{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T08:46:09Z","timestamp":1788597969077,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"Research Grants Council of the University Grants Committee of Hong Kong","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"the National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"National Institutes of Health, United States of America","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"National Institutes of Health, United States of America","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"National Institutes of Health, United States of America","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"National Institutes of Health, United States of America","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"National Institutes of Health, United States of America","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"National Institutes of Health, United States of America","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"National Institutes of Health, United States of America","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"National Institutes of Health, United States of America","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"National Institutes of Health, United States of America","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"National Institutes of Health, United States of America","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"National Institutes of Health, United States of America","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"National Institutes of Health, United States of America","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"National Institutes of Health, United States of America","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"National Institutes of Health, United States of America","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"National Institutes of Health, United States of America","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"Research Grants Council of Hong Kong","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"Research Grants Council of Hong Kong","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"Research Grants Council of Hong Kong","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"Research Grants Council of Hong Kong","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"Research Grants Council of Hong Kong","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"Research Grants Council of Hong Kong","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"Research Grants Council of Hong Kong","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"Research Grants Council of Hong Kong","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"Research Grants Council of Hong Kong","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"Research Grants Council of Hong Kong","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"Research Grants Council of Hong Kong","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"Research Grants Council of Hong Kong","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"Research Grants Council of Hong Kong","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"Research Grants Council of Hong Kong","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"Research Grants Council of Hong Kong","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"the Health and Medical Research Fund","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"the Health and Medical Research Fund","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"the Health and Medical Research Fund","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"the Health and Medical Research Fund","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"the Health and Medical Research Fund","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"the Health and Medical Research Fund","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"the Health and Medical Research Fund","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"the Health and Medical Research Fund","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"the Health and Medical Research Fund","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"the Health and Medical Research Fund","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"the Health and Medical Research Fund","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"the Health and Medical Research Fund","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"the Health and Medical Research Fund","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"the Health and Medical Research Fund","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"the Health and Medical Research Fund","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"the United States National Academy of Medicine","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"the United States National Academy of Medicine","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"the United States National Academy of Medicine","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"the United States National Academy of Medicine","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"the United States National Academy of Medicine","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"the United States National Academy of Medicine","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"the United States National Academy of Medicine","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"the United States National Academy of Medicine","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"the United States National Academy of Medicine","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"the United States National Academy of Medicine","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"the United States National Academy of Medicine","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"the United States National Academy of Medicine","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"the United States National Academy of Medicine","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"the United States National Academy of Medicine","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"the United States National Academy of Medicine","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"the Food and Health Bureau of the Hong Kong SAR Government","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"European Union\u2019s Horizon 2020 programme EDCMET","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"Academy of Finland","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"Academy of Finland","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"Academy of Finland","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"Academy of Finland","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"Academy of Finland","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"Academy of