Batoul Srour, Sylvain Gervason, Maren Hellen Hoock, Beata Monfort, Kristian Want, Djabir Larkem, Nadine Trabelsi, Gautier Landrot, Andrea Zitolo, Emiliano Fonda, Emilien Etienne, Guillaume Gerbaud, Christina Sophia Müller, Jonathan Oltmanns, Jesse B. Gordon, Vishal Yadav, Malgorzata Kleczewska, Marcin Jelen, Michel B. Toledano, Rafal Dutkiewicz, David P. Goldberg, Volker Schünemann, Bruno Guigliarelli, Bénédicte Burlat, Christina Sizun, Benoit D’Autréaux, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Technische Universität Kaiserslautern (TU Kaiserslautern), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Bioénergétique et Ingénierie des Protéines (BIP ), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Johns Hopkins University (JHU), Medical University of Gdańsk, University of Gdańsk (UG), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and ANR-17-CE11-0021,FRATAXUR,Bases moléculaires et structurales de la biogenèse des centres fer-soufre permettant d'élucider la fonction moléculaire de la frataxine(2017)
Subjects: Iron-Sulfur Proteins, Sulfonylurea Compounds, Colloid and Surface Chemistry, Escherichia coli Proteins, Iron, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cysteine, General Chemistry, Biochemistry, Sulfur, Catalysis
Abstract: International audience; Iron−sulfur (Fe−S) clusters are prosthetic groups of proteins biosynthesized on scaffold proteins by highly conserved multi-protein machineries. Biosynthesis of Fe−S clusters into the ISCU scaffold protein is initiated by ferrous iron insertion, followed by sulfur acquisition, via a still elusive mechanism. Notably, whether iron initially binds to the ISCU cysteine-rich assembly site or to a cysteine-less auxiliary site via N/O ligands remains unclear. We show here by SEC, circular dichroism (CD), and Mossbauer spectroscopies that iron binds to the assembly site of the monomeric form of prokaryotic and eukaryotic ISCU proteins via either one or two cysteines, referred to the 1-Cys and 2-Cys forms, respectively. The latter predominated at pH 8.0 and correlated with the Fe−S cluster assembly activity, whereas the former increased at a more acidic pH, together with free iron, suggesting that it constitutes an intermediate of the iron insertion process. Iron not binding to the assembly site was non-specifically bound to the aggregated ISCU, ruling out the existence of a structurally defined auxiliary site in ISCU. Characterization of the 2-Cys form by site-directed mutagenesis, CD, NMR, X-ray absorption, Mossbauer, and electron paramagnetic resonance spectroscopies showed that the iron center is coordinated by four strictly conserved amino acids of the assembly site, Cys35, Asp37, Cys61, and His103, in a tetrahedral geometry. The sulfur receptor Cys104 was at a very close distance and apparently bound to the iron center when His103 was missing, which may enable iron-dependent sulfur acquisition. Altogether, these data provide the structural basis to elucidate the Fe−S cluster assembly process and establish that the initiation of Fe−S cluster biosynthesis by insertion of a ferrous iron in the assembly site of ISCU is a conserved mechanism.
Published: 2022
Full Text: View/download PDF

6. Refined Treatment Response Criteria for Indolent Systemic Mastocytosis Proposed by the ECNM-AIM Consortium

Author: Pyatilova, Polina, Akin, Cem, Álvarez-Twose, Iván, Arock, Michel, Bonadonna, Patrizia, Brockow, Knut, Butterfield, Joseph H., Broesby-Olsen, Sigurd, Carter, Melody C., Castells, Mariana, George, Tracy I., Gotlib, Jason, Greiner, Georg, Gulen, Theo, Hartmann, Karin, Hermine, Olivier, Horny, Hans-Peter, Jawhar, Mohamad, Lange, Magdalena, Lyons, Jonathan J., Maurer, Marcus, Metcalfe, Dean D., Nedoszytko, Boguslaw, Niedoszytko, Marek, Orfao, Alberto, Reiter, Andreas, Schwaab, Juliana, Sotlar, Karl, Sperr, Wolfgang R., Triggiani, Massimo, Valent, Peter, Siebenhaar, Frank, National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Medical University of Gdańsk, Austrian Science Fund, and Publica
Subjects: Mastocytosis, Systemic, Mast cell activation, Mast cells, Mastocytosis, Response criteria, Signs, Symptoms, Quality of Life, Humans, Immunology and Allergy, Tryptases
Abstract: Indolent systemic mastocytosis (ISM) has a favorable prognosis and normal life expectancy. However, many patients suffer from mast cell (MC) mediator-related symptoms, which significantly affect quality of life (QoL). Cutaneous, gastrointestinal, and neurological complaints, musculoskeletal pain, and the presence of skin lesions, anaphylaxis, and osteoporosis are the main symptoms and signs in ISM and must be assessed in all patients before and during treatment. Validated mastocytosis-specific patient-reported outcome measures (PROMs) should be used for this purpose. Serum tryptase and KIT D816V allele burden are recommended as secondary outcome parameters, noting that they do not reflect the severity of signs, symptoms, and related QoL impairment, but indirectly express MC burden. Changes from baseline of 90%, 60%, and 30% indicate complete response >90%, major response 60% to 90%, partial response 30% to 60%, and no response, M. C. Carter, J. J. Lyons, and D. D. Metcalfe were supported by the Division of Intramural Research, National Institutes of Allergic and Infectious Diseases, and National Institutes of Health. M. Niedoszytko was supported by the Medical University of Gdansk grant 02-0141/07/231. P. Valent was supported by the Austrian Science Fund (FWF) grant # P32470-B.
Published: 2022
Full Text: View/download PDF

7. Phenotypic characterization of seven individuals with <scp>Marbach–Schaaf</scp> neurodevelopmental syndrome

Author: Felix Marbach, Beata S. Lipska‐Ziętkiewicz, Agata Knurowska, Vincent Michaud, Henri Margot, James Lespinasse, Frédéric Tran Mau Them, Christine Coubes, Joohyun Park, Sarah Grosch, Cristiana Roggia, Ute Grasshoff, Louisa Kalsner, Anne‐Sophie Denommé‐Pichon, Alexandra Afenjar, Bénédicte Héron, Boris Keren, Pilar Caro, Christian P. Schaaf, Heidelberg University, University of Gdańsk (UG), Medical University of Gdańsk, Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre Hospitalier Métropole Savoie [Chambéry], Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Unité fonctionnelle d' Innovation en Diagnostic Génomique des Maladies Rares (CHU Dijon) (UF6254), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Tübingen, School of Medicine [University of Connecticut], University of Connecticut (UCONN), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Baylor College of Medicine (BCM), Baylor University, and Admin, Oskar
Subjects: Adult, Pain insensitivity, Autism Spectrum Disorder, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Global developmental delay, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Syndrome, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Cohort Studies, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Phenotype, Neurodevelopmental disorder, PRKAR1B, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neurodevelopmental Disorders, Genetics, Protein kinase a complex, Animals, Humans, Genetics (clinical)
Abstract: International audience; We present the phenotypes of seven previously unreported patients with Marbach-Schaaf neurodevelopmental syndrome, all carrying the same recurrent heterozygous missense variant c.1003C>T (p.Arg335Trp) in PRKAR1B. Clinical features of this cohort include global developmental delay and reduced sensitivity to pain, as well as behavioral anomalies. Only one of the seven patients reported here was formally diagnosed with autism spectrum disorder (ASD), while ASD-like features were described in others, overall indicating a lower prevalence of ASD in Marbach-Schaaf neurodevelopmental syndrome than previously assumed. The clinical spectrum of the current cohort is similar to that reported in the initial publication, delineating a complex developmental disorder with behavioral and neurologic features. PRKAR1B encodes the regulatory subunit R1beta of the protein kinase A complex (PKA), and is expressed in the adult and embryonal central nervous system in humans. PKA is crucial to a plethora of cellular signaling pathways, and its composition of different regulatory and catalytic subunits is cell-type specific. We discuss potential molecular disease mechanisms underlying the patients' phenotypes with respect to the different known functions of PKA in neurons, and the phenotypes of existing R1beta-deficient animal models.
Published: 2022
Full Text: View/download PDF

8. COVID-19 infection in patients on long-term home parenteral nutrition for chronic intestinal failure

Author: Loris Pironi, Denise Jezerski, Jacek Sobocki, Simon Lal, Tim Vanuytsel, Miriam Theilla, Anna S. Sasdelli, Cecile Chambrier, Konrad Matysiak, Umberto Aimasso, Henrik H. Rasmussen, Amelia Jukes, Marek Kunecki, David Seguy, Stéphane M. Schneider, Joanne Daniels, Florian Poullenot, Manpreet S. Mundi, Przemysław Matras, Marcin Folwarski, Adriana Crivelli, Nicola Wyer, Lars Ellegard, Lidia Santarpia, Marianna Arvanitakis, Corrado Spaggiari, Georg Lamprecht, Francesco W. Guglielmi, Antonella Lezo, Sabrina Layec, Esther Ramos Boluda, Anat Guz-Mark, Paolo Gandullia, Cristina Cuerda, Emma Osland, Maria I. Spagnuolo, Zeljko Krznaric, Luisa Masconale, Brooke Chapman, María Maíz-Jiménez, Paolo Orlandoni, Mariana Hollanda Martins da Rocha, M. Nuria Virgili-Casas, Maryana Doitchinova-Simeonova, Laszlo Czako, Andrè Van Gossum, Lorenzo D'Antiga, Looi C. Ee, Daruneewan Warodomwichit, Marina Taus, Sanja Kolaček, Ronan Thibault, Giovanna Verlato, Aurora E. Serralde-Zúñiga, José I. Botella-Carretero, Pilar Serrano Aguayo, Gabriel Olveira, Sirinuch Chomtho, Veeradej Pisprasert, Georgijs Moisejevs, Ana Zugasti Murillo, Ma Estrella Petrina Jáuregui, Marta Bueno Díez, Mohammad Shukri Jahit, Narumon Densupsoontorn, Ali Tamer, Giorgia Brillanti, Francisca Joly, University of Bologna/Università di Bologna, Cleveland Clinic, Centre of Postgraduate Medical Education, University of Manchester [Manchester], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Tel Aviv University (TAU), Hospices Civils de Lyon (HCL), Poznan University of Life Sciences (Uniwersytet Przyrodniczy w Poznaniu) (PULS), Città della Salute e della Scienza University-Hospital, Aalborg University [Denmark] (AAU), University Hospital of Wales (UHW), University of Lódź, CHU Lille, Centre Hospitalier Universitaire de Nice (CHU Nice), Nottingham University Hospitals NHS Trust (NUH), CHU Bordeaux [Bordeaux], Mayo Clinic and Mayo College of Medicine, Rochester, Medical University of Lublin, Medical University of Gdańsk, Hospital Universitario Fundacion Favaloro, University Hospital Coventry, Sahlgrenska Academy at University of Gothenburg [Göteborg], University of Naples Federico II = Università degli studi di Napoli Federico II, Hôpital Erasme [Bruxelles], Clinique Saint-Yves [Rennes], CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidad de Málaga [Málaga] = University of Málaga [Málaga], Mahidol University [Bangkok], University of Sakarya, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and The project of the ESPEN database for Chronic Intestinal Failure was promoted by the ESPEN Executive Committee in 2013, was approved by the ESPEN Council and was supported by an ESPEN grant.
Subjects: Home parenteral nutrition, Nutrition and Dietetics, Pandemic, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Epidemiology, SARS-CoV-2, Endocrinology, Diabetes and Metabolism, COVID-19, 03.02. Klinikai orvostan, Intestinal failure, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Background and aimsTo investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN).MethodsPeriod of observation: March 1st, 2020 March 1st, 2021. Inclusion criteria: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up.ResultsSixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths.ConclusionsIn patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death. Background and aimsTo investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN).MethodsPeriod of observation: March 1st, 2020 March 1st, 2021. Inclusion criteria: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up.ResultsSixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths.ConclusionsIn patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death.
Published: 2023
Full Text: View/download PDF

9. Identification of QTLs affecting scopolin and scopoletin biosynthesis in Arabidopsis thaliana

Author: Alexandre Olry, Leszek Kadziński, Bogdan Banecki, Anna Gwizdek-Wisniewska, Ewa Lojkowska, Joanna Siwinska, Anna Ihnatowicz, Rafał Banasiuk, Intercollegiate Faculty of Biotechnology of University of Gdansk, Laboratory of Plant Protection and Biotechnology, Medical University of Gdańsk-University of Gdańsk, Gdansk Medical University, Laboratoire Agronomie et Environnement (LAE), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Intercollegiate Faculty of Biotechnology, Intercollegiate Faculty of Biotechnology of University, Laboratory of Plant Protection and Biotechnology, Department of Plant Breeding and Genetics, Max Planck Institute for Plant Breeding Research (MPIPZ), Ihnatowicz, Anna, University of Gdańsk (UG)-Medical University of Gdańsk, and Medical University of Gdańsk-University of Gdańsk (UG)
Subjects: QTL mapping, Quantitative Trait Loci, Population, Arabidopsis, [SDV.SA.AGRO]Life Sciences [q-bio]/Agricultural sciences/Agronomy, Plant Science, Quantitative trait locus, Plant Roots, chemistry.chemical_compound, Plant-environment interaction, Glucosides, Coumarins, Scopoletin, Arabidopsis thaliana, heterocyclic compounds, Secondary metabolism, education, Scopolin, Genetics, education.field_of_study, biology, Chromosome Mapping, 15. Life on land, biology.organism_classification, chemistry, Biosynthetic process, Natural variation, Research Article
Abstract: Scopoletin and its glucoside scopolin are important secondary metabolites synthesized in plants as a defense mechanism against various environmental stresses. They belong to coumarins, a class of phytochemicals with significant biological activities that is widely used in medical application and cosmetics industry. Although numerous studies showed that a variety of coumarins occurs naturally in several plant species, the details of coumarins biosynthesis and its regulation is not well understood. It was shown previously that coumarins (predominantly scopolin and scopoletin) occur in Arabidopsis thaliana (Arabidopsis) roots, but until now nothing is known about natural variation of their accumulation in this model plant. Therefore, the genetic architecture of coumarins biosynthesis in Arabidopsis has not been studied before., Here, the variation in scopolin and scopoletin content was assessed by comparing seven Arabidopsis accessions. Subsequently, a quantitative trait locus (QTL) mapping was performed with an Advanced Intercross Recombinant Inbred Lines (AI-RILs) mapping population EstC (Est-1 × Col). In order to reveal the genetic basis of both scopolin and scopoletin biosynthesis, two sets of methanol extracts were made from Arabidopsis roots and one set was additionally subjected to enzymatic hydrolysis prior to quantification done by high-performance liquid chromatography (HPLC). We identified one QTL for scopolin and five QTLs for scopoletin accumulation. The identified QTLs explained 13.86% and 37.60% of the observed phenotypic variation in scopolin and scopoletin content, respectively. In silico analysis of genes located in the associated QTL intervals identified a number of possible candidate genes involved in coumarins biosynthesis., Together, our results demonstrate for the first time that Arabidopsis is an excellent model for studying the genetic and molecular basis of natural variation in coumarins biosynthesis in plants. It additionally provides a basis for fine mapping and cloning of the genes involved in scopolin and scopoletin biosynthesis. Importantly, we have identified new loci for this biosynthetic process.
Published: 2014
Full Text: View/download PDF

10. [i]Dickeya solani[/i] sp nov., a pectinolytic plant-pathogenic bacterium isolated from potato ([i]Solanum tuberosum[/i])

Author: Brion Duffy, E.H. Nijhuis, Marta Potrykus, Leighton Pritchard, Ian K. Toth, John G. Elphinstone, Malgorzata Waleron, Ilse Cleenwerck, Valérie Hélias, Valentin Pflüger, Shula Manulis, Linda Garlant, Malgorzata J. Kowalewska, Leah Tsror, G. S. Saddler, Paul De Vos, Joël F. Pothier, Minna Pirhonen, Ewa Lojkowska, Neil Parkinson, Jan M. van der Wolf, Plant Research International, Wageningen University and Research [Wageningen] (WUR), Science and Advice for Scottish Agriculture, Food and Environment Research Agency, The James Hutton Institute, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk-University of Gdańsk (UG), BCCM/LMG Bacteria Collection, Universiteit Gent = Ghent University [Belgium] (UGENT), Department of Applied Biology, Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institute of Natural Resource Sciences, Zürich University of Applied Sciences (ZHAW), Plant Protection Division, Agroscope, Mabritec AG, Volcani Center, Department of Plant Pathology and Weed Research, Agricultural Research Organization, Universiteit Gent = Ghent University (UGENT), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-AGROCAMPUS OUEST, Wageningen University and Research Centre [Wageningen] (WUR), Medical University of Gdańsk-University of Gdańsk, Ghent University [Belgium] (UGENT), AGROCAMPUS OUEST-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Recherche Agronomique (INRA)
Subjects: DNA, Bacterial, relatedness, Indoles, Pectobacterium, Biovar, chrysanthemi, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Pectobacterium chrysanthemi, Dickeya, clonality, genus, Microbiology, strains, Intergenic region, Enterobacteriaceae, RNA, Ribosomal, 16S, dnaX, Israel, Phylogeny, Ecology, Evolution, Behavior and Systematics, Plant Diseases, Solanum tuberosum, 2. Zero hunger, mallei, biology, clade, pseudomallei, Fatty Acids, Nucleic Acid Hybridization, General Medicine, 570: Biologie, biology.organism_classification, Dickeya dadantii, Bacterial Typing Techniques, Europe, Genes, Bacterial, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Pectins, PRI BIOINT Ecological Interactions, identification, Dickeya solani, Multilocus Sequence Typing
Abstract: Pectinolytic bacteria have been recently isolated from diseased potato plants exhibiting blackleg and slow wilt symptoms found in a number of European countries and Israel. These Gram-reaction-negative, motile, rods were identified as belonging to the genus Dickeya , previously the Pectobacterium chrysanthemi complex ( Erwinia chrysanthemi ), on the basis of production of a PCR product with the pelADE primers, 16S rRNA gene sequence analysis, fatty acid methyl esterase analysis, the production of phosphatases and the ability to produce indole and acids from α-methylglucoside. Differential physiological assays used previously to differentiate between strains of E. chrysanthemi , showed that these isolates belonged to biovar 3. Eight of the isolates, seven from potato and one from hyacinth, were analysed together with 21 reference strains representing all currently recognized taxa within the genus Dickeya . The novel isolates formed a distinct genetic clade in multilocus sequence analysis (MLSA) using concatenated sequences of the intergenic spacer (IGS), as well as dnaX, recA, dnaN, fusA, gapA, purA, rplB, rpoS and gyrA. Characterization by whole-cell MALDI-TOF mass spectrometry, pulsed field gel electrophoresis after digestion of whole-genome DNA with rare-cutting restriction enzymes, average nucleotide identity analysis and DNA–DNA hybridization studies, showed that although related to Dickeya dadantii , these isolates represent a novel species within the genus Dickeya , for which the name Dickeya solani sp. nov. (type strain IPO 2222T = LMG25993T = NCPPB4479T) is proposed.
Published: 2014
Full Text: View/download PDF

11. Conserved histidine of metal transporter AtNRAMP1 is crucial for optimal plant growth under manganese deficiency at chilling temperatures

Author: Joanna Siwinska, Anna Ihnatowicz, Andrew A. Meharg, Manus Carey, Matthieu Reymond, Maarten Koornneef, Intercollegiate Faculty of Biotechnology of University, Laboratory of Plant Protection and Biotechnology, University of Gdańsk (UG)-Medical University of Gdańsk, Department of Plant Breeding and Genetics, Max Planck Institute for Plant Breeding Research (MPIPZ), Intercollegiate Faculty of Biotechnology of University of Gdansk, Laboratory of Plant Protection and Biotechnology, Institute for Global Food Security [Belfast], Queen's University [Belfast] (QUB), Laboratory of Genetics, Wageningen University and Research [Wageningen] (WUR), Institut Jean-Pierre Bourgin (IJPB), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Max Planck Society, University of Gdansk (Gdansk University) [538-M031-B145-13], Medical University of Gdańsk-University of Gdańsk, Institute for Global Food Security, Wageningen University and Research Centre [Wageningen] (WUR), and University of Gdańsk-Medical University of Gdańsk
Subjects: Chlorophyll, Physiology, iron transport, [SDV]Life Sciences [q-bio], Arabidopsis, Plant Science, yeast saccharomyces-cerevisiae, Gene Expression Regulation, Plant, nramp family, Arabidopsis thaliana, 2. Zero hunger, chemistry.chemical_classification, drosophila-melanogaster, Chlorosis, biology, manganese (Mn) deficiency, Chromosome Mapping, ion transporters, environmental stress, Cold Temperature, Complementation, Phenotype, Laboratory of Genetics, Essential nutrient, environment, AtNRAMP1, Genotype, chlorosis, arabidopsis-thaliana, Laboratorium voor Erfelijkheidsleer, Photosynthesis, Manganese deficiency (plant), calcareous soil, Botany, Histidine, Alleles, plant-soil interactions, diploid strains, Manganese, photosynthesis, Arabidopsis Proteins, Membrane Transport Proteins, Sequence Analysis, DNA, biology.organism_classification, chemistry, Seedlings, metal transporter, Gene-Environment Interaction, barley hordeum-vulgare, chilling temperatures
Abstract: Manganese (Mn) is an essential nutrient required for plant growth, in particular in the process of photosynthesis. Plant performance is influenced by various environmental stresses including contrasting temperatures, light or nutrient deficiencies. The molecular responses of plants exposed to such stress factors in combination are largely unknown. [br/]Screening of 108 Arabidopsis thaliana (Arabidopsis) accessions for reduced photosynthetic performance at chilling temperatures was performed and one accession (Hog) was isolated. Using genetic and molecular approaches, the molecular basis of this particular response to temperature (GxE interaction) was identified.[br/]Hog showed an induction of a severe leaf chlorosis and impaired growth after transfer to lower temperatures. We demonstrated that this response was dependent on the nutrient content of the soil. Genetic mapping and complementation identified NRAMP1 as the causal gene. Chlorotic phenotype was associated with a histidine to tyrosine (H239Y) substitution in the allele of Hog NRAMP1. This led to lethality when Hog seedlings were directly grown at 4 degrees C. [br/]Chemical complementation and hydroponic culture experiments showed that Mn deficiency was the major cause of this GxE interaction. For the first time, the NRAMP-specific highly conserved histidine was shown to be crucial for plant performance.
Published: 2014
Full Text: View/download PDF

