{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:11Z","timestamp":1784557031529,"version":"3.55.0"},"reference-count":32,"publisher":"Bioscientifica","issue":"5","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,8]]},"abstract":"<jats:p>\n                    Conditions related to cardiometabolic disease, including metabolic syndrome and type 2 diabetes, are common among men with Klinefelter syndrome (KS). The molecular mechanisms underlying this aberrant metabolism in KS are largely unknown, although there is an assumption that chronic testosterone deficiency plays a role. This cross-sectional study compared plasma metabolites in 31 pubertal adolescent males with KS to 32 controls of similar age (14 \u00b1 2 years), pubertal stage, and body mass index\n                    <jats:italic>z<\/jats:italic>\n                    -score of 0.1 \u00b1 1.2 and then between testosterone-treated (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200916) and untreated males with KS. The plasma metabolome in males with KS was distinctly different from that in controls, with 22% of measured metabolites having a differential abundance and seven metabolites nearly completely separating KS from controls (area under the curve &gt; 0.9,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). Multiple saturated free fatty acids were higher in KS, while mono- and polyunsaturated fatty acids were lower, and the top significantly enriched pathway was mitochondrial \u03b2-oxidation of long-chain saturated fatty acids (enrichment ratio 16,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). In contrast, there were no observed differences in metabolite concentrations between testosterone-treated and untreated individuals with KS. In conclusion, the plasma metabolome profile in adolescent males with KS is distinctly different from that in males without KS independent of age, obesity, pubertal development, or testosterone treatment status and is suggestive of differences in mitochondrial \u03b2-oxidation.\n                  <\/jats:p>","DOI":"10.1530\/ec-22-0523","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T11:40:27Z","timestamp":1678275627000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":3,"title":["Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism"],"prefix":"10.1530","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0304-9550","authenticated-orcid":true,"given":"Shanlee M","family":"Davis","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"},{"name":"eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhianna","family":"Urban","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"D\u2019Alessandro","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A","family":"Reisz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine L","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Kelsey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Howell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"},{"name":"eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"},{"name":"eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Zeitler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"},{"name":"eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Baker II","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Acta Paediatrica","first-page":"871","article-title":"Body composition, metabolic syndrome and type 2 diabetes in Klinefelter syndrome","volume":"100","author":"Gravholt","year":"2011","unstructured":"Gravholt CHJensen ASHost C & Bojesen A. Body composition, metabolic syndrome and type 2 diabetes in Klinefelter syndrome. Acta Paediatrica2011100871\u2013877. (https:\/\/doi.org\/10.1111\/j.1651-2227.2011.02233.x)"},{"key":"bib2","series-title":"Diabetes Care","first-page":"1591","article-title":"The metabolic syndrome is frequent in Klinefelter's syndrome and is associated with abdominal obesity and hypogonadism","volume":"29","author":"Bojesen","year":"2006","unstructured":"Bojesen AKristensen KBirkebaek NHFedder JMosekilde LBennett PLaurberg PFrystyk JFlyvbjerg AChristiansen JS, The metabolic syndrome is