Finland","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"Academy of Finland","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"Academy of Finland","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"Academy of Finland","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"Academy of Finland","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"Academy of Finland","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"Academy of Finland","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"Academy of Finland","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"Academy of Finland","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"Academy of Finland","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"Medical Research Council (MRC) UK","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"Medical Research Council (MRC) UK","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"Medical Research Council (MRC) UK","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"Medical Research Council (MRC) UK","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"Medical Research Council (MRC) UK","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"Medical Research Council (MRC) UK","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"Medical Research Council (MRC) UK","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"Medical Research Council (MRC) UK","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"Medical Research Council (MRC) UK","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"Medical Research Council (MRC) UK","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"Medical Research Council (MRC) UK","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"Medical Research Council (MRC) UK","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"Medical Research Council (MRC) UK","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"Medical Research Council (MRC) UK","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"Medical Research Council (MRC) UK","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"Medical Research Council Biotechnology and Biological Sciences Research Council PREcisE","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"University of Oulu Grant","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"University of Oulu Grant","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"University of Oulu Grant","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"University of Oulu Grant","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"University of Oulu Grant","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"University of Oulu Grant","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"University of Oulu Grant","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"University of Oulu Grant","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"University of Oulu Grant","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"University of Oulu Grant","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"University of Oulu Grant","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"University of Oulu Grant","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"University of Oulu Grant","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"University of Oulu Grant","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"University of Oulu Grant","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"Oulu University Hospital","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"Oulu University Hospital","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"Oulu University Hospital","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"Oulu University Hospital","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"Oulu University Hospital","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"Oulu University Hospital","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"Oulu University Hospital","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"Oulu University Hospital","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"Oulu University Hospital","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"Oulu University Hospital","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"Oulu University Hospital","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"Oulu University Hospital","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"Oulu University Hospital","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"Oulu University Hospital","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"Oulu University Hospital","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"Ministry of Health and Social Affairs","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"Ministry of Health and Social Affairs","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"Ministry of Health and Social Affairs","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"Ministry of Health and Social Affairs","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"Ministry of Health and Social Affairs","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"Ministry of Health and Social Affairs","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"Ministry of Health and Social Affairs","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"Ministry of Health and Social Affairs","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"Ministry of Health and Social Affairs","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"Ministry of Health and Social Affairs","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"Ministry of Health and Social Affairs","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"Ministry of Health and Social Affairs","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"Ministry of Health and Social Affairs","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"Ministry of Health and Social Affairs","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"Ministry of Health and Social Affairs","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"National Institute for Health and Welfare, Helsinki","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"Regional Institute of Occupational Health, Oulu, Finland","award":["54231"],"award-info":[{"award-number":["54231"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["825762"],"award-info":[{"award-number":["825762"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["24300796"],"award-info":[{"award-number":["24300796"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["24302031"],"award-info":[{"award-number":["24302031"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["285547"],"award-info":[{"award-number":["285547"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["G0601653"],"award-info":[{"award-number":["G0601653"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["JPI HDHL\/EU-H2020"],"award-info":[{"award-number":["JPI