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Keiko Ohkuwa Department of Surgery, Ito Hospital, Tokyo, Japan

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Kiminori Sugino Department of Surgery, Ito Hospital, Tokyo, Japan

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Mitsuji Nagahama Department of Surgery, Ito Hospital, Tokyo, Japan

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Wataru Kitagawa Department of Surgery, Ito Hospital, Tokyo, Japan

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Kenichi Matsuzu Department of Surgery, Ito Hospital, Tokyo, Japan

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Akifumi Suzuki Department of Surgery, Ito Hospital, Tokyo, Japan

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Chisato Tomoda Department of Surgery, Ito Hospital, Tokyo, Japan

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Kiyomi Hames Department of Surgery, Ito Hospital, Tokyo, Japan

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Junko Akaishi Department of Surgery, Ito Hospital, Tokyo, Japan

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Chie Masaki Department of Surgery, Ito Hospital, Tokyo, Japan

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Koichi Ito Department of Surgery, Ito Hospital, Tokyo, Japan

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infiltration and cytokines that induce angiogenesis. Moreover, lymphocytes control the host’s immune function, and lymphocyte depletion impairs the host’s antitumor immunity, leading to worsened prognosis ( 28 , 29 ). Hence, NLR is regarded to reflect the

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Chun-feng Lu Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Wang-shu Liu Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Xiao-qin Ge Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Feng Xu Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Jian-bin Su Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Xue-qin Wang Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Yan Wang Department of Geriatrics, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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, environmental factors, and immune system dysfunction are all implicated in GD pathogenesis, among which immune system dysfunction plays the most important role ( 2 ). As an autoimmune disease, relapsing cases of GD are common, and remission time is uncertain

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Mírian Romitti Thyroid Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

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Vitor C Fabris Gynecological Endocrinology Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre, and Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

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Patricia K Ziegelmann Postgraduate Program in Epidemiology and Department of Statistics, Institute of Mathematics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

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Ana Luiza Maia Thyroid Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

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Poli Mara Spritzer Gynecological Endocrinology Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre, and Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

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studies describing similar prevalence of antiovarian autoantibodies in women with PCOS and controls ( 19 ), leading to the proposal of systemic immune activation by nonorgan-specific autoantibodies in PCOS ( 20 ). This could explain the recurrent

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R A M Quax Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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J A M van Laar Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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R van Heerebeek Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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K Greiner Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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E Ben-Chetrit Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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M Stanford Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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G R Wallace Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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F Fortune Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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M Ghabra Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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M Soylu Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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J M W Hazes Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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S W J Lamberts Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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J H Kappen Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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P M van Hagen Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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J W Koper Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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R A Feelders Departments of Internal Medicine, Immunology, St John's Hospital, Department of Medicine, Department of Ophthalmology, Academic Unit of Ophthalmology, Department of Oral Medicine, University Hospital, Department of Ophthalmology, Department of Rheumatology, Erasmus MC, University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

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) . Interestingly, BD also displays some features distinctive of autoimmune processes. First, cellular immunity is disturbed in BD as exemplified by autoreactive T cells-targeting heat shock protein 60 (8) . For many autoimmune disorders, autoreactive T cells are a

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Fei Wu Department of Nuclear Medicine, Yancheng City No. 1 People’s Hospital, Yancheng, China
Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Chaoming Mao Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Xiao Mou Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Chengcheng Xu Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Tingting Zheng Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Ling Bu Department of Clinical Medicine, Jiangsu Health Vocational College, Nanjing, China

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Xuan Luo Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Qingyan Lu Department of Laboratory Medicine, Xuzhou Central Hospital, Xuzhou, China

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Xuefeng Wang Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China

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Introduction Hashimoto’s thyroiditis (HT) is a very common organ-specific autoimmune disease in which the Th1-mediated immune response contributes to the destruction of thyroid follicular cells (TFCs) ( 1 ). In recent years, many studies have

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Weiwei He School of Medicine, Xiamen University, Xiamen, China
Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, China

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Caoxin Huang Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, China

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Xiulin Shi Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, China
Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China

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Menghua Wu School of Medicine, Xiamen University, Xiamen, China
Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, China

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Han Li School of Medicine, Xiamen University, Xiamen, China
Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, China

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Qiuhong Liu School of Medicine, Xiamen University, Xiamen, China
Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, China

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Xiaofang Zhang Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, China

