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1. Isolation of Burkholderia pseudomallei from a goat in New Caledonia: implications for animal and human health monitoring and serological tool comparison

Author

Anais Desoutter, Thomas Deshayes, Fabien Vorimore, Bernice Klotoe, Benoit Durand, Julien Colot, Gabriel Wagner-Lichtenegger, Ivo Steinmetz, Apichai Tuanyok, and Karine Laroucau

Subjects
Burkholderia pseudomallei, New Caledonia, Goat, Serology, ELISA, Luminex, Veterinary medicine, SF600-1100
Abstract

Abstract Background Melioidosis is a serious bacterial infection caused by Burkholderia pseudomallei, a gram-negative bacterium commonly found in soil and water. It can affect both humans and animals, and is endemic in regions such as Southeast Asia and Northern Australia. In recent years, there have been reports of an emergence of human melioidosis in other areas, including New Caledonia. Results During standard laboratory analysis in New Caledonia in 2021, a strain of B. pseudomallei was isolated from a goat. The strain was characterized using both MLST and WGS techniques and was found to cluster with previously described local human strains from the area. In parallel, several serological tests (CFT, ELISA, Luminex (Hcp1, GroEL, BPSS1840), arrays assay and a latex agglutination test) were performed on animals from the farm where the goat originated, and/or from three other neighboring farms. Using two commercial ELISA kits, seropositive animals were found only on the farm where the infected goat originated and tests based on recombinant proteins confirmed the usefulness of the Hcp1 protein for the diagnosis of melioidosis in animals. Conclusions Despite the regular reports of human cases, this is the first confirmed case of melioidosis in an animal in New Caledonia. These results confirm the presence of the bacterium in the region and highlight the importance of vigilance for both animal and human health. It is critical that all health partners, including breeders, veterinarians, and biologists, work together to monitor and prevent the spread of the disease.

Published
2024
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2. Real-Time Precision in 3D Concrete Printing: Controlling Layer Morphology via Machine Vision and Learning Algorithms

Author

João M. Silva, Gabriel Wagner, Rafael Silva, António Morais, João Ribeiro, Sacha Mould, Bruno Figueiredo, João M. Nóbrega, and Paulo J. S. Cruz

Subjects
3DCP, additive manufacturing, computational modeling, automation, machine learning, computer vision, Engineering machinery, tools, and implements, TA213-215, Technological innovations. Automation, HD45-45.2
Abstract

3D concrete printing (3DCP) requires precise adjustments to parameters to ensure accurate and high-quality prints. However, despite technological advancements, manual intervention still plays a prominent role in this process, leading to errors and inconsistencies in the final printed part. To address this issue, machine learning vision models have been developed and utilized to analyze captured images and videos of the printing process, detecting defects and deviations. The data collected enable automatic adjustments to print settings, improving quality without the need for human intervention. This work first examines various techniques for real-time and offline corrections. It then introduces a specialized computer vision setup designed for real-time control in robotic 3DCP. Our main focus is on a specific aspect of machine learning (ML) within this system, called speed control, which regulates layer width by adjusting the robot motion speed or material flow rate. The proposed framework consists of three main elements: (1) a data acquisition and processing pipeline for extracting printing parameters and constructing a synthetic training dataset, (2) a real-time ML model for parameter optimization, and (3) a depth camera installed on a customized 3D-printed rotary mechanism for close-range monitoring of the printed layer.

Published
2024
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3. Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease

Author

Sebastian Cremer, Lisa Pilgram, Alexander Berkowitsch, Melanie Stecher, Siegbert Rieg, Mariana Shumliakivska, Denisa Bojkova, Julian Uwe Gabriel Wagner, Galip Servet Aslan, Christoph Spinner, Guillermo Luxán, Frank Hanses, Sebastian Dolff, Christiane Piepel, Clemens Ruppert, Andreas Guenther, Maria Madeleine Rüthrich, Jörg Janne Vehreschild, Kai Wille, Martina Haselberger, Hanno Heuzeroth, Arne Hansen, Thomas Eschenhagen, Jindrich Cinatl, Sandra Ciesek, Stefanie Dimmeler, Stefan Borgmann, Andreas Zeiher, and on behalf of the LEOSS study group

Subjects
Medicine, Science
Abstract

Aims Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity. Methods and results We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59–0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43–0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; pConclusion These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.