frequent in Klinefelter's syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care2006291591\u20131598. (https:\/\/doi.org\/10.2337\/dc06-0145)"},{"key":"bib3","series-title":"Hormone Molecular Biology and Clinical Investigation","first-page":"431","article-title":"Androgen deficiency and mitochondrial dysfunction: implications for fatigue, muscle dysfunction, insulin resistance, diabetes, and cardiovascular disease","volume":"8","author":"Traish","year":"2011","unstructured":"Traish AMAbdallah B & Yu G. Androgen deficiency and mitochondrial dysfunction: implications for fatigue, muscle dysfunction, insulin resistance, diabetes, and cardiovascular disease. Hormone Molecular Biology and Clinical Investigation20118431\u2013444. (https:\/\/doi.org\/10.1515\/HMBCI.2011.132)"},{"key":"bib4","series-title":"American Journal of Medical Genetics. Part C, Seminars in Medical Genetics","first-page":"327","article-title":"High prevalence of cardiometabolic risk features in adolescents with 47,XXY\/Klinefelter syndrome","volume":"184","author":"Davis","year":"2020","unstructured":"Davis SMDeKlotz SNadeau KJKelsey MMZeitler PS & Tartaglia NR. High prevalence of cardiometabolic risk features in adolescents with 47,XXY\/Klinefelter syndrome. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics2020184327\u2013333. (https:\/\/doi.org\/10.1002\/ajmg.c.31784)"},{"key":"bib5","series-title":"Journal of Endocrinological Investigation","first-page":"1675","article-title":"Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis","volume":"43","author":"Pizzocaro","year":"2020","unstructured":"Pizzocaro AVena WCondorelli RRadicioni ARastrelli GPasquali DSelice RFerlin AForesta CJannini EA, Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis. Journal of Endocrinological Investigation2020431675\u20131687. (https:\/\/doi.org\/10.1007\/s40618-020-01299-1)"},{"key":"bib6","series-title":"Nature Reviews. Molecular Cell Biology","first-page":"451","article-title":"Metabolomics: beyond biomarkers and towards mechanisms","volume":"17","author":"Johnson","year":"2016","unstructured":"Johnson CHIvanisevic J & Siuzdak G. Metabolomics: beyond biomarkers and towards mechanisms. Nature Reviews. Molecular Cell Biology201617451\u2013459. (https:\/\/doi.org\/10.1038\/nrm.2016.25)"},{"key":"bib7","series-title":"Journal of Clinical Investigation","first-page":"20","article-title":"Integrative omics approaches provide biological and clinical insights: examples from mitochondrial diseases","volume":"130","author":"Khan","year":"2020","unstructured":"Khan SInce-Dunn GSuomalainen A & Elo LL. Integrative omics approaches provide biological and clinical insights: examples from mitochondrial diseases. Journal of Clinical Investigation202013020\u201328. (https:\/\/doi.org\/10.1172\/JCI129202)"},{"key":"bib8","series-title":"Transfusion","first-page":"108","article-title":"Testosterone replacement therapy in blood donors modulates erythrocyte metabolism and susceptibility to hemolysis in cold storage","volume":"61","year":"2021","unstructured":"Alexander K, Hazegh K, Fang F, Sinchar D, Kiss JE, Page GP, D'Alessandro A & Kanias T. Testosterone replacement therapy in blood donors modulates erythrocyte metabolism and susceptibility to hemolysis in cold storage. Transfusion202161108\u2013123. (https:\/\/doi.org\/10.1111\/trf.16141)"},{"key":"bib9","series-title":"Metabolomics","first-page":"603","article-title":"Prediction of intracellular metabolic states from extracellular metabolomic data","volume":"11","author":"Aurich","year":"2015","unstructured":"Aurich MKPaglia GRolfsson \u00d3Hrafnsdottir SMagnusdottir MStefaniak MMPalsson B\u00d8Fleming RM & Thiele I. Prediction of intracellular metabolic states from extracellular metabolomic data. Metabolomics201511603\u2013619. (https:\/\/doi.org\/10.1007\/s11306-014-0721-3)"},{"key":"bib10","series-title":"Nature Reviews. Endocrinology","first-page":"617","article-title":"Acylcarnitines--old actors auditioning for new roles in metabolic physiology","volume":"11","author":"McCoin","year":"2015","unstructured":"McCoin CSKnotts TA & Adams