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Yan Zhao Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, China

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Xuejun Li Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China
Fujian Provincial Key Laboratory of Translational Medicine for Diabetes, Xiamen, China
Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China
Xiamen Clinical Medical Center for Endocrine and Metabolic Diseases, Xiamen Diabetes Prevention and Treatment Center, Xiamen, China

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assembly, and extracellular structural organization ( Fig. 8D ). Functional annotation analysis of MEgreenyellow and MEturquoise co-expression modules showed that their functions were both characterized by immune response-related pathways (Supplementary Fig

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Suvanjaa Sivalingam Department of Internal Medicine, Hospital of Southern Jutland, Sønderborg, Denmark

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Marianne Thvilum Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Thomas Heiberg Brix Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark

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Laszlo Hegedüs Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark
Department of Clinical Research, University of Southern Denmark, Odense M, Denmark

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Frans Brandt Department of Internal Medicine, Hospital of Southern Jutland, Sønderborg, Denmark
Department of Regional Health Research, University of Southern Denmark, Odense M, Denmark

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environmental triggers in a number of autoimmune diseases, including GD ( 11 , 12 ). Infections have been suggested to induce thyroid immunity by various mechanisms such as mimicking self-antigens, superantigen T-cell activation and inducing expression of human

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Thorben Hoffmann Department of Pediatrics, and Adolescent Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany

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Yousef Ashraf Tawfik Morcos Department of Pediatrics, and Adolescent Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

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Ruth Janoschek Department of Pediatrics, and Adolescent Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany

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Eva-Maria Turnwald Department of Pediatrics, and Adolescent Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany

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Antje Gerken Department of Pediatrics, and Adolescent Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

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Annette Müller Center for Pediatric Pathology at the University Hospital Cologne, Cologne, Germany

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Gerhard Sengle Department of Pediatrics, and Adolescent Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany
Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
Cologne Center for Musculoskeletal Biomechanics (CCMB), Cologne, Germany

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Jörg Dötsch Department of Pediatrics, and Adolescent Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany

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Sarah Appel Department of Pediatrics, and Adolescent Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany

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Eva Hucklenbruch-Rother Department of Pediatrics, and Adolescent Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany

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epithelium of the amnion displayed immunoreactivity ( Fig. 4B Amnion; black arrow). Additionally, immune cells all over the placenta displayed marked asprosin immunoreactivity ( Fig. 4B Chorion, Amnion, Decidua; white arrows). In the maternal part of the

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Liselot Koelman Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
Institute of Nutritional Science, University of Potsdam, Potsdam, Germany

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Robin Reichmann Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany

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Claudia Börnhorst Department of Biometry and Data Management, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany

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Matthias B Schulze Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany
Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
German Center for Diabetes Research (DZD), Neuherberg, Germany

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Cornelia Weikert Department of Food Safety, German Federal Institute for Risk Assessment, Berlin, Germany
Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin, Germany

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Ronald Biemann Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany

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Berend Isermann Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany

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Andreas Fritsche Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany

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Krasimira Aleksandrova Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany
Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany

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chemoattractant activity on various immune cells, including macrophages, dendritic cells, and natural killer cells with key roles in both innate and adaptive immunity ( 2 ). It was further rediscovered as an adipokine that is expressed in the adipocytes and was

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Marra Jai Aghajani Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia
School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia

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Tara Laurine Roberts Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia
School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
South West Sydney Clinical School, UNSW Sydney, Sydney, Australia

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Tao Yang School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
Saint Vincent’s Clinical School, UNSW Sydney, Sydney, Australia
SydPath, Saint Vincent’s Hospital, Sydney, Australia

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Charles Eugenio McCafferty Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia
School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia

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Nicole J Caixeiro Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia
School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
Centre for Oncology Education and Research Translation (CONCERT), Liverpool, New South Wales, Australia

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Paul DeSouza Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia
School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
South West Sydney Clinical School, UNSW Sydney, Sydney, Australia

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Navin Niles Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia
School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia
Department of Head & Neck Surgery, Liverpool Hospital, Liverpool, New South Wales, Australia
Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia

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the capabilities of standard clinicopathological staging, influence treatment direction and optimise patient benefit from novel anti-tumour agents is vital. Programmed cell death 1 (PD-1) is an immune checkpoint receptor inducibly expressed on

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