Published
2021

4. Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

Author

Douglas F. Easton, Mads Thomassen, Georgia Chenevix-Trench, Kristiina Aittomäki, Marjanka K. Schmidt, Hebon Investigators, Esther M. John, Irene L. Andrulis, Maartje J. Hooning, Antonis C. Antoniou, Swe-Brca Investigators, Caroline Maria Rossing, Penny Soucy, Jacques Simard, Michael T. Parsons, Julie M. Cunningham, Paul A. James, Joe Dennis, Gabriel Wagner, Melissa C. Southey, Susan M. Domchek, Eric Hahnen, kConFab Investigators, Goska Leslie, Sofia Khan, Katherine L. Nathanson, Rita K. Schmutzler, Anna Jakubowska, Jeffrey N. Weitzel, Taru A. Muranen, Heli Nevanlinna, Barbara Wappenschmidt, Drakoulis Yannoukakos, Judy Garber, Marc Tischkowitz, Conxi Lázaro, Inge Søkilde Pedersen, Carl Blomqvist, Amanda B. Spurdle, Christian F. Singer, Susan L. Slager, Lesley McGuffog, Rainer Fagerholm, Manuel R. Teixeira, Medical Oncology, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, University of Helsinki, Helsinki University Hospital Area, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, Muranen, Taru A. [0000-0002-5895-1808], Cunningham, Julie M. [0000-0002-8159-3025], Dennis, Joe [0000-0003-4591-1214], Leslie, Goska [0000-0001-5756-6222], Parsons, Michael T. [0000-0003-3242-8477], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F. [0000-0003-2444-3247], Spurdle, Amanda B. [0000-0003-1337-7897], Pedersen, Inge Sokilde [0000-0002-9902-8040], Nathanson, Katherine L. [0000-0002-6740-0901], Lazaro, Conxi [0000-0002-7198-5906], Andrulis, Irene L. [0000-0002-4226-6435], Teixeira, Manuel R. [0000-0002-4896-5982], James, Paul [0000-0002-4361-4657], Weitzel, Jeffrey N. [0000-0001-6714-092X], Jakubowska, Anna [0000-0002-5650-0501], Yannoukakos, Drakoulis [0000-0001-7509-3510], Schmidt, Marjanka K. [0000-0002-2228-429X], Nevanlinna, Heli [0000-0002-0916-2976], Apollo - University of Cambridge Repository, Muranen, Taru A [0000-0002-5895-1808], Cunningham, Julie M [0000-0002-8159-3025], Parsons, Michael T [0000-0003-3242-8477], Easton, Douglas F [0000-0003-2444-3247], Spurdle, Amanda B [0000-0003-1337-7897], Nathanson, Katherine L [0000-0002-6740-0901], Andrulis, Irene L [0000-0002-4226-6435], Teixeira, Manuel R [0000-0002-4896-5982], Weitzel, Jeffrey N [0000-0001-6714-092X], and Schmidt, Marjanka K [0000-0002-2228-429X]

Subjects
0301 basic medicine, Oncology, Etiology, Genome-wide association study, Genome-wide association studies, Germline, 0302 clinical medicine, Breast cancer, PRIMARY THERAPY, Pharmacology (medical), skin and connective tissue diseases, Cancer genetics, RISK, medicine.diagnostic_test, Hazard ratio, article, INTERNATIONAL EXPERT CONSENSUS, Tumor Pathology, OVARIAN, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, 030220 oncology & carcinogenesis, Etiologia, EXPRESSION, medicine.medical_specialty, GENES, 3122 Cancers, 631/208/205/2138, lcsh:RC254-282, Càncer de mama, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, 631/67/68, Genetic variation, REVEALS, medicine, Radiology, Nuclear Medicine and imaging, Genetic testing, IDENTIFICATION, business.industry, FALSE DISCOVERY, Cancer, medicine.disease, 030104 developmental biology, CELLS, 692/4028/67/1347, business
Abstract

Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03–6.30, P = 3.1 × 10−9). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics.