12. A tumor volume and performance status model to predict outcome before treatment in diffuse large B-cell lymphoma

Author: Catherine Thieblemont, Loic Chartier, Ulrich Dührsen, Umberto Vitolo, Sally F. Barrington, Jan M. Zaucha, Laetitia Vercellino, Maria Gomes Silva, Ines Patrocinio-Carvalho, Pierre Decazes, Pierre-Julien Viailly, Herve Tilly, Alina Berriolo-Riedinger, Oliver Casasnovas, Andreas Hüttmann, Hajira Ilyas, N. George Mikhaeel, Joel Dunn, Anne-Ségolène Cottereau, Christine Schmitz, Lale Kostakoglu, Joseph N. Paulson, Tina Nielsen, Michael Meignan, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The Lymphoma Academic Research Organisation [Lyon] (LYSARC), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), King‘s College London, Guy's and St Thomas' Hospital [London], Medical University of Gdańsk, Service de Médecine Nucléaire [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], University of Virginia, Genentech, Inc. [San Francisco], F. Hoffmann-La Roche [Basel], CHU Henri Mondor, and leboeuf, Christophe
Subjects: Clinical Trials as Topic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Medizin, Humans, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Lymphoma, Large B-Cell, Diffuse, Neoplasm Recurrence, Local, Tumor Burden
Abstract: Aggressive large B-cell lymphoma (LBCL) has variable outcomes. Current prognostic tools use factors for risk stratification that inadequately identify patients at high risk of refractory disease or relapse before initial treatment. A model associating 2 risk factors, total metabolic tumor volume (TMTV) >220 cm3 (determined by fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography) and performance status (PS) ≥2, identified as prognostic in 301 older patients in the REMARC trial (#NCT01122472), was validated in 2174 patients of all ages treated in 2 clinical trials, PETAL (Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas; N = 510) and GOYA (N = 1315), and in real-world clinics (N = 349) across Europe and the United States. Three risk categories, low (no factors), intermediate (1 risk factor), and high (2 risk factors), significantly discriminated outcome in most of the series. Patients with 2 risk factors had worse outcomes than patients with no risk factors in the PETAL, GOYA, and real-world series. Patients with intermediate risk also had significantly worse outcomes than patients with no risk factors. The TMTV/Eastern Cooperative Oncology Group-PS combination outperformed the International Prognostic Index with a positive C-index for progression-free survival and overall survival in most series. The combination of high TMTV > 220 cm3 and ECOG-PS ≥ 2 is a simple clinical model to identify aggressive LBCL risk categories before treatment. This combination addresses the unmet need to better predict before treatment initiation for aggressive LBCL the patients likely to benefit the most or not at all from therapy.
Published: 2022
Full Text: View/download PDF

13. Serologic Surveillance for SARS-CoV-2 Infection among Wild Rodents, Europe

Author: Vincent Bourret, Lara Dutra, Hussein Alburkat, Sanna Mäki, Ella Lintunen, Marine Wasniewski, Ravi Kant, Maciej Grzybek, Vinaya Venkat, Hayder Asad, Julien Pradel, Marie Bouilloud, Herwig Leirs, Valeria Carolina Colombo, Vincent Sluydts, Peter Stuart, Andrew McManus, Jana A. Eccard, Jasmin Firozpoor, Christian Imholt, Joanna Nowicka, Aleksander Goll, Nathan Ranc, Guillaume Castel, Nathalie Charbonnel, Tarja Sironen, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Unité de recherche Comportement et Ecologie de la Faune Sauvage (CEFS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de la rage et de la faune sauvage de Nancy (LRFSN), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Medical University of Gdańsk, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), University of Antwerp (UA), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), University of Potsdam = Universität Potsdam, Julius Kühn-Institute, Munster Technological University (MTU), Julius Kühn-Institut (JKI), BiodivErsA3, Our research was funded through the European H2020 (WP 2018-2020) call and the 2018–2019 BiodivERsA joint call for research proposals, under the BiodivErsA3 ERA-Net COFUND program and cofunded by Agence Nationale de la Recherche, Research Foundation–Flanders, National Science Centre, Poland, Deutsche Programme 2021–2030. The National Science Centre, Poland, supported M.G., J.N., and A.G. under the BiodivERsA3 program (2019/31/Z/NZ8/04028).Sampling from Thuringia (Germany) was funded by the DFG Priority Program 1374.Trapping data from this study will be available in Germany in the Biodiversity Exploratories Information System (https://doi.org/10.17616/R32P9Q).Forschungsgemeinschaft, and the EPA Research, European Project: 101052342,Biodiversa+, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), funded from Agence Nationale de la Recherche, Research FoundationFlanders, National Science Centre, Poland, Deutsche Forschungsgemeinschaft, and the EPA Research Programme 2021-2030. The National Science Centre, Poland, supported M.G., J.N., and A.G. under the BiodivERsA3 program (2019/31/Z/NZ8/04028). Sampling from Thuringia (Germany) was funded by the DFG Priority Program 1374, European Project: 138572,FCT::,BiodivERsA/2014,BiodivERsA/0001/2014(2015), Medicum, Faculty of Veterinary Medicine, Department of Virology, Emerging Infections Research Group, Faculty Common Matters (Faculty of Medicine), Helsinki One Health (HOH), and Viral Zoonosis Research Unit
Subjects: Microbiology (medical), Epidemiology, serology, Rodentia, serologic tests, Antibodies, Viral, respiratory infections, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, Animals, Humans, viruses, severe acute respiratory infection coronavirus 2, 11832 Microbiology and virology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, SARS-CoV-2, COVID-19, zoonoses, Europe, Infectious Diseases, serosurveillance, coronavirus disease, 3121 General medicine, internal medicine and other clinical medicine, rodents, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: We report results from serologic surveillance for exposure to SARS-CoV-2 among 1,237 wild rodents and small mammals across Europe. All samples were negative, with the possible exception of 1. Despite suspected potential for human-to-rodent spillover, no evidence of widespread SARS-CoV-2 circulation in rodent populations has been reported to date.Esitämme tulokset serologisesta tutkimuksesta, jossa seulottiin SARS-CoV-2 tartuntojen varalta 1,237 luonnonvaraista jyrsijää ja piennisäkästä eri puolilta Eurooppaa. Kaikki näytteet olivat negatiivisia, yhtä näytettä lukuun ottamatta. SARS-CoV-2:n läikkymisen ihmisistä jyrsijöihin on arveltu olevan mahdollista, mutta todisteet viruksen laajamittaisesta leviämisestä jyrsijäpopulaatioissa puuttuvat.
Published: 2022
Full Text: View/download PDF

14. Acyl-CoA:lysophosphatidylcholine acyltransferase from the unicellular diatom Phaeodactylum tricornutum (PtLPCAT1) is involved in triacylglycerol and galactoglycerolipid synthesis and enhances eicosapentaenoic acid accumulation in recombinant oleaginous yeast

Author: You, Lingjie, Jouhet, Juliette, Maréchal, Eric, Amato, Alberto, Hao, Xiahui, Zhang, Donghui, Banaś, Antoni, Gong, Yangmin, Chinese Academy of Agricultural Sciences (CAAS), LIPID, Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Yangtze University, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, grant from the National Natural Science Foundation of China n° 31961133008, NCN, Poland, No. UMO-2018/30/Q/NZ3/00497, IDEX UGA CDP Glyco@Alps, Institut Carnot 3BCAR, ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), and ANR-11-BTBR-0008,OCEANOMICS,Biotechnologies et bioressources pour la valorisation des écosystèmes marins planctoniques(2011)
Subjects: Yarrowia lipolytica, MESH: Triglycerides, eicosapentaenoic acid, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, MESH: Eicosapentaenoic Acid, CRISPR/Cas9 eicosapentaenoic acid LPCAT Phaeodactylum tricornutum Yarrowia lipolytica, LPCAT, MESH: Acyltransferases, Phaeodactylum tricornutum, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, MESH: 1-Acylglycerophosphocholine O-Acyltransferase, MESH: Acyl Coenzyme A, CRISPR/Cas9, MESH: Diatoms
Abstract: International audience
Published: 2022
Full Text: View/download PDF

15. Interaction Mechanism Between the HSV-1 Glycoprotein B and the Antimicrobial Peptide Amyloid-β

Author: Karine Bourgade, Eric H. Frost, Gilles Dupuis, Jacek M. Witkowski, Benoit Laurent, Charles Calmettes, Charles Ramassamy, Mathieu Desroches, Serafim Rodrigues, Tamás Fülöp, Centre de Recherche sur le Vieillissement (CSSS-IUGS), Institut Universitaire de Gériatrie de Sherbrooke (CSSS-IUGS), Université de Sherbrooke / Sherbrooke University (UdS), Medical University of Gdańsk, Medical University of Gdansk, Centre de recherche sur le vieillissement - CSSS-UIGS (Université de Sherbrooke), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Mathématiques pour les Neurosciences (MATHNEURO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Mathematical, Computational and Experimental Neuroscience [Bilbao] (MCEN), Basque Center for Applied Mathematics (BCAM), and Ikerbasque - Basque Foundation for Science
Subjects: Psychiatry and Mental health, Clinical Psychology, General Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], FRET, interaction, Alzheimer's disease, Geriatrics and Gerontology, glycoprotein B, HSV-1, amyloid-beta
Abstract: Background: Unravelling the mystery of Alzheimer's disease (AD) requires urgent resolution given the worldwide increase of the aging population. There is a growing concern that the current leading AD hypothesis, the amyloid cascade hypothesis, does not stand up to validation with respect to emerging new data. Indeed, several paradoxes are being discussed in the literature, for instance, both the deposition of the amyloid-β peptide (Aβ) and the intracellular neurofibrillary tangles could occur within the brain without any cognitive pathology. Thus, these paradoxes suggest that something more fundamental is at play in the onset of the disease and other key and related pathomechanisms must be investigated. Objective: The present study follows our previous investigations on the infectious hypothesis, which posits that some pathogens are linked to late onset AD. Our studies also build upon the finding that Aβ is a powerful antimicrobial agent, produced by neurons in response to viral infection, capable of inhibiting pathogens as observed in in vitro experiments. Herein, we ask what are the molecular mechanisms in play when Aβ neutralizes infectious pathogens? Methods: To answer this question, we probed at nanoscale lengths with FRET (Förster Resonance Energy Transfer), the interaction between Aβ peptides and glycoprotein B (responsible of virus-cell binding) within the HSV-1 virion Results: The experiments show an energy transfer between Aβ peptides and glycoprotein B when membrane is intact. No energy transfer occurs after membrane disruption or treatment with blocking antibody. Conclusion: We concluded that Aβ insert into viral membrane, close to glycoprotein B, and participate in virus neutralization., Ikerbasque GV-AI-HEALTH Inria Associated Team "NeuroTransSF"
Published: 2022
Full Text: View/download PDF

16. Enhanced mismatch negativity in harmonic compared with inharmonic sounds

Author: Peter Vuust, Barbara Tillmann, Anne Caclin, Krzysztof Basiński, Lesly Fornoni, Elvira Brattico, Fanny Cholvy, J. Nasielski, D. R. Quiroga-Martinez, Aarhus University [Aarhus], University of California [Berkeley] (UC Berkeley), University of California (UC), Medical University of Gdańsk, Utrecht University [Utrecht], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), and Tillmann, Barbara
Subjects: Computer science, Speech recognition, Mismatch negativity, Amusia, event-related potentials, P3a, medicine, Natural sounds, Oddball paradigm, General Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Brain, Electroencephalography, Fundamental frequency, medicine.disease, auditory perception, Sound, pitch perception, Acoustic Stimulation, harmonicity, Evoked Potentials, Auditory, Harmonic, Timbre, Music, amusia
Abstract: Many natural sounds have frequency spectra composed of integer multiples of a fundamental frequency. This property, known as harmonicity, plays an important role in auditory information processing. However, the extent to which harmonicity influences the processing of sound features beyond pitch is still unclear. This is interesting because harmonic sounds have lower information entropy than inharmonic sounds. According to predictive processing accounts of perception, this property could produce more salient neural responses due to the brain’s weighting of sensory signals according to their uncertainty. In the present study, we used electroencephalography to investigate brain responses to harmonic and inharmonic sounds commonly occurring in music: piano tones and hi-hat cymbal sounds. In a multi-feature oddball paradigm, we measured mismatch negativity (MMN) and P3a responses to timbre, intensity, and location deviants in listeners with and without congenital amusia—an impairment of pitch processing. As hypothesized, we observed larger amplitudes and earlier latencies (for both MMN and P3a) in harmonic compared to inharmonic sounds. These harmonicity effects were modulated by sound feature. Moreover, the difference in P3a latency between harmonic and inharmonic sounds was larger for controls than amusics. We propose an explanation of these results based on predictive coding and discuss the relationship between harmonicity, information entropy, and precision weighting of prediction errors.
Published: 2022
Full Text: View/download PDF

17. Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial

Author: Solange Peters, Rafal Dziadziuszko, Alessandro Morabito, Enriqueta Felip, Shirish M. Gadgeel, Parneet Cheema, Manuel Cobo, Zoran Andric, Carlos H. Barrios, Masafumi Yamaguchi, Eric Dansin, Pongwut Danchaivijitr, Melissa Johnson, Silvia Novello, Michael S. Mathisen, Sarah M. Shagan, Erica Schleifman, Jin Wang, Mark Yan, Simonetta Mocci, David Voong, David A. Fabrizio, David S. Shames, Todd Riehl, David R. Gandara, Tony Mok, Institut Català de la Salut, [Peters S] Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland. [Dziadziuszko R] Medical University of Gdańsk, Gdańsk, Poland. [Morabito A] Istituto Nazionale Tumori ‘Fondazione G Pascale’, IRCCS, Naples, Italy. [Felip E] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Gadgeel SM] Henry Ford Cancer Institute/Henry Ford Health System, Detroit, MI, USA. [Cheema P] William Osler Health System, University of Toronto, Brampton, Ontario, Canada, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Lung Neoplasms, phase 3 trial, Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Marcadors tumorals, terapéutica::terapia biológica::inmunomodulación::inmunoterapia [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], blood-based tumor, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], factores biológicos::biomarcadores::marcadores tumorales [COMPUESTOS QUÍMICOS Y DROGAS], Atezolizumab versus chemotherapy, NSCLC, blood-based tumor, mutational burden, phase 3 trial, General Medicine, Pulmons - Càncer - Immunoteràpia, Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung [DISEASES], neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES], NSCLC, Antibodies, Monoclonal, Humanized, Other subheadings::Other subheadings::/drug therapy [Other subheadings], General Biochemistry, Genetics and Molecular Biology, Atezolizumab versus chemotherapy, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Humans, Immunotherapy, Biological Factors::Biomarkers::Biomarkers, Tumor [CHEMICALS AND DRUGS], mutational burden
Abstract: Non-small-cell lung cancer; Predictive markers Càncer de pulmó de cèl·lules no petites; Marcadors predictius Cáncer de pulmón de células no pequeñas; Marcadores predictivos Tumor mutational burden (TMB) is being explored as a predictive biomarker for cancer immunotherapy outcomes in non-small cell lung cancer. BFAST (NCT03178552)—an open-label, global, multicohort trial—evaluated the safety and efficacy of first-line targeted therapies or immunotherapy in patients with unresectable Stage IIIB or IV advanced or metastatic non-small cell lung cancer who were selected for biomarker status using blood-based targeted next-generation sequencing. In the Phase 3 cohort C evaluating blood-based (b)TMB as a biomarker of atezolizumab efficacy, patients with bTMB of ≥10 (N = 471) were randomized 1:1 to receive atezolizumab or platinum-based chemotherapy per local standard of care. Cohort C did not meet its primary endpoint of investigator-assessed progression-free survival in the population with bTMB of ≥16 (hazard ratio, 0.77; 95% confidence interval: 0.59, 1.00; P = 0.053). Adverse events leading to treatment withdrawal occurred in 10% of patients in the atezolizumab arm and 20% in the chemotherapy arm. Adverse events of special interest occurred in 42% of patients in the atezolizumab arm and 26% in the chemotherapy arm. A prespecified exploratory analysis compared the bTMB clinical trial assay with the FoundationOne Liquid Companion Diagnostic assay and showed high concordance between assays. Additional exploration of bTMB to identify optimal cutoffs, confounding factors, assay improvements or cooperative biomarkers is warranted.
Published: 2022

18. ATP and its N-substituted analogues: parameterization, molecular dynamics simulation and conformational analysis

Author: Gruszczyński, Paweł, Smalara, Krzysztof, Obuchowski, Michał, Kaźmierkiewicz, Rajmund, Faculty of Chemistry [Univ Gdańsk], University of Gdańsk (UG), Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Department of Medical Biotechnology, and Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk
Subjects: Conformational analysis, Molecular dynamics, Simulated annealing, Adenosine triphosphate
Abstract: International audience; In this work we used a combination of classical molecular dynamics and simulated annealing techniques to shed more light on the conformational flexibility of 12 adenosine triphosphate (ATP) analogues in a water environment. We present simulations in AMBER force field for ATP and 12 published analogues [Shah et al. (1997) Proc Natl Acad Sci USA 94: 3565-3570]. The calculations were carried out using the generalized Born (GB) solvation model in the presence of the cation Mg. The ion was placed at a close distance (2 Å) from the charged oxygen atoms of the beta and gamma phosphate groups of the −3 negatively charged ATP analogue molecules. Analysis of the results revealed the distribution of inter-proton distances H8-H1′ and H8-H2′ versus the torsion angle ψ (C4-N9-C1′-O4′) for all conformations of ATP analogues. There are two gaps in the distribution of torsion angle ψ values: the first is between −30 and 30 degrees and is described by cis-conformation; and the second is between 90 and 175 degrees, which mostly covers a region of anti conformation. Our results compare favorably with results obtained in experimental assays [Jiang and Mao (2002) Polyhedron 21:435-438].
Published: 2010
Full Text: View/download PDF

19. Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Author: Eric Frost, Pascale B. Beauregard, Adam Plotka, Abdelouahed Khalil, Jacek M. Witkowski, Arnold R. Eiser, Anis Larbi, Tamas Fulop, Annelise E. Barron, Francois P.J. Bernier, Serafim Rodrigues, Katsuiku Hirokawa, Shreyansh Tripathi, Ton Bunt, Benoit Laurent, Christian Bocti, Mathieu Desroches, Centre de recherche sur le vieillissement - CSSS-UIGS (Université de Sherbrooke), University of Delhi, Basque Center for Applied Mathematics (BCAM), Basque Center for Applied Mathematics, Ikerbasque - Basque Foundation for Science, Mathématiques pour les Neurosciences (MATHNEURO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Côte d'Azur (UCA), Izumi Biosciences Inc., Leonard Davis Institute of Health Economics, University of Pennsylvania, Morinaga Milk Industry Co., Université de Sherbrooke / Sherbrooke University (UdS), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Medical University of Gdańsk, Tokyo Medical and Dental University [Japan] (TMDU), and Agency for science, technology and research [Singapore] (A*STAR)
Subjects: brain, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], Review, Disease, neuroinflammation, 03 medical and health sciences, mild cognitive impairment, 0302 clinical medicine, Immune system, Immunity, medicine, Dementia, Risk factor, ComputingMilieux_MISCELLANEOUS, Neuroinflammation, antimicrobial immunity, treatment, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Neurodegeneration, medicine.disease, 030227 psychiatry, Immunology, Etiology, business, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract: Alzheimer’s disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. However, many studies showed that Aβ is a frequent consequence of many challenges/pathologic processes occurring in the brain for decades. A key factor, sustained by experimental data, is that low-grade infection leading to production and deposition of Aβ, which has antimicrobial activity, precedes the development of clinically apparent AD. This infection is chronic, low grade, largely clinically silent for decades because of a nearly efficient antimicrobial immune response in the brain. A chronic inflammatory state is induced that results in neurodegeneration. Interventions that appear to prevent, retard or mitigate the development of AD also appear to modify the disease. In this review, we conceptualize further that the changes in the brain antimicrobial immune response during aging and especially in AD sufferers serve as a foundation that could lead to improved treatment strategies for preventing or decreasing the progression of AD in a disease-modifying treatment.
Published: 2021
Full Text: View/download PDF

20. Vitamin D Enhances Anticancer Properties of Cediranib, a VEGFR Inhibitor, by Modulation of VEGFR2 Expression in Melanoma Cells

Author: Anna Piotrowska, Fernando Pereira Beserra, Justyna Marta Wierzbicka, Joanna Irena Nowak, Michał Aleksander Żmijewski, Medical University of Gdańsk, and Universidade Estadual Paulista (UNESP)
Subjects: anti-angiogenic therapy, VEGFR, Cancer Research, Oncology, melanoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, VEGFR inhibitors, calcipotriol, cediranib, vitamin D, neoplasms, RC254-282, Original Research
Abstract: Made available in DSpace on 2022-04-28T19:49:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-24 Regardless of the recent groundbreaking introduction of personalized therapy, melanoma continues to be one of the most lethal skin malignancies. Still, a substantial proportion of patients either fail to respond to the therapy or will relapse over time, representing a challenging clinical problem. Recently, we have shown that vitamin D enhances the effectiveness of classical chemotherapeutics in the human malignant melanoma A375 cell line. In search for new combination strategies and adjuvant settings to improve melanoma patient outcomes in the current study, the effects of cediranib (AZD2171), an oral tyrosine kinase inhibitor of VEGFR1-3, PDGFR, and c-KIT, used in combination either with 1,25(OH)2D3 or with low-calcemic analog calcipotriol were tested on four human malignant melanoma cell lines (A375, MNT-1, RPMI-7951, and SK-MEL-28). Melanoma cells were pretreated with vitamin D and subsequently exposed to cediranib. We observed a marked decrease in melanoma cell proliferation (A375 and SK-MEL-28), G2/M cell cycle arrest, and a significant decrease in melanoma cell mobility in experimental conditions used (A375). Surprisingly, concurrently with a very desirable decrease in melanoma cell proliferation and mobility, we noticed the upregulation of VEGFR2 at both protein and mRNA levels. No effect of vitamin D was observed in MNT-1 and RPMI-7951 melanoma cells. It seems that vitamin D derivatives enhance cediranib efficacy by modulation of VEGFR2 expression in melanoma cells expressing VEGFR2. In conclusion, our experiments demonstrated that vitamin D derivatives hold promise as novel adjuvant candidates to conquer melanoma, especially in patients suffering from vitamin D deficiency. However, further extensive research is indispensable to reliably assess their potential benefits for melanoma patients. Department of Histology Faculty of Medicine Medical University of Gdańsk Institute of Biosciences São Paulo State University Institute of Biosciences São Paulo State University
Published: 2021
Full Text: View/download PDF