SH. Acylcarnitines--old actors auditioning for new roles in metabolic physiology. Nature Reviews. Endocrinology201511617\u2013625. (https:\/\/doi.org\/10.1038\/nrendo.2015.129)"},{"key":"bib11","series-title":"European Journal of Endocrinology","first-page":"801","article-title":"Human chorionic gonadotropin stimulation gives evidence of differences in testicular steroidogenesis in Klinefelter syndrome, as assessed by liquid chromatography-tandem mass spectrometry","volume":"174","author":"Belli","unstructured":"Belli SSanti DLeoni EDall'Olio EFanelli FMezzullo MPelusi CRoli LTagliavini STrenti T, Human chorionic gonadotropin stimulation gives evidence of differences in testicular steroidogenesis in Klinefelter syndrome, as assessed by liquid chromatography-tandem mass spectrometry. European Journal of Endocrinology174801\u2013811. (https:\/\/doi.org\/10.1530\/EJE-15-1224)"},{"key":"bib12","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"738","article-title":"Plasma melatonin concentration before and during testosterone replacement in Klinefelter's syndrome: relation to hepatic indolamine metabolism and sympathoadrenal activity","volume":"86","author":"Caglayan","year":"2001","unstructured":"Caglayan SOzata MOzisik GTuran MBolu EOktenli CArslan NErbil KGul D & Ozdemir IC. Plasma melatonin concentration before and during testosterone replacement in Klinefelter's syndrome: relation to hepatic indolamine metabolism and sympathoadrenal activity. Journal of Clinical Endocrinology and Metabolism200186738\u2013743. (https:\/\/doi.org\/10.1210\/jcem.86.2.7225)"},{"key":"bib13","series-title":"Andrology","first-page":"421","article-title":"Low INSL3 in Klinefelter syndrome is related to osteocalcin, testosterone treatment and body composition, as well as measures of the hypothalamic-pituitary-gonadal axis","volume":"2","author":"Overvad","year":"2014","unstructured":"Overvad SBay KBojesen A & Gravholt CH. Low INSL3 in Klinefelter syndrome is related to osteocalcin, testosterone treatment and body composition, as well as measures of the hypothalamic-pituitary-gonadal axis. Andrology20142421\u2013427. (https:\/\/doi.org\/10.1111\/j.2047-2927.2014.00204.x)"},{"key":"bib14","series-title":"Rapid Communications in Mass Spectrometry","first-page":"663","article-title":"A three-minute method for high-throughput quantitative metabolomics and quantitative tracing experiments of central carbon and nitrogen pathways","volume":"31","author":"Nemkov","year":"2017","unstructured":"Nemkov THansen KC & D'Alessandro A. A three-minute method for high-throughput quantitative metabolomics and quantitative tracing experiments of central carbon and nitrogen pathways. Rapid Communications in Mass Spectrometry201731663\u2013673. (https:\/\/doi.org\/10.1002\/rcm.7834)"},{"key":"bib15","series-title":"Methods in Molecular Biology","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-1-4939-9236-2_2","article-title":"High-throughput metabolomics: isocratic and gradient mass spectrometry-based methods","volume":"1978","author":"Nemkov","year":"2019","unstructured":"Nemkov TReisz JAGehrke SHansen KC & D'Alessandro A. High-throughput metabolomics: isocratic and gradient mass spectrometry-based methods. Methods in Molecular Biology2019197813\u201326. (https:\/\/doi.org\/10.1007\/978-1-4939-9236-2_2)"},{"key":"bib16","series-title":"Nature","first-page":"117","article-title":"Chaperone-mediated autophagy sustains haematopoietic stem-cell function","volume":"591","author":"Dong","year":"2021","unstructured":"Dong SWang QKao YRDiaz ATasset IKaushik SThiruthuvanathan VZintiridou ANieves EDzieciatkowska M, Chaperone-mediated autophagy sustains haematopoietic stem-cell function. Nature2021591117\u2013123. (https:\/\/doi.org\/10.1038\/s41586-020-03129-z)"},{"key":"bib17","series-title":"Nature Metabolism","first-page":"1459","article-title":"Nitrogen recycling buffers against ammonia toxicity from skeletal muscle breakdown in hibernating arctic ground squirrels","volume":"2","author":"Rice","year":"2020","unstructured":"Rice SATen Have GAMReisz JAGehrke SStefanoni DFrare CBarati