Published
2020

5. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Author

Daniel R. Barnes, Matti A. Rookus, Lesley McGuffog, Goska Leslie, Thea M. Mooij, Joe Dennis, Nasim Mavaddat, Julian Adlard, Munaza Ahmed, Kristiina Aittomäki, Nadine Andrieu, Irene L. Andrulis, Norbert Arnold, Banu K. Arun, Jacopo Azzollini, Judith Balmaña, Rosa B. Barkardottir, Daniel Barrowdale, Javier Benitez, Pascaline Berthet, Katarzyna Białkowska, Amie M. Blanco, Marinus J. Blok, Bernardo Bonanni, Susanne E. Boonen, Åke Borg, Aniko Bozsik, Angela R. Bradbury, Paul Brennan, Carole Brewer, Joan Brunet, Saundra S. Buys, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Lise Lotte Christensen, Wendy K. Chung, Kathleen B.M. Claes, Chrystelle Colas, Marie-Agnès Collonge-Rame, Capucine Delnatte, Laurence Faivre, Sophie Giraud, Christine Lasset, Véronique Mari, Noura Mebirouk, Emmanuelle Mouret-Fourme, Hélène Schuster, Dominique Stoppa-Lyonnet, Antonis Antoniou, Jackie Cook, Rosemarie Davidson, Douglas Easton, Ros Eeles, D. Gareth Evans, Debra Frost, Helen Hanson, Louise Izatt, Kai-ren Ong, Lucy Side, Aoife O’Shaughnessy-Kirwan, Marc Tischkowitz, Lisa Walker, Mary B. Daly, Miguel de la Hoya, Robin de Putter, Peter Devilee, Orland Diez, Yuan Chun Ding, Susan M. Domchek, Cecilia M. Dorfling, Martine Dumont, Bent Ejlertsen, Christoph Engel, Lenka Foretova, Florentia Fostira, Michael Friedlander, Eitan Friedman, Patricia A. Ganz, Judy Garber, Andrea Gehrig, Anne-Marie Gerdes, Paul Gesta, Gord Glendon, Andrew K. Godwin, David E. Goldgar, Anna González-Neira, Mark H. Greene, Daphne Gschwantler-Kaulich, Eric Hahnen, Ute Hamann, Julia Hentschel, Frans B.L. Hogervorst, Maartje J. Hooning, Judit Horvath, Chunling Hu, Peter J. Hulick, Evgeny N. Imyanitov, Georgia Chenevix-Trench, Kelly-Anne Phillips, Amanda Spurdle, Marinus Blok, Frans Hogervorst, Maartje Hooning, Marco Koudijs, Arjen Mensenkamp, Hanne Meijers-Heijboer, Matti Rookus, Klaartje van Engelen, Catherine Noguès, Claudine Isaacs, Angel Izquierdo, Anna Jakubowska, Paul A. James, Ramunas Janavicius, Esther M. John, Vijai Joseph, Beth Y. Karlan, Karin Kast, Torben A. Kruse, Ava Kwong, Yael Laitman, Conxi Lazaro, Jenny Lester, Fabienne Lesueur, Annelie Liljegren, Jennifer T. Loud, Jan Lubiński, Phuong L. Mai, Siranoush Manoukian, Hanne E.J. Meijers-Heijboer, Alfons Meindl, Arjen R. Mensenkamp, Austin Miller, Marco Montagna, Semanti Mukherjee, Anna Marie Mulligan, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Dieter Niederacher, Finn Cilius Nielsen, Liene Nikitina-Zake, Edith Olah, Olufunmilayo I. Olopade, Ana Osorio, Claus-Eric Ott, Laura Papi, Sue K. Park, Michael T. Parsons, Inge Sokilde Pedersen, Bernard Peissel, Ana Peixoto, Paolo Peterlongo, Georg Pfeiler, Karolina Prajzendanc, Miquel Angel Pujana, Paolo Radice, Juliane Ramser, Susan J. Ramus, Johanna Rantala, Gad Rennert, Harvey A. Risch, Mark Robson, Karina Rønlund, Ritu Salani, Leigha Senter, Payal D. Shah, Priyanka Sharma, Lucy E. Side, Christian F. Singer, Thomas P. Slavin, Penny Soucy, Melissa C. Southey, Amanda B. Spurdle, Doris Steinemann, Zoe Steinsnyder, Christian Sutter, Yen Yen Tan, Manuel R. Teixeira, Soo Hwang Teo, Darcy L. Thull, Silvia Tognazzo, Amanda E. Toland, Alison H. Trainer, Nadine Tung, Elizabeth J. van Rensburg, Ana Vega, Jeroen Vierstraete, Gabriel Wagner, Shan Wang-Gohrke, Barbara Wappenschmidt, Jeffrey N. Weitzel, Siddhartha Yadav, Xin Yang, Drakoulis Yannoukakos, Dario Zimbalatti, Kenneth Offit, Mads Thomassen, Fergus J. Couch, Rita K. Schmutzler, Jacques Simard, Douglas F. Easton, Antonis C. Antoniou, Pediatric surgery, Human genetics, CCA - Cancer biology and immunology, CCA - Cancer Treatment and quality of life, Amsterdam Reproduction & Development (AR&D), Apollo - University of Cambridge Repository, University of Cambridge [UK] (CAM), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Chapel Allerton Hospital, Great Ormond Street Hospital for Children [London] (GOSH), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Université Paris sciences et lettres (PSL), Mount Sinai Hospital [Toronto, Canada] (MSH), University of Toronto (University of Toronto), Christian-Albrechts University of Kiel, The University of Texas M.D. Anderson Cancer Center [Houston], Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], CIBER de Enfermedades Raras (CIBERER), Spanish National Cancer Research Center (CNIO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Pomeranian Medical University [Szczecin] (PUM), University of California (UC), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], European Institute of Oncology IRCCS [Milan, Italy] (EIO), Zealand University Hospital [Roskilde, Denmark], Lund University [Lund], National Institute of Oncology [Budapest, Hungary], Abramson Cancer Center [philadelphia], University of Pennsylvania-Perelman School of Medicine, University of Pennsylvania, Institute of Genetic Medicine [Newcastle], Newcastle University [Newcastle], Royal Devon & Exeter Hospital, Exeter, UK, Catalan Institute of Oncology [Barcelone, Espagne], Huntsman Cancer Institute [Salt Lake City], University of Utah, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Pisa University Hospital, Peter MacCallum Cancer Centre [Melbourne, Australie], University of Melbourne, Aarhus University Hospital, Columbia University [New York], Ghent University Hospital, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Sheffield Children's NHS Foundation Trust, Fox Chase Cancer Center, Queen Elizabeth University Hospital (Glasgow), Centre hospitalier universitaire de Nantes (CHU Nantes), Leiden University Medical Center (LUMC), Beckman Research Institute of the City of Hope, Abramson Cancer Center, University of Pretoria [South Africa], Centre Hospitalier Universitaire de Québec Research Center [Canada], Royal Marsden NHS Foundation Trust, Copenhagen University Hospital, Leipzig University, University of Manchester [Manchester], Manchester Academic Health Science Centre (MAHSC), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Masaryk Memorial Cancer Institute (MMCI), Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research 'Demokritos' (NCSR), NHMRC Clinical Trials Centre [Camperdown NSW 2050, Australie], Chaim Sheba Medical Center, Tel Aviv University (TAU), Jonsson Comprehensive Cancer Center, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Dana-Farber Cancer Institute [Boston], University of Würzburg, Rigshospitalet [Copenhagen], Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Hospices Civils de Lyon (HCL), University of Kansas [Kansas City], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Medizinische Universität Wien = Medical University of Vienna, University of Cologne, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Lancashire NHS Foundation Trust, University Hospital Leipzig, Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Mayo Clinic, NorthShore University HealthSystem [Evanston, IL, USA], The University of Chicago Medicine [Chicago], N. N. Petrov Institute of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Guy's and St Thomas' NHS Foundation Trust [London, UK], Peter MacCallum Cancer Center, East Melbourne, Peter MacCallum Cancer Center, Vilnius University [Vilnius], The State Scientific Research Institute Nature Research Centre, Vilnius, Lithuania, Stanford University School of Medicine [CA, USA], Memorial Sloane Kettering Cancer Center [New York], Cedars-Sinai Medical Center, Technische Universität Dresden = Dresden University of Technology (TU Dresden), University Medical Center [Utrecht], Odense University Hospital [Odense, Denmark], The Hong Kong Hereditary Breast Cancer Family Registry, The University of Hong Kong (HKU), Hong Kong Sanatorium and Hospital [Hong Kong] (HKSH), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), David Geffen School of Medicine [Los Angeles], Fondation MINES ParisTech, Karolinska Institutet [Stockholm], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Amsterdam UMC - Amsterdam University Medical Center, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Radboud University Medical Center [Nijmegen], Roswell Park Cancer Institute [Buffalo], Veneto Institute of Oncology IOV-IRCCS [Padua, Italy], University of Toronto, University Health Network, University Hospital Düsseldorf, Latvian Biomedical Research and Study Centre [Rīga], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), University of Chicago, Birmingham Women's and Children's NHS Foundation Trust, Cambridge University Hospitals - NHS (CUH), Charité Campus Virchow-Klinikum (CVK), Università degli Studi di Firenze = University of Florence (UniFI), Seoul National University College of Medicine [Séoul, Corée du Sud] (SNUCM), Seoul National University [Seoul] (SNU), QIMR Berghofer Medical Research Institute, Aalborg University [Denmark] (AAU), IRCCS Istituto Nazionale dei Tumori [Milano], Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Klinikum rechts der Isar [Munich, Germany], University of New South Wales [Sydney] (UNSW), Garvan Institute of medical research, Technion Faculty of Medicine [Haifa, Israel], Yale School of Medicine [New Haven, Connecticut] (YSM), Vejle Hospital [Danemark], Ohio State University [Columbus] (OSU), Centre de lutte contre le cancer Paul-Strauss, Institut de Cancérologie de Strasbourg Europe (ICANS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Kansas Medical Center [Kansas City, KS, USA], Princess Anne Hospital, City of Hope Comprehensive Cancer Center [Duarte], Monash University [Clayton], Cancer Council Victoria [Melbourne, VIC, Australia], Hannover Medical School [Hannover] (MHH), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Heidelberg University Hospital [Heidelberg], Institute of Biomedical Sciences Abel Salazar - ICBAS [Porto, Portugal], Malaysia and University Malaya Cancer Research Institute, Faculty of Medicine, University of Malaya [Kuala Lumpur, Malaisie], University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), McGill University = Université McGill [Montréal, Canada], Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Fundación Pública Galega Medicina Xenómica - SERGAS [Santiago de Compostela, Spain] (Grupo de Medicina Xenómica), CIBER de Enfermedades Raras (CIBERER)-Universidade de Santiago de Compostela [Spain] (USC ), Instituto de Investigaciones Sanitarias, Universidade de Santiago de Compostela [Spain] (USC ), Universiteit Gent = Ghent University (UGENT), Oxford University Hospitals NHS Trust, University of Oxford, Universitätsklinikum Ulm - University Hospital of Ulm, University Hospital of Cologne [Cologne], Mayo Clinic [Rochester], Collaborators : Pascaline Berthet, Chrystelle Colas, Marie-Agnès Collonge-Rame, Capucine Delnatte, Laurence Faivre, Sophie Giraud, Christine Lasset, Véronique Mari, Noura Mebirouk, Emmanuelle Mouret-Fourme, Hélène Schuster, Dominique Stoppa-Lyonnet, Julian Adlard, Munaza Ahmed, Antonis Antoniou, Daniel Barrowdale, Paul Brennan, Carole Brewer, Jackie Cook, Rosemarie Davidson, Douglas Easton, Ros Eeles, D Gareth Evans, Debra Frost, Helen Hanson, Louise Izatt, Kai-Ren Ong, Lucy Side, Aoife O'Shaughnessy-Kirwan, Marc Tischkowitz, Lisa Walker, Georgia Chenevix-Trench, Kelly-Anne Phillips, Amanda Spurdle, Marinus Blok, Peter Devilee, Frans Hogervorst, Maartje Hooning, Marco Koudijs, Arjen Mensenkamp, Hanne Meijers-Heijboer, Matti Rookus, Klaartje van Engelen, Nadine Andrieu, Catherine Noguès, Dupuis, Christine, Institut Català de la Salut, [Barnes DR, McGuffog L, Leslie G, Dennis J] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Rookus MA, Mooij TM] The Netherlands Cancer Institute, Department of Epidemiology (PSOE), Amsterdam, The Netherlands. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Barnes, Daniel [0000-0002-3781-7570], Leslie, Goska [0000-0001-5756-6222], Dennis, Joe [0000-0003-4591-1214], Mavaddat, Nasim [0000-0003-0307-055X], RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), Universiteit Leiden, Roswell Park Cancer Institute [Buffalo] (RPCI), Medical Oncology, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, Helsinki University Hospital Area, Department of Obstetrics and Gynecology, Biosciences, HUS Gynecology and Obstetrics, University of Helsinki, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), MINES ParisTech - École nationale supérieure des mines de Paris, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Pomeranian Medical University, University of California, University of Pennsylvania [Philadelphia]-Perelman School of Medicine, University of Pennsylvania [Philadelphia], University of Leipzig [Leipzig, Allemagne], Masaryk Memorial Cancer Institute (RECAMO), Tel Aviv University [Tel Aviv], University of California-University of California, University of Münster, Amsterdam UMC, Technical University of Munich (TUM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Garvan Institute of Medical Research [Sydney, Australia], Yale University School of Medicine, Vejle Hospital, University of Kansas Medical Center [Lawrence], Université Paris Descartes (Paris 5), University of Malaya [Kuala Lumpur, Malaisie], Universiteit Gent = Ghent University [Belgium] (UGENT), and University of Oxford [Oxford]