HDHL\/EU-H2020"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["65354"],"award-info":[{"award-number":["65354"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["2\/97"],"award-info":[{"award-number":["2\/97"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["8\/97"],"award-info":[{"award-number":["8\/97"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["23\/251\/97"],"award-info":[{"award-number":["23\/251\/97"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["160\/97"],"award-info":[{"award-number":["160\/97"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["190\/97"],"award-info":[{"award-number":["190\/97"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["54121"],"award-info":[{"award-number":["54121"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["50621"],"award-info":[{"award-number":["50621"]}]},{"name":"Jenny and Antti Wihuri Foundation","award":["54231"],"award-info":[{"award-number":["54231"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Branched-chain amino acids are critical metabolic intermediates that can indicate increased risk of cardiometabolic disease when levels are elevated or, alternatively, suggest sufficient mitochondrial energy metabolism and reserve in old age. The interpretation of BCAA levels can be context-dependent, and it remains unclear whether abnormal levels can inform prognosis. This prospective longitudinal study aimed to determine the interrelationship between mortality hazard and fasting serum BCAA levels among older men and women aged \u226565 years with or without hypertension and diabetes mellitus. At baseline (0Y), fasting serum BCAA concentration in 2997 community-living older men and women were measured. Approximately 14 years later (14Y), 860 study participants returned for repeat measurements. Deaths were analysed and classified into cardiovascular and non-cardiovascular causes using International Classification of Diseases codes. Survival analysis and multivariable Cox regression were performed. During a median follow-up of 17Y, 971 (78.6%) non-cardiovascular and 263 (21.4%) cardiovascular deaths occurred among 1235 (41.2%) deceased (median age, 85.8 years [IQR 81.7\u201389.7]). From 0Y to 14Y, BCAA levels declined in both sexes, whereas serum creatinine concentration increased (both p &lt; 0.0001). In older adults without hypertension or diabetes mellitus, the relationship between mortality hazard and BCAA level was linear and above-median BCAA levels were associated with improved survival, whereas in the presence of cardiometabolic disease the relationship was U-shaped. Overall, adjusted Cox regression determined that each 10% increment in BCAA concentration was associated with a 7% (p = 0.0002) and 16% (p = 0.0057) reduction in mortality hazard estimated at 0Y and 14Y, respectively. Our findings suggested that abnormally high or low (dyshomeostatic) BCAA levels among older adults with hypertension and\/or diabetes mellitus were associated with increased mortality, whereas in those with neither disease, increased BCAA levels was associated with improved survival, particularly in the oldest-old.<\/jats:p>","DOI":"10.3390\/biom13081252","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T09:57:02Z","timestamp":1692179822000},"page":"1252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Divergent Survival Outcomes Associated with Elevated Branched-Chain Amino Acid Levels among Older Adults with or without Hypertension and Diabetes: A Validated, Prospective, Longitudinal Follow-Up Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8209-9467","authenticated-orcid":false,"given":"Erik","family":"Fung","sequence":"first","affiliation":[{"name":"Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Gerald Choa Cardiac Research Centre and Laboratory for Heart Failure + Circulation Research, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, Hong Kong SAR, China"},{"name":"Neural, Vascular, Metabolic Biology Programme, and Ministry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Division of Cardiology, Department of Medicine, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5821-7953","authenticated-orcid":false,"given":"Kwan Hung","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Gerald Choa Cardiac Research Centre and Laboratory for Heart Failure + Circulation Research, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9253-3549","authenticated-orcid":false,"given":"Timothy","family":"Kwok","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"CUHK Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leong-Ting","family":"Lui","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Gerald Choa Cardiac Research Centre and Laboratory for Heart Failure + Circulation Research, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4145-540X","authenticated-orcid":false,"given":"Saranya","family":"Palaniswamy","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK"},{"name":"Center for Life Course Health Research, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9278-230X","authenticated-orcid":false,"given":"Queenie","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee-Ling","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia"},{"name":"Asia Diabetes Foundation, Shatin, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petri","family":"Wiklund","sequence":"additional","affiliation":[{"name":"Faculty of Sport and Health Sciences, University of Jyv\u00e4skyl\u00e4, 40014 Jyv\u00e4skyl\u00e4, Finland"},{"name":"The Exercise Translational Medicine Center and Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4423-8331","authenticated-orcid":false,"given":"Suyi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Gerald Choa Cardiac Research Centre and Laboratory for Heart Failure + Circulation Research, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany K.","family":"Elshorbagy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK"},{"name":"Department of Physiology, Faculty of Medicine, University of Alexandria, Alexandria 21526, Egypt"},{"name":"Department of Public Health and Primary Healthcare, School of Public Health, Imperial College London, London W2 1PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Refsum","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK"},{"name":"Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3382-9096","authenticated-orcid":false,"given":"Jason C. S.","family":"Leung","sequence":"additional","affiliation":[{"name":"CUHK Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8927-6764","authenticated-orcid":false,"given":"Alice P. S.","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Asia Diabetes Foundation, Shatin, Hong Kong SAR, China"},{"name":"Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1325-1194","authenticated-orcid":false,"given":"Juliana C. N.