21. Climber exhibits first clinical manifestation of spinocerebellar ataxia on Karakoram expedition

Author: Robert K Szymczak, Magdalena Sawicka, Jan Pyrzowski, Medical University of Gdańsk, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, Hal Sorbonne Université
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, General Medicine, Inherited disease, nervous system diseases, High altitude, Expeditions, Humans, Spinocerebellar Ataxias, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Spinocerebellar ataxia, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurodegeneration, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Spinocerebellar ataxias are rare, genetically inherited diseases. Their typical symptoms include disturbances in gait, balance and uncoordinated movements, but these abnormalities, when appear at altitude, might also suggest high-altitude cerebral edema. We described the first clinical manifestation of spinocerebellar ataxia of a climber from Poland on a Karakoram expedition.
Published: 2021
Full Text: View/download PDF

22. Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment

Author: Xiaoqin Zou, Théo Mauri, Hang Shi, Shaowen Zhu, Justas Dapkūnas, Yuanfei Sun, Didier Barradas-Bautista, Raphael A. G. Chaleil, Ragul Gowthaman, Sohee Kwon, Xianjin Xu, Zuzana Jandova, Genki Terashi, Ryota Ashizawa, Petras J. Kundrotas, Shuang Zhang, Tunde Aderinwale, Jian Liu, Sandor Vajda, Paul A. Bates, Jianlin Cheng, Daisuke Kihara, Luis A. Rodríguez-Lumbreras, Carlos A. Del Carpio Muñoz, Liming Qiu, Guillaume Brysbaert, Jorge Roel-Touris, Česlovas Venclovas, Tereza Clarence, Rui Yin, Amar Singh, Patryk A. Wesołowski, Rafał Ślusarz, Adam Liwo, Guangbo Yang, Agnieszka S. Karczyńska, Yoshiki Harada, Sergei Kotelnikov, Yuya Hanazono, Charlotte W. van Noort, Marc F. Lensink, Jonghun Won, Adam K. Sieradzan, Israel Desta, Xufeng Lu, Charles Christoffer, Anna Antoniak, Taeyong Park, Sheng-You Huang, Tsukasa Nakamura, Brian G. Pierce, Usman Ghani, Yang Shen, Luigi Cavallo, Chaok Seok, Hao Li, Nurul Nadzirin, Ghazaleh Taherzadeh, Jacob Verburgt, Rodrigo V. Honorato, Artur Giełdoń, Jeffrey J. Gray, Dima Kozakov, Ming Liu, Shan Chang, Eiichiro Ichiishi, Manon Réau, Rui Duan, Francesco Ambrosetti, Johnathan D. Guest, Juan Fernández-Recio, Alexandre M. J. J. Bonvin, Ilya A. Vakser, Farhan Quadir, Yumeng Yan, Ren Kong, Sameer Velankar, Sergei Grudinin, Mateusz Kogut, Mikhail Ignatov, Yasuomi Kiyota, Hyeonuk Woo, Shoshana J. Wodak, Ameya Harmalkar, Shinpei Kobayashi, Panagiotis I. Koukos, Zhen Cao, Kliment Olechnovič, Cezary Czaplewski, Xiao Wang, Agnieszka G. Lipska, Kathryn A. Porter, Peicong Lin, Emilia A. Lubecka, Nasser Hashemi, Bin Liu, Mayuko Takeda-Shitaka, Karolina Zięba, Dzmitry Padhorny, Zhuyezi Sun, Daipayan Sarkar, Romina Oliva, Andrey Alekseenko, Siri Camee van Keulen, Mireia Rosell, Raj S. Roy, Brian Jiménez-García, Jinsol Yang, Martyna Maszota-Zieleniak, Cancer Research UK, Department of Energy and Climate Change (UK), European Commission, Institut National de Recherche en Informatique et en Automatique (France), Medical Research Council (UK), Japan Society for the Promotion of Science, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), National Institute of General Medical Sciences (US), National Institutes of Health (US), National Natural Science Foundation of China, National Science Foundation (US), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Biomolecular Modelling Laboratory [London], The Francis Crick Institute [London], Jiangsu University of Technology [Changzhou], Department of Electrical Engineering and Computer Science [Columbia] (EECS), University of Missouri [Columbia] (Mizzou), University of Missouri System-University of Missouri System, Institute for Data Science and Informatics [Columbia], University of Gdańsk (UG), Faculty of Electronics, Telecommunications and Informatics [GUT Gdańsk] (ETI), Gdańsk University of Technology (GUT), Medical University of Gdańsk, Graduate School of Medical Sciences [Nagoya], Nagoya City University [Nagoya, Japan], International University of Health and Welfare Hospital (IUHW Hospital), Department of Chemical and Biomolecular Engineering [Baltimore], Johns Hopkins University (JHU), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Innopolis University, Boston University [Boston] (BU), Russian Academy of Sciences [Moscow] (RAS), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Universidad de La Rioja (UR), Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Données, Apprentissage et Optimisation (DAO), Laboratoire Jean Kuntzmann (LJK), Université Grenoble Alpes (UGA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Huazhong University of Science and Technology [Wuhan] (HUST), Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Graduate School of Information Sciences [Sendaï], Tohoku University [Sendai], National Institutes for Quantum and Radiological Science and Technology (QST), University of Maryland [Baltimore], King Abdullah University of Science and Technology (KAUST), University of Naples Federico II, Texas A&M University [Galveston], Seoul National University [Seoul] (SNU), Kitasato University, University of Kansas [Lawrence] (KU), Vilnius University [Vilnius], University of Missouri System, VIB-VUB Center for Structural Biology [Bruxelles], VIB [Belgium], Sub NMR Spectroscopy, Sub Overig UiLOTS, Sub Mathematics Education, NMR Spectroscopy, Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, European Bioinformatics Institute [Hinxton] [EMBL-EBI], Department of Electrical Engineering and Computer Science [Columbia] [EECS], Faculty of Chemistry [Univ Gdańsk], Faculty of Electronics, Telecommunications and Informatics [GUT Gdańsk] [ETI], International University of Health and Welfare Hospital [IUHW Hospital], Johns Hopkins University [JHU], Stony Brook University [SUNY] [SBU], Department of Biomedical Engineering [Boston], Instituto de Ciencias de la Vid y el Vino [ICVV], Huazhong University of Science and Technology [Wuhan] [HUST], Indiana University - Purdue University Indianapolis [IUPUI], National Institutes for Quantum and Radiological Science and Technology [QST], King Abdullah University of Science and Technology [KAUST], Università degli Studi di Napoli 'Parthenope' = University of Naples [PARTHENOPE], Seoul National University [Seoul] [SNU], University of Kansas [Lawrence] [KU], University of Missouri [Columbia] [Mizzou], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), University of Naples Federico II = Università degli studi di Napoli Federico II, European Project: 675728,H2020,H2020-EINFRA-2015-1,BioExcel(2015), European Project: 823830,H2020-EU.1.4.1.3. Development, deployment and operation of ICT-based e-infrastructures, H2020-EU.1.4. EXCELLENT SCIENCE - Research Infrastructures ,BioExcel-2(2019), European Project: 777536,H2020-EU.1.4.1.3. Development, deployment and operation of ICT-based e-infrastructures, and H2020-EU.1.4. EXCELLENT SCIENCE - Research Infrastructures,EOSC-hub(2018)
Subjects: Models, Molecular, blind prediction, CAPRI, CASP, docking, oligomeric state, protein assemblies, protein complexes, protein docking, protein–protein interaction, template-based modeling, Computer science, [SDV]Life Sciences [q-bio], Machine learning, computer.software_genre, Biochemistry, Article, protein-protein interaction, 03 medical and health sciences, Sequence Analysis, Protein, Structural Biology, Server, Protein Interaction Domains and Motifs, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Binding Sites, business.industry, 030302 biochemistry & molecular biology, Computational Biology, Proteins, 3. Good health, Molecular Docking Simulation, Artificial intelligence, business, computer, Software
Abstract: We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70–75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70–80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands., Cancer Research UK, Grant/Award Number: FC001003; Changzhou Science and Technology Bureau, Grant/Award Number: CE20200503; Department of Energy and Climate Change, Grant/Award Numbers: DE-AR001213, DE-SC0020400, DE-SC0021303; H2020 European Institute of Innovation and Technology, Grant/Award Numbers: 675728, 777536, 823830; Institut national de recherche en informatique et en automatique (INRIA), Grant/Award Number: Cordi-S; Lietuvos Mokslo Taryba, Grant/Award Numbers: S-MIP-17-60, S-MIP-21-35; Medical Research Council, Grant/Award Number: FC001003; Japan Society for the Promotion of Science KAKENHI, Grant/Award Number: JP19J00950; Ministerio de Ciencia e Innovación, Grant/Award Number: PID2019-110167RB-I00; Narodowe Centrum Nauki, Grant/Award Numbers: UMO-2017/25/B/ST4/01026, UMO-2017/26/M/ST4/00044, UMO-2017/27/B/ST4/00926; National Institute of General Medical Sciences, Grant/Award Numbers: R21GM127952, R35GM118078, RM1135136, T32GM132024; National Institutes of Health, Grant/Award Numbers: R01GM074255, R01GM078221, R01GM093123, R01GM109980, R01GM133840, R01GN123055, R01HL142301, R35GM124952, R35GM136409; National Natural Science Foundation of China, Grant/Award Number: 81603152; National Science Foundation, Grant/Award Numbers: AF1645512, CCF1943008, CMMI1825941, DBI1759277, DBI1759934, DBI1917263, DBI20036350, IIS1763246, MCB1925643; NWO, Grant/Award Number: TOP-PUNT 718.015.001; Wellcome Trust, Grant/Award Number: FC001003
Published: 2021
Full Text: View/download PDF

23. Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

Author: Jean-Pierre Bellenger, Benoit Laurent, Nabil Bosco, Tamas Fulop, Katsuiku Hirokawa, Eric Frost, Pascale B. Beauregard, Abdelouahed Khalil, David Dumoulin, Weili Xu, Mathieu Desroches, Simon Lévesque, Stephen C. Cunnane, Annelise E. Barron, Anis Larbi, Charles Ramassamy, Michael Catanzaro, Serafim Rodrigues, Usma Munawara, Crystal Tze Ying Tan, Jacek M. Witkowski, Centre de recherche sur le vieillissement - CSSS-UIGS (Université de Sherbrooke), Università degli Studi di Pavia = University of Pavia (UNIPV), Agency for science, technology and research [Singapore] (A*STAR), Tokyo Medical and Dental University [Japan] (TMDU), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Université de Sherbrooke / Sherbrooke University (UdS), INRS-Centre Armand-Frappier Sante Biotechnologie, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Ikerbasque - Basque Foundation for Science, Basque Center for Applied Mathematics (BCAM), Basque Center for Applied Mathematics, Mathématiques pour les Neurosciences (MATHNEURO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Côte d'Azur (UCA), and Medical University of Gdańsk
Subjects: 0301 basic medicine, Aging, Immunology, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], free radicals, Systemic inflammation, Peripheral blood mononuclear cell, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Dementia, Macrophage, Neuroinflammation, MCI neuroinflammation, Microglia, business.industry, Monocyte, Research, [SCCO.NEUR]Cognitive science/Neuroscience, RC952-954.6, phagocytosis, RC581-607, medicine.disease, cytokines, 3. Good health, macrophages, 030104 developmental biology, medicine.anatomical_structure, Geriatrics, Immunologic diseases. Allergy, medicine.symptom, business, monocytes, signaling, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract: Background Alzheimer’s disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD. Objectives AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease. Results We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation. Conclusion Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention.
Published: 2021
Full Text: View/download PDF

24. Syndromic neurodevelopmental disorder associated with de novo variants in DDX23

Author: Aida Telegrafi, Susanne Liptay, Korbinian M. Riedhammer, Katherine G. Langley, Florencia del Viso, Ilaria Parenti, Divya Ramachandra, Jolanta Wierzba, Lynne M. Bird, Joseph Porrmann, Sophie Gößwein, Isabelle Thiffault, Richard Steet, Michael J. Lyons, Neda Zadeh, William Boyce Burns, Boris Keren, Kendra Engleman, Heather M. McLaughlin, Delphine Héron, Shivarajan Manickavasagam Amudhavalli, Raymond J. Louie, Andrea Fischer, Frank J. Kaiser, Red Hat Inc., The Greenwood Genetic Center, University of California, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Advocate Hope Children's Hospital, Children's Mercy Hospital [Kansas City], Universität Duisburg-Essen [Essen], Medical University of Gdańsk, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Genetics Center, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Invitae Corporation, GeneDx [Gaithersburg, MD, USA], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Technical University of Munich (TUM), University of California (UC), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Male, 0301 basic medicine, RNA helicase, DEAD box, Autism Spectrum Disorder, RNA Splicing, Medizin, Mutation, Missense, [SDV.GEN] Life Sciences [q-bio]/Genetics, 030105 genetics & heredity, Genomic Instability, DEAD-box RNA Helicases, 03 medical and health sciences, Neurodevelopmental disorder, Seizures, Intellectual Disability, Genetics, medicine, Humans, Genetic Predisposition to Disease, Global developmental delay, Child, Gene, Genetics (clinical), RNA, Double-Stranded, [SDV.GEN]Life Sciences [q-bio]/Genetics, biology, neurodevelopment, Infant, Newborn, Infant, Helicase, RNA, medicine.disease, RNA Helicase A, 030104 developmental biology, Neurodevelopmental Disorders, Child, Preschool, RNA splicing, biology.protein, Female, DDX23
Abstract: The DEAD/DEAH box RNA helicases are a superfamily of proteins involved in the processing and transportation of RNA within the cell. A growing literature supports this family of proteins as contributing to various types of human disorders from neurodevelopmental disorders to syndromes with multiple congenital anomalies. This article presents a cohort of nine unrelated individuals with de novo missense alterations in DDX23 (Dead-Box Helicase 23). The gene is ubiquitously expressed and functions in RNA splicing, maintenance of genome stability, and the sensing of double-stranded RNA. Our cohort of patients, gathered through GeneMatcher, exhibited features including tone abnormalities, global developmental delay, facial dysmorphism, autism spectrum disorder, and seizures. Additionally, there were a variety of other findings in the skeletal, renal, ocular, and cardiac systems. The missense alterations all occurred within a highly conserved RecA-like domain of the protein, and are located within or proximal to the DEAD box sequence. The individuals presented in this article provide evidence of a syndrome related to alterations in DDX23 characterized predominantly by atypical neurodevelopment.
Published: 2021
Full Text: View/download PDF

25. Interfaces with Structure Dynamics of the Workhorses from Cells Revealed through Cross-Linking Mass Spectrometry (CLMS)

Author: Robin Fahraeus, Javier A. Alfaro, Umesh Kalathiya, Etienne Coyaud, Ted R. Hupp, David R. Goodlett, Monikaben Padariya, Jakub Faktor, Medical University of Gdańsk, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, University of Edinburgh, University of Victoria [Canada] (UVIC), INSERM, Université de Lille, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192, and University of Victoria [Canada] [UVIC]
Subjects: protein–protein, Protein Conformation, [SDV]Life Sciences [q-bio], Dna interaction, lcsh:QR1-502, Computational biology, Review, Mass spectrometry, Proteomics, 01 natural sciences, Biochemistry, protein–DNA, lcsh:Microbiology, Mass Spectrometry, 03 medical and health sciences, chemistry.chemical_compound, proteomics, proteinprotein, protein-DNA, protein–RNA interactions, structural biology, Animals, Humans, Molecular Biology, Topology (chemistry), 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, protein-RNA interactions, chemical cross-linkers, Biomolecule, 010401 analytical chemistry, cross-linking mass spectrometry, RNA, Proteins, CLMS, DNA, 0104 chemical sciences, chemistry, Structural biology, Protein Binding
Abstract: International audience; The fundamentals of how protein-protein/RNA/DNA interactions influence the structures and functions of the workhorses from the cells have been well documented in the 20th century. A diverse set of methods exist to determine such interactions between different components, particularly, the mass spectrometry (MS) methods, with its advanced instrumentation, has become a significant approach to analyze a diverse range of biomolecules, as well as bring insights to their biomolecular processes. This review highlights the principal role of chemistry in MS-based structural proteomics approaches, with a particular focus on the chemical cross-linking of protein-protein/DNA/RNA complexes. In addition, we discuss different methods to prepare the cross-linked samples for MS analysis and tools to identify cross-linked peptides. Cross-linking mass spectrometry (CLMS) holds promise to identify interaction sites in larger and more complex biological systems. The typical CLMS workflow allows for the measurement of the proximity in three-dimensional space of amino acids, identifying proteins in direct contact with DNA or RNA, and it provides information on the folds of proteins as well as their topology in the complexes. Principal CLMS applications, its notable successes, as well as common pipelines that bridge proteomics, molecular biology, structural systems biology, and interactomics are outlined.
Published: 2021
Full Text: View/download PDF

26. Epigenetic Changes in Neoplastic Mast Cells and Potential Impact in Mastocytosis

Author: Marek Niedoszytko, Michel Arock, Peter Valent, Edyta Wieczorek, Gunnar Nilsson, Ewa Jabłońska, Bogusław Nedoszytko, Edyta Reszka, Nofer Institute of Occupational Medicine (NIOM), Medizinische Universität Wien = Medical University of Vienna, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Karolinska University Hospital [Stockholm], and Medical University of Gdańsk
Subjects: 0301 basic medicine, DNMT3A, Review, DNA Methyltransferase 3A, Epigenesis, Genetic, Pathogenesis, lcsh:Chemistry, 0302 clinical medicine, Neoplasm, TET2, DNA (Cytosine-5-)-Methyltransferases, Mast Cells, Systemic mastocytosis, lcsh:QH301-705.5, Spectroscopy, mastocytosis, DNA methylation, microRNA, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Mast cell, 3. Good health, Computer Science Applications, DNA-Binding Proteins, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Catalysis, Dioxygenases, Inorganic Chemistry, 03 medical and health sciences, Mastocytosis, Systemic, Proto-Oncogene Proteins, demethylating agents, medicine, Humans, Epigenetics, Physical and Theoretical Chemistry, Molecular Biology, epigenetics, business.industry, Organic Chemistry, medicine.disease, Repressor Proteins, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Mutation, Cancer research, Bone marrow, business
Abstract: International audience; Systemic mastocytosis (SM) is a hematologic neoplasm with abnormal accumulation of mast cells in various organ systems such as the bone marrow, other visceral organs and skin. So far, only little is known about epigenetic changes contributing to the pathogenesis of SM. In the current article, we provide an overview of epigenetic changes that may occur and be relevant to mastocytosis, including mutations in genes involved in epigenetic processes, such as TET2, DNMT3A and ASXL1, and global and gene-specific methylation patterns in neoplastic cells. Moreover, we discuss methylation-specific pathways and other epigenetic events that may trigger disease progression in mast cell neoplasms. Finally, we discuss epigenetic targets and the effects of epigenetic drugs, such as demethylating agents and BET-targeting drugs, on growth and viability of neoplastic mast cells. The definitive impact of these targets and the efficacy of epigenetic therapies in advanced SM need to be explored in future preclinical studies and clinical trials.
Published: 2021
Full Text: View/download PDF

27. Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA

Author: Jere Reijula, De Yun Wang, Ralph Mösges, Tomohisa Iinuma, Jean Luc Fauquert, Nelson Rosario, Yehia El-Gamal, René Maximiliano Gómez, Tari Haahtela, Vincenzo Patella, Lorenzo Cecchi, Petr Panzner, Yoshitaka Okamoto, Oliver Pfaar, Luis Caraballo, Paulo Augusto Moreira Camargos, Filip Raciborski, Florin Mihaltan, Ken Ohta, Brian J. Lipworth, Kimi Okubo, Juan Carlos Ivancevich, Fulvio Braido, Ioana Agache, Frederico S. Regateiro, Neven Miculinic, Tuula Vasankari, R. Emuzyte, Arunas Valiulis, Yousser Mohammad, Torsten Zuberbier, Osman M. Yusuf, Ewa Jassem, Cezmi A. Akdis, Jean Bousquet, Alessandro Fiocchi, Jan Hagemann, Claus Bachert, Davor Plavec, K. S. Bennoor, Marek Jutel, Désirée Larenas-Linnemann, Stephen Montefort, Stefano Del Giacco, Przemyslaw Kardas, Erkka Valovirta, Mark S. Dykewicz, Antonio Valero, Wienczyslawa Czarlewski, Thomas B. Casale, Gabrielle L. Onorato, Omer Kalayci, Ludger Klimek, Joaquin Sastre, João Fonseca, Siân Williams, Karl Christian Bergmann, Marek Niedoszytko, Bilun Gemicioglu, Mario E. Zernotti, Musa Khaitov, H. Neffen, Robert M. Naclerio, Joaquim Mullol, Ana Pereira, Piotr Kuna, Michael Makris, Maria Teresa Ventura, Ioanna Tsiligianni, Dirceu Solé, Arzu Yorgancioglu, Charlotte Suppli-Ulrik, M. Gotua, Emmanuel P. Prokopakis, Dana Wallace, Jorge Maspero, Wytske Fokkens, Eckard Hamelmann, Antonino Romano, Dejan Dokic, Todor A. Popov, Violeta Kvedariene, Derek K. Chu, Anna Bedbrook, Dermot Ryan, Motohiro Ebisawa, Tomas Chivato, Giovanni Passalacqua, Menachem Rottem, Mário Morais-Almeida, Victoria Cardona, Bolesław Samoliński, Cristiana Stellato, Nikolaos G. Papadopoulos, Milan Sova, Jaime Correia-de-Sousa, Sietze Reitsma, Cemal Cingi, Francesca Puggioni, Robyn E O'Hehir, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, HUS Internal Medicine and Rehabilitation, Department of Public Health, Clinicum, Keuhkosairauksien yksikkö, Helsinki University Hospital Area, University of Helsinki, University Medical Center of the Johannes Gutenberg-University Mainz, 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), University of Wrocław [Poland] (UWr), Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Transilvania University of Brasov, Humboldt University Of Berlin, Medical Consulting Czarlewski, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), MASK-air, Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], National Institute of Diseases of the Chest and Hospital (NIDCH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Ospedale Policlinico San Martino [Genoa], Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), University of Cartagena, Foundation for the Development of Medical and Biological Sciences (FUNDEMEB), Vall d'Hebron University Hospital [Barcelona], Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], University of South Florida [Tampa] (USF), Azienda Usl Toscana centro [Firenze], CEU-San Pablo University and HM-Hospitals School of Medicine, McMaster University [Hamilton, Ontario], Eskisehir Osmangazi University, Universidade do Minho = University of Minho [Braga], Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], The International Primary Care Respiratory Group (IPCRG), Università degli Studi di Cagliari = University of Cagliari (UniCa), Sts. Cyril and Methodius University, Saint Louis University School of Medicine [St Louis], Sagamihara National Hospital [Kanagawa, Japan], Ain Shams University (ASU), Vilnius University [Vilnius], Service de Pédiatrie Générale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Bambino Gesù Children’s Hospital [Rome, Italy], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto = University of Porto, CUF Porto Hospital, Cerrahpasa Faculty of Medicine, Istanbul University, ALAS Medical Institute, Center for Allergy and Immunology Research [Tbilisi], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Universität Bielefeld = Bielefeld University, Chiba University Hospital, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Medical University of Gdańsk, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Medical University of Łódź (MUL), Federal Medicobiological Agency [Moscow, Russian Federation], Hospital Medica Sur [Mexico City, Mexico], Ninewells Hospital and Medical School [Dundee], University General Hospital ' Attikon ' [Athens, Greece], Argentine Association of Allergy and Immunology, Marius Nasta Institute of Pneumology, Tishreen University, Université de Damas = Damascus University, University of Malta [Malta], Hospital CUF Descobertas, Clinical Research International Ltd [Hamburg, Germany] (CRI), Johns Hopkins University School of Medicine [Baltimore], Nemours/Alfred I. du Pont Hospital for Children, Monash University [Melbourne], Tokyo National Hospital, Nippon Medical School [Tokyo, Japon], Medicine Charles University and General Faculty Hospital in Prague, Royal Manchester Children's Hospital, University of Manchester [Manchester], Università degli studi di Genova = University of Genoa (UniGe), 'Santa Maria della Speranza' Hospital, Philipps Universität Marburg = Philipps University of Marburg, J.J. Strossmayer University of Osijek, Children’s Hospital Srebrnjak [Zagreb, Croatia], St. Ivan Rilski University Hospital, University of Crete [Heraklion] (UOC), IRCCS Humanitas [Rozzano, Italy], Medical University of Warsaw - Poland, Centro Hospitalar e Universitário [Coimbra], Amsterdam UMC - Amsterdam University Medical Center, Istituto di Ricovero e Cura a Carattere Scientifico [Troina, Italy] (IRCCS), Oasi Maria Santissima Srl [Troina, Italy], Clinica G.B. Morgagni (Fondazione Mediterranea), Pontifical Catholic University of Paraná (PUCPR), Pontifícia Universidade Católica do Paraná (PUCPR), Ha’Emek Medical Center [Afula, Israel], Pediatric Endocrine Institute [Afula, Israel], Usher Institute of Population Health Sciences and Informatics [Edinburgh, U.K.], University of Edinburgh, Federal University of Sao Paulo (Unifesp), University Hospital Olomouc [Czech Republic], University of Salerno (UNISA), Copenhagen University Hospital, Universitat de Barcelona (UB), European Academy of Paediatrics (EAP/UEMS-SP), University of Turku, Suomen Terveystalo Allergy Clinic, Finnish Lung Health Association, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Nova Southeastern University (NSU), Yong Loo Lin School of Medicine [Singapore], Department of Biology, Faculty of Sciences & Liberal Arts, Celal Bayar University, Manisa Celal Bayar University, The Allergy & Asthma Institute, Pakistan (IPCRG), Universidad Nacional de Villa María, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Allergiezentrum Wiesbaden, Salvy-Córdoba, Nathalie, Ear, Nose and Throat, and AII - Inflammatory diseases
Subjects: 0301 basic medicine, Allergy, MESH: Asthma, Common Cold, allergic rhinitis, common cold, cough, COVID-19, smell, Consensus, Humans, SARS-CoV-2, Asthma, Rhinitis, Allergic, Disease, Care, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, MESH: COVID-19, Rhinitis, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Common cold, 3. Good health, MESH: Rhinitis, Allergic, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Original Article, medicine.symptom, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Immunology, Signs and symptoms, Asymptomatic, 03 medical and health sciences, Allergic, COVID‐19, Internal medicine, medicine, MESH: SARS-CoV-2, MESH: Consensus, MESH: Humans, business.industry, Rhinitis, Sinusitis, and Upper Airway Disease, CARE, medicine.disease, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ORIGINAL ARTICLES, Airway, business, MESH: Common Cold
Abstract: Background Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. Methods A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. Results Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). Conclusions This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.
Published: 2021
Full Text: View/download PDF

28. A Challenge for Allergologist: Application of Allergy Diagnostic Methods in Mast Cell Disorders

Author: Cem Akin, Theo Gülen, Jan Romantowski, Peter Valent, Knut Brockow, Michel Arock, Magdalena Lange, Bogusław Nedoszytko, Aleksandra Górska, Marta Gruchała-Niedoszytko, Marek Niedoszytko, Medical University of Gdańsk, Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, and Medizinische Universität Wien = Medical University of Vienna
Subjects: 0301 basic medicine, Allergy, Wasp Venoms, Review, medicine.disease_cause, Pathogenesis, lcsh:Chemistry, 0302 clinical medicine, Allergen, Vegetables, Mast Cells, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, lcsh:QH301-705.5, Spectroscopy, mastocytosis, Anti-Inflammatory Agents, Non-Steroidal, MCAS, Fishes, General Medicine, Syndrome, Mast cell, ddc, 3. Good health, Computer Science Applications, medicine.anatomical_structure, hypersensitivity, Anaphylaxis, Food Hypersensitivity, Diagnostic methods, Catalysis, Inorganic Chemistry, Diagnosis, Differential, 03 medical and health sciences, Allergists, medicine, anaphylaxis, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, Anesthetics, business.industry, Organic Chemistry, Allergens, medicine.disease, mast cell, Hymenoptera, Basophil activation, 030104 developmental biology, 030228 respiratory system, lcsh:Biology (General), lcsh:QD1-999, Concomitant, Fruit, Immunology, Tryptases, business
Abstract: International audience; Primary and secondary mast cell activation syndromes (MCAS) can occur in patients with mastocytosis. During the past few years our knowledge about the pathogenesis and disease-triggering mechanisms in MCAS and mastocytosis have increased substantially. Whereas mastocytosis is characterized by an accumulation of neoplastic (clonal) mast cells (MC) in various organ systems, MCAS is defined by a massive and systemic activation of these cells. Mast cells are crucial effector cells in allergic diseases, thus their elevated number and activation can cause severe anaphylactic reactions and MCAS in patients with mastocytosis. However, these cells may also degranulate spontaneously or degranulate in response to non-allergic triggers leading to clinical symptoms. In mastocytosis patients, such symptoms may lead to the diagnosis of a primary MCAS. The diagnosis of a concomitant allergy in mastocytosis patients is challenging. In these patients, a mixed form (primary and secondary) of MCAS may be diagnosed. These patients may also suffer from life-threatening anaphylactic reactions when exposed to allergens. In these cases, the possibility of severe side effects of in vivo provocations can sometimes also limit diagnostic evaluations. In the current article, we discuss the diagnosis and management of patients suffering from mastocytosis and concomitant MCAS, with special emphasis on novel diagnostic tests and management, including allergen microarrays, recombinant allergen analysis, basophil activation tests, optimal prophylaxis, and specific therapies
Published: 2021
Full Text: View/download PDF

29. Risdiplam treatment has not led to retinal toxicity in patients with spinal muscular atrophy

Author: Gemma Tremolada, Lutz Mueller, Nora Denk, Birgit Jaber, Sabine Fürst-Recktenwald, Ksenija Gorni, Shannon Beres, Emmanuel Barreau, Melissa SantaMaria, Renata S. Scalco, Agnieszka Waskowska, Lorenzo Orazi, Steven Kane, Bjoern Jacobsen, Giulia Maria Amorelli, Stefania Bianchi Marzoli, Stephane Nave, Giovanni Baranello, Diletta Santarsiero, Shigeko Yashiro, Robert C. Sergott, Eugenio Mercuri, Marianne Gerber, Wills Eye Hospital, Jefferson (Philadelphia University + Thomas Jefferson University), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Stanford University, Columbia University Medical Center (CUMC), Columbia University [New York], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Medical University of Gdańsk, National Center for Global Health and Medicine [Japan] (NCGM), F. Hoffmann-La Roche [Basel], and Pagès, Nathalie
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Visual acuity, Adolescent, genetic structures, [SDV]Life Sciences [q-bio], RG7916 TREATMENT, Retina, Muscular Atrophy, Spinal, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Ophthalmology, EXPLORATORY OUTCOMES, Humans, Medicine, Child, Adverse effect, Research Articles, Clinical Trials as Topic, medicine.diagnostic_test, business.industry, General Neuroscience, Fundus photography, Infant, Retinal, Spinal muscular atrophy, Middle Aged, medicine.disease, SMA, [SDV] Life Sciences [q-bio], Clinical trial, Pyrimidines, 030104 developmental biology, Neuromuscular Agents, chemistry, Child, Preschool, SAFETY, Eye disorder, Female, Neurology (clinical), medicine.symptom, business, Azo Compounds, 030217 neurology & neurosurgery, Research Article
Abstract: International audience; Objective: Evaluation of ophthalmologic safety with focus on retinal safety in patients with spinal muscular atrophy (SMA) treated with risdiplam (EVRYSDI®), a survival of motor neuron 2 splicing modifier associated with retinal toxicity in monkeys. Risdiplam was approved recently for the treatment of patients with SMA, aged ≥ 2 months in the United States, and is currently under Health Authority review in the EU.Methods: Subjects included patients with SMA aged 2 months-60 years enrolled in the FIREFISH, SUNFISH, and JEWELFISH clinical trials for risdiplam. Ophthalmologic assessments, including functional assessments (age-appropriate visual acuity and visual field) and imaging (spectral domain optical coherence tomography [SD-OCT], fundus photography, and fundus autofluorescence [FAF]), were conducted at baseline and every 2-6 months depending on study and assessment. SD-OCT, FAF, fundus photography, and threshold perimetry were evaluated by an independent, masked reading center. Adverse events (AEs) were reported throughout the study.Results: A total of 245 patients receiving risdiplam were assessed. Comprehensive, high-quality, ophthalmologic monitoring assessing retinal structure and visual function showed no retinal structural or functional changes. In the youngest patients, SD-OCT findings of normal retinal maturation were observed. AEs involving eye disorders were not suggestive of risdiplam-induced toxicity and resolved with ongoing treatment.Interpretation: Extensive ophthalmologic monitoring conducted in studies in patients with SMA confirmed that risdiplam does not induce ophthalmologic toxicity in pediatric or adult patients with SMA at the therapeutic dose. These results suggest that safety ophthalmologic monitoring is not needed in patients receiving risdiplam, as also reflected in the United States Prescribing Information for risdiplam.
Published: 2021
Full Text: View/download PDF

30. Sleep and daytime problems during the COVID-19 pandemic and effects of coronavirus infection, confinement and financial suffering: A multinational survey using a harmonised questionnaire

Author: Markku Partinen, Brigitte Holzinger, Charles M Morin, Colin Espie, Frances Chung, Thomas Penzel, Christian Benedict, Courtney J Bolstad, Jonathan Cedernaes, Rachel Ngan Yin Chan, Yves Dauvilliers, Luigi De Gennaro, Fang Han, Yuichi Inoue, Kentaro Matsui, Damien Leger, Ana Suely Cunha, Ilona Merikanto, Sergio Mota-Rolim, Michael Nadorff, Giuseppe Plazzi, Jules Schneider, Mariusz Sieminski, Yun-Kwok Wing, Bjørn Bjorvatn, Department of Neurosciences, Clinicum, HUS Neurocenter, SLEEPWELL Research Program, Research Programs Unit, Herrada, Anthony, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki Sleep Clinic [Helsinki], Medizinische Universität Wien = Medical University of Vienna, Centre de recherche de l’Institut universitaire en santé mentale de Québec [Canada] (CERVO), Département de réadaptation (Faculté de médecine de l'Université Laval) [Canada], Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval)-Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), University of Oxford, University Health Network, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Uppsala University, Mississippi State University [Mississippi], Northwestern University Feinberg School of Medicine, The Chinese University of Hong Kong [Hong Kong], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Peking University [Beijing], Tokyo Medical University, Tokyo Women's Medical University (TWMU), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sommeil-Vigilance-Fatigue et Santé Publique (VIFASOM (URP_7330)), Institut de Recherche Biomédicale des Armées (IRBA)-Université Paris Cité (UPCité), Universidade Federal do Rio Grande do Norte [Natal] (UFRN), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Medical University of Gdańsk, Haukeland University Hospital, and University of Bergen (UiB)
Subjects: [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Epidemiology, insomnia, COVID-19, pandemic, sleep, stress, depression, epidemiology, social medicine, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Surveys and Questionnaires, MESH: COVID-19, 030212 general & internal medicine, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Sleep Quality, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, sleep medicine, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, 3. Good health, Sleep Quality, Neurology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Adult, MESH: Pandemics, Social medicine, 03 medical and health sciences, anxiety disorders, Anxiety disorders, Sleep medicine, Humans, SARS-CoV-2, Pandemics, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: SARS-CoV-2, MESH: Surveys and Questionnaires, MESH: Humans, neurology, 3112 Neurosciences, MESH: Adult, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, LOCKDOWN, MESH: Female, 030217 neurology & neurosurgery
Abstract: ObjectivesSleep is important for human health and well-being. No previous study has assessed whether the COVID-19 pandemic impacts sleep and daytime function across the globe.MethodsThis large-scale international survey used a harmonised questionnaire. Fourteen countries participated during the period of May–August 2020. Sleep and daytime problems (poor sleep quality, sleep onset and maintenance problems, nightmares, hypnotic use, fatigue and excessive sleepiness) occurring ‘before’ and ‘during’ the pandemic were investigated. In total, 25 484 people participated and 22 151 (86.9%) responded to the key parameters and were included. Effects of COVID-19, confinement and financial suffering were considered. In the fully adjusted logistic regression models, results (weighted and stratified by country) were adjusted for gender, age, marital status, educational level, ethnicity, presence of sleep problems before COVID-19 and severity of the COVID-19 pandemic in each country at the time of the survey.ResultsThe responders were mostly women (64%) with a mean age 41.8 (SD 15.9) years (median 39, range 18–95). Altogether, 3.0% reported having had COVID-19; 42.2% reported having been in confinement; and 55.9% had suffered financially. All sleep and daytime problems worsened during the pandemic by about 10% or more. Also, some participants reported improvements in sleep and daytime function. For example, sleep quality worsened in about 20% of subjects and improved in about 5%. COVID-19 was particularly associated with poor sleep quality, early morning awakening and daytime sleepiness. Confinement was associated with poor sleep quality, problems falling asleep and decreased use of hypnotics. Financial suffering was associated with all sleep and daytime problems, including nightmares and fatigue, even in the fully adjusted logistic regression models.ConclusionsSleep problems, fatigue and excessive sleepiness increased significantly worldwide during the first phase of the COVID-19 pandemic. Problems were associated with confinement and especially with financial suffering.
Published: 2021
Full Text: View/download PDF

31. How our Dreams Changed During the COVID-19 Pandemic: Effects and Correlates of Dream Recall Frequency - a Multinational Study on 19,355 Adults

Author: Damien Leger, Brigitte Holzinger, Kentaro Matsui, Markku Partinen, Thomas Penzel, Ngan Yin Chan, Ilona Merikanto, Mariusz Siemiński, Giuseppe Plazzi, Serena Scarpelli, Colin A. Espie, Yves Dauvilliers, Sérgio A. Mota-Rolim, Charles M. Morin, Eirin Fränkl, Yun Kwok Wing, Yuichi Inoue, Frances Chung, Michael R. Nadorff, Tainá Macêdo, Luigi De Gennaro, Courtney J. Bolstad, Bjørn Bjorvatn, Medizinische Universität Wien = Medical University of Vienna, Department of Psychology [University of Roma 'La Sapienza'], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Mississippi State University [Mississippi], Baylor College of Medicine (BCM), Baylor University, Haukeland University Hospital, University of Bergen (UiB), The Chinese University of Hong Kong [Hong Kong], University of Toronto, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Nuffield Department of Clinical Neurosciences [Oxford], University of Oxford [Oxford], Tokyo Medical University, Japan Somnology Center, Sommeil-Vigilance-Fatigue et Santé Publique (VIFASOM (URP_7330)), Institut de Recherche Biomédicale des Armées (IRBA)-Université Paris Cité (UPC), Centre du Sommeil et de la Vigilance [Paris], Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universidade Federal do Rio Grande do Norte [Natal] (UFRN), National Center of Neurology and Psychiatry National Institute of Mental Health (NCNP), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Finnish Institute for Health and Welfare [Helsinki, Finland] (FIHW), Orton Orthopaedic Hospital (Orton Ltd), Centre de recherche de l’Institut universitaire en santé mentale de Québec [Canada] (CERVO), Département de réadaptation (Faculté de médecine de l'Université Laval) [Canada], Faculté de médecine de l'Université Laval [Québec] (ULaval)-Faculté de médecine de l'Université Laval [Québec] (ULaval), Terveystalo Oy, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], IRCCS Istituto delle Scienze Neurologiche di Bologna [Bologna, Italy], Ospedale Bellaria [Bologna, Italy], Università degli Studi di Modena e Reggio Emilia (UNIMORE), Medical University of Gdańsk, Clinical and Behavioral Neurology - Neuroscienze e riabilitazione, IRCCS Fondazione Santa Lucia [Roma], Faculty of Psychology [Vienna], University of Vienna [Vienna], SLEEPWELL Research Program, Faculty of Medicine, Department of Neurosciences, Clinicum, and HUS Neurocenter
Subjects: Neurophysiology and neuropsychology, RC435-571, Logistic regression, REM sleep behavior disorder, 050105 experimental psychology, Collective threat, Mental health, Parasomnia, Sleep, Sleep disorder, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, McNemar's test, collective threat, Nature and Science of Sleep, medicine, 0501 psychology and cognitive sciences, sleep, sleep disorder, mental health, parasomnia, Applied Psychology, Depression (differential diagnoses), Original Research, Psychiatry, business.industry, QP351-495, 05 social sciences, 3112 Neurosciences, medicine.disease, 3. Good health, 3121 General medicine, internal medicine and other clinical medicine, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Anxiety, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Objective Many have reported odd dreams during the pandemic. Given that dreams are associated with mental health, understanding these changes could provide crucial information about wellbeing during the pandemic. This study explored associations between COVID-19 and dream recall frequency (DRF), and related social, health, and mental health factors. Methods We conducted a cross-sectional web survey of 19,355 individuals in 14 countries from May to July 2020. We collected data on COVID-19, mental health, sleep and DRF during the pandemic. We performed McNemar Tests to compare low (, Video abstract Point your SmartPhone at the code above. If you have a QR code reader, the video abstract will appear. Or use: https://youtu.be/Qerns3HLO7o
Published: 2021
Full Text: View/download PDF

32. Zero-crossing patterns reveal subtle epileptiform discharges in the scalp EEG

Author: Amal Fouad, Joanna Jedrzejczak, Mariusz Siemiński, Michel Le Van Quyen, Jan Pyrzowski, Jean Eudes Le Douget, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ain Shams University (ASU), Medical University of Gdańsk, Medical Centre for Postgraduate Education [Warsaw, Poland], Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and HAL-SU, Gestionnaire
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Computer science, Science, Electroencephalography, Audiology, Article, Temporal lobe, Young Adult, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, medicine, Humans, Ictal, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Child, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Neocortex, medicine.diagnostic_test, Diagnostic markers, Middle Aged, Scalp eeg, medicine.disease, Zero crossing, medicine.anatomical_structure, Epilepsy, Temporal Lobe, Scalp, Medicine, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Electrocorticography, 030217 neurology & neurosurgery, Biomarkers
Abstract: Clinical diagnosis of epilepsy depends heavily on the detection of interictal epileptiform discharges (IEDs) from scalp electroencephalographic (EEG) signals, which by purely visual means is far from straightforward. Here, we introduce a simple signal analysis procedure based on scalp EEG zero-crossing patterns which can extract the spatiotemporal structure of scalp voltage fluctuations. We analyzed simultaneous scalp and intracranial EEG recordings from patients with pharmacoresistant temporal lobe epilepsy. Our data show that a large proportion of intracranial IEDs manifest only as subtle, low-amplitude waveforms below scalp EEG background and could, therefore, not be detected visually. We found that scalp zero-crossing patterns allow detection of these intracranial IEDs on a single-trial level with millisecond temporal precision and including some mesial temporal discharges that do not propagate to the neocortex. Applied to an independent dataset, our method discriminated accurately between patients with epilepsy and normal subjects, confirming its practical applicability.
Published: 2021
Full Text: View/download PDF