Subjects
0301 basic medicine, Oncology, endocrine system diseases, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], [SDV]Life Sciences [q-bio], Càncer d'ovari, Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES], MODIFIERS, Diàtesi, SUSCEPTIBILITY, Carcinoma, Ovarian Epithelial, PRS, 0302 clinical medicine, Breast cancer, 3123 Gynaecology and paediatrics, Risk Factors, Medicine and Health Sciences, Medicine, Genetics(clinical), genetics, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, Genetics (clinical), Ovarian Neoplasms, education.field_of_study, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], BRCA1 Protein, Hazard ratio, Absolute risk reduction, 1184 Genetics, developmental biology, physiology, article, ASSOCIATION, neoplasias::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas::carcinoma epitelial de ovario [ENFERMEDADES], ddc, 3. Good health, [SDV] Life Sciences [q-bio], ovarian cancer, 030220 oncology & carcinogenesis, Female, Cohort study, medicine.medical_specialty, Heterozygote, Population, 3122 Cancers, Single-nucleotide polymorphism, Breast Neoplasms, MUTATION CARRIERS, Ovaris - Càncer - Aspectes genètics, Càncer de mama, 03 medical and health sciences, breast cancer, SDG 3 - Good Health and Well-being, Ovarian cancer, BRCA1/2, Internal medicine, Humans, Genetic Predisposition to Disease, education, Retrospective Studies, fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS], BRCA2 Protein, IDENTIFICATION, business.industry, Neoplasms::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms::Carcinoma, Ovarian Epithelial [DISEASES], Retrospective cohort study, ALLELES, medicine.disease, BRCA1, BRCA2, MODEL, PATHOLOGY, 030104 developmental biology, Mutation, Mama - Càncer - Aspectes genètics, 3111 Biomedicine, business
Abstract

