{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:41:52Z","timestamp":1787838112007,"version":"build-2784847793"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T00:00:00Z","timestamp":1484265600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T00:00:00Z","timestamp":1484265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Association between diabetes mellitus (diabetes) and risk of knee osteoarthritis (KOA) is confounded by high body mass index (BMI), a strong risk factor for both conditions. We evaluated the association between diabetes and incidence of total knee replacement (TKR) due to severe KOA in the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese men and women, aged 45\u201374 years at recruitment in 1993\u20131998, and re-interviewed in 1999\u20132004. Height, weight, lifestyle factors and history of diabetes were obtained through in-person interviews at recruitment and re-interview. Incident cases of TKR were identified via record linkage with nationwide hospital discharge database. Subjects with\/without prevalent diabetes had comparable BMI (24.0\u2009kg\/m<jats:sup>2<\/jats:sup> versus 23.0\u2009kg\/m<jats:sup>2<\/jats:sup>). After an average of 14-years, 1,973 subjects had TKR attributable to KOA. Compared to subjects without diabetes, hazard ratio (HR) of TKR for subjects with diabetes was 0.63 [95% confidence interval (CI), 0.52\u20130.75] after controlling for BMI and other risk factors. An inverse association was also observed between incident diabetes at re-interview and subsequent risk of TKR (HR\u2009=\u20090.74; 95% CI\u2009=\u20090.58\u20130.94). The inverse diabetes-TKR risk association was similar by gender and across three categories of BMI. Our study does not support diabetes as a risk factor of KOA.<\/jats:p>","DOI":"10.1038\/srep40671","type":"journal-article","created":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T10:12:15Z","timestamp":1484302335000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Diabetes mellitus and the risk of total knee replacement among Chinese in Singapore, the Singapore Chinese Health Study"],"prefix":"10.1038","volume":"7","author":[{"given":"Ying-Ying","family":"Leung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Carson","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Wei","family":"Ang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Min","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woon-Puay","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,13]]},"reference":[{"key":"BFsrep40671_CR1","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1016\/S0140-6736(12)61729-2","volume":"380","author":"T Vos","year":"2012","unstructured":"Vos, T. et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990\u20132010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2163\u20132196, doi: 10.1016\/S0140-6736(12)61729-2 (2012).","journal-title":"Lancet"},{"key":"BFsrep40671_CR2","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1136\/annrheumdis-2013-204763","volume":"73","author":"M Cross","year":"2014","unstructured":"Cross, M. et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 73, 1323\u20131330, doi: 10.1136\/annrheumdis-2013-204763 (2014).","journal-title":"Ann Rheum Dis"},{"key":"BFsrep40671_CR3","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.joca.2009.08.010","volume":"18","author":"M Blagojevic","year":"2010","unstructured":"Blagojevic, M., Jinks, C., Jeffery, A. & Jordan, K. P. Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage 18, 24\u201333, doi: 10.1016\/j.joca.2009.08.010 (2010).