ZCoker RHD'Alessandro ADeutz NEP, Nitrogen recycling buffers against ammonia toxicity from skeletal muscle breakdown in hibernating arctic ground squirrels. Nature Metabolism202021459\u20131471. (https:\/\/doi.org\/10.1038\/s42255-020-00312-4)"},{"key":"bib18","series-title":"Biometrika","first-page":"491","article-title":"Adaptive linear step-up procedures that control the false discovery rate","volume":"93","author":"Benjamini","year":"2006","unstructured":"Benjamini YKrieger AM & Yekutieli D. Adaptive linear step-up procedures that control the false discovery rate. Biometrika200693491\u2013507. (https:\/\/doi.org\/10.1093\/biomet\/93.3.491)"},{"key":"bib19","series-title":"Metabolomics","article-title":"A comparative evaluation of the generalised predictive ability of eight machine learning algorithms across ten clinical metabolomics data sets for binary classification","volume":"15","author":"Mendez","year":"2019","unstructured":"Mendez KMReinke SN & Broadhurst DI. A comparative evaluation of the generalised predictive ability of eight machine learning algorithms across ten clinical metabolomics data sets for binary classification. Metabolomics201915 150. (https:\/\/doi.org\/10.1007\/s11306-019-1612-4)"},{"key":"bib20","series-title":"FASEB Journal","first-page":"336","article-title":"Acylcarnitines: potential implications for skeletal muscle insulin resistance","volume":"29","author":"Aguer","year":"2015","unstructured":"Aguer CMcCoin CSKnotts TAThrush ABOno-Moore KMcPherson RDent RHwang DHAdams SH & Harper ME. Acylcarnitines: potential implications for skeletal muscle insulin resistance. FASEB Journal201529336\u2013345. (https:\/\/doi.org\/10.1096\/fj.14-255901)"},{"key":"bib21","series-title":"Cell Metabolism","first-page":"606","article-title":"Interplay between lipids and branched-chain amino acids in development of insulin resistance","volume":"15","author":"Newgard","year":"2012","unstructured":"Newgard CB. Interplay between lipids and branched-chain amino acids in development of insulin resistance. Cell Metabolism201215606\u2013614. (https:\/\/doi.org\/10.1016\/j.cmet.2012.01.024)"},{"key":"bib22","series-title":"Nature Reviews. Endocrinology","first-page":"723","article-title":"Branched-chain amino acids in metabolic signalling and insulin resistance","volume":"10","author":"Lynch","year":"2014","unstructured":"Lynch CJ & Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nature Reviews. Endocrinology201410723\u2013736. (https:\/\/doi.org\/10.1038\/nrendo.2014.171)"},{"key":"bib23","series-title":"Journal of Clinical Medicine","article-title":"Metabolic fingerprint of Turner syndrome","volume":"9","author":"Bugajska","year":"2020","unstructured":"Bugajska JBerska JWojcik MStarzyk JB & Sztefko K. Metabolic fingerprint of Turner syndrome. Journal of Clinical Medicine20209 664. (https:\/\/doi.org\/10.3390\/jcm9030664)"},{"key":"bib24","series-title":"Journal of Proteome Research","first-page":"4368","article-title":"Metabolic profiling of plasma in overweight\/obese and lean men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC-Q-TOF MS)","volume":"9","author":"Kim","year":"2010","unstructured":"Kim JYPark JYKim OYHam BMKim HJKwon DYJang Y & Lee JH. Metabolic profiling of plasma in overweight\/obese and lean men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC-Q-TOF MS). Journal of Proteome Research201094368\u20134375. (https:\/\/doi.org\/10.1021\/pr100101p)"},{"key":"bib25","series-title":"Journal of Human Nutrition and Dietetics","first-page":"334","article-title":"Examining the association between serum free fatty acids and blood levels of testosterone","volume":"34","author":"Kao","year":"2021","unstructured":"Kao CCYang ZYCheng YW & Chen WL. Examining the association between serum free fatty acids and blood levels of testosterone. Journal of Human Nutrition and Dietetics202134334\u2013344. (https:\/\/doi.org\/10.1111\/jhn.12828)"},{"key":"bib26","series-title":"Prostaglandins, Leukotrienes, and Essential Fatty Acids","article-title":"Dietary supplementation with docosahexaenoic acid rich fish oil increases circulating