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Simon Schimmack European Pancreas Center, Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany

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Yongchao Yang European Pancreas Center, Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
Department of Burns and Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, China

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Klaus Felix European Pancreas Center, Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany

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Markus Herbst European Pancreas Center, Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany

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Yixiong Li Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China

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Miriam Schenk European Pancreas Center, Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany

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Frank Bergmann Institute of Pathology, Heidelberg University, Heidelberg, Germany

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Thilo Hackert European Pancreas Center, Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany

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Oliver Strobel European Pancreas Center, Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany

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of primary antibodies. ELISA and PETIA The determination of CRP and IL-6 levels in cell extracts and culture supernatants was performed using human C-Reactive-Protein ELISA Kit (Abcam) and human interleukin-6 ELISA Kit (Abcam) according to the

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T S Nilsen Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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L Thorsen Department of Oncology, Oslo University Hospital, Oslo, Norway

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C Kirkegaard Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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I Ugelstad Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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S D Fosså Department of Oncology, Oslo University Hospital, Oslo, Norway

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T Raastad Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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performed using a double-antibody sandwich ELISA developed within our laboratory. Each sub cellular fraction was analysed separately and later combined to give the total cellular amount. A monoclonal capture antibody against HSP27 (25ng per well; mouse anti

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Nadia Sabbah Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, France
Hôpital de Cayenne, Service d’Endocrinologie et des Maladies Métaboliques, Cayenne, Guyane Française

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Peter Wolf Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, France
Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

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Céline Piedvache Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Unité de Recherche Clinique, Le Kremlin-Bicêtre, France

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Séverine Trabado Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Le Kremlin-Bicêtre, France

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Tristan Verdelet Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, France

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Catherine Cornu Centre d’Investigation Clinique, INSERM CIC1407/UMR5558, Hospices Civils de Lyon, Bron, France

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Jean-Claude Souberbielle Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Service d’Explorations Fonctionnelles, Paris, France

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Philippe Chanson Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, France

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standard, IGF1 RIACT, Mediagnost ELISA, and Mediagnost RIA) are provided in our previous publication ( 3 , 6 ). The main characteristics of the two new assays and the mathematical models used to determine the normative data, where relevant as provided by

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Irvin M Modlin Wren Laboratories, Yale University School of Medicine, 35 NE Industrial Road, Branford, Connecticut, USA

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Harry Aslanian Wren Laboratories, Yale University School of Medicine, 35 NE Industrial Road, Branford, Connecticut, USA

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Lisa Bodei Wren Laboratories, Yale University School of Medicine, 35 NE Industrial Road, Branford, Connecticut, USA
Wren Laboratories, Yale University School of Medicine, 35 NE Industrial Road, Branford, Connecticut, USA

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Ignat Drozdov Wren Laboratories, Yale University School of Medicine, 35 NE Industrial Road, Branford, Connecticut, USA

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Mark Kidd Wren Laboratories, Yale University School of Medicine, 35 NE Industrial Road, Branford, Connecticut, USA

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ELISA using the DAKO Kit as described previously (22, 23, 32) . Study groups The clinical characteristics and details of the cases are included in Tables 1 and 2 . These included Group 1: prospectively collected NETs ( n =125) and Group 2

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Shenglong Le Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland

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Leiting Xu Medical School, Ningbo University, Ningbo, China

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Moritz Schumann Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, Cologne, Germany
The Key Laboratory of Systems Biomedicine, Ministry of Education, and Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China

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Na Wu Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland

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Timo Törmäkangas Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland

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Markku Alén Department of Medical Rehabilitation, Oulu University Hospital, Oulu, Finland

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Sulin Cheng Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
The Key Laboratory of Systems Biomedicine, Ministry of Education, and Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China

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Petri Wiklund Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
Department of Epidemiology and Biostatistics, Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland

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centrifugation and stored immediately at −80°C until analysis. The samples from different time points were analyzed by one technician using the same kits and instrument. Estradiol (E2), testosterone and SHBG were determined by ELISA (NovaTec Immunodiagnostica

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Ningning Gong Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, China
Department of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, China

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Cuixia Gao Department of Ultrasonic Diagnosis, Gansu Provincial Hospital, Lanzhou, China

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Xuedi Chen Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, China

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Yu Wang Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, China

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Limin Tian Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, China

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-α and ET-1 concentrations were detected by ELISA kits (Enzyme-linked Biotechnology Co., Ltd., Shanghai, China). Real-time PCR Total RNA was extracted using TRIzol (Invitrogen). Gene expression was detected by RT-PCR, 800 ng RNA samples were

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Djeda Belharazem Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Matthias Kirchner Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany
Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Franziska Geissler Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Peter Bugert Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Martin Spahn Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Burkhard Kneitz Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Hubertus Riedmiller Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Christian Sauer Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Stefan Küffer Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Lutz Trojan Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Christian Bolenz Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Maurice Stephan Michel Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Alexander Marx Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Philipp Ströbel Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany
Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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the peqGold Blood RNA Kit (PeqLab, Erlangen, Germany) according to the manufacturer's instructions. ELISA ELISA assays to detect serum IGF2 and IGFBP3 were purchased from Diagnostic System Laboratories (Webster, TX, USA) and performed according to the

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Chenghao Piao Department of Radiology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Xiaojie Wang Department of Human Anatomy, Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Shiqiao Peng Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of China

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Xinyu Guo Department of Obstetrics, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Hui Zhao Department of Laboratory Medicine, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Li He Department of Gastroenterology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Yan Zeng Department of Obstetrics, The Second Affiliated Hospital of Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Fan Zhang Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, People’s Republic of China

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Kewen Zhu Department of Human Anatomy, Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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Yiwei Wang Department of Human Anatomy, Shenyang Medical College, Shenyang City, Liaoning Province, People’s Republic of China

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cord blood IL-34 concentrations Serum and cord blood IL-34 levels were analysed by ELISA (R&D Systems). In general, plates coated with IL-34 antibody were cultured with five-fold of thinned serum at room temperature for 2 h. The plates were washed and

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P G Murray Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK
Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK

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D Hanson Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK

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T Coulson Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK

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A Stevens Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK

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A Whatmore Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK

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R L Poole Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK

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D J Mackay Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK

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G C M Black Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK
Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK

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P E Clayton Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK
Centre for Paediatrics and Child Health, Faculty of Medicine, Centre for Genetic Medicine, 5th Floor Research, Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK

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cells per field were examined for each cell line and the experiment was repeated on three occasions. A Leica CTR 5000 microscope was used to visualise the cells incorporating EdU. Cleaved caspase-3 ELISA Cleaved caspase-3 was measured with the PathScan

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A J Varewijck Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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A J van der Lely Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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S J C M M Neggers Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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S W J Lamberts Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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L J Hofland Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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J A M J L Janssen Erasmus MC, Department of Internal Medicine, Division of Endocrinology, 's-Gravendijkwal 230, Room D-443, 3015 CE Rotterdam, The Netherlands

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Angeles, CA, USA). Serum IGFBP1 was measured by the ELISA (intra-assay CV value was 7.4% and inter-assay CV value was 6.8%) (Mediagnost GmBH, Reutlingen, Germany). Serum glucose was determined with a standard laboratory method. S-Klotho was determined

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