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep40671_CR4","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.jbspin.2011.05.015","volume":"79","author":"L Jiang","year":"2012","unstructured":"Jiang, L. et al. Body mass index and susceptibility to knee osteoarthritis: a systematic review and meta-analysis. Joint Bone Spine 79, 291\u2013297, doi: 10.1016\/j.jbspin.2011.05.015 (2012).","journal-title":"Joint Bone Spine"},{"key":"BFsrep40671_CR5","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.joca.2014.10.011","volume":"23","author":"YY Leung","year":"2015","unstructured":"Leung, Y. Y. et al. Association between body mass index and risk of total knee replacement, the Singapore Chinese Health Study. Osteoarthritis and cartilage\/OARS, Osteoarthritis Research Society 23, 41\u201347, doi: 10.1016\/j.joca.2014.10.011 (2015).","journal-title":"Osteoarthritis and cartilage\/OARS, Osteoarthritis Research Society"},{"key":"BFsrep40671_CR6","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1136\/ard.2008.089748","volume":"68","author":"LS Lohmander","year":"2009","unstructured":"Lohmander, L. S., Gerhardsson de Verdier, M., Rollof, J., Nilsson, P. M. & Engstrom, G. Incidence of severe knee and hip osteoarthritis in relation to different measures of body mass: a population-based prospective cohort study. Ann Rheum Dis 68, 490\u2013496, doi: 10.1136\/ard.2008.089748 (2009).","journal-title":"Ann Rheum Dis"},{"key":"BFsrep40671_CR7","doi-asserted-by":"publisher","first-page":"R31","DOI":"10.1186\/ar2636","volume":"11","author":"Y Wang","year":"2009","unstructured":"Wang, Y. et al. Relationship between body adiposity measures and risk of primary knee and hip replacement for osteoarthritis: a prospective cohort study. Arthritis Res Ther 11, R31, doi: 10.1186\/ar2636 (2009).","journal-title":"Arthritis Res Ther"},{"key":"BFsrep40671_CR8","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1136\/ard.2010.146399","volume":"70","author":"F Berenbaum","year":"2011","unstructured":"Berenbaum, F. Diabetes-induced osteoarthritis: from a new paradigm to a new phenotype. Ann Rheum Dis 70, 1354\u20131356, doi: 10.1136\/ard.2010.146399 (2011).","journal-title":"Ann Rheum Dis"},{"key":"BFsrep40671_CR9","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/1471-2458-9-88","volume":"9","author":"DP Guh","year":"2009","unstructured":"Guh, D. P. et al. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health 9, 88, doi: 10.1186\/1471-2458-9-88 (2009).","journal-title":"BMC Public Health"},{"key":"BFsrep40671_CR10","doi-asserted-by":"publisher","first-page":"e19930","DOI":"10.1371\/journal.pone.0019930","volume":"6","author":"P Boffetta","year":"2011","unstructured":"Boffetta, P. et al. Body mass index and diabetes in Asia: a cross-sectional pooled analysis of 900,000 individuals in the Asia cohort consortium. PLoS One 6, e19930, doi: 10.1371\/journal.pone.0019930 (2011).","journal-title":"PLoS One"},{"key":"BFsrep40671_CR11","first-page":"13","volume":"7","author":"H Waine","year":"1961","unstructured":"Waine, H., Nevinny, D., Rosenthal, J. & Joffe, I. B. Association of osteoarthritis and diabetes mellitus. Tufts Folia Med 7, 13\u201319 (1961).","journal-title":"Tufts Folia Med"},{"key":"BFsrep40671_CR12","doi-asserted-by":"publisher","first-page":"403","DOI":"10.2337\/dc12-0924","volume":"36","author":"G Schett","year":"2013","unstructured":"Schett, G. et al. Diabetes is an independent predictor for severe osteoarthritis: results from a longitudinal cohort study. Diabetes Care 36, 403\u2013409, doi: 10.2337\/dc12-0924 (2013).","journal-title":"Diabetes Care"},{"key":"BFsrep40671_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/RHU.0b013e31827cd578","volume":"19","author":"M Nieves-Plaza","year":"2013","unstructured":"Nieves-Plaza, M., Castro-Santana, L. E., Font, Y. M., Mayor, A. M. & Vila, L. M. Association of hand or knee osteoarthritis with diabetes mellitus in a population of Hispanics from Puerto Rico. J Clin Rheumatol 19, 1\u20136, doi: 10.1097\/RHU.0b013e31827cd578 (2013).","journal-title":"J Clin Rheumatol"},{"key":"BFsrep40671_CR14","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/j.joca.2015.03.031","volume":"23","author":"KB King","year":"2015","unstructured":"King, K. B. & Rosenthal, A. K. The adverse effects of diabetes on osteoarthritis: update on clinical evidence and molecular mechanisms. Osteoarthritis Cartilage 23, 841\u2013850, doi: 10.1016\/j.joca.2015.03.031 (2015).