levels of testosterone in overweight and obese men","volume":"163","author":"Abbott","year":"2020","unstructured":"Abbott KBurrows TLAcharya SThota RN & Garg ML. Dietary supplementation with docosahexaenoic acid rich fish oil increases circulating levels of testosterone in overweight and obese men. Prostaglandins, Leukotrienes, and Essential Fatty Acids2020163 102204. (https:\/\/doi.org\/10.1016\/j.plefa.2020.102204)"},{"key":"bib27","series-title":"Journal of Lipid Research","first-page":"546","article-title":"Oxidative modification of low density lipoprotein in normal and hyperlipidemic patients: effect of lysophosphatidylcholine composition on vascular relaxation","volume":"38","author":"Chen","year":"1997","unstructured":"Chen LLiang BFroese DELiu SWong JTTran KHatch GMMymin DKroeger EAMan RY, Oxidative modification of low density lipoprotein in normal and hyperlipidemic patients: effect of lysophosphatidylcholine composition on vascular relaxation. Journal of Lipid Research199738546\u2013553. (https:\/\/doi.org\/10.1016\/S0022-2275(2037262-X)"},{"key":"bib28","series-title":"Glia","first-page":"327","article-title":"Mechanisms of lysophosphatidylcholine-induced demyelination: a primary lipid disrupting myelinopathy","volume":"66","author":"Plemel","year":"2018","unstructured":"Plemel JRMichaels NJWeishaupt NCaprariello AVKeough MBRogers JAYukseloglu ALim JPatel VVRawji KS, Mechanisms of lysophosphatidylcholine-induced demyelination: a primary lipid disrupting myelinopathy. Glia201866327\u2013347. (https:\/\/doi.org\/10.1002\/glia.23245)"},{"key":"bib29","series-title":"International Journal of Molecular Sciences","article-title":"An updated review of lysophosphatidylcholine metabolism in human diseases","volume":"20","author":"Law","year":"2019","unstructured":"Law SHChan MLMarathe GKParveen FChen CH & Ke LY. An updated review of lysophosphatidylcholine metabolism in human diseases. International Journal of Molecular Sciences201920 1149. (https:\/\/doi.org\/10.3390\/ijms20051149)"},{"key":"bib30","series-title":"Cell Biochemistry and Function","first-page":"175","article-title":"Influence of testosterone on polyunsaturated fatty acid biosynthesis in Sertoli cells in culture","volume":"23","author":"Hurtado de Catalfo","year":"2005","unstructured":"Hurtado de Catalfo GE & de Gomez Dumm IN. Influence of testosterone on polyunsaturated fatty acid biosynthesis in Sertoli cells in culture. Cell Biochemistry and Function200523175\u2013180. (https:\/\/doi.org\/10.1002\/cbf.1135)"},{"key":"bib31","series-title":"Lipids","first-page":"1014","article-title":"Influence of testosterone administration on the biosynthesis of unsaturated fatty acids in male and female rats","volume":"24","author":"Marra","year":"1989","unstructured":"Marra CA & de Alaniz MJ. Influence of testosterone administration on the biosynthesis of unsaturated fatty acids in male and female rats. Lipids1989241014\u20131019. (https:\/\/doi.org\/10.1007\/BF02544071)"},{"key":"bib32","series-title":"Metabolites","article-title":"Pre-analytical factors that affect metabolite stability in human urine, plasma, and serum: a review","volume":"9","author":"Stevens","year":"2019","unstructured":"Stevens VLHoover EWang Y & Zanetti KA. Pre-analytical factors that affect metabolite stability in human urine, plasma, and serum: a review. Metabolites20199 156. (https:\/\/doi.org\/10.3390\/metabo9080156)"}],"container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/12\/5\/EC-22-0523.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/12\/5\/EC-22-0523.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/12\/5\/EC-22-0523.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:46:02Z","timestamp":1784555162000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/ec\/article\/1146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,8]]},"references-count":32,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.1530\/ec-22-0523","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.08.30.21262854","asserted-by":"object"}]},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,8]]}}}