{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:38:37Z","timestamp":1791923917260,"version":"4.3.4"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T00:00:00Z","timestamp":1439856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T00:00:00Z","timestamp":1439856000000},"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>Excess aldosterone secretion in patients with primary aldosteronism (PA) impairs their cardiovascular system. Heart rhythm complexity analysis, derived from heart rate variability (HRV), is a powerful tool to quantify the complex regulatory dynamics of human physiology. We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that underwent adrenalectomy and 25 patients with essential hypertension (EH). The heart rate data were analyzed by conventional HRV and heart rhythm complexity analysis including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We found APA patients had significantly decreased DFA\u03b12 on DFA analysis and decreased area 1\u20135, area 6\u201315 and area 6\u201320 on MSE analysis (all p\u2009&lt;\u20090.05). Area 1\u20135, area 6\u201315, area 6\u201320 in the MSE study correlated significantly with log-transformed renin activity and log-transformed aldosterone-renin ratio (all p\u2009&lt;\u2009=\u20090.01). The conventional HRV parameters were comparable between PA and EH patients. After adrenalectomy, all the altered DFA and MSE parameters improved significantly (all p\u2009&lt;\u20090.05). The conventional HRV parameters did not change. Our result suggested that heart rhythm complexity is impaired in APA patients and this is at least partially reversed by adrenalectomy.<\/jats:p>","DOI":"10.1038\/srep11249","type":"journal-article","created":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T09:15:13Z","timestamp":1439889313000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Reversible heart rhythm complexity impairment in patients with primary aldosteronism"],"prefix":"10.1038","volume":"5","author":[{"given":"Yen-Hung","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vin-Cent","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Men-Tzung","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Ming","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Sheng","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan-Dun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Lwun","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Stowasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Kang","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,8,18]]},"reference":[{"key":"BFsrep11249_CR1","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s11906-010-0134-2","volume":"12","author":"GP Rossi","year":"2010","unstructured":"Rossi, G. P. Prevalence and diagnosis of primary aldosteronism. Current hypertension reports 12, 342\u2013348 (2010).","journal-title":"Current hypertension reports"},{"key":"BFsrep11249_CR2","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.jacc.2005.01.015","volume":"45","author":"P Milliez","year":"2005","unstructured":"Milliez, P. et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 45, 1243\u20131248 (2005).","journal-title":"J Am Coll Cardiol"},{"key":"BFsrep11249_CR3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1161\/01.HYP.0000023182.68420.EB","volume":"40","author":"GP Rossi","year":"2002","unstructured":"Rossi, G. P. et al. Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Hypertension 40, 23\u201327 (2002).","journal-title":"Hypertension"},{"key":"BFsrep11249_CR4","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.atherosclerosis.2011.12.003","volume":"221","author":"YH Lin","year":"2012","unstructured":"Lin, Y. H. et al. Adrenalectomy improves increased carotid intima-media thickness and arterial stiffness in patients with aldosterone producing adenoma. Atherosclerosis 221, 154\u2013159 (2012).","journal-title":"Atherosclerosis"},{"key":"BFsrep11249_CR5","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1097\/HJH.0b013e3283550f93","volume":"30","author":"YH Lin","year":"2012","unstructured":"Lin, Y. H. et al. Adrenalectomy