Contains fulltext : 229292.pdf (Publisher’s version ) (Open Access) PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. METHODS: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. RESULTS: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10(-72)). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10(-22)) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10(-12)) carriers. The associations in the prospective cohort were similar. CONCLUSION: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.

Published
2020

6. LMO3 reprograms visceral adipocyte metabolism during obesity

Author

Josefine Lindroos-Christensen, Oswald Wagner, Martina Fondi, Julia Husa, Marion Gröger, Hedwig Sutterlüty, Elisa Einwallner, Florian Klinglmüller, Sabine Rauscher, Anna Fenzl, Martin Bilban, Sophia Derdak, Florian W. Kiefer, Thomas Mohr, Gregor Hoermann, Harald Esterbauer, Lei Cao, Silviya Wolkerstorfer, Nadine Witzeneder, and Gabriel Wagner

Subjects
Glucose uptake, Adipose tissue, Gene Expression, White adipose tissue, Oxidative Phosphorylation, chemistry.chemical_compound, Mice, 0302 clinical medicine, Adipocyte, Drug Discovery, Brown adipose tissue, Adipocytes, Insulin, Adiponectin secretion, Genetics (clinical), 0303 health sciences, Glucose Transporter Type 4, biology, LIM Domain Proteins, Mitochondria, medicine.anatomical_structure, Visceral adipose tissue, Molecular Medicine, Original Article, Disease Susceptibility, Oxidation-Reduction, Protein Binding, medicine.medical_specialty, 030209 endocrinology & metabolism, Intra-Abdominal Fat, Models, Biological, 03 medical and health sciences, Internal medicine, 3T3-L1 Cells, medicine, Animals, Humans, Obesity, 030304 developmental biology, Adaptor Proteins, Signal Transducing, Gene Expression Profiling, PPAR gamma, Insulin receptor, Disease Models, Animal, Endocrinology, Glucose, chemistry, Gene Expression Regulation, biology.protein, LMO3, Energy Metabolism, GLUT4, Biomarkers
Abstract

Abstract Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. We recently identified LIM domain only 3 (LMO3) in human mature visceral adipocytes; however, its function in these cells is currently unknown. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high-fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics, as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain or loss of LMO3 expression, respectively. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. LMO3 expression in eWAT significantly improved insulin sensitivity and healthy visceral adipose tissue expansion in diet-induced obesity, paralleled by increased serum adiponectin. In vitro, LMO3 expression in 3T3-L1 adipocytes increased PPARγ transcriptional activity, insulin-stimulated GLUT4 translocation and glucose uptake, as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. Mechanistically, LMO3 induced the PPARγ coregulator Ncoa1, which was required for LMO3 to enhance glucose uptake and mitochondrial oxidative gene expression. In human mature adipocytes, LMO3 overexpression promoted, while silencing of LMO3 suppressed mitochondrial oxidative capacity. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose metabolism, insulin sensitivity, mitochondrial function, and adiponectin secretion. Together with increased PPARγ activity and Ncoa1 expression, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity. Key messages LMO3 increases beneficial visceral adipose tissue expansion and insulin sensitivity in vivo. LMO3 increases glucose uptake and oxidative mitochondrial activity in adipocytes. LMO3 increases nuclear coactivator 1 (Ncoa1). LMO3-enhanced glucose uptake and mitochondrial gene expression requires Ncoa1.