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep40671_CR15","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1111\/j.1476-5381.2012.01911.x","volume":"166","author":"AJ King","year":"2012","unstructured":"King, A. J. The use of animal models in diabetes research. Br J Pharmacol 166, 877\u2013894, doi: 10.1111\/j.1476-5381.2012.01911.x (2012).","journal-title":"Br J Pharmacol"},{"key":"BFsrep40671_CR16","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S0140-6736(03)15268-3","volume":"363","author":"WHOE Consultation","year":"2004","unstructured":"Consultation, W. H. O. E. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363, 157\u2013163, doi: 10.1016\/S0140-6736(03)15268-3 (2004).","journal-title":"Lancet"},{"key":"BFsrep40671_CR17","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1001\/jama.2009.726","volume":"301","author":"JC Chan","year":"2009","unstructured":"Chan, J. C. et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 301, 2129\u20132140, doi: 10.1001\/jama.2009.726 (2009).","journal-title":"JAMA"},{"key":"BFsrep40671_CR18","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1016\/j.joca.2012.06.006","volume":"20","author":"N Yoshimura","year":"2012","unstructured":"Yoshimura, N. et al. Accumulation of metabolic risk factors such as overweight, hypertension, dyslipidaemia, and impaired glucose tolerance raises the risk of occurrence and progression of knee osteoarthritis: a 3-year follow-up of the ROAD study. Osteoarthritis Cartilage 20, 1217\u20131226, doi: 10.1016\/j.joca.2012.06.006 (2012).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep40671_CR19","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1207\/S15327914nc392_5","volume":"39","author":"JH Hankin","year":"2001","unstructured":"Hankin, J. H. et al. Singapore Chinese Health Study: development, validation, and calibration of the quantitative food frequency questionnaire. Nutr Cancer 39, 187\u2013195, doi: 10.1207\/S15327914nc392_5 (2001).","journal-title":"Nutr Cancer"},{"key":"BFsrep40671_CR20","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1093\/ajcn\/88.4.979","volume":"88","author":"AO Odegaard","year":"2008","unstructured":"Odegaard, A. O. et al. Coffee, tea, and incident type 2 diabetes: the Singapore Chinese Health Study. Am J Clin Nutr 88, 979\u2013985 (2008).","journal-title":"Am J Clin Nutr"},{"key":"BFsrep40671_CR21","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1038\/sj.bjc.6605496","volume":"102","author":"WP Koh","year":"2010","unstructured":"Koh, W. P., Yuan, J. M., Wang, R., Lee, H. P. & Yu, M. C. Body mass index and smoking-related lung cancer risk in the Singapore Chinese Health Study. Br J Cancer 102, 610\u2013614, doi: 10.1038\/sj.bjc.6605496 (2010).","journal-title":"Br J Cancer"},{"key":"BFsrep40671_CR22","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.joca.2014.03.013","volume":"22","author":"YY Leung","year":"2014","unstructured":"Leung, Y. Y. et al. Cigarette smoking and risk of total knee replacement for severe osteoarthritis among Chinese in Singapore\u2013the Singapore Chinese health study. Osteoarthritis and cartilage\/OARS, Osteoarthritis Research Society 22, 764\u2013770, doi: 10.1016\/j.joca.2014.03.013 (2014).","journal-title":"Osteoarthritis and cartilage\/OARS, Osteoarthritis Research Society"},{"key":"BFsrep40671_CR23","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0883-5403(96)80159-8","volume":"11","author":"CA