33. Social jetlag changes during the COVID-19 pandemic as a predictor of insomnia - A multi-national survey study

Author: Brandão, Luiz Eduardo Mateus, Martikainen, Teemu, Merikanto, Ilona, Holzinger, Brigitte, Morin, Charles M, Espie, Colin A, Bolstad, Courtney J, Leger, Damien, Chung, Frances, Plazzi, Giuseppe, Dauvilliers, Yves, Matsui, Kentaro, De Gennaro, Luigi, Sieminski, Mariusz, Nadorff, Michael R, Chan, Ngan Yin, Wing, Yun Kwok, Mota-Rolim, Sérgio Arthuro, Inoue, Yuichi, Partinen, Markku, Benedict, Christian, Bjorvatn, Bjorn, Cedernaes, Jonathan, Salvy-Córdoba, Nathalie, Uppsala University Hospital, Finnish Institute for Health and Welfare [Helsinki, Finland] (FIHW), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Orton Orthopaedic Hospital (Orton Ltd), Medizinische Universität Wien = Medical University of Vienna, Université Laval [Québec] (ULaval), Centre de recherche de l’Institut universitaire en santé mentale de Québec [Canada] (CERVO), Département de réadaptation (Faculté de médecine de l'Université Laval) [Canada], Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval)-Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Nuffield Department of Primary Care Health Sciences, University of Oxford, University of Oxford, Mississippi State University [Mississippi], Sommeil-Vigilance-Fatigue et Santé Publique (VIFASOM (URP_7330)), Institut de Recherche Biomédicale des Armées (IRBA)-Université Paris Cité (UPCité), Toronto Western Hospital, Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), National Center of Neurology and Psychiatry National Institute of Mental Health, Department of Clinical Laboratory and Department of Sleep-Wake Disorders (NCNP), Tokyo Women's Medical University (TWMU), Department of Psychology [University of Roma 'La Sapienza'], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Istituto delle Scienze Neurologiche di Bologna, Partenaires INRAE, Medical University of Gdańsk, Baylor College of Medicine (BCM), Baylor University, City University of Hong Kong [Hong Kong] (CUHK), Federal University of Rio Grande do Norte, Natal, RN, Brazil, Tokyo Medical University, Helsinki Sleep Clinic [Helsinki], Uppsala Universitet [Uppsala], Haukeland University Hospital, University of Bergen (UiB), Feinberg School of Medicine, Northwestern University [Evanston], SLEEPWELL Research Program, Department of Psychology and Logopedics, Department of Neurosciences, Clinicum, and HUS Neurocenter
Subjects: BNSQ, ISI, midsleep, MSFsc, PHQ-4, psychological distress, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Psychological distress, SLEEP HYGIENE, 3124 Neurology and psychiatry, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], ANXIETY, CHRONOTYPE, Original Research, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, 3112 Neurosciences, Public Health, Global Health, Social Medicine and Epidemiology, DEPRESSION, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Midsleep, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HEALTH, LOCKDOWN
Abstract: Purpose: Lifestyle and work habits have been drastically altered by restrictions due to the COVID-19 pandemic. Whether the associated changes in sleep timing modulate the risk of suffering from symptoms of insomnia, the most prevalent sleep disorder, is however incompletely understood. Here, we evaluate the association between the early pandemic-associated change in 1) the magnitude of social jetlag (SJL) – ie, the difference between sleep timing on working vs free days – and 2) symptoms of insomnia. Patients and Methods: A total of 14,968 anonymous participants (mean age: 40 years; 64% females) responded to a standardized internet-based survey distributed across 14 countries. Using logistic multivariate regression, we examined the association between the degree of social jetlag and symptoms of insomnia, controlling for important confounders like social restriction extension, country specific COVID-19 severity and psychological distress, for example. Results: In response to the pandemic, participants reported later sleep timing, especially during workdays. Most participants (46%) exhibited a reduction in their SJL, whereas 20% increased it; and 34% reported no change in SJL. Notably, we found that both increased and decreased SJL, as a result of the COVID-19 pandemic, were associated with later sleep midpoint (indicating a later chronotype) as well as more recurrent and moderate-to-severe symptoms of insomnia (about 23– 54% higher odds ratio than subjects with unchanged SJL). Primarily those with reduced SJL shifted their bedtimes to a later timepoint, compared with those without changes in SJL. Conclusion: Our findings offer important insights into how self-reported changes to the stability of sleep/wake timing, as reflected by changes in SJL, can be a critical marker of the risk of experiencing insomnia-related symptoms – even when individuals manage to reduce their social jetlag. These findings emphasize the clinical importance of analyzing sleep-wake regularity. publishedVersion
Published: 2021
Full Text: View/download PDF

34. Immunosenescence and Altered Vaccine Efficiency in Older Subjects: A Myth Difficult to Change

Author: Tamas Fulop, Anis Larbi, Graham Pawelec, Alan A. Cohen, Guillaume Provost, Abedelouahed Khalil, Guy Lacombe, Serafim Rodrigues, Mathieu Desroches, Katsuiku Hirokawa, Claudio Franceschi, Jacek M. Witkowski, Centre de recherche sur le vieillissement - CSSS-UIGS (Université de Sherbrooke), Agency for science, technology and research [Singapore] (A*STAR), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Health Sciences North Research Institute [Sudbury], Department of Family Medicine, Université de Sherbrooke, Ikerbasque - Basque Foundation for Science, Basque Center for Applied Mathematics (BCAM), Basque Center for Applied Mathematics, Mathématiques pour les Neurosciences (MATHNEURO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Côte d'Azur (UCA), Tokyo Medical and Dental University [Japan] (TMDU), Institute of Neurological Sciences of Bologna IRCCS, and Medical University of Gdańsk
Subjects: immunosenescence, Pharmacology, pneumococcal vaccine, [SCCO.NEUR]Cognitive science/Neuroscience, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], Immunology, tipping point, vaccination, immunobiography, trained immunity, Infectious Diseases, Drug Discovery, herpes–zoster vaccine, inflammaging, Pharmacology (medical), influenza vaccine, adaptive complex systems, COVID-19 vaccine, mathematical model
Abstract: Organismal ageing is associated with many physiological changes, including differences in the immune system of most animals. These differences are often considered to be a key cause of age-associated diseases as well as decreased vaccine responses in humans. The most often cited vaccine failure is seasonal influenza, but, while it is usually the case that the efficiency of this vaccine is lower in older than younger adults, this is not always true, and the reasons for the differential responses are manifold. Undoubtedly, changes in the innate and adaptive immune response with ageing are associated with failure to respond to the influenza vaccine, but the cause is unclear. Moreover, recent advances in vaccine formulations and adjuvants, as well as in our understanding of immune changes with ageing, have contributed to the development of vaccines, such as those against herpes zoster and SARS-CoV-2, that can protect against serious disease in older adults just as well as in younger people. In the present article, we discuss the reasons why it is a myth that vaccines inevitably protect less well in older individuals, and that vaccines represent one of the most powerful means to protect the health and ensure the quality of life of older adults., Inria Associated Team "NeuroTransSF"
Published: 2022
Full Text: View/download PDF

35. Diagnosis, Classification and Management of Mast Cell Activation Syndromes (MCAS) in the Era of Personalized Medicine

Author: Bogusław Nedoszytko, Cem Akin, Peter Valent, Patrizia Bonadonna, Marek Niedoszytko, Karin Hartmann, Jan Romantowski, Knut Brockow, Aleksandra Górska, Michel Arock, Lawrence B. Schwartz, Massimo Triggiani, Dean D. Metcalfe, Frank Siebenhaar, Medizinische Universität Wien = Medical University of Vienna, University of Michigan [Dearborn], University of Michigan System, Medical University of Gdańsk, University Hospital Basel [Basel], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), University of Salerno (UNISA), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Virginia Commonwealth University (VCU), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Technical University of Munich (TUM), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Mast cell activation syndrome, Allergy, [SDV]Life Sciences [q-bio], Hereditary alpha tryptasemia, Mastocytosis, IgE, Review, Catalysis, Allergic inflammation, Inorganic Chemistry, Diagnosis, Differential, lcsh:Chemistry, 03 medical and health sciences, 0302 clinical medicine, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, Mast Cells, Physical and Theoretical Chemistry, Precision Medicine, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, business.industry, Organic Chemistry, General Medicine, medicine.disease, Mast cell, ddc, 3. Good health, Computer Science Applications, 030104 developmental biology, medicine.anatomical_structure, 030228 respiratory system, lcsh:Biology (General), lcsh:QD1-999, Immunology, Etiology, Personalized medicine, medicine.symptom, business, Anaphylaxis
Abstract: International audience; Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE-dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell (MC) disorders, and hereditary alpha tryptasemia (HAT). MCA-related symptoms range from mild to severe to life-threatening. The severity of MCA-related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual's baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC-stabilizing or mediator-targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where KIT-mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE-dependent allergy or other reactive MCA-triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor KIT-mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where KIT-mutated MCs, IgE-dependent allergies and sometimes HAT are detected. These patients may suffer from life-threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE-blocking antibodies, anti-mediator-type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co-morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine.
Published: 2020
Full Text: View/download PDF

36. Targeting Infectious Agents as a Therapeutic Strategy in Alzheimer’s Disease

Author: Francois P.J. Bernier, Mathieu Desroches, Usma Munawara, Jacek M. Witkowski, Tamas Fulop, Michele Catanzaro, Anis Larbi, Katsuiku Hirokawa, Eric Frost, Pascale B. Beauregard, Jean-Philippe Bellenger, Serafim Rodrigues, Abdelouahed Khalil, David Dumoulin, Andrea Guidolin, Annelise E. Barron, Centre de recherche sur le vieillissement - CSSS-UIGS (Université de Sherbrooke), Agency for science, technology and research [Singapore] (A*STAR), University of Tunis El Manar, Mathématiques pour les Neurosciences (MATHNEURO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Ikerbasque - Basque Foundation for Science, Basque Center for Applied Mathematics (BCAM), Basque Center for Applied Mathematics, Morinaga Milk Industry Co., Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Tokyo Medical and Dental University [Japan] (TMDU), Université de Sherbrooke / Sherbrooke University (UdS), and Medical University of Gdańsk
Subjects: Senescence, Amyloid, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], Plaque, Amyloid, Systemic inflammation, Article, 03 medical and health sciences, 0302 clinical medicine, Immune system, Anti-Infective Agents, Alzheimer Disease, medicine, Dementia, Humans, Pharmacology (medical), Microbiome, Neuroinflammation, ComputingMilieux_MISCELLANEOUS, Inflammation, Innate immune system, Amyloid beta-Peptides, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Neurodegeneration, medicine.disease, Immunity, Innate, 030227 psychiatry, Psychiatry and Mental health, Immunology, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Alzheimer’s disease (AD) is the most prevalent dementia in the world. Its cause(s) are presently largely unknown. The most common explanation for AD, now, is the amyloid cascade hypothesis, which states that the cause of AD is senile plaque forma- tion by the amyloid β peptide, and the formation of neurofibrillary tangles by hyperphosphorylated tau. A second, burgeoning theory by which to explain AD is based on the infection hypothesis. Much experimental and epidemiological data support the involvement of infections in the development of dementia. According to this mechanism, the infection either directly or via microbial virulence factors precedes the formation of amyloid β plaques. The amyloid β peptide, possessing antimicrobial properties, may be beneficial at an early stage of AD, but becomes detrimental with the progression of the disease, concomi- tantly with alterations to the innate immune system at both the peripheral and central levels. Infection results in neuroinflam- mation, leading to, and sustained by, systemic inflammation, causing eventual neurodegeneration, and the senescence of the immune cells. The sources of AD-involved microbes are various body microbiome communities from the gut, mouth, nose, and skin. The infection hypothesis of AD opens a vista to new therapeutic approaches, either by treating the infection itself or modulating the immune system, its senescence, or the body’s metabolism, either separately, in parallel, or in a multi-step way., Basque Government under the grant “Artificial Intelligence in BCAM number EXP. 2019/00432”
Published: 2020
Full Text: View/download PDF

37. ESMO Management and treatment adapted recommendations in the COVID-19 era: Breast Cancer

Author: Azambuja, Evandro de, Trapani, Dario, Loibl, Sibylle, Delaloge, Suzette, Senkus, Elzbieta, Criscitiello, Carmen, Poortman, Philip, Gnant, Michael, Di Cosimo, Serena, Cortés, Javier, Cardoso, Fatima, Paluch-Shimon, Shani, Curigliano, Giuseppe, Universitat Autònoma de Barcelona. Departament de Medicina, Institut Català de la Salut, [de Azambuja E] Institut Jules Bordet and l’Université Libre de Bruxelles (U.LB), Brussels, Belgium. [Trapani D] European Institute of Oncology (IEO) IRCCS, Milan, Italy. [Loibl S] GBG Forschungs GmbH, Neu-Isenburg, Germany. [Delaloge S] Oncology, Gustave Roussy and Paris-Saclay University, Villejuif, Île-de-France, France. [Senkus E] Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland. [Criscitiello C] European Institute of Oncology IRCCS, Milan, Italy. [Cortes J] IOB, Institute of Oncology, Quiron Group (Madrid & Barcelona). Vall d'Hebron institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Cancer Research, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Psychological intervention, Review, COVID-19 (Malaltia), Radiation Oncology -- methods, Health care, Pandemic, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Otros calificadores::/terapia [Otros calificadores], media_common, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Surgical Oncology -- methods, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Telemedicine, Surgical Oncology, Oncology, Preparedness, ESMO adapted recommendations, Female, Public Health, Coronavirus Infections, Autonomy, medicine.medical_specialty, media_common.quotation_subject, Pneumonia, Viral, Telemedicine -- methods, Context (language use), Breast Neoplasms, lcsh:RC254-282, Betacoronavirus, breast cancer, Nursing, Breast Neoplasms -- diagnosis -- therapy, medicine, Humans, Quality (business), Pandemics, business.industry, SARS-CoV-2, Health Priorities, Public health, COVID-19, Généralités, Other subheadings::/therapy [Other subheadings], Pneumonia, Viral -- epidemiology -- virology, Coronavirus, Mama - Càncer - Tractament, Radiation Oncology, Business, Human medicine, Coronavirus Infections -- epidemiology -- virology
Abstract: The global preparedness and response to the rapid escalation to severe acute respiratory syndrome coronavirus (SARS-CoV)-2-related disease (COVID-19) to a pandemic proportion has demanded the formulation of a reliable, useful and evidence-based mechanism for health services prioritisation, to achieve the highest quality standards of care to all patients. The prioritisation of high value cancer interventions must be embedded in the agenda for the pandemic response, ensuring that no inconsistency or discrepancy emerge in the health planning processes. The aim of this work is to organise health interventions for breast cancer management and research in a tiered framework (high, medium, low value), formulating a scheme of prioritisation per clinical cogency and intrinsic value or magnitude of benefit. The public health tools and schemes for priority setting in oncology have been used as models, aspiring to capture clinical urgency, value in healthcare, community goals and fairness, while respecting the principles of benevolence, non-maleficence, autonomy and justice. We discuss the priority health interventions across the cancer continuum, giving a perspective on the role and meaning to maintain some services (undeferrable) while temporarily abrogate some others (deferrable). Considerations for implementation and the essential link to pre-existing health services, especially primary healthcare, are addressed, outlining a framework for the development of effective and functional services, such as telemedicine. The discussion covers the theme of health systems strategising, and why oncology care, in particular breast cancer care, should be maintained in parallel to pandemic control measures, providing a pragmatic clinical model within the broader context of public healthcare schemes., SCOPUS: re.j, info:eu-repo/semantics/published
Published: 2020

38. A multiplatform approach: HPLC, GC and NMR for urinary metabolomic analysis of muscle-invasive bladder cancer

Author: Jacyna, Julia, Wawrzyniak, Renata, Malet-Martino, Myriam, BALAYSSAC, Stéphane, Gilard, Véronique, Sawicka, Aleksandra, Kordalewska, Marta, Nowicki, Łukasz, Kurek, Eliza, Bulska, Ewa, Markuszewski, Marcin, Medical University of Gdansk, Medical University of Gdańsk, Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique (SPCMIB), 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)-Centre National de la Recherche Scientifique (CNRS), and Warsaw University of Technology [Warsaw]
Subjects: [CHIM]Chemical Sciences, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

39. Genetic variation in IL-10 influences the progression of hepatitis B infection

Author: Eloi R. Verrier, Tomasz Romanowski, Magda Rybicka, Anna Woziwodzka, Krzysztof P. Bielawski, Marcin Dręczewski, Alicja Sznarkowska, Piotr Stalke, Thomas F. Baumert, univOAK, Archive ouverte, University of Gdańsk (UG), Medical University of Gdańsk, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), and Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ
Subjects: Male, 0301 basic medicine, HBsAg, Cirrhosis, medicine.disease_cause, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, Hbv, 030212 general & internal medicine, Il10, Liver injury, Single-nucleotide polymorphism, General Medicine, Middle Aged, Hepatitis B, Interleukin-10, 3. Good health, Infectious Diseases, Liver, Hepatocellular carcinoma, Disease Progression, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Adult, Microbiology (medical), 030106 microbiology, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Polymorphism, Single Nucleotide, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Hepatitis B, Chronic, medicine, Humans, lcsh:RC109-216, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Alleles, Hepatitis B virus, Hepatitis B Surface Antigens, business.industry, Haplotype, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Fibrosis, digestive system diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Immunology, business
Abstract: The outcomes of hepatitis B virus (HBV) infection vary substantially among affected individuals, providing evidence of the role of host genetic background in the susceptibility to HBV persistence and the dynamics of liver injury progression to cirrhosis and hepatocellular carcinoma (HCC). Six single-nucleotide polymorphisms within the interleukin 10 gene (IL10) were genotyped by MALDI-TOF mass spectrometry in 857 patients with chronic HBV infection (CHB), 48 patients with resolved HBV infection, and 100 healthy volunteers. Associations of the selected polymorphisms with susceptibility to chronic HBV infection, liver injury progression, and outcomes were investigated. IL10 -819T (rs1800871), -592A (rs1800872), and +504T (rs3024490) alleles were associated with treatment-induced hepatitis B surface antigen (HBsAg) seroclearance. Additionally, IL10 ATAC haplotype increased the chance of HBsAg loss and was significantly more frequent in patients with less liver injury. Moreover rs1800871TT, rs1518110TT, rs1800872AA, and rs3024490TT genotypes were identified as predictors of a lower FIB-4 score (
Published: 2020
Full Text: View/download PDF

40. Aligning the good practice mask with the objectives of the European innovation partnership on active and healthy ageing