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Asia Diabetes Foundation, Shatin, Hong Kong SAR, China"},{"name":"Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2149-0630","authenticated-orcid":false,"given":"Marjo-Riitta","family":"J\u00e4rvelin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK"},{"name":"Center for Life Course Health Research, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland"},{"name":"Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UK"},{"name":"Unit of Primary Health Care, Oulu University Hospital, 90014 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7593-3081","authenticated-orcid":false,"given":"Jean","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"CUHK Jockey Club Institute of Ageing, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,16]]},"reference":[{"key":"ref_1","unstructured":"(2023, April 29). United Nations. Available online: https:\/\/www.un.org\/en\/global-issues\/ageing."},{"key":"ref_2","unstructured":"GBD 2019 Diseases and Injuries Collaborators (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 396, 1204\u20131222. Erratum in Lancet 2020, 396, 1562."},{"key":"ref_3","first-page":"100483","article-title":"The rising burden of non-communicable diseases in the Americas and the impact of population aging: A secondary analysis of available data","volume":"21","author":"Hambleton","year":"2023","journal-title":"Lancet Reg. Health Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1161\/CIRCULATIONAHA.110.005645","article-title":"Trends in mortality from all causes and cardiovascular disease among hypertensive and nonhypertensive adults in the United States","volume":"123","author":"Ford","year":"2011","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1016\/S0140-6736(14)60685-1","article-title":"Blood pressure and incidence of twelve cardiovascular diseases: Lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people","volume":"383","author":"Rapsomaniki","year":"2014","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e535","DOI":"10.1161\/CIR.0000000000000450","article-title":"Contributory Risk and Management of Comorbidities of Hypertension, Obesity, Diabetes Mellitus, Hyperlipidemia, and Metabolic Syndrome in Chronic Heart Failure: A Scientific Statement From the American Heart Association","volume":"134","author":"Bozkurt","year":"2016","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2021","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_8","unstructured":"NCD Risk Factor Collaboration (NCD-RisC) (2021). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: A pooled analysis of 1201 population-representative studies with 104 million participants. Lancet, 398, 957\u2013980."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41569-022-00760-3","article-title":"Branched-chain amino acids in cardiovascular disease","volume":"20","author":"McGarrah","year":"2023","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nrendo.2014.171","article-title":"Branched-chain amino acids in metabolic signalling and insulin resistance","volume":"10","author":"Lynch","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1161\/HYPERTENSIONAHA.118.10919","article-title":"Branched-Chain Amino Acids as Critical Switches in Health and Disease","volume":"72","author":"Zhang","year":"2018","journal-title":"Hypertension"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1161\/HYPERTENSIONAHA.119.13735","article-title":"Concentration of Branched-Chain Amino Acids Is a Strong Risk Marker for Incident Hypertension","volume":"74","author":"Groothof","year":"2019","journal-title":"Hypertension"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1161\/CIRCULATIONAHA.115.020226","article-title":"Catabolic Defect of Branched-Chain Amino Acids Promotes Heart Failure","volume":"133","author":"Sun","year":"2016","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e3253","DOI":"10.1002\/dmrr.3253","article-title":"Circulating branched-chain amino acids and incident heart failure in type 2 diabetes: The Hong Kong Diabetes Register","volume":"36","author":"Lim","year":"2020","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.lfs.2018.08.011","article-title":"Increased branched-chain amino acid levels are associated with long-term adverse cardiovascular events in patients with STEMI and acute heart failure","volume":"209","author":"Du","year":"2018","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15809","DOI":"10.1038\/s41598-018-34245-6","article-title":"Relationships between circulating branched chain amino acid concentrations and risk of adverse cardiovascular events in patients with STEMI treated with PCI","volume":"8","author":"Du","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e002157","DOI":"10.1161\/CIRCGEN.118.002157","article-title":"Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women","volume":"11","author":"Tobias","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/s42255-019-0059-2","article-title":"Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control","volume":"1","author":"Cogger","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1177\/2047487318797395","article-title":"Diastolic left ventricular function in relation to circulating metabolic biomarkers in a population study","volume":"26","author":"Zhang","year":"2019","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.lfs.2015.06.021","article-title":"Branched-chain amino acids ameliorate heart failure with cardiac cachexia in rats","volume":"137","author":"Tanada","year":"2015","journal-title":"Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.cmet.2010.08.016","article-title":"Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice","volume":"12","author":"Ragni","year":"2010","journal-title":"Cell Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1161\/CIRCULATIONAHA.111.067827","article-title":"Metabolite profiling identifies pathways associated with metabolic risk in humans","volume":"125","author":"Cheng","year":"2012","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1093\/eurheartj\/ehs424","article-title":"A diabetes-predictive amino acid score and future cardiovascular disease","volume":"34","author":"Magnusson","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"88882","DOI":"10.18632\/oncotarget.21489","article-title":"Association of circulating branched-chain amino acids with cardiometabolic traits differs between adults and the oldest-old","volume":"8","author":"Sun","year":"2017","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e003330","DOI":"10.1161\/CIRCGEN.121.003330","article-title":"Association of Plasma Branched-Chain Amino Acid With Biomarkers of Inflammation and Lipid Metabolism in Women","volume":"14","author":"Hamaya","year":"2021","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1093\/gerona\/glz192","article-title":"Branched Chain Amino Acids, Cardiometabolic Risk Factors and Outcomes in Older Men: The Concord Health and Ageing in Men Project","volume":"75","author":"Ribeiro","year":"2020","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e919","DOI":"10.1016\/S2468-2667(21)00208-5","article-title":"Understanding longevity in Hong Kong: A comparative study with long-living, high-income countries","volume":"6","author":"Ni","year":"2021","journal-title":"Lancet Public Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s12603-009-0193-8","article-title":"Impact of childhood experience of famine on late life health","volume":"14","author":"Woo","year":"2010","journal-title":"J. Nutr. Health Aging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1093\/ije\/dym149","article-title":"Experience of famine and bone health in post-menopausal women","volume":"36","author":"Kin","year":"2007","journal-title":"Int. J. Epidemiol."