Mancuso","year":"1996","unstructured":"Mancuso, C. A., Ranawat, C. S., Esdaile, J. M., Johanson, N. A. & Charlson, M. E. Indications for total hip and total knee arthroplasties. Results of orthopaedic surveys. J Arthroplasty 11, 34\u201346 (1996).","journal-title":"J Arthroplasty"},{"key":"BFsrep40671_CR24","first-page":"251","volume":"8","author":"MA Cimmino","year":"1990","unstructured":"Cimmino, M. A. & Cutolo, M. Plasma glucose concentration in symptomatic osteoarthritis: a clinical and epidemiological survey. Clin Exp Rheumatol 8, 251\u2013257 (1990).","journal-title":"Clin Exp Rheumatol"},{"key":"BFsrep40671_CR25","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.joca.2012.02.644","volume":"20","author":"CA Karvonen-Gutierrez","year":"2012","unstructured":"Karvonen-Gutierrez, C. A., Sowers, M. R. & Heeringa, S. G. Sex dimorphism in the association of cardiometabolic characteristics and osteophytes-defined radiographic knee osteoarthritis among obese and non-obese adults: NHANES III. Osteoarthritis Cartilage 20, 614\u2013621, doi: 10.1016\/j.joca.2012.02.644 (2012).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep40671_CR26","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1002\/art.24739","volume":"61","author":"M Sowers","year":"2009","unstructured":"Sowers, M. et al. Knee osteoarthritis in obese women with cardiometabolic clustering. Arthritis Rheum 61, 1328\u20131336, doi: 10.1002\/art.24739 (2009).","journal-title":"Arthritis Rheum"},{"key":"BFsrep40671_CR27","first-page":"1118","volume":"22","author":"DJ Hart","year":"1995","unstructured":"Hart, D. J., Doyle, D. V. & Spector, T. D. Association between metabolic factors and knee osteoarthritis in women: the Chingford Study. J Rheumatol 22, 1118\u20131123 (1995).","journal-title":"J Rheumatol"},{"key":"BFsrep40671_CR28","doi-asserted-by":"publisher","first-page":"3049","DOI":"10.1007\/s11999-013-3026-3","volume":"471","author":"KB King","year":"2013","unstructured":"King, K. B., Findley, T. W., Williams, A. E. & Bucknell, A. L. Veterans with diabetes receive arthroplasty more frequently and at a younger age. Clin Orthop Relat Res 471, 3049\u20133054, doi: 10.1007\/s11999-013-3026-3 (2013).","journal-title":"Clin Orthop Relat Res"},{"key":"BFsrep40671_CR29","first-page":"1218","volume":"18","author":"E Bagge","year":"1991","unstructured":"Bagge, E., Bjelle, A., Eden, S. & Svanborg, A. Factors associated with radiographic osteoarthritis: results from the population study 70-year-old people in Goteborg. J Rheumatol 18, 1218\u20131222 (1991).","journal-title":"J Rheumatol"},{"key":"BFsrep40671_CR30","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/oxfordjournals.aje.a114939","volume":"128","author":"JJ Anderson","year":"1988","unstructured":"Anderson, J. J. & Felson, D. T. Factors associated with osteoarthritis of the knee in the first national Health and Nutrition Examination Survey (HANES I). Evidence for an association with overweight, race, and physical demands of work. Am J Epidemiol 128, 179\u2013189 (1988).","journal-title":"Am J Epidemiol"},{"key":"BFsrep40671_CR31","first-page":"716","volume":"23","author":"MI Frey","year":"1996","unstructured":"Frey, M. I., Barrett-Connor, E., Sledge, P. A., Schneider, D. L. & Weisman, M. H. The effect of noninsulin dependent diabetes mellitus on the prevalence of clinical osteoarthritis. A population based study. J Rheumatol 23, 716\u2013722 (1996).","journal-title":"J Rheumatol"},{"key":"BFsrep40671_CR32","doi-asserted-by":"publisher","first-page":"3177","DOI":"10.1210\/jc.2014-1043","volume":"99","author":"D Shin","year":"2014","unstructured":"Shin, D. Association between metabolic syndrome, radiographic knee osteoarthritis, and intensity of knee pain: results of a national survey. J Clin Endocrinol Metab 99, 3177\u20133183, doi: 10.1210\/jc.2014-1043 (2014).","journal-title":"J Clin Endocrinol Metab"},{"key":"BFsrep40671_CR33","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.joca.2008.07.003","volume":"17","author":"G Engstrom","year":"2009","unstructured":"Engstrom, G., Gerhardsson de Verdier, M., Rollof, J., Nilsson, P. M. & Lohmander, L. S. C-reactive protein, metabolic syndrome and incidence of severe hip and knee osteoarthritis. A population-based cohort study. Osteoarthritis Cartilage 17, 168\u2013173, doi: 10.1016\/j.joca.2008.07.003 (2009).","journal-title":"Osteoarthritis Cartilage"},{"key":"BFsrep40671_CR34","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1002\/art.38651","volume":"66","author":"SM Hussain","year":"2014","unstructured":"Hussain, S. M. et al. Incidence of total knee and hip replacement for osteoarthritis in relation to circulating sex steroid hormone concentrations in women. Arthritis Rheumatol 66, 2144\u20132151, doi: 10.1002\/art.38651 (2014).","journal-title":"Arthritis Rheumatol"},{"key":"BFsrep40671_CR35","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1128\/IAI.68.5.2925-2929.2000","volume":"68","author":"H Amano","year":"2000","unstructured":"Amano, H. et al. Impairment of endotoxin-induced macrophage inflammatory protein 2 gene expression in alveolar macrophages in streptozotocin-induced diabetes in mice. Infect Immun 68, 2925\u20132929 (2000).","journal-title":"Infect Immun"},{"key":"BFsrep40671_CR36","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.2337\/diabetes.49.9.1451","volume":"49","author":"SN Zykova","year":"2000","unstructured":"Zykova, S. N. et al. Altered cytokine and nitric oxide secretion in vitro by macrophages from diabetic type II-like db\/db mice. Diabetes 49, 1451\u20131458 (2000).","journal-title":"Diabetes"},{"key":"BFsrep40671_CR37","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/art.1780350313","volume":"35","author":"CA Horn","year":"1992","unstructured":"Horn, C. A. et al. Impairment of osteophyte formation in hyperglycemic patients with type II diabetes mellitus and knee osteoarthritis. Arthritis Rheum 35, 336\u2013342 (1992).","journal-title":"Arthritis Rheum"},{"key":"BFsrep40671_CR38","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.intimp.2013.03.020","volume":"16","author":"KY Kang","year":"2013","unstructured":"Kang, K. Y. et al. Metformin downregulates Th17 cells differentiation and attenuates murine autoimmune arthritis. Int Immunopharmacol 16, 85\u201392, doi: 10.1016\/j.intimp.2013.03.020 (2013).","journal-title":"Int Immunopharmacol"},{"key":"BFsrep40671_CR39","doi-asserted-by":"publisher","first-page":"973986","DOI":"10.1155\/2014\/973986","volume":"2014","author":"HJ Son","year":"2014","unstructured":"Son, H. J. et al. Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17\/Treg balance and osteoclastogenesis. Mediators Inflamm 2014, 973986, doi: 10.1155\/2014\/973986 (2014).","journal-title":"Mediators Inflamm"},{"key":"BFsrep40671_CR40","doi-asserted-by":"crossref","unstructured":"Hu, F. B. Obesity epidemiology. (Oxford University Press, 2008).","DOI":"10.1093\/acprof:oso\/9780195312911.001.0001"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep40671.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep40671","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep40671.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T21:52:41Z","timestamp":1671832361000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep40671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,13]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,2,1]]}},"alternative-id":["BFsrep40671"],"URL":"https:\/\/doi.org\/10.1038\/srep40671","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,13]]},"assertion":[{"value":"10 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 December 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"40671"}}