Published
2020

7. Transcriptional heterogeneity of fibroblasts is a hallmark of the aging heart

Author

Ramon, Vidal, Julian Uwe Gabriel, Wagner, Caroline, Braeuning, Cornelius, Fischer, Ralph, Patrick, Lukas, Tombor, Marion, Muhly-Reinholz, David, John, Magdalena, Kliem, Thomas, Conrad, Nuno, Guimarães-Camboa, Richard, Harvey, Stefanie, Dimmeler, and Sascha, Sauer

Subjects
Male, Aging, Mice, Myocardium, Animals, Heart, Fibroblasts, Transcriptome, Vascular Calcification, Serpins, Research Article
Abstract

Aging is a major risk factor for cardiovascular disease. Although the impact of aging has been extensively studied, little is known regarding the aging processes in cells of the heart. Here we analyzed the transcriptomes of hearts of 12-week-old and 18-month-old mice by single-nucleus RNA-sequencing. Among all cell types, aged fibroblasts showed most significant differential gene expression, increased RNA dynamics, and network entropy. Aged fibroblasts exhibited significantly changed expression patterns of inflammatory, extracellular matrix organization angiogenesis, and osteogenic genes. Functional analyses indicated deterioration of paracrine signatures between fibroblasts and endothelial cells in old hearts. Aged heart-derived fibroblasts had impaired endothelial cell angiogenesis and autophagy and augmented proinflammatory response. In particular, expression of Serpine1 and Serpine2 were significantly increased and secreted by old fibroblasts to exert antiangiogenic effects on endothelial cells, an effect that could be significantly prevented by using neutralizing antibodies. Moreover, we found an enlarged subpopulation of aged fibroblasts expressing osteoblast genes in the epicardial layer associated with increased calcification. Taken together this study provides system-wide insights and identifies molecular changes of aging cardiac fibroblasts, which may contribute to declined heart function.

Published
2019

9. RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer

Author

Daniel Branstetter, Manolo D’Arcangelo, Linnea La Fleur, Luigi Tortola, Shane J. F. Cronin, Josef M. Penninger, Verena Sigl, Michael Bergqvist, Roberto Nitsch, Lukas Kenner, Helmut Popper, Shuan Rao, Karolina Edlund, Stephan Handschuh, John M. Rossi, Simon Ekman, Reiner A. Wimmer, Alexander Jais, Astrid Hagelkruys, Ivona Kozieradzki, Thomas Lendl, Johan Botling, Maria Novatchkova, Jude Canon, Michael Orthofer, Gabriel Wagner, William C. Dougall, Fred R. Hirsch, Iris Uribesalgo, Hiroshi Takayanagi, and Patrick Micke

Subjects
Male, 0301 basic medicine, Lung Neoplasms, Cell Respiration, Respiratory Mucosa, Biology, Mitochondrion, RANK, Energy homeostasis, Proto-Oncogene Proteins p21(ras), Mice, 03 medical and health sciences, Genetics, medicine, Animals, Homeostasis, Humans, Gonadal Steroid Hormones, Receptor, Lung cancer, Lung, energy homeostasis, Cells, Cultured, Cancer och onkologi, Receptor Activator of Nuclear Factor-kappa B, Clinical Laboratory Medicine, respiratory system, medicine.disease, Mitochondria, respiratory tract diseases, lung cancer, Klinisk laboratoriemedicin, 030104 developmental biology, medicine.anatomical_structure, Denosumab, Alveolar Epithelial Cells, Cancer and Oncology, Immunology, Cancer cell, Neoplastic Stem Cells, Cancer research, Female, lung cancer stem-like cells, Energy Metabolism, Research Paper, Developmental Biology, medicine.drug
Abstract

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRasG12D in mouse lung epithelial cells markedly impairs the progression of KRasG12D-driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRasG12D-driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer.

Published
2017

10. Trapped in a net: network analysis for network governance

Author

Karin Grasenick, Gabriel Wagner, and Kristina Zumbusch

Subjects
Automated data, Politics, Knowledge management, business.industry, Corporate governance, Network governance, Strategic management, Business, Library and Information Sciences, Social network analysis, Computer Science Applications, Network analysis, Strategic intelligence
Abstract

PurposeEspecially at the regional level co‐operation is seen as a prerequisite for innovation and competitiveness. Hence, political interest in fostering knowledge intensive networks is high. New forms of governance and additional strategic intelligence for decision makers are requested. Thus potential of the social network analysis (SNA) is discussed as methodology providing the information needed for strategic management of innovation networks. The aim of this paper is to assess the impact as a regional governance tool.Design/methodology/approachFirst, benefits and risks of innovation networks are discussed based on literature review. Second, the potentials of the SNA for their systematic monitoring are examined. Herewith specific attention was paid to the manageability and reduction of complexity to demonstrate SNA applicability for network governance. Analysis was based on automated data retrieval of electronic documents available, e.g. at governmental institutions, research databases, and the internet. Results are exemplified by studying knowledge intensive networks in Styria.FindingsThe applied set of IT based tools and visualisation of regional co‐operations based on SNA provides a comprehensive view of the interdependencies and the embeddedness of different institutions as well as actors of the region. Based on this visualisation conclusions are drawn concerning network management by analysing specific attributes of interest, concerning partners, cooperative behaviour, balance of power, openness and embeddedness of the network.Originality/valueNetwork benefits success may not be achieved automatically. Strategic management is crucial for success. The paper demonstrates how social network analysis may be applied on automatic retrieved data on involved organisations and key players to strengthening the strategic intelligence of (regional) decision makers and help them meet the governance challenges of the network economy.