Author: Bousquet, J. and Farrell, J. and Onorato, G.L. and Bedbrook, A. and Czarlewski, W. and Micheli, Y. and Arnavielhe, S. and Illario, M. and Ansotegui, I.J. and Anto, J.M. and Bachert, C. and Basagaña, X. and Bédard, A. and Benveniste, S. and Bergmann, K.C. and Bewick, M. and Bindslev-Jensen, C. and Bjermer, L. and Blain, H. and Bosnic-Anticevich, S. and Bosse, I. and Braido, F. and Brussino, L. and Camuzat, T. and Canonica, G.W. and Cardona, V. and Carreiro Martins, P. and Cecchi, L. and Chavannes, N.H. and Chu, D.K. and Correia da Sousa, J. and Costa, D.J. and Costa, E. and Cruz, A.A. and da Silva, J. and Devillier, P. and de Feo, G. and de Vries, G. and Dray, G. and Ebisawa, M. and Erhola, M. and Fauquert, J.L. and Fokkens, W.J. and Fonseca, J. and Fontaine, J.M. and Gemicioğlu, B. and Haahtela, T. and Heffler, E. and Hellings, P.W. and Ivancevich, J.C. and Jassem, E. and Jutel, M. and Kaidashev, I. and Kalayci, O. and Klimek, L. and Kowalski, M.L. and Kull, I. and Kuna, P. and Kvedariene, V. and la Grutta, S. and Laune, D. and Larenas-Linnemann, D. and Ierodiakonou, D. and Le, L.T.T. and Lourenço, O. and Makris, M. and Menditto, E. and Monti, R. and Morais-Almeida, M. and Münter, L. and Muraro, A. and Murray, R. and Maurer, M. and Melén, E. and Mösges, R. and Mullol, J. and Niedoszytko, M. and O'Hehir, R.E. and Okamoto, Y. and Papadopoulos, N.G. and Passalacqua, G. and Patella, V. and Pereira, A.M. and Pfaar, O. and Pham-Thi, N. and Portejoie, F. and Price, D. and Prokopakis, E.P. and Psarros, F. and Raciborski, F. and Regateiro, F. and Reitsma, S. and Roche, N. and Rolland, C. and Ryan, D. and Samolinski, B. and Sastre, J. and Scadding, G.K. and Schmid-Grendelmeier, P. and Schünemann, H.J. and Shamji, M. and Sheikh, A. and Stellato, C. and Suppli-Ulrik, C. and Somekh, D. and Sova, M. and Todo Bom, A. and Tomazic, P.V. and Toppila-Salmi, S. and Triggiani, M. and Tsiligianni, I. and Valero, A. and Valiulis, A. and Valovirta, E. and van Eerd, M. and Vasankari, T. and Ventura, M.T. and Wallace, D. and Waserman, S. and Yorgancioglu, A. and Zidarn, M. and Zuberbier, T., CHU Arnaud de Villeneuve, Montpellier, France, MACVIA-France, 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, Montigny le Bretonneux, France, Euforea, Brussels, Belgium, Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany, Department of Dermatology and Allergy, Berlin Institute of Health, Comprehensive Allergy Center, Berlin, Germany, LANUA International Healthcare Consultancy, Belfast, Northern Ireland, United Kingdom, Medical Consulting Czarlewski, Levallois, France, KYomed INNOV, Montpellier, France, Division for Health Innovation, Campania Region and Federico II University Hospital Naples (R&D Unit and Department of Public Health), Naples, Italy, Department of Allergy and Immunology, Hospital Quirónsalud Bizkaia, Erandio, Spain, ISGlobAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, Hospital del Mar Research Institute (IMIM), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, Universitat Pompeu Fabra (UPF), Barcelona, Spain, Upper Airways Research Laboratory, Department of ENT, Ghent University Hospital, Ghent, Belgium, National Center of Expertise in Cognitive Stimulation (CEN STIMCO), Broca Hospital, Paris, France, Mines ParisTech CRI - PSL Research University, Fontainebleau, France, iQ4U Consultants Ltd, London, United Kingdom, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense Research Center for Anaphylaxis (ORCA), Odense, Denmark, Department of Respiratory Medicine and Allergology, Lund University, Lund, Sweden, Department of Geriatrics, Montpellier University Hospital, Montpellier, France, EA 2991, Euromov, University, Montpellier, France, Woolcock Institute of Medical Research, University of Sydney and Woolcock Emphysema Centre and Sydney Local Health District, Glebe, Australia, La Rochelle, France, University of Genoa, Department of Internal Medicine, DiMI) and IRCCS Ospedale Policlinico San Martino, Genova, Italy, Department of Medical Sciences, Allergy and Clinical Immunology Unit, University of Torino, Mauriziano Hospital, Torino, Italy, Région Occitanie, Montpellier, France, Personalized Medicine Clinic Asthma and Allergy, Humanitas Clinical and Research Center IRCCS, Rozzano (MI), Italy, Allergy Section, Department of Internal Medicine, Hospital Vall d'Hebron and ARADyAL Research Network, Barcelona, Spain, Serviço de Imunoalergologia, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central, Lisbon, Portugal, CEDOC-CHRC, Faculdade de Ciências Médicas (FCM), Universidade Nova de Lisboa, Lisbon, Portugal, SOS Allergology and Clinical Immunology, USL Toscana Centro, Prato, Italy, Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands, Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada, Division of Clinical Immunology and Allergy, Department of Medicine, McMaster University, Hamilton, Canada, Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal, ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal, Nîmes, France, UCIBIO, REQUIMTE, Faculty of Pharmacy, and Competence Center on Active and Healthy Ageing of University of Porto (AgeUPNetWork), University of Porto, Porto, Portugal, ProAR - Nucleo de Excelencia em Asma, Federal University of Bahia, Salvador, Brazil, WHO GARD Planning Group, Salvador, Brazil, Allergy Service, University Hospital of Federal University of Santa Catarina (HU-UFSC), Florianópolis, Brazil, UPRES EA220, Pôle des Maladies des Voies Respiratoires, Hôpital Foch, Université Paris-Saclay, Suresnes, France, Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Salerno, Italy, Peercode BV, Geldermalsen, Netherlands, IMT Mines Alès, Université Montpellier, France, Clinical Reserch Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Japan, National Insitute for Health and Welfare, Helsinki, Finland, CHU Clermont-Ferrand, Unité d'allergologie de l'enfant, Pôle pédiatrique, Hôpital Estaing, Clermont-Ferrand, France, Department of Otorhinolaryngology, Amsterdam University Medical Centres, AMC, Amsterdam, Netherlands, CINTESIS, Center for Research in Health Technology and Information Systems, Faculdade de Medicina da Universidade do Porto, Porto, Portugal, Medida, Lda, Porto, Portugal, Reims, France, Department of Pulmonary Diseases, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istambul, Turkey, Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland, 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, Department of Allergology, Medical University of Gdańsk, Gdańsk, Poland, Department of Clinical Immunology, Wrocław Medical University, Poland, Ukrainina Medical Stomatological Academy, Poltava, Ukraine, Pediatric Allergy and Asthma Unit, Hacettepe University School of Medicine, Ankara, Turkey, Center for Rhinology and Allergology, Wiesbaden, Germany, Department of Immunology and Allergy, Healthy Ageing Research Center, Medical University of Lodz, Poland, Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden, Sach's Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Poland, Institute of Biomedical Sciences, Department of Pathology, Faculty of Medicine, Vilnius University, Institute of Clinical Medicine, Clinic of Chest diseases and Allergology, Faculty of Medicine, Vilnius, Lithuania, Institute for Research and Biomedical Innovation (IRIB), National Research Council (CNR), Palermo, Italy, Center of Excellence in Asthma and Allergy, Médica Sur Clinical Foundation and Hospital, México City, Mexico, Department of Social Medicine, Faculty of Medicine, University of Crete, International Primary Care Respiratory Group, Crete, Greece, International Primary Care Respiratory Group IPCRG, Aberdeen, United Kingdom, University of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam, Faculty of Health Sciences and CICS - UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal, Allergy Unit 'D Kalogeromitros', 2nd Department of Dermatology and Venereology, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece, CIRFF, Center of Pharmacoeconomics, University of Naples Federico II, Naples, Italy, Allergy Center, CUF Descobertas Hospital, Lisbon, Portugal, Danish Commitee for Health Education, Copenhagen East, Denmark, Food Allergy Referral Centre Veneto Region, Department of Women and Child Health, Padua General University Hospital, Padua, Italy, MedScript, Paraparaumu, New Zealand, Optimum Patient Care, Cambridge, United Kingdom, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Institute of Medical Statistics, and Computational Biology, Medical Faculty, University of Cologne, Germany and CRI-Clinical Research International-Ltd, Hamburg, Germany, Rhinology Unit and Smell Clinic, Department of ENT, Hospital Clínic, Barcelona, Spain, Clinical and Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia, Department of Immunology, Monash University, Melbourne, Australia, Department of Otorhinolaryngology, Chiba University Hospital, Chiba, Japan, Division of Infection, Immunity and Respiratory Medicine, Royal Manchester Children's Hospital, University of Manchester, Manchester, United Kingdom, Department of Allergy, 2nd Pediatric Clinic, Athens General Children's Hospital 'P&A Kyriakou,', University of Athens, Athens, Greece, Allergy and Respiratory Diseases, Ospedale Policlino San Martino, University of Genoa, Italy, Division of Allergy and Clinical Immunology, Department of Medicine, Agency of Health ASL Salerno, Santa Maria della Speranza Hospital, Salerno, Italy, Allergy Unit, CUF-Porto Hospital and Institute, Porto, Portugal, Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Germany, Department of Allergy, Pasteur Institute, Paris, France, Observational and Pragmatic Research Institute, Singapore, Singapore, Department of Otorhinolaryngology, University of Crete, School of Medicine, Heraklion, Greece, Allergy Department, Athens Naval Hospital, Athens, Greece, Department of Prevention of Envinronmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland, Imunoalergologia, Centro Hospitalar Universitário de Coimbra, Faculty of Medicine, University of Coimbra, Portugal, Pneumologie et Soins Intensifs Respiratoires, Hôpitaux Universitaires Paris, Centre Hôpital Cochin, Paris, France, Association Asthme et Allergie, Paris, France, Allergy and Respiratory Research Group, University of Edinburgh, Edinburgh, United Kingdom, Faculty of Medicine, Autnonous University of Madrid, Spain, Royal National TNE Hospital, University College London, London, United Kingdom, Allergy Unit, Department of Dermatology, University Hospital of Zurich, Zürich, Switzerland, Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Imperial College London, London, United Kingdom, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom, Department of Respiratory Medicine, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark, European Health Futures Forum (EHFF), Dromahair, Ireland, Department of Respiratory Medicine, University Hospital Olomouc, Olomouc, Czech Republic, Imunoalergologia, Centro Hospitalar Universitário de Coimbra, Faculty of Medicine, University of Coimbra, Coimbra, Portugal, Department of General ORL, H1NS, Medical University of Graz, Graz, Austria, Vilnius University Faculty of Medicine, Institute of Clinical Medicine, Institute of Health Sciences, Vilnius, Lithuania, European Academy of Paediatrics (EAP/UEMS-SP), Brussels, Belgium, Department of Lung Diseases and Clinical Immunology, University of Turku and Terveystalo Allergy Clinic, Turku, Finland, FILHA, Finnish Lung Association, Helsinki, Finland, University of Bari Medical School, Unit of Geriatric Immunoallergology, Bari, Italy, Nova Southeastern University, Fort Lauderdale, FL, United States, Department of Pulmonary Diseases, Celal Bayar University, Faculty of Medicine, Manisa, Turkey, and University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia
Abstract: The reference sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) were renewed in 2019. The DG Santé good practice Mobile Airways Sentinel networK was reviewed to meet the objectives of the EIP on AHA. It included 1) Management of care process, 2) Blueprint of digital transformation, 3) EIP on AHA, innovation to market, 4) Community for monitoring and assessment framework, 5) Political, organizational, technological and financial readiness, 6) Contributing to European co-operation and transferability, 7) Delivering evidence of impact against the triple win approach, 8) Contribution to the European Digital Transformation of Health and Care and 9) scale of demonstration and deployment of innovation. © 2020 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https:// creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Published: 2020

41. National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio : a pooled analysis of 458 population-based studies in Asian and Western countries