},{"key":"ref_30","unstructured":"Centre for Health Protection (2023, May 06). Hypertension, Available online: https:\/\/www.chp.gov.hk\/en\/healthtopics\/content\/25\/35390.html."},{"key":"ref_31","unstructured":"World Health Organization (2020). HEARTS D: Diagnosis and Management of Type 2 Diabetes (HEARTS-D), World Health Organization. Available online: https:\/\/apps.who.int\/iris\/rest\/bitstreams\/1274478\/retrieve."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1093\/gerona\/62.7.738","article-title":"A comparison of two approaches to measuring frailty in elderly people","volume":"62","author":"Rockwood","year":"2007","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"115082","DOI":"10.1016\/j.bone.2019.115082","article-title":"Circulating amino acids are associated with bone mineral density decline and ten-year major osteoporotic fracture risk in older community-dwelling adults","volume":"129","author":"Su","year":"2019","journal-title":"Bone"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1161\/CIRCGENETICS.114.000216","article-title":"Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics","volume":"8","author":"Soininen","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4017","DOI":"10.1021\/acs.jproteome.8b00567","article-title":"Combining Mass Spectrometry and NMR Improves Metabolite Detection and Annotation","volume":"17","author":"Bhinderwala","year":"2018","journal-title":"J. Proteome Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41597-023-01949-y","article-title":"Quality control and removal of technical variation of NMR metabolic biomarker data in ~120,000 UK Biobank participants","volume":"10","author":"Ritchie","year":"2023","journal-title":"Sci. Data"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"831556","DOI":"10.3389\/fendo.2022.831556","article-title":"Hyperglycemia and Physical Impairment in Frail Hypertensive Older Adults","volume":"13","author":"Pansini","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12933-021-01442-z","article-title":"Correlation of physical and cognitive impairment in diabetic and hypertensive frail older adults","volume":"21","author":"Mone","year":"2022","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e724","DOI":"10.1016\/S2666-7568(21)00251-8","article-title":"Characterising frailty, metrics of continuous glucose monitoring, and mortality hazards in older adults with type 2 diabetes on insulin therapy (HARE): A prospective, observational cohort study","volume":"2","author":"Fung","year":"2021","journal-title":"Lancet Healthy Longev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.ahj.2012.02.005","article-title":"Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease","volume":"163","author":"Shah","year":"2012","journal-title":"Am. Heart J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"106459","DOI":"10.1016\/j.isci.2023.106459","article-title":"Association of branched-chain amino acids with mortality-the Ludwigshafen Risk and Cardiovascular Health (LURIC) study","volume":"26","author":"Moissl","year":"2023","journal-title":"iScience"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Reisinger, A.C., Posch, F., Hackl, G., Marsche, G., Sourij, H., Bourgeois, B., Eller, K., Madl, T., and Eller, P. (2021). Branched-Chain Amino Acids Can Predict Mortality in ICU Sepsis Patients. Nutrients, 13.","DOI":"10.3390\/nu13093106"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e003729","DOI":"10.1161\/CIRCGEN.122.003729","article-title":"Circulating Banched-Chain Amino Acids, Incident Cardiovascular Disease, and Mortality in the African American Study of Kidney Disease and Hypertension","volume":"16","author":"Luo","year":"2023","journal-title":"Circ Genom Precis Med"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1038\/s41467-022-31249-9","article-title":"A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes","volume":"13","author":"Vanweert","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1001\/jamacardio.2019.0295","article-title":"Burden of cardiovascular diseases in China, 1990\u20132016: Findings from the 2016 Global Burden of Disease Study","volume":"4","author":"Liu","year":"2019","journal-title":"JAMA Cardiol"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s12933-022-01551-3","article-title":"Landscape of cardiometabolic risk factors in Chinese population: A narrative review","volume":"21","author":"Li","year":"2022","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990\u20132019: Update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.1161\/CIR.0000000000001052","article-title":"Heart disease and stroke statistics\u20142022 update: A report from the American Heart Association","volume":"145","author":"Tsao","year":"2022","journal-title":"Circulation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6647","DOI":"10.1021\/pr100798r","article-title":"Metabolome-wide association study identifies multiple biomarkers that discriminate north and south Chinese populations at differing risks of cardiovascular disease: INTERMAP study","volume":"9","author":"Yap","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.atherosclerosis.2019.04.225","article-title":"Association between plasma essential amino acids and atherogenic lipid profile in a Chinese population: A cross-sectional study","volume":"286","author":"Wang","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.jacl.2019.09.002","article-title":"Association between dyslipidemia and plasma levels of branched-chain amino acids in the Japanese population without diabetes mellitus","volume":"13","author":"Fukushima","year":"2019","journal-title":"J. Clin. Lipidol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Gojda, J., and Cahova, M. (2021). Gut Microbiota as the Link between Elevated BCAA Serum Levels and Insulin Resistance. Biomolecules, 11.","DOI":"10.3390\/biom11101414"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/8\/1252\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:34:51Z","timestamp":1760128491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/8\/1252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,16]]},"references-count":53,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["biom13081252"],"URL":"https:\/\/doi.org\/10.3390\/biom13081252","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,16]]}}}