Published
2008

11. IMPLANTAÇÃO DE PLANO DE INCENTIVO ÀS VENDAS EM UMA REDE DE DROGARIAS.

Author

Alexandre Gabriel, Wagner, Kawamoto Júnior, Luiz Teruo, Ruggero, Niube, Seige Ianaguivara, Eduardo, and Marcelo Sanchez, Wagner

Subjects
LABOR incentives, GENERIC drugs, DRUGSTORES, CONTROL groups, TICKETS
Abstract

Copyright of Journal of Management Analysis / Revista Gestão em Análise is the property of Revista Gestao em Analise and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2019
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12. TITITI, DISSE-ME-DISSE E BAFAFÁ - A presença das empresas nas colunas de variedades dos jornais de Manaus

Author

Gabriel Wagner de França Mar and Celia Maria da Silva Carvalho

Subjects
COMUNICAÇÃO: RELAÇÕES PÚBLICAS E PROPAGANDA [CIÊNCIAS SOCIAIS APLICADAS], Coluna social, Comunicação empresarial
Abstract

Made available in DSpace on 2016-09-23T15:13:04Z (GMT). No. of bitstreams: 1 Colunas_Sociais_[Relatorio_Final].pdf: 18514408 bytes, checksum: 0bc7ad3a2f3d92b1c94f3e09f37cf136 (MD5) Previous issue date: 2011-07-01 FAPEAM As assessorias e os profissionais de comunicação tendem a buscar, continuamente, por espaços para divulgar matérias de interesse corporativo ou institucional, que sejam significativas ao olhar público, buscando o reconhecimento público direto e consecutivamente, o fortalecimento do seu conceito e de sua imagem na sociedade. As colunas de variedade da metrópole manauara têm aumentado seu espaço para a divulgação das empresas e organizações, abrindo espaço para mais uma ramificação da atuação da Comunição Empresarial.

Published
2011

13. Evaluation of Government Funding in RTDI from a Systems Perspective in Austria. Synthesis Report

Author

Ulf Glöckner, Karl Aiginger, Gabriele Gerhardter, Jürgen Streicher, Michael Astor, Michael Peneder, Simon Pohn-Weidinger, Rahel Falk, Daniel Riesenberg, Sascha Ruhland, Susanne Sieber, Iris Fischl, Andreas Reinstaller, Jürgen Janger, Georg Klose, Austria Wifo, Sabine Mayer, Markus Gruber, Stephan Heinrich, Gabriel Wagner, Sonja Sheikh, and Michael Böheim

Subjects
Competition (economics), Government, Intervention (law), Promotion (rank), Excellence, media_common.quotation_subject, Business, Education policy, Market share, Public administration, Autonomy, media_common
Abstract

In the spring of 2008, WIFO, KMU Forschung Austria, Prognos AG in Germany and convelop were jointly commissioned by the Austrian Federal Ministry for Transport, Innovation and Technology and the Austrian Federal Ministry of Economy, Family and Youth to perform a systems evaluation of the country's research promotion and funding activities. Based on their findings, six recommendations were developed for a change in Austrian RTDI policy as outlined below: 1. to move from a narrow to a broader approach in RTDI policy (links to education policy, consideration of the framework for innovation such as competition, international perspectives and mobility); 2. to move from an imitation to a frontrunner strategy (striving for excellence and market leadership in niche and high-quality segments, increasing market shares in advanced sectors and technology fields, and operating in segments of relevance for society); 3. to move from a fragmented approach to public intervention to a more coordinated and consistent approach(explicit economic goals, internal and external challenges and reasoning for public intervention); 4. to move from a multiplicity of narrowly defined funding programmes to a flexible, dynamic policy that uses a broader definition of its tasks and priorities (key technology and research segments as priority-action fields, adequate financing of clusters and centres of excellence); 5. to move from an unclear to a precisely defined allocation of responsibilities between ministries and other players in the field (high-ranking steering group at government level, monitoring by a Science, Research and Innovation Council); 6. to move from red-tape-bound to a modern management of public intervention (institutional separation between ministries formulating policies and agencies executing them, e.g., by "progressive autonomy").

Published
2009

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