Author: NCD Risk Factor Collaboration (NCD-RisC), [missing], Taddei, Cristina, Jackson, Rod, Zhou, Bin, Bixby, Honor, Danaei, Goodarz, Di Cesare, Mariachiara, Kuulasmaa, Kari, Hajifathalian, Kaveh, Bentham, James, Bennett, James E, Aekplakorn, Wichai, Cifkova, Renata, Dallongeville, Jean, DeBacquer, Dirk, Giampaoli, Simona, Gudnason, Vilmundur, Khang, Young-Ho, Laatikainen, Tiina, Mann, JimI, Marques-Vidal, Pedro, Mensah, George A, Müller-Nurasyid, Martina, Ninomiya, Toshiharu, Petkeviciene, Janina, Rodríguez-Artalejo, Fernando, Servais, Jennifer, Söderberg, Stefan, Stavreski, Bill, Wilsgaard, Tom, Zdrojewski, Tomasz, Zhao, Dong, Stevens, Gretchen A, Savin, Stefan, Cowan, Melanie J, Riley, Leanne M, Ezzati, Majid, Adams, Robert J, Ahrens, Wolfgang, Amouyel, Philippe, Amuzu, Antoinette, Anderssen, Sigmund A, Ariansen, Inger, Arveiler, Dominique, Aspelund, Thor, Auvinen, Juha, Avdicová, Mária, Banach, Maciej, Bandosz, Piotr, Banegas, José R, Barbagallo, Carlo M, Bata, Iqbal, Baur, Louise A, Beaglehole, Robert, Bernotiene, Gailute, Bi, Yufang, Bienek, Asako, Björkelund, Cecilia, Bo, Simona, Boehm, Bernhard O, Bonaccio, Marialaura, Bongard, Vanina, Borchini, Rossana, Borghs, Herman, Breckenkamp, Juergen, Brenner, Hermann, Bruno, Graziella, Busch, Markus A, Cabrera de León, Antonio, Capuano, Vincenzo, Casanueva, Felipe F, Casas, Juan-Pablo, Caserta, Carmelo A, Censi, Laura, Chen, Fangfang, Chen, Shuohua, Chirlaque, María-Dolores, Cho, Belong, Cho, Yumi, Chudek, Jerzy, Claessens, Frank, Clarke, Janine, Clays, Els, Cooper, Cyrus, Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Crujeiras, Ana B, Cui, Liufu, D'Arrigo, Graziella, Dauchet, Luc, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, De Smedt, Delphine, Dennison, Elaine, Deschamps, Valérie, DiCastelnuovo, Augusto, Dobson, Annette J, Donfrancesco, Chiara, Döring, Angela, Drygas, Wojciech, Du, Yong, Dziankowska-Zaborszczyk, Elzbieta, Eggertsen, Robert, Ekelund, Ulf, Elosua, Roberto, Eriksson, Johan G, Evans, Alun, Faeh, David, Felix-Redondo, Francisco J, Fernández-Bergés, Daniel, Ferrari, Marika, Ferrieres, Jean, Finn, Joseph D, Forslund, Ann-Sofie, Forsner, Maria, Frontera, Guillermo, Fujita, Yuki, Gaciong, Zbigniew, Galvano, Fabio, Gao, Jingli, Garcia-de-la-Hera, Manoli, Garnett, Sarah P, Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Gianfagna, Francesco, Gill, Tiffany K, Giovannelli, Jonathan, Goltzman, David, GonzalezGross, Marcela, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dušan, Gregor, Ronald D, Grodzicki, Tomasz, Grosso, Giuseppe, Gruden, Grabriella, Gu, Dongfeng, Guallar-Castillón, Pilar, Gudmundsson, Elias F, Guessous, Idris, Gunnlaugsdottir, Johanna, Gutzwiller, Felix, Hardy, Rebecca, Hata, Jun, Haugsgjerd, Teresa, Hayes, Alison J, He, Jiang, He, Yuna, Herrala, Sauli, TapaniHihtaniemi, Ilpo, Hobbs, Michael, Hopman, Wilma M, MaríaHuerta, José, Huybrechts, Inge, Iacoviello, Licia, Iannone, Anna G, Ikeda, Nayu, Iwasaki, Masanori, Jamrozik, Konrad, Janszky, Imre, Jarvelin, Marjo-Riitta, Jasienska, Grazyna, Jennings, Garry, Jeong, Seung-lyeal, QiangJiang, Chao, Joffres, Michel, Jokelainen, Jari J, Jonas, Jost B, Jóźwiak, Jacek, Kajantie, Eero O, Kauhanen, Jussi, Keil, Ulrich, Keinänen-Kiukaanniemi, Sirkka, Kersting, Mathilde, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Kim, Jeongseon, Kim, Yeon-Yong, Klumbiene, Jurate, Knoflach, Michael, Ko, Stephanie, Kolle, Elin, Korpelainen, Raija, Koskinen, Seppo, Kouda, Katsuyasu, Kratzer, Wolfgang, Kriemler, Susi, Krokstad, Steinar, Kujala, Urho M, Kurjata, Pawel, HingLam, Tai, Lanska, Vera, Lappas, Georg, Laugsand, Lars E, Lee, Jeonghee, Lehtimäki, Terho, Li, Yanping, Lilly, Christa L, Lin, Xu, Lind, Lars, Lissner, Lauren, Liu, Jing, Lopez-Garcia, Esther, Lorbeer, Roberto, EugenioLozano, José, Luksiene, Dalia, Lundqvist, Annamari, Lundqvist, Robert, Lytsy, Per, Ma, Guansheng, Machi, Suka, Maggi, Stefania, Magliano, Dianna J, Manzato, Enzo, Mathiesen, Ellisiv B, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, Meirhaeghe, Aline, Meisinger, Christa, Metcalf, Patricia, Mi, Jie, Miller, Jody C, Moreno, Luis A, Morin, Suzanne, Mossakowska, Malgorzata, Muiesan, Maria L, Mursu, Jaakko, Nakamura, Harunobu, Námešná, Jana, Nauck, Matthias, MariaNavarrete-Muñoz, Eva, Neal, William A, Nenko, Ilona, Niiranen, Teemu J, Ning, Guang, Noale, Marianna, Norie, Sawada, Noto, Davide, O'Neill, Terence, O'Reilly, Dermot, Oh, Kyungwon, Olafsson, Örn, MichelPaccaud, Fred, Pajak, Andrzej, Palmieri, Luigi, Panza, Francesco, Parnell, Winsome R, Peltonen, Markku, Peters, Annette, Petersmann, Astrid, Pigeot, Iris, Pilotto, Lorenza, Piwonska, Aleksandra, Plans-Rubió, Pedro, Porta, Miquel, Price, Jacqueline F, Puder, Jardena J, Puhakka, Soile E, Radisauskas, Ricardas, Raitakari, Olli, Ramos, Rafel, Redon, Josep, Rigo, Fernando, Rodriguez-Perez, MaríadelCristo, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G R, Ruidavets, Jean-Bernard, Rutkowski, Marcin, Salanave, Benoit, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Sans, Susana, Saramies, Jouko L, Saum, Kai-Uwe, Scheidt-Nave, Christa, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schöttker, Ben, Sebert, Sylvain, Sen, Abhijit, Shaw, Jonathan E, Shibuya, Kenji, WookShin, Dong, Shiri, Rahman, Simons, Judith, Simons, Leon A, Sjöström, Michael, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Solfrizzi, Vincenzo, Sonestedt, Emily, Soumare, Aicha, Staessen, Jan A, Stathopoulou, Maria G, Steene-Johannessen, Jostein, Stehle, Peter, Stieber, Jutta, Stöckl, Doris, Stokwiszewski, Jakub, Sundström, Johan, Suriyawongpaisal, Paibul, Tamosiunas, Abdonas, JooTan, Eng, Taylor, Anne, Tell, Grethe, Thijs, Lutgarde, Tolonen, HannaK, Topór-Madry, Roman, JoséTormo, María, Torrent, Maties, Tsugane, Shoichiro, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Tzourio, Christophe, Uusitalo, Hannu M T, Van Herck, Koen, Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lars, Vega, Tomas, Veronesi, Giovanni, Vioque, Jesus, Virtanen, JyrkiK, Visvikis-Siest, Sophie, Vollenweider, Peter, Voutilainen, Sari, Vrijheid, Martine, Wagner, Aline, Wagner, Anne, Wang, Ming-Dong, Wang, Qian, XingWang, Ya, Wannamethee, S Goya, Wei, Wenbin, Whincup, Peter H, Wiecek, Andrzej, Willeit, Johann, Willeit, Peter, Wojtyniak, Bogdan, Wong, Andrew, Woodward, Mark, GiwercmanWu, Aleksander, Wu, Frederick C, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yan, Weili, Yang, Xiaoguang, Ye, Xingwang, Yoshihara, Akihiro, Zambon, Sabina, Zhao, Wenhua, Imperial College London, University of Auckland [Auckland], Harvard T.H. Chan School of Public Health, Middlesex University, National Institute for Health and Welfare [Helsinki], Weill Medical College of Cornell University [New York], University of Kent [Canterbury], Mahidol University [Bangkok], Charles University [Prague] (CU), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Universiteit Gent = Ghent University [Belgium] (UGENT), Istituto Superiore di Sanita [Rome], Icelandic Heart Association [Kopavogur, Iceland] (IHA), Seoul National University [Seoul] (SNU), University of Otago [Dunedin, Nouvelle-Zélande], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Helmholtz-Zentrum München (HZM), Kyushu University [Fukuoka], Universidad Autonoma de Madrid (UAM), CIBER de Epidemiología y Salud Pública (CIBERESP), Umeå University, The Arctic University of Norway (UiT), Medical University of Gdańsk, Capital University of Medical Sciences [Beijing] (CUMS), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Adelaide, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), London School of Hygiene and Tropical Medicine (LSHTM), Norwegian School of Sport Sciences = Norges idrettshøgskole [Oslo] (NIH), Norwegian Institute of Public Health [Oslo] (NIPH), Université de Strasbourg (UNISTRA), University of Iceland [Reykjavik], University of Oulu, Regional Authority of Public Health [Slovaquia] (RAPH), Ministry of Health of the Slovak Republic [Slovaquia], Medical University of Łódź (MUL), Università degli studi di Palermo - University of Palermo, Dalhousie University [Halifax], The University of Sydney, Public Health Agency of Canada, University of Gothenburg (GU), University of Turin, Nanyang Technological University [Singapour], Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Università degli studi di Napoli Federico II, Faculté de Médecine [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Universität Bielefeld = Bielefeld University, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Robert Koch Institute [Berlin] (RKI), Universidad de La Laguna [Tenerife - SP] (ULL), Universidade de Santiago de Compostela [Spain] (USC ), University College of London [London] (UCL), University of Silesia in Katowice, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Southampton, Biomolécules et inflammation pulmonaire, Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Santé publique France - French National Public Health Agency [Saint-Maurice, France], University of Queensland [Brisbane], IMIM-Hospital del Mar, Generalitat de Catalunya, Queen's University [Belfast] (QUB), Universität Zürich [Zürich] = University of Zurich (UZH), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, University of Manchester [Manchester], Kindai University, Medical University of Warsaw - Poland, Università degli studi di Catania [Catania], Geneva University Hospital (HUG), Universitá degli Studi dell’Insubria, McGill University = Université McGill [Montréal, Canada], Universidad Politécnica de Madrid (UPM), Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institute for Clinical and Experimental Medicine (IKEM), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Bergen (UiB), Tulane University, Chinese Center for Disease Control and Prevention, Oulu University Hospital [Oulu], The University of Western Australia (UWA), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Niigata University, Norwegian University of Science and Technology (NTNU), Simon Fraser University (SFU.ca), University of Eastern Finland, Westfälische Wilhelms-Universität Münster (WWU), Innsbruck Medical University [Austria] (IMU), Universitätsklinikum Ulm - University Hospital of Ulm, University of Jyväskylä (JYU), The University of Hong Kong (HKU), Sahlgrenska Academy at University of Gothenburg [Göteborg], Tampere University Hospital, University of Tampere [Finland], West Virginia University [Morgantown], University of Chinese Academy of Sciences [Beijing] (UCAS), Uppsala Universitet [Uppsala], Universität Greifswald - University of Greifswald, Peking University [Shenzhen], The Jikei University School of Medicine, Baker Heart and Diabetes Institute (AUSTRALIA), Universita degli Studi di Padova, University of Edinburgh, University of Zaragoza - Universidad de Zaragoza [Zaragoza], International Institute of Molecular and Cell Biology [Warsaw] (IIMCB), Università degli Studi di Brescia [Brescia], Konan University [Kobe, Japan], University of Turku, Shanghai Jiao Tong University School of Medicine, Department of Epidemiology and Biostatistics, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, Department of Epidemiology, Health Economics and Public Health, UMR 558 INSERM, Université de Toulouse, Centre Hospitalier Universitaire de Toulouse, Unité de Surveillance et d'Epidémiologie Nutritionnelle (USEN), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut de Veille Sanitaire (INVS)-Université Paris 13 (UP13), Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain, parent, Department of Chronic Disease Prevention, Institute for plasma research, Institute for Plasma Research, Department of Biosciences and Nutrition, Karolinska Institutet [Stockholm], Department of Reproductive Endocrinology, University of Bari Aldo Moro (UNIBA), Nutritional Epidemiology, Department of Clinical Sciences, Clinical Research Center, Lund University [Lund]-Lund University [Lund], Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Applied Food Science, Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Research Unit Hypertension and Cardiovascular Epidemiology [Louvain, Belgique], Studies Coordinating Centre [Louvain, Belgique], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), National Cancer Center, University of Kuopio, Epidémiologie cardiovasculaire et métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Tampere University, Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Norwegian University of Science and Technology [Trondheim] (NTNU), Departamento de Salud Pública, Universidad Miguel Hernández [Elche] (UMH), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Department of Internal Medicine, School of Public Health and Clinical Nutrition, Epidemiologia Ambiental, Centre for Research in Environmental Epidemiology (CREAL)-Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP) of Pamplona-Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Department of Epidemiology and Public Health, EA 3430, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Medical University of Silesia (SUM), University of Innsbruck, National Institute of Hygiene Warsaw, The Georges Institute for International Health, Naval Research Laboratory (NRL), Grant numbers 101506/Z/13/Z and Research Training Fellowship 203616/Z/16/Z, Ministry of Health of the Czech Republic (grant number 15-27109A), UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología, HUS Children and Adolescents, Department of Public Health, Universidad Autónoma de Madrid (UAM), Università degli studi di Torino = University of Turin (UNITO), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), CHU Toulouse [Toulouse], Université Paris 13 (UP13)-Institut de Veille Sanitaire (INVS)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM), Taddei, C, Zhou, B, Bixby, H, Danaei, G, Di Cesare, M, Kuulasmaa, K, Hajifathalian, K, Bentham, J, Bennett, JE, Aekplakorn, W, Cifkova, R, Dallongeville, J, DeBacquer, D, Giampaoli, S, Gudnason, V, Khang, Y-O, Laatikainen, T, Mann, JI, Marques-Vidal, P, Mensah, GA, Müller-Nurasyid, M, Ninomiya, T, Petkeviciene, J, Rodríguez-Artalejo, F, Servais, J, Söderberg, S, Stavreski, B, Wilsgaard, T, Zdrojewski, T, Zhao, D, Stevens, GA, Savin, S, Cowan, Mj, Riley, LM, Ezzati, M, Adams, R, Ahrens, W, Amouyel, P, Amuzu, A, Anderssen, SA, Ariansen, I, Arveiler, D, Aspelund, T, Auvinen, A, Avdicová, M, Banach, M, Bandosz, P, Banegas. JR, Barbagallo, CM, Bata, I, Baur, LA, Beaglehole, R, Bennet, JE, Bernotiene, G, Bi, Y, Bienek, A, Björkelund, C, Bo, S, Boehm, BO, Bonaccio, M, Bongard, V, Borchini, R, Borghs, H, Breckenkamp, J, Brenner, H, Bruno, G, Busch, MA, CabreradeLeón, A, Capuano, V, Casanueva, FF, Casas, J-P, Caserta, CA, Censi, L, Chen, F, Chen, S, Chirlaque, M-D, Cho, B, Cho, Y, Chudek, J, Claessens, F, Clarke, J, Clays, E, Cooper, C, Costanzo, S, Cottel, D, Cowell C, Crujeiras, AB, Cui, L, D'Arrigo, G, Dauchet, L, De Backer, G, De Bacquer, D, de Gaetano, G, De Henauw, S, De Smedt, D, Dennison, E, Desschamps, V, Di Castelnuovo, A, Dobson, AJ, Donfrancesco, C, Döring, A, Doua, K, Drygas, W, Du, Y, Dziankowska-Zaborszczyk, E, Eggertsen, R, Ekelund, U, Elousa, R, Eriksson, JG, Evans, A, Faeh, D, Felix-Redondo, FJ, Fernández-Bergés, D, Ferrari, M, Ferrieres, J, Finn, JD, Forslund, A-S, Forsner, M, Frontera, G, Fujita, Y, Gaciong, Z, Galvano, F, Gao, J, Garcia-de-la-Hera, M, Garnett, SP, Gaspoz, J-M, Gasul, L, Gates, L, Gianfagna, F, Gill, TK, Giovannelli, J, Goltzman, D, GonzalezGross, M, Gottrand, F, Graff-Iversen, S, Grafnetter, D, Gregor, RD, Grodzicki, T, Grosso, G, Gruden, G, Gu, D, Guallar-Castillón, P, Gudmundsson, EF, Guessous, I, Gunnlaugsdottir J, Gutzwiller, F, Hardy, R, Hata, J, Haugsgjerd, T, Hayes, AJ, He, H, He, Y, Herrala, S, Hihtaniemi, IP, Hobbs, M, Hopman, WM, Huerta, JM, Huybrechts, I, Iacoviello, L, Iannone, AG, Ikeda, N, Iwasaki, M, Jackson, R, Jamrozi, K, Janszky, I, Jarvelin, M-R, Jasienska, G, Jennings, G, Jeong, S-L, Jiang, CQ, Joffres, M, Jokelainen, JJ, Jonas, JB, Jóźwiak, J, Kajantie, EO, Kauhanen, K, Keil, U, Keinänen-Kiukaanniemi, S, Kersting, M, Khang, Y-H, Kiechl-Kohlendorfer, U, Kiechl, S, Kim, J, Kim, Y-Y, Klumbiene, J, Knoflach, M, Ko, S, Kolle, E, Korpelainen, R, Koskinen, S, Kouda, K, Kratzer, W, Kriemler, S, Krokstad, S, Kujala,UM, Kurjata, P, Lam, TH, Lanska, V, Lappas , G, Laugsand, LE, Lee, J, Lehtimäki, T, Li, Y, Lilly, C, Lin, X, Lind, L, Lissner, L, Liu, J, Lopez-Garcia, E, Lorbeer, R, Lozano, JE, Luksiene, D, Lundqvist, A, Lundqvist, R, Lytsy, P, Ma, G, Machi, S, Maggi, S, Magliano, DJ, Manzato, E, Mathiesen, EB, McLachlan, S, McLean, RM, Meirhaeghe, A, Metcalf, P, Mi, JM, Miller, JC, Moreno, LA, Morin, S, Mossakowska, M, Muiesan, ML, Mursu, J, Nakamura, H, Námešná, J, Navarrete-Muñoz, EM, Neal, WA, Nenko, I, Niiranen, T, Ning, G, Noale, M, Norie, S, Noto, Davide, O’Neill, T, O'Reilly, D, Oh, K, Olafsson, O, Paccaud, F, Pajak, A, Palmieri, L, Panza, F, Parnell, WR, Peltonen, M, Peters, A, Petersmann, A, P Pigeot, I, Pilotto, L, Piwonska, A, Pedro Plans-Rubió, P, Porta, M, Price, JF, Puder, JJ, Puhakka, SE, Radisauskas, R, Raitakari, O, Ramos, R, Redon, J, Rigo, F, Rodriguez-Perez, MdC, Romaguera, D, Ronkainen, K, Rosengren, A, Roy, JGR, Ruidavets, JB, Rutkowski, M, Salanave, B, Salmeron, D, Salomaa, V, Salonen, JT, Salvetti, M, Sans, S, Saramies, JL, Saum, K-U, Scheidt-Nave, C, Schienkiewitz, A, Schipf, S, Schmidt, CO, Schottker, B, Sebert S, Sen, A, Shaw, JE, Shibuya, K, Shin, DO, Shiri, R, Simons, J, Simons, LA, Sjostrom, M, Slowikowska-Hilczer, J, Slusarczyk, P, Solfrizzi, V, Sonestedt, E, Soumare, A, Staessen, JA, Stathopoulou, MG, Steene-Johannessen, J, Stehle, P, Stieber, J, Stöckl, D, Stokwiszewski, J, Sundström, J, Suriyawongpaisal, P, Tamosiunas, A, Tan, E, Taylor, A, Tell, G, Thijs, L, Tolonen, HK, Topór-Madry, R, Tormo, MJ, Torrent, M, Tsugane, S, Tuomainen, T-P, Tuomilehto, J, Tzourio, C, Uusitalo, HMT, Van Herck, K, Vanderschueren, D, Vanuzzo, D, Vatten, L, Vega, T, Veronesi, G, Vioque, P, Virtanen, JK, Visvikis-Siest, S, Vollenweider, P, Voutilainen, S, Vrijheid, M, Wagner, A, Wang, M-D, Wang, Q, Wang YX, Wannamethee, SG, Wei, W, Whincup, PH, Wiecek, A, Willeit, J, Willeit, P, Wojtyniak, B, Wong, A, Woodward, M, Wu, FC, JianFeng Wu, JF, Wu, SL, Xu, H, Xu, L, Yan, W, Yang, X, Ye, X, Yoshihara, A, Zambon, S, Zhao, W, NCD Risk Factor Collaboration (NCD-RisC), Jackson, R., Zhou, B., Bixby, H., Danaei, G., Di Cesare, M., Kuulasmaa, K., Hajifathalian, K., Bentham, J., Bennett, J.E., Aekplakorn, W., Cifkova, R., Dallongeville, J., DeBacquer, D., Giampaoli, S., Gudnason, V., Khang, Y.H., Laatikainen, T., Mann, J., Marques-Vidal, P., Mensah, G.A., Müller-Nurasyid, M., Ninomiya, T., Petkeviciene, J., Rodríguez-Artalejo, F., Servais, J., Söderberg, S., Stavreski, B., Wilsgaard, T., Zdrojewski, T., Zhao, D., Stevens, G.A., Savin, S., Cowan, M.J., Riley, L.M., Ezzati, M., Adams, R.J., Ahrens, W., Amouyel, P., Amuzu, A., Anderssen, S.A., Ariansen, I., Arveiler, D., Aspelund, T., Auvinen, J., Avdicová, M., Banach, M., Bandosz, P., Banegas, J.R., Barbagallo, C.M., Bata, I., Baur, L.A., Beaglehole, R., Bernotiene, G., Bi, Y., Bienek, A., Björkelund, C., Bo, S., Boehm, B.O., Bonaccio, M., Bongard, V., Borchini, R., Borghs, H., Breckenkamp, J., Brenner, H., Bruno, G., Busch, M.A., Cabrera de León, A., Capuano, V., Casanueva, F.F., Casas, J.P., Caserta, C.A., Censi, L., Chen, F., Chen, S., Chirlaque, M.D., Cho, B., Cho, Y., Chudek, J., Claessens, F., Clarke, J., Clays, E., Cooper, C., Costanzo, S., Cottel, D., Cowell, C., Crujeiras, A.B., Cui, L., D'Arrigo, G., Dauchet, L., De Backer, G., De Bacquer, D., de Gaetano, G., De Henauw, S., De Smedt, D., Dennison, E., Deschamps, V., DiCastelnuovo, A., Dobson, A.J., Donfrancesco, C., Döring, A., Drygas, W., Du, Y., Dziankowska-Zaborszczyk, E., Eggertsen, R., Ekelund, U., Elosua, R., Eriksson, J.G., Evans, A., Faeh, D., Felix-Redondo, F.J., Fernández-Bergés, D., Ferrari, M., Ferrieres, J., Finn, J.D., Forslund, A.S., Forsner, M., Frontera, G., Fujita, Y., Gaciong, Z., Galvano, F., Gao, J., Garcia-de-la-Hera, M., Garnett, S.P., Gaspoz, J.M., Gasull, M., Gates, L., Gianfagna, F., Gill, T.K., Giovannelli, J., Goltzman, D., GonzalezGross, M., Gottrand, F., Graff-Iversen, S., Grafnetter, D., Gregor, R.D., Grodzicki, T., Grosso, G., Gruden, G., Gu, D., Guallar-Castillón, P., Gudmundsson, E.F., Guessous, I., Gunnlaugsdottir, J., Gutzwiller, F., Hardy, R., Hata, J., Haugsgjerd, T., Hayes, A.J., He, J., He, Y., Herrala, S., TapaniHihtaniemi, I., Hobbs, M., Hopman, W.M., MaríaHuerta, J., Huybrechts, I., Iacoviello, L., Iannone, A.G., Ikeda, N., Iwasaki, M., Jamrozik, K., Janszky, I., Jarvelin, M.R., Jasienska, G., Jennings, G., Jeong, S.L., QiangJiang, C., Joffres, M., Jokelainen, J.J., Jonas, J.B., Jóźwiak, J., Kajantie, E.O., Kauhanen, J., Keil, U., Keinänen-Kiukaanniemi, S., Kersting, M., Kiechl-Kohlendorfer, U., Kiechl, S., Kim, J., Kim, Y.Y., Klumbiene, J., Knoflach, M., Ko, S., Kolle, E., Korpelainen, R., Koskinen, S., Kouda, K., Kratzer, W., Kriemler, S., Krokstad, S., Kujala, U.M., Kurjata, P., HingLam, T., Lanska, V., Lappas, G., Laugsand, L.E., Lee, J., Lehtimäki, T., Li, Y., Lilly, C.L., Lin, X., Lind, L., Lissner, L., Liu, J., Lopez-Garcia, E., Lorbeer, R., EugenioLozano, J., Luksiene, D., Lundqvist, A., Lundqvist, R., Lytsy, P., Ma, G., Machi, S., Maggi, S., Magliano, D.J., Manzato, E., Mathiesen, E.B., McLachlan, S., McLean, R.M., McLean, S.B., Meirhaeghe, A., Meisinger, C., Metcalf, P., Mi, J., Miller, J.C., Moreno, L.A., Morin, S., Mossakowska, M., Muiesan, M.L., Mursu, J., Nakamura, H., Námešná, J., Nauck, M., MariaNavarrete-Muñoz, E., Neal, W.A., Nenko, I., Niiranen, T.J., Ning, G., Noale, M., Norie, S., Noto, D., O'Neill, T., O'Reilly, D., Oh, K., Olafsson, Ö., MichelPaccaud, F., Pajak, A., Palmieri, L., Panza, F., Parnell, W.R., Peltonen, M., Peters, A., Petersmann, A., Pigeot, I., Pilotto, L., Piwonska, A., Plans-Rubió, P., Porta, M., Price, J.F., Puder, J.J., Puhakka, S.E., Radisauskas, R., Raitakari, O., Ramos, R., Redon, J., Rigo, F., Rodriguez-Perez, M., Romaguera, D., Ronkainen, K., Rosengren, A., Ruidavets, J.B., Rutkowski, M., Salanave, B., Salmerón, D., Salomaa, V., Salonen, J.T., Salvetti, M., Sans, S., Saramies, J.L., Saum, K.U., Scheidt-Nave, C., Schienkiewitz, A., Schipf, S., Schmidt, C.O., Schöttker, B., Sebert, S., Sen, A., Shaw, J.E., Shibuya, K., WookShin, D., Shiri, R., Simons, J., Simons, L.A., Sjöström, M., Slowikowska-Hilczer, J., Slusarczyk, P., Solfrizzi, V., Sonestedt, E., Soumare, A., Staessen, J.A., Stathopoulou, M.G., Steene-Johannessen, J., Stehle, P., Stieber, J., Stöckl, D., Stokwiszewski, J., Sundström, J., Suriyawongpaisal, P., Tamosiunas, A., JooTan, E., Taylor, A., Tell, G., Thijs, L., Tolonen, H., Topór-Madry, R., JoséTormo, M., Torrent, M., Tsugane, S., Tuomainen, T.P., Tuomilehto, J., Tzourio, C., Van Herck, K., Vanderschueren, D., Vanuzzo, D., Vatten, L., Vega, T., Veronesi, G., Vioque, J., Virtanen, J., Visvikis-Siest, S., Vollenweider, P., Voutilainen, S., Vrijheid, M., Wagner, A., Wang, M.D., Wang, Q., XingWang, Y., Wannamethee, S.G., Wei, W., Whincup, P.H., Wiecek, A., Willeit, J., Willeit, P., Wojtyniak, B., Wong, A., Woodward, M., GiwercmanWu, A., Wu, F.C., Wu, S., Xu, H., Xu, L., Yan, W., Yang, X., Ye, X., Yoshihara, A., Zambon, S., Zhao, W., Universiteit Gent = Ghent University (UGENT), Istituto Superiore di Sanità (ISS), Helmholtz Zentrum München = German Research Center for Environmental Health, Kyushu University, The Arctic University of Norway [Tromsø, Norway] (UiT), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Catania = University of Catania (Unict), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Università degli Studi di Padova = University of Padua (Unipd), Università degli Studi di Brescia = University of Brescia (UniBs), Service Epidémiologie clinique et santé publique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Laboratoire Chrono-environnement (UMR 6249) (LCE), Leopold Franzens Universität Innsbruck - University of Innsbruck, National Institute of Public Health - National Institute of Hygiene [Poland], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Medical University of Silesia, Katowice, University of Helsinki, National Institute for Health and Welfare, University of Helsinki, University of Helsinki, and University of Helsinki, Finnish Institute of Occupational Health
Subjects: Male, gupo de ascendencia continental asiática, Settore MED/09 - Medicina Interna, Total Cholesterol, Ldl Cholesterol, Hdl Cholesterol, Blood Lipids, Multi-country Study, Epidemiology, kolesteroli, humanos, Blood lipids, BLOOD-PRESSURE, 030204 cardiovascular system & hematology, triglicéridos, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, HDL cholesterol, Medicine and Health Sciences, CARDIOVASCULAR RISK-FACTORS, Medicine, 030212 general & internal medicine, mediana edad, lípidos, Public, Environmental & Occupational Health, 2. Zero hunger, anciano, education.field_of_study, Age Factors, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Middle Aged, colesterol, adulto, kansainvälinen vertailu, Lipids, 3142 Public health care science, environmental and occupational health, 3. Good health, Europe, Cholesterol, Population Surveillance, LDL cholesterol, SERUM-LIPIDS, Female, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, Adult, Asian Continental Ancestry Group, Canada, Total cholesterol, blood lipids, multi-country study, medicine.medical_specialty, Asia, Medicina, European Continental Ancestry Group, Population, Nursing, HDL-kolesteroli, White People, DIETARY-FAT, 03 medical and health sciences, Sex Factors, Asian People, kansanterveys, vigilancia de la población, Humans, CORONARY-HEART-DISEASE, ddc:610, LDL-kolesteroli, education, Triglycerides, METAANALYSIS, Aged, INDIVIDUAL DATA, Science & Technology, business.industry, Omvårdnad, blood lipid, Cholesterol, HDL, Ecological study, nutritional and metabolic diseases, Cholesterol, LDL, United States, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Cholesterol/blood, Lipids/blood, Population Surveillance/methods, Triglycerides/blood, chemistry, WORLDWIDE TRENDS, Multi-country study, grupo de ascendencia continental europea, business, HIGH-DENSITY-LIPOPROTEIN, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography, Lipoprotein
Abstract: Artículo con numerosos autores. Sólo quedan reflejados el primero, los pertenecientes a la UAM y el colectivo, Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and non-HDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since ∼1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at ∼0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as ∼0.7 per decade in Swiss men (equivalent to ∼26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol., This work was supported by the Wellcome Trust (grant numbers 101506/Z/13/Z and Research Training Fellowship 203616/Z/16/Z). R.C. acknowledges funding from the Ministry of Health of the Czech Republic (grant number 15-27109A)
Published: 2020
Full Text: View/download PDF

42. Active benzimidazole derivatives targeting the MmpL3 transporter in Mycobacterium abscessus

Author: Laurent Kremer, Matt D. Johansen, Jarosław Dziadek, Katarzyna Gobis, Alan P. Kozikowski, Mickaël Blaise, Jean-Louis Herrmann, Clément Raynaud, Wassim Daher, Françoise Roquet-Banères, Oluseye K. Onajole, Schistosomiase, paludisme et inflammation, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Infection et inflammation chronique (2I), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre d'économie de la Sorbonne (CES), Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1), Roosevelt University [Chicago], Starwise Therapeutics LLC [Chicago], Service de Microbiologie [Garches], Hôpital Raymond Poincaré [AP-HP], Polish Academy of Sciences (PAN), Medical University of Gdańsk, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was supported by the Association Gregory Lemarchal and Vaincre la Mucoviscidose (RIF20180502320) and by the National Science Centre (Krakow, Poland) on the basis of decision number DEC-2017/25/B/NZ7/00124. MDJ received a post-doctoral fellowship granted by Labex EpiGenMed, an «Investissements d’avenir» program (ANR-10-LABX-12-01)., and Blaise, Mickael
Subjects: 0301 basic medicine, Benzimidazole, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Tuberculosis, medicine.drug_class, [SDV]Life Sciences [q-bio], 030106 microbiology, Antibiotics, Mycobacterium abscessus, benzimidazole, Microbiology, Mycolic acid, Mycobacterium tuberculosis, 03 medical and health sciences, chemistry.chemical_compound, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, mycolic acid, medicine, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, biology, therapeutic activity, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, zebrafish, bacterial infections and mycoses, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, In vitro, 3. Good health, MmpL3, 030104 developmental biology, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Nontuberculous mycobacteria, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; The prevalence of pulmonary infections due to non-tuberculous mycobacteria such as Mycobacterium abscessus, has been increasing and surpassing tuberculosis (TB) in some industrialized countries. Due to intrinsic resistance to most antibiotics that drastically limits conventional chemotherapeutic treatment options, new anti-M. abscessus therapeutics are urgently needed against this emerging pathogen. Extensive screening of a library of benzimidazole derivatives that were previously shown to be active against Mycobacterium tuberculosis led to the identification of a lead compound exhibiting very potent in vitro activity against a wide panel of M. abscessus clinical strains. Designated EJMCh-6, this compound, a 2-(2-cyclohexylethyl)-5,6-dimethyl-1H-benzo[d]imidazole), also exerted a very strong activity against intramacrophage-residing M. abscessus. Moreover, treatment of infected zebrafish embryos with EJMCh-6 correlated with a significantly increased embryo survival and a decrease in the bacterial burden as compared to untreated fish. Insights into the mechanism of action were inferred from the generation of spontaneous benzimidazole-resistant strains and the identification of a large set of missense mutations in MmpL3; the mycolic acid transporter in mycobacteria. Over-expression of the mutated mmpL3 alleles in a susceptible M. abscessus strain was associated with high resistance levels to EJMCh-6 and to other known MmpL3 inhibitors. Mapping the mutations conferring resistance on a MmpL3 three-dimensional homology model defined a potential EJMCh-6-binding cavity. These data emphasize a yet unexploited chemical structure class against M. abscessus with promising translational developments for the treatment of M. abscessus lung diseases.
Published: 2019
Full Text: View/download PDF

43. European task force on atopic dermatitis position paper

Author: Regina Fölster-Holst, Thomas Werfel, Michael J. Cork, Alain Taieb, Julien Seneschal, Carle Paul, Åke Svensson, Carsten Flohr, Thomas Bieber, Phyllis I. Spuls, Sébastien Barbarot, Uwe Gieler, J. Ring, Christian Vestergaard, L.B. von Kobyletzki, Stéphanie Christen-Zaech, Jacob P. Thyssen, M S de Bruin-Weller, DirkJan Hijnen, Ulf Darsow, Andreas Wollenberg, J. F. Stalder, Magdalena Trzeciak, Carlo Gelmetti, Pavel V Chernyshov, Dagmar Simon, M. Deleuran, B. Kunz, L. De Raeve, Surgical clinical sciences, Dermatology, Skin function and permeability, APH - Methodology, APH - Quality of Care, Aarhus University Hospital, Ludwig Maximilians University of Munich, Hôpital Municipal de Munich, Partenaires INRAE, Centre hospitalier universitaire de Nantes (CHU Nantes), Lausanne University Hospital, University of Amsterdam [Amsterdam] (UvA), King‘s College London, Medical University of Gdańsk, Lund University [Lund], Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], University of Bonn, Hannover Medical School [Hannover] (MHH), Department of Dermatology, Venerology and Allergology, Universitätsklinikum Würzburg, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Justus-Liebig-Universität Gießen (JLU), University of Sheffield, Vrije Universiteit Brussel (VUB), Dermatologikum Hamburg, Universität Bern- University of Bern [Bern], National Medical University Kief, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Università degli Studi di Milano [Milano] (UNIMI), Christine Kühne Center, University Medical Center [Utrecht], University of Copenhagen = Københavns Universitet (KU), ProdInra, Migration, Ludwig-Maximilians University [Munich] (LMU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Università degli Studi di Milano = University of Milan (UNIMI), and University of Copenhagen = Københavns Universitet (UCPH)
Subjects: 0301 basic medicine, Male, Pediatrics, Azathioprine, disease flares, Ultraviolet therapy, Preconception Care, 030207 dermatology & venereal diseases, 0302 clinical medicine, tacrolimus ointment, Dermatitis, Atopic/therapy, guidelines, Dermatologic Agents/therapeutic use, Atopic dermatitis, calcineurin inhibitors, 3. Good health, Europe, Infectious Diseases, Female, Ultraviolet Therapy, eczema, pregnancy, treatment options, medicine.drug, Adult, medicine.medical_specialty, Advisory Committees, Dermatology, Dermatitis, Atopic, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, children, medicine, Humans, Lactation, Pregnancy, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Chlorhexidine, birth outcomes, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, Tacrolimus, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, antirheumatic drugs, maternal stress, Position paper, Dermatologic Agents, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine.
Published: 2019
Full Text: View/download PDF

44. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials

Author: Christine H. Chung, Chia-Chi Lin, Chao Hua Chiu, Christian Rolfo, Yuichiro Ohe, Yu Chung Li, Daniel Shao-Weng Tan, Byoung Chul Cho, Thomas John, Fabrice Barlesi, Alexander Drilon, Young Kwang Chae, Rafal Dziadziuszko, Myung-Ju Ahn, Matthew G Krebs, Susan Eng, Na Cui, Takashi Seto, B. Simmons, Gregory A. Otterson, Ann D. Johnson, Koichi Goto, Todd Riehl, Timothy R. Wilson, Sang We Kim, Haruyasu Murakami, Hendrick Tobias Arkenau, Filippo de Braud, Robert C. Doebele, Christos S. Karapetis, Edna Chow-Maneval, Manish R. Patel, Hans Prenen, Alice T. Shaw, Jürgen Wolf, Salvatore Siena, Università degli Studi di Milano = University of Milan (UNIMI), Medical University of Gdańsk, Medical University of Gdansk, Assistance Publique - Hôpitaux de Marseille (APHM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Antwerp University Hospital [Edegem] (UZA), Fraunhofer Institute for Reliability and Microintegration (Fraunhofer IZM), Fraunhofer (Fraunhofer-Gesellschaft), Sankalchand Patel College of Engineering,Visnagar, India, Universität des Saarlandes [Saarbrücken], City of Hope Medical Center, Università degli Studi di Milano [Milano] (UNIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), and Trial Investigators
Subjects: 0301 basic medicine, Oncology, Male, medicine.medical_specialty, Indazoles, Lung Neoplasms, Time Factors, Population, Entrectinib, Antineoplastic Agents, Neutropenia, 03 medical and health sciences, 0302 clinical medicine, Clinical Trials, Phase II as Topic, Internal medicine, Carcinoma, Non-Small-Cell Lung, Proto-Oncogene Proteins, Biomarkers, Tumor, Medicine, Humans, Multicenter Studies as Topic, Progression-free survival, Lung cancer, Adverse effect, education, Protein Kinase Inhibitors, education.field_of_study, Manchester Cancer Research Centre, Clinical Trials, Phase I as Topic, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Middle Aged, Protein-Tyrosine Kinases, medicine.disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Progression-Free Survival, respiratory tract diseases, 3. Good health, Clinical trial, 030104 developmental biology, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Benzamides, Female, Human medicine, Gene Fusion, business
Abstract: Summary Background Recurrent gene fusions, such as ROS1 fusions, are oncogenic drivers of various cancers, including non-small-cell lung cancer (NSCLC). Up to 36% of patients with ROS1 fusion-positive NSCLC have brain metastases at the diagnosis of advanced disease. Entrectinib is a ROS1 inhibitor that has been designed to effectively penetrate and remain in the CNS. We explored the use of entrectinib in patients with locally advanced or metastatic ROS1 fusion-positive NSCLC. Methods We did an integrated analysis of three ongoing phase 1 or 2 trials of entrectinib (ALKA-372-001, STARTRK-1, and STARTRK-2). The efficacy-evaluable population included adult patients (aged ≥18 years) with locally advanced or metastatic ROS1 fusion-positive NSCLC who received entrectinib at a dose of at least 600 mg orally once per day, with at least 12 months' follow-up. All patients had an Eastern Cooperative Oncology Group performance status of 0–2, and previous cancer treatment (except for ROS1 inhibitors) was allowed. The primary endpoints were the proportion of patients with an objective response (complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1) and duration of response, and were evaluated by blinded independent central review. The safety-evaluable population for the safety analysis included all patients with ROS1 fusion-positive NSCLC in the three trials who received at least one dose of entrectinib (irrespective of dose or duration of follow-up). These ongoing studies are registered with ClinicalTrials.gov , NCT02097810 (STARTRK-1) and NCT02568267 (STARTRK-2), and EudraCT, 2012–000148–88 (ALKA-372-001). Findings Patients were enrolled in ALKA-372-001 from Oct 26, 2012, to March 27, 2018; in STARTRK-1 from Aug 7, 2014, to May 10, 2018; and in STARTRK-2 from Nov 19, 2015 (enrolment is ongoing). At the data cutoff date for this analysis (May 31, 2018), 41 (77%; 95% CI 64–88) of 53 patients in the efficacy-evaluable population had an objective response. Median follow-up was 15·5 monhts (IQR 13·4–20·2). Median duration of response was 24·6 months (95% CI 11·4–34·8). In the safety-evaluable population, 79 (59%) of 134 patients had grade 1 or 2 treatment-related adverse events. 46 (34%) of 134 patients had grade 3 or 4 treatment-related adverse events, with the most common being weight increase (ten [8%]) and neutropenia (five [4%]). 15 (11%) patients had serious treatment-related adverse events, the most common of which were nervous system disorders (four [3%]) and cardiac disorders (three [2%]). No treatment-related deaths occurred. Interpretation Entrectinib is active with durable disease control in patients with ROS1 fusion-positive NSCLC, and is well tolerated with a manageable safety profile, making it amenable to long-term dosing in these patients. These data highlight the need to routinely test for ROS1 fusions to broaden therapeutic options for patients with ROS1 fusion-positive NSCLC. Funding Ignyta/F Hoffmann-La Roche.
Published: 2019
Full Text: View/download PDF

45. Patient-reported outcomes from the randomized phase III ALEX study of alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer

Author: Evgeny Levchenko, Eveline Nüesch, Ting Liu, Nick Pavlakis, Solange Peters, Bogdana Balas, Silvia Novello, Marco Platania, Teresa Moran, Emmanuel Mitry, Julio Oliveira, Maurice Pérol, Rita Chiari, Krzysztof Konopa, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Petrov Research Insitut of Oncology, Fondazione Ospedale San Camillo [Venezia] (IRCCS), Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), University of Turin, F. Hoffmann-La Roche [Basel], and Medical University of Gdańsk
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Alectinib, Male, Cancer Research, medicine.medical_specialty, Randomization, Lung Neoplasms, [SDV]Life Sciences [q-bio], Population, Carbazoles, Chest pain, NSCLC, 03 medical and health sciences, 0302 clinical medicine, Crizotinib, Piperidines, Internal medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Anaplastic Lymphoma Kinase, Patient Reported Outcome Measures, education, Lung cancer, ALK-positive, Patient-reported outcomes, education.field_of_study, business.industry, Hazard ratio, Middle Aged, medicine.disease, Prognosis, 3. Good health, Survival Rate, 030104 developmental biology, Oncology, Tolerability, 030220 oncology & carcinogenesis, Quality of Life, Female, medicine.symptom, business, medicine.drug
Abstract: Objectives: Alectinib demonstrated superior efficacy and a safety profile that compared favorably with crizotinib in treatment-na ve ALK + non-small-cell lung cancer (NSCLC) in the phase III ALEX study. We present patient-reported outcomes (PROs) from ALEX to assess disease burden, treatment-related symptom tolerability, and health-related quality of life (HRQoL) with alectinib versus crizotinib. Materials and Methods: Patients were randomized to receive alectinib 600 mg or crizotinib 250 mg twice daily until disease progression, death, or withdrawal. Pre-specified PRO endpoints were: mean change from baseline in symptoms, HRQoL, and functioning; and time to deterioration (TTD) in cough, dyspnea, chest pain, arm/shoulder pain, fatigue, and a composite of three symptoms (cough, dyspnea, chest pain). PRO data were collected using EORTC QLQ-C30 and LC13 questionnaires. Raw scores were standardized to a 0-100-point range, with a >= 10-point score change defined as clinically meaningful. TTD was defined as the time from randomization until confirmed clinically meaningful deterioration (i.e., a 10-point score change from baseline). Results: Baseline completion rates and characteristics were balanced in the PRO-evaluable population (alectinib n = 100, 66%; crizotinib n = 97, 64%). On average, alectinib-treated patients reported clinically meaningful improvements in lung cancer symptoms for longer than crizotinib-treated patients. Between-treatment differences in lung cancer symptoms tended to favor alectinib from 11.1 months (45 weeks) onwards, around the time of median PFS with crizotinib (11.1 months). TTD in lung cancer symptoms was similar between treatment arms, despite longer duration of symptom improvement with alectinib; composite symptom endpoint (hazard ratio 1.10 [95% confidence interval: 0.72-1.68]). Duration of clinically meaningful improvement in HRQoL was longer with alectinib versus crizotinib (Week 88 vs. Week 68, respectively). Better patient-reported tolerability was observed with alectinib versus crizotinib on common treatment-related symptoms. Conclusion: PRO data support the superior efficacy and tolerability of alectinib relative to crizotinib demonstrated in the ALEX study.
Published: 2019
Full Text: View/download PDF

46. Physical Stability and Viscoelastic Properties of Co-Amorphous Ezetimibe/Simvastatin System

Author: Justyna Knapik-Kowalczuk, Marian Paluch, Karolina Jurkiewicz, Wiesław Sawicki, Natália T. Correia, Krzysztof Chmiel, University of Silesia in Katowice, Unité Matériaux et Transformations - UMR 8207 (UMET), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Medical University of Gdańsk, Université de Lille, CNRS, INRAE, ENSCL, and Unité Matériaux et Transformations (UMET) - UMR 8207
Subjects: Diffraction, Materials science, Pharmaceutical Science, lcsh:Medicine, lcsh:RS1-441, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 030226 pharmacology & pharmacy, Viscoelasticity, Article, lcsh:Pharmacy and materia medica, 03 medical and health sciences, 0302 clinical medicine, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, co-amorphous, Drug Discovery, medicine, simvastatin, Component (thermodynamics), lcsh:R, Plasticizer, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 021001 nanoscience & nanotechnology, Amorphous solid, Devitrification, Chemical engineering, solubility enhancement, ezetimibe, melt viscosity, [PHYS.COND.CM-MS]Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Molecular Medicine, Ezetimibe/simvastatin, 0210 nano-technology, Ternary operation, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], medicine.drug
Abstract: The purpose of this paper is to examine the physical stability as well as viscoelastic properties of the binary amorphous ezetimibe&ndash, simvastatin system. According to our knowledge, this is the first time that such an amorphous composition is prepared and investigated. The tendency toward re-crystallization of the amorphous ezetimibe&ndash, simvastatin system, at both standard storage and elevated temperature conditions, have been studied by means of X-ray diffraction (XRD). Our investigations have revealed that simvastatin remarkably improves the physical stability of ezetimibe, despite the fact that it works as a plasticizer. Pure amorphous ezetimibe, when stored at room temperature, begins to re-crystallize after 14 days after amorphization. On the other hand, the ezetimibe-simvastatin binary mixture (at the same storage conditions) is physically stable for at least 1 year. However, the devitrification of the binary amorphous composition was observed at elevated temperature conditions (T = 373 K). Therefore, we used a third compound to hinder the re-crystallization. Finally, both the physical stability as well as viscoelastic properties of the ternary systems containing different concentrations of the latter component have been thoroughly investigated.
Published: 2019
Full Text: View/download PDF

47. Clinical characteristics, antihypertensive medication use and blood pressure control among patients with treatment-resistant hypertension

Author: Carcel, Cheryl, Neal, Bruce, Oparil, Suzanne, Rogers, Kris, Narkiewicz, Krzysztof, Wang, Ji Guang, Schiffrin, Ernesto, Poulter, Neil, Azizi, Michel, Chalmers, John, HULOT, Jean-Sébastien, The George Institute for Global Health India, The University of Sydney, Royal Prince Alfred Hospital [Sydney, Australia], Imperial College London, University of Alabama at Birmingham [ Birmingham] (UAB), Medical University of Gdańsk, School of Medicine [Shanghai Jiaotong University], Shanghai Jiaotong University, McGill University = Université McGill [Montréal, Canada], CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; Objective: We evaluated the characteristics of patients with treatment-resistant hypertension (TRH) and the prevalence of TRH in a large multicountry sample of specialist tertiary centres.Methods: The Survey of PatIents with treatment ResIstant hyperTension (SPIRIT) study was a retrospective review of medical records of patients seen at tertiary centres located in Western Europe, Eastern Europe, North America, South America, Australia and Asia. Data on demographics, medical history and medication use were extracted from medical records. Prevalence and incidence of TRH were based upon estimated catchment populations.Results: On thousand, five hundred and fifty-five patients from 76 centres were included, mostly from centres that specialize in hypertension (55%), cardiology (11%) or nephrology (19%). Mean age was 64, 60% were men, 62% were Caucasian, 36% had chronic kidney disease, 41% had diabetes, 12% were smokers and 31% had a previous cardiovascular event. Daytime and night-time ambulatory blood pressure (BP) was the most frequently used measurement for diagnosis (82%). Ninety-five percent of patients were prescribed diuretics, 93% an inhibitor of the renin-angiotensin system, 86% a calcium channel blocker, 74% a beta-blocker and 36% an aldosterone antagonist. The overall estimated mean incidence of TRH was 5.8 per 100 000 per year (ranging between 2.3 and 14.0 across regions) and the corresponding estimated mean prevalence of TRH was 23.9 per 100 000 (ranging between 7.6 and 90.5 across regions).Conclusion: Observed variation likely reflects real differences in patient characteristics and physician management practices across regions and specialities but may also reflect differences in patient selection and errors in estimation of catchment population across participating centres.
Published: 2019
Full Text: View/download PDF

48. Mitigating anticipated effects of systematic errors supports sister-group relationship between Xenacoelomorpha and Ambulacraria

Author: Albert J. Poustka, Richard R. Copley, Katharina J. Hoff, Steven Müller, Heiner Kuhl, Bernd Timmermann, Tomoe Hikosaka-Katayama, Pedro Martinez, Philipp H. Schiffer, Christophe Dessimoz, Florian Mertes, Bartlomiej Tomiczek, Morgane Thomas-Chollier, Daryl Domman, Matthias Horn, Andreas Wallberg, Maximilian J. Telford, Thomas Hankeln, Noriyuki Satoh, Marta Chiodin, Hiroaki Nakano, Hervé Philippe, Matthew L. Rowe, Maurice R. Elphick, Jonathan P. Rast, Canadian Institute for Advanced Research (CIFAR), Station d'écologie théorique et expérimentale (SETE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Max Planck Institute for Molecular Genetics (MPIMG), Max-Planck-Gesellschaft, Dahlem Center for Complex Quantum Systems & Fachbereich Physik, Freie Universität Berlin, Universitat de Barcelona (UB), New York University School of Medicine, NYU System (NYU), Universität Greifswald - University of Greifswald, University College of London [London] (UCL), Department of Computer Science (Queen Mary University of London), Queen Mary University of London (QMUL), Université de Lausanne (UNIL), Medical University of Gdańsk, The Wellcome Trust Sanger Institute [Cambridge], University of Vienna [Vienna], Los Alamos National Laboratory (LANL), Max-Planck-Institut für Informatik (MPII), Leibniz Institute of Freshwater Ecology and Inland Fisheries (IGB), Marine Genomics Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Hiroshima City University, Université de Tsukuba = University of Tsukuba, Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), GENterprise Genomics, University Medical Center [Mainz], Helmholtz-Zentrum München (HZM), Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Emory University School of Medicine, Emory University [Atlanta, GA], Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institució Catalana de Recerca i Estudis Avançats (ICREA), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Helmholtz Zentrum München = German Research Center for Environmental Health, and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Xenoturbella, Ambulacraria, media_common.quotation_subject, Acoelomorpha, Metazoa, Nephrozoa, Phylogenomics, Phylogeny, Systematic Error, Context (language use), phylogeny, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, General Biochemistry, Genetics and Molecular Biology, systematic error, 03 medical and health sciences, 0302 clinical medicine, Animals, Simplicity, Chordata, media_common, Long branch attraction, biology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], phylogenomics, biology.organism_classification, Biological Evolution, Invertebrates, Xenacoelomorpha, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, 030104 developmental biology, Sister group, Evolutionary biology, Outgroup, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, Echinodermata
Abstract: International audience; Xenoturbella and the acoelomorph worms (Xenacoelomorpha) are simple marine animals with controversial affinities. They have been placed as the sister group of all other bilaterian animals (Nephrozoa hypothesis), implying their simplicity is an ancient characteristic ]; alternatively, they have been linked to the complex Ambulacraria (echinoderms and hemichordates) in a clade called the Xenambulacraria , suggesting their simplicity evolved by reduction from a complex ancestor. The difficulty resolving this problem implies the phylogenetic signal supporting the correct solution is weak and affected by inadequate modeling, creating a misleading non-phylogenetic signal. The idea that the Nephrozoa hypothesis might be an artifact is prompted by the faster molecular evolutionary rate observed within the Acoelomorpha. Unequal rates of evolution are known to result in the systematic artifact of long branch attraction, which would be predicted to result in an attraction between long-branch acoelomorphs and the outgroup, pulling them toward the root . Other biases inadequately accommodated by the models used can also have strong effects, exacerbated in the context of short internal branches and long terminal branches . We have assembled a large and informative dataset to address this problem. Analyses designed to reduce or to emphasize misleading signals show the Nephrozoa hypothesis is supported under conditions expected to exacerbate errors, and the Xenambulacraria hypothesis is preferred in conditions designed to reduce errors. Our reanalyses of two other recently published datasets produce the same result. We conclude that the Xenacoelomorpha are simplified relatives of the Ambulacraria.
Published: 2019
Full Text: View/download PDF

49. European Population of Pectobacterium punjabense: Genomic Diversity, Tuber Maceration Capacity and a Detection Tool for This Rarely Occurring Potato Pathogen

Author: Pauline Dewaegeneire, Denis Faure, Jan M. van der Wolf, Jérémy Cigna, Didier Andrivon, Valérie Hélias, Krzysztof Waleron, Angélique Laurent, Malgorzata Waleron, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Fédération Nationale des Producteurs de Plants de Pomme de Terre (FN3PT), Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Medical University of Gdańsk, Wageningen University and Research [Wageningen] (WUR), The French Federation of Seed Potato Growers (FN3PT), The National Science Centre, Poland, project Opus 9 [2015/17/B/NZ9/01730], Université de Rennes (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: 0106 biological sciences, 0301 basic medicine, Microbiology (medical), Pectobacterium, [SDV]Life Sciences [q-bio], Blackleg, Dickeya, 01 natural sciences, Microbiology, Article, genomic diversity, Pectobacterium punjabense, detection qPCR TaqMan assay, Biointeractions and Plant Health, 03 medical and health sciences, Virology, TaqMan, Maceration (wine), lcsh:QH301-705.5, Pathogen, 2. Zero hunger, Genetics, biology, Strain (biology), Bacteria Present, biology.organism_classification, 030104 developmental biology, lcsh:Biology (General), [SDE]Environmental Sciences, soft rot enterobacteria, maceration tuber, 010606 plant biology & botany
Abstract: Enterobacteria belonging to the Pectobacterium and Dickeya genera are responsible for soft rot and blackleg diseases occurring in many crops around the world. Since 2016, the number of described species has more than doubled. However, some new species, such as Pectobacterium punjabense, are often poorly characterized, and little is known about their genomic and phenotypic variation. Here, we explored several European culture collections and identified seven strains of P. punjabense. All were collected from potato blackleg symptoms, sometimes from a long time ago, i.e., the IFB5596 strain isolated almost 25 years ago. We showed that this species remains rare, with less than 0.24% of P. punjabense strains identified among pectinolytic bacteria present in the surveyed collections. The analysis of the genomic diversity revealed the non-clonal character of P. punjabense species. Furthermore, the strains showed aggressiveness differences. Finally, a qPCR Taqman assay was developed for rapid and specific strain characterization and for use in diagnostic programs.
Published: 2021
Full Text: View/download PDF

50. European Society of Surgical Oncology's strategy for clinical research: Paving the way for a culture of research in cancer surgery

Author: Evrard, S., Velde, C. van de, Noordhoek, I., Caballero, C., Ceelen, W., Polom, K., Kolacinska, A., Allum, W., D'Ugo, D., Malik, H.Z., Rubio, I.T., Wyld, L., Leidenius, M., Rivoire, M., Zoras, O., Polkowski, W., Poston, G.J., Audisio, R.A., Kovacs, T., Gonzalez-Moreno, S., European Soc Surgical Oncology, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, Helsinki University Hospital Area, Institut Bergonié [Bordeaux], UNICANCER, Leiden University Medical Center (LUMC), Medical University of Gdańsk, Medical University of Łódź (MUL), Royal Marsden NHS Foundation Trust, Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Clínica Universidad de Navarra [Pamplona], Centre Léon Bérard [Lyon], and University of Liverpool
Subjects: Biomedical Research, Oncopolicy, [SDV]Life Sciences [q-bio], Settore MED/18 - CHIRURGIA GENERALE, 3122 Cancers, Translational research, law.invention, Clinical research, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Clinical studies, Surgical oncology, law, Medicine, Humans, 030212 general & internal medicine, Societies, Medical, Medical education, Clinical Trials as Topic, business.industry, General Medicine, 3126 Surgery, anesthesiology, intensive care, radiology, Culturally Competent Care, 3. Good health, Clinical trial, Europe, Surgical Oncology, Oncology, Research Design, 030220 oncology & carcinogenesis, Action plan, Position paper, Portfolio, Surgery, business
Abstract: As part of its mission to promote the best surgical care for cancer patients, the European Society of Surgical Oncology (ESSO) has been developing multiple programmes for clinical research along with its educational portfolio. This position paper describes the different research activities of the Society over the past decade and an action plan for the upcoming five years to lead innovative and high quality surgical oncology research. ESSO proposes to consider pragmatic research methodologies as a complement to randomised clinical trials (RCT), advocates for increased funding and operational support in conducting research and aims to enable young surgeons to be active in research and establish partnerships for translational research activities.
Published: 2018
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

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

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

5,066 results on '"Medical University of Gdańsk"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources