{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:23:28Z","timestamp":1790875408331,"version":"4.1.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100006108","name":"national center for advancing translational sciences","doi-asserted-by":"publisher","award":["5UL1TR001878-05"],"award-info":[{"award-number":["5UL1TR001878-05"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"national institute of general medical sciences","doi-asserted-by":"crossref","award":["1T32GM136573-01"],"award-info":[{"award-number":["1T32GM136573-01"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"national institute of diabetes and digestive and kidney diseases","doi-asserted-by":"publisher","award":["5K23DK102659-03"],"award-info":[{"award-number":["5K23DK102659-03"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"national institute of diabetes and digestive and kidney diseases","doi-asserted-by":"publisher","award":["5R03DK114491-02"],"award-info":[{"award-number":["5R03DK114491-02"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002108","name":"friedreich's ataxia research alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Friedreich\u2019s ataxia (FRDA) is a neurodegenerative disease caused by decreased expression of frataxin, a protein involved in many cellular metabolic processes, including mitochondrial oxidative phosphorylation (OXPHOS). Our objective was to assess skeletal muscle oxidative metabolism in vivo in adults with FRDA as compared to adults without FRDA using chemical exchange saturation transfer (CrCEST) MRI, which measures free creatine (Cr) over time following an in-magnet plantar flexion exercise.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Participants included adults with FRDA (<jats:italic>n<\/jats:italic>\u2009=\u200911) and healthy adults (<jats:italic>n<\/jats:italic>\u2009=\u200925). All underwent 3-Tesla CrCEST MRI of the calf before and after in-scanner plantar flexion exercise. Participants also underwent whole-body dual-energy X-ray absorptiometry (DXA) scans to measure body composition and completed questionnaires to assess physical activity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found prolonged post-exercise exponential decline in CrCEST (\u03c4Cr) in the lateral gastrocnemius (LG, 274\u00a0s vs. 138\u00a0s, <jats:italic>p<\/jats:italic>\u2009=\u20090.01) in adults with FRDA (vs. healthy adults), likely reflecting decreased OXPHOS capacity. Adults with FRDA (vs. healthy adults) also engaged different muscle groups during exercise, as indicated by muscle group-specific changes in creatine with exercise (\u2206CrCEST), possibly reflecting decreased coordination. Across all participants, increased adiposity and decreased usual physical activity were associated with smaller \u2206CrCEST.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In FRDA, CrCEST MRI may be a useful biomarker of muscle-group-specific decline in OXPHOS capacity that can be leveraged to track within-participant changes over time. Appropriate participant selection and further optimization of the exercise stimulus will enhance the utility of this technique.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-021-10821-1","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T18:32:31Z","timestamp":1634322751000},"page":"2527-2538","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["In vivo assessment of OXPHOS capacity using 3\u00a0T CrCEST MRI in Friedreich\u2019s ataxia"],"prefix":"10.1007","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3239-0563","authenticated-orcid":false,"given":"Gayatri Maria","family":"Schur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Dunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Dedio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Wade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn","family":"Tamaroff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithya","family":"Mitta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinder","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shana E.","family":"McCormack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"issue":"10","key":"10821_CR1","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1001\/archneur.65.10.1296","volume":"65","author":"M Pandolfo","year":"2008","unstructured":"Pandolfo M (2008) Friedreich ataxia. Arch Neurol 65(10):1296\u20131303","journal-title":"Arch Neurol"},{"key":"10821_CR2","doi-asserted-by":"publisher","first-page":"130","DOI":"10.3389\/fphar.2014.00130","volume":"5","author":"A Martelli","year":"2014","unstructured":"Martelli A, Puccio H (2014) Dysregulation of cellular iron metabolism in Friedreich ataxia: from primary iron-sulfur cluster deficit to mitochondrial iron accumulation. Front Pharmacol 5:130","journal-title":"Front Pharmacol"},{"issue":"20","key":"10821_CR3","doi-asserted-by":"publisher","first-page":"11492","DOI":"10.1073\/pnas.96.20.11492","volume":"96","author":"R Lodi","year":"1999","unstructured":"Lodi R, Cooper JM, Bradley JL et al (1999) Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia. Proc Natl Acad Sci USA 96(20):11492\u201311495","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"10821_CR4","first-page":"1143","volume":"34","author":"IR Lanza","year":"2011","unstructured":"Lanza IR, Bhagra S, Nair KS, Port JD (2011) Measurement of human skeletal muscle oxidative capacity by 31P-MR spectroscopy: a cross-validation with in vitro measurements. J Magn 34(5):1143\u20131150","journal-title":"J Magn"},{"issue":"10","key":"10821_CR5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020348","volume":"2","author":"JR Zierath","year":"2004","unstructured":"Zierath JR, Hawley JA (2004) Skeletal muscle fiber type: influence on contractile and metabolic properties. PLoS Biol 2(10):e348","journal-title":"PLoS Biol"},{"issue":"2","key":"10821_CR6","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1007\/s40134-013-0010-3","volume":"1","author":"F Kogan","year":"2013","unstructured":"Kogan F, Hariharan H, Reddy R (2013) Chemical exchange saturation transfer (CEST) imaging: description of technique and potential clinical applications. Curr Radiol Rep 1(2):102\u2013114","journal-title":"Curr Radiol Rep"},{"issue":"4","key":"10821_CR7","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1002\/mrm.22761","volume":"65","author":"PC Van Zijl","year":"2011","unstructured":"Van Zijl PC, Yadav NN (2011) Chemical exchange saturation transfer (CEST): what is in a name and what isn\u2019t? Magn Reson Med 65(4):927\u2013948","journal-title":"Magn Reson Med"},{"issue":"1","key":"10821_CR8","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1002\/mrm.24641","volume":"71","author":"F Kogan","year":"2014","unstructured":"Kogan F, Haris M, Singh A et al (2014) Method for high-resolution imaging of creatine in vivo using chemical exchange saturation transfer. Magn Reson Med 71(1):164\u2013172","journal-title":"Magn Reson Med"},{"issue":"18","key":"10821_CR9","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.88207","volume":"1","author":"C DeBrosse","year":"2016","unstructured":"DeBrosse C, Nanga RP, Wilson N et al (2016) Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders. JCI Insight. 1(18):e88207","journal-title":"JCI Insight."},{"issue":"7Suppl 2","key":"10821_CR10","doi-asserted-by":"publisher","first-page":"S148","DOI":"10.1097\/01.ASN.0000070149.78399.CE","volume":"14","author":"HI Feldman","year":"2003","unstructured":"Feldman HI, Appel LJ, Chertow GM et al (2003) The Chronic renal insufficiency cohort (CRIC) study: design and methods. J Am Soc Nephrol JASN. 14(7Suppl 2):S148\u2013S153","journal-title":"J Am Soc Nephrol JASN."},{"key":"10821_CR11","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1002\/mrm.21873","volume":"61","author":"M Kim","year":"2009","unstructured":"Kim M, Gillen J, Landman BA et al (2009) Water saturation shift referencing (WASSR) for chemical exchange saturation transfer (CEST) experiments. Magn Reson Med 61:1441\u20131450","journal-title":"Magn Reson Med"},{"issue":"4","key":"10821_CR12","doi-asserted-by":"publisher","first-page":"3015","DOI":"10.1016\/j.neuroimage.2009.11.054","volume":"49","author":"S Volz","year":"2010","unstructured":"Volz S, N\u00f6th U, Rotarska-Jagiela A, Deichmann R (2010) A fast B1-mapping method for the correction and normalization of magnetization transfer ratio maps at 3 T. Neuroimage 49(4):3015\u20133026","journal-title":"Neuroimage"},{"key":"10821_CR13","doi-asserted-by":"publisher","unstructured":"Wilson NE (2016) ExerciseCEST. Zenodo. https:\/\/doi.org\/10.5281\/zenodo.59640.Aug4","DOI":"10.5281\/zenodo.59640.Aug4"},{"key":"10821_CR14","unstructured":"North American Association for the Study of Obesity, National Heart, Lung, Blood Institute, & NHLBI Obesity Education Initiative (2000) The practical guide: identification, evaluation, and treatment of overweight and obesity in adults. National Institutes of Health, National Heart, Lung, and Blood Institute, NHLBI Obesity Education Initiative, North American Association for the Study of Obesity."},{"issue":"6","key":"10821_CR15","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/S0960-8966(00)00108-5","volume":"10","author":"M Vorgerd","year":"2000","unstructured":"Vorgerd M, Sch\u00f6ls L, Hardt C et al (2000) Mitochondrial impairment of human muscle in Friedreich ataxia in vivo. Neuromuscul Disord 10(6):430\u2013435","journal-title":"Neuromuscul Disord"},{"issue":"3","key":"10821_CR16","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/S0304-3940(01)01892-4","volume":"306","author":"L Sch\u00f6ls","year":"2001","unstructured":"Sch\u00f6ls L, Vorgerd M, Schillings M et al (2001) Idebenone in patients with Friedreich ataxia. Neurosci Lett 306(3):169\u2013172","journal-title":"Neurosci Lett"},{"issue":"7","key":"10821_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069229","volume":"8","author":"W Nachbauer","year":"2013","unstructured":"Nachbauer W, Boesch S, Schneider R et al (2013) Bioenergetics of the calf muscle in Friedreich ataxia patients measured by 31P-MRS before and after treatment with recombinant human erythropoietin. PLoS ONE 8(7):e69229","journal-title":"PLoS ONE"},{"issue":"10","key":"10821_CR18","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1016\/j.biocel.2013.05.016","volume":"45","author":"S Ciciliot","year":"2013","unstructured":"Ciciliot S, Rossi AC, Dyar KA et al (2013) Muscle type and fiber type specificity in muscle wasting. Int J Biochem Cell Biol 45(10):2191\u20132199","journal-title":"Int J Biochem Cell Biol"},{"issue":"4","key":"10821_CR19","doi-asserted-by":"publisher","first-page":"895","DOI":"10.2337\/diacare.29.04.06.dc05-1854","volume":"29","author":"A Oberbach","year":"2006","unstructured":"Oberbach A, Bossenz Y, Lehmann S et al (2006) Altered fiber distribution and fiber-specific glycolytic and oxidative enzyme activity in skeletal muscle of patients with type 2 diabetes. Diabetes Care 29(4):895\u2013900","journal-title":"Diabetes Care"},{"issue":"13","key":"10821_CR20","doi-asserted-by":"publisher","first-page":"2452","DOI":"10.1093\/hmg\/ddp183","volume":"18","author":"G Coppola","year":"2009","unstructured":"Coppola G, Marmolino D, Lu D et al (2009) Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPAR\u03b3 pathway as a therapeutic target in Friedreich\u2019s ataxia. Hum Mol Genet 18(13):2452\u20132461","journal-title":"Hum Mol Genet"},{"issue":"6","key":"10821_CR21","doi-asserted-by":"publisher","first-page":"E1191","DOI":"10.1152\/ajpendo.00416.2001","volume":"282","author":"CJ Tanner","year":"2002","unstructured":"Tanner CJ, Barakat HA, Dohm GL et al (2002) Muscle fiber type is associated with obesity and weight loss. Am J Physiol Endocrinol Metabol 282(6):E1191\u2013E1196","journal-title":"Am J Physiol Endocrinol Metabol"},{"issue":"1570","key":"10821_CR22","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1098\/rstb.2010.0294","volume":"366","author":"JM Wakeling","year":"2011","unstructured":"Wakeling JM, Blake OM, Wong I et al (2011) Movement mechanics as a determinate of muscle structure, recruitment and coordination. Philosoph Trans Royal Soc B Biolog Sci 366(1570):1554\u20131564","journal-title":"Philosoph Trans Royal Soc B Biolog Sci"},{"issue":"12","key":"10821_CR23","doi-asserted-by":"publisher","first-page":"3402","DOI":"10.1093\/brain\/awl149","volume":"129","author":"TD Jeppesen","year":"2006","unstructured":"Jeppesen TD, Schwartz M, Olsen DB et al (2006) Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy. Brain 129(12):3402\u20133412","journal-title":"Brain"},{"issue":"12","key":"10821_CR24","doi-asserted-by":"publisher","first-page":"2086","DOI":"10.1249\/01.mss.0000177341.89478.06","volume":"37","author":"MA Tarnopolsky","year":"2005","unstructured":"Tarnopolsky MA, Raha S (2005) Mitochondrial myopathies: diagnosis, exercise intolerance, and treatment options. Med Sci Sports Exerc 37(12):2086\u20132093","journal-title":"Med Sci Sports Exerc"},{"issue":"7","key":"10821_CR25","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/j.apmr.2010.04.007","volume":"91","author":"BE Drinkard","year":"2010","unstructured":"Drinkard BE, Keyser RE, Paul SM et al (2010) Exercise capacity and idebenone intervention in children and adolescents with Friedreich ataxia. Arch Phys Med Rehabil 91(7):1044\u20131050","journal-title":"Arch Phys Med Rehabil"},{"issue":"9","key":"10821_CR26","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/gim.2014.177","volume":"17","author":"S Parikh","year":"2015","unstructured":"Parikh S, Goldstein A, Koenig MK et al (2015) Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med 17(9):689\u2013701","journal-title":"Genet Med"},{"issue":"1","key":"10821_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-56847-4","volume":"10","author":"H Zhao","year":"2020","unstructured":"Zhao H, Lewellen BM, Wilson RJ et al (2020) Long-term voluntary running prevents the onset of symptomatic Friedreich\u2019s ataxia in mice. Sci Rep 10(1):1\u20131","journal-title":"Sci Rep"},{"issue":"1","key":"10821_CR28","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1093\/epirev\/mxm008","volume":"29","author":"G Vazquez","year":"2007","unstructured":"Vazquez G, Duval S, Jacobs DR Jr, Silventoinen K (2007) Comparison of body mass index, waist circumference, and waist\/hip ratio in predicting incident diabetes: a meta-analysis. Epidemiol Rev 29(1):115\u2013128","journal-title":"Epidemiol Rev"},{"issue":"11","key":"10821_CR29","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1038\/sj.ijo.0801401","volume":"24","author":"SC Savva","year":"2000","unstructured":"Savva SC, Tornaritis M, Savva ME et al (2000) Waist circumference and waist-to-height ratio are better predictors of cardiovascular disease risk factors in children than body mass index. Int J Obes 24(11):1453\u20131458","journal-title":"Int J Obes"},{"issue":"1","key":"10821_CR30","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/0022-510X(73)90023-3","volume":"18","author":"M Johnson","year":"1973","unstructured":"Johnson M, Polgar J, Weightman D, Appleton D (1973) Data on the distribution of fibre types in thirty-six human muscles: an autopsy study. J Neurol Sci 18(1):111\u2013129","journal-title":"J Neurol Sci"},{"issue":"3","key":"10821_CR31","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/BF00587415","volume":"348","author":"PD Gollnick","year":"1974","unstructured":"Gollnick PD, Sj\u00f6din B, Karlsson J et al (1974) Human soleus muscle: a comparison of fiber composition and enzyme activities with other leg muscles. Pflugers Arch 348(3):247\u2013255","journal-title":"Pflugers Arch"},{"issue":"4","key":"10821_CR32","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1152\/jappl.1989.66.4.1756","volume":"66","author":"PA Tesch","year":"1989","unstructured":"Tesch PA, Thorsson A, Fujitsuka N (1989) Creatine phosphate in fiber types of skeletal muscle before and after exhaustive exercise. J Appl Physiol 66(4):1756\u20131759","journal-title":"J Appl Physiol"},{"key":"10821_CR33","doi-asserted-by":"crossref","unstructured":"Papa S (1996) Mitochondrial oxidative phosphorylation changes in the life span. Molecular aspects and physiopathological implications. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 1276(2):87\u2013105","DOI":"10.1016\/0005-2728(96)00077-1"},{"key":"10821_CR34","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.13329","author":"P Zamani","year":"2021","unstructured":"Zamani P, Proto EA, Wilson N et al (2021) Multimodality assessment of heart failure with preserved ejection fraction skeletal muscle reveals differences in the machinery of energy fuel metabolism. ESC Heart Fail. https:\/\/doi.org\/10.1002\/ehf2.13329","journal-title":"ESC Heart Fail"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-021-10821-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-021-10821-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-021-10821-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T14:17:50Z","timestamp":1650550670000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-021-10821-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,15]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10821"],"URL":"https:\/\/doi.org\/10.1007\/s00415-021-10821-1","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,15]]},"assertion":[{"value":"2 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ravinder Reddy is a co-inventor on patent \"CEST MRI Methods for Imaging of Metabolites and the Use of Same as Biomarkers.\" Neil Wilson is currently an employee of Siemens Medical Solutions USA. All other authors have no conflict of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This study was performed under an approved Institutional Review Board protocol of the University of Pennsylvania (clincaltrials.gov: NCT02154711) and was conducted according to the Declaration of Helsinki. Written, informed consent for all participants were obtained.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standard"}}]}}