reverses myocardial fibrosis in patients with primary aldosteronism. J Hypertens 30, 1606\u20131613 (2012).","journal-title":"J Hypertens"},{"key":"BFsrep11249_CR6","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1210\/endo-118-2-819","volume":"118","author":"EP Gomez-Sanchez","year":"1986","unstructured":"Gomez-Sanchez, E. P. Intracerebroventricular infusion of aldosterone induces hypertension in rats. Endocrinology 118, 819\u2013823 (1986).","journal-title":"Endocrinology"},{"key":"BFsrep11249_CR7","doi-asserted-by":"crossref","first-page":"4756","DOI":"10.1210\/jc.2010-0823","volume":"95","author":"AC Kontak","year":"2010","unstructured":"Kontak, A. C. et al. Reversible sympathetic overactivity in hypertensive patients with primary aldosteronism. The Journal of clinical endocrinology and metabolism 95, 4756\u20134761 (2010).","journal-title":"The Journal of clinical endocrinology and metabolism"},{"key":"BFsrep11249_CR8","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1161\/01.HYP.17.6.1057","volume":"17","author":"E Miyajima","year":"1991","unstructured":"Miyajima, E. et al. Muscle sympathetic nerve activity in renovascular hypertension and primary aldosteronism. Hypertension 17, 1057\u20131062 (1991).","journal-title":"Hypertension"},{"key":"BFsrep11249_CR9","doi-asserted-by":"crossref","first-page":"R1873","DOI":"10.1152\/ajpregu.00471.2007","volume":"294","author":"T Matsukawa","year":"2008","unstructured":"Matsukawa, T. & Miyamoto, T. Does infusion of ANG II increase muscle sympathetic nerve activity in patients with primary aldosteronism? American journal of physiology. Regulatory, integrative and comparative physiology 294, R1873\u20131879 (2008).","journal-title":"Regulatory, integrative and comparative physiology"},{"issue":"5","key":"BFsrep11249_CR10","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1161\/01.CIR.93.5.1043","volume":"93","author":"Task Force of the European Society Electrophysiology","year":"1996","unstructured":"Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation 93, 1043\u20131065 (1996).","journal-title":"Circulation"},{"key":"BFsrep11249_CR11","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1161\/01.CIR.94.11.2850","volume":"94","author":"H Tsuji","year":"1996","unstructured":"Tsuji, H. et al. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation 94, 2850\u20132855 (1996).","journal-title":"Circulation"},{"key":"BFsrep11249_CR12","doi-asserted-by":"publisher","first-page":"R367","DOI":"10.1186\/cc2948","volume":"8","author":"AJ Seely","year":"2004","unstructured":"Seely, A. J. & Macklem, P. T. Complex systems and the technology of variability analysis. Critical care 8, R367\u2013384, 10.1186\/cc2948 (2004).","journal-title":"Critical care"},{"key":"BFsrep11249_CR13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1600-0404.2010.01384.x","volume":"123","author":"HK Yuan","year":"2011","unstructured":"Yuan, H. K. et al. Acute increase of complexity in the neurocardiovascular dynamics following carotid stenting. Acta neurologica Scandinavica 123, 187\u2013192 (2011).","journal-title":"Acta neurologica Scandinavica"},{"key":"BFsrep11249_CR14","doi-asserted-by":"crossref","first-page":"068102","DOI":"10.1103\/PhysRevLett.89.068102","volume":"89","author":"M Costa","year":"2002","unstructured":"Costa, M., Goldberger, A. L. & Peng, C. K. Multiscale entropy analysis of complex physiologic time series. Physical review letters 89, 068102 (2002).","journal-title":"Physical review letters"},{"key":"BFsrep11249_CR15","doi-asserted-by":"crossref","first-page":"e18699","DOI":"10.1371\/journal.pone.0018699","volume":"6","author":"YL Ho","year":"2011","unstructured":"Ho, Y. L., Lin, C., Lin, Y. H. & Lo, M. T. The prognostic value of non-linear analysis of heart rate variability in patients with congestive heart failure--a pilot study of multiscale entropy. PLoS One 6, e18699 (2011).","journal-title":"PLoS One"},{"key":"BFsrep11249_CR16","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1136\/jnnp-2014-308389","volume":"86","author":"SC Tang","year":"2015","unstructured":"Tang, S. C. et al. Complexity of heart rate variability predicts outcome in intensive care unit admitted patients with acute stroke. Journal of neurology, neurosurgery and psychiatry 86, 95\u2013100 (2015).","journal-title":"Journal of neurology, neurosurgery and psychiatry"},{"key":"BFsrep11249_CR17","doi-asserted-by":"crossref","first-page":"e6642","DOI":"10.1371\/journal.pone.0006642","volume":"4","author":"S Ahmad","year":"2009","unstructured":"Ahmad, S. et al. Continuous multi-parameter heart rate variability analysis heralds onset of sepsis in adults. PLoS One 4, e6642 (2009).","journal-title":"PLoS One"},{"key":"BFsrep11249_CR18","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1186\/s13054-014-0548-3","volume":"18","author":"YH Lin","year":"2014","unstructured":"Lin, Y. H. et al. Multi-scale symbolic entropy analysis provides prognostic prediction in patients receiving extracorporeal life support. Critical care 18, 548 (2014).","journal-title":"Critical care"},{"key":"BFsrep11249_CR19","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S0002-9149(00)01312-6","volume":"87","author":"TH Makikallio","year":"2001","unstructured":"Makikallio, T. H. et al. Fractal analysis and time- and frequency-domain measures of heart rate variability as predictors of mortality in patients with heart failure. The American journal of cardiology 87, 178\u2013182 (2001).","journal-title":"The American journal of cardiology"},{"key":"BFsrep11249_CR20","doi-asserted-by":"crossref","first-page":"021906","DOI":"10.1103\/PhysRevE.71.021906","volume":"71","author":"M Costa","year":"2005","unstructured":"Costa, M., Goldberger, A. L. & Peng, C. K. Multiscale entropy analysis of biological signals. Physical review. E, Statistical, nonlinear and soft matter physics 71, 021906 (2005).","journal-title":"Physical review. E, Statistical, nonlinear and soft matter physics"},{"key":"BFsrep11249_CR21","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1161\/01.CIR.0000047275.25795.17","volume":"107","author":"MT La Rovere","year":"2003","unstructured":"La Rovere, M. T. et al. Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patients. Circulation 107, 565\u2013570 (2003).","journal-title":"Circulation"},{"key":"BFsrep11249_CR22","doi-asserted-by":"crossref","first-page":"e560","DOI":"10.1097\/CCM.0000000000000299","volume":"42","author":"B Vandendriessche","year":"2014","unstructured":"Vandendriessche, B. et al. A multiscale entropy-based tool for scoring severity of systemic inflammation. Critical care medicine 42, e560\u2013569 (2014).","journal-title":"Critical care medicine"},{"key":"BFsrep11249_CR23","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jss.2009.03.086","volume":"156","author":"WP Riordan Jr.","year":"2009","unstructured":"Riordan, W. P., Jr., Norris, P. R., Jenkins, J. M. & Morris, J. A., Jr. Early loss of heart rate complexity predicts mortality regardless of mechanism, anatomic location, or severity of injury in 2178 trauma patients. The Journal of surgical research 156, 283\u2013289 (2009).","journal-title":"The Journal of surgical research"},{"key":"BFsrep11249_CR24","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1046\/j.1523-1755.2000.00971.x","volume":"57","author":"ER de Kloet","year":"2000","unstructured":"de Kloet, E. R. et al. Brain mineralocorticoid receptors and centrally regulated functions. Kidney international 57, 1329\u20131336 (2000).","journal-title":"Kidney international"},{"key":"BFsrep11249_CR25","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1161\/01.HYP.17.3.357","volume":"17","author":"GD Thomas","year":"1991","unstructured":"Thomas, G. D., O\u2019Hagan, K. P. & Zambraski, E. J. Chemical sympathectomy alters the development of hypertension in miniature swine. Hypertension 17, 357\u2013362 (1991).","journal-title":"Hypertension"},{"key":"BFsrep11249_CR26","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1161\/HYPERTENSIONAHA.109.147058","volume":"55","author":"DW Wray","year":"2010","unstructured":"Wray, D. W. & Supiano, M. A. Impact of aldosterone receptor blockade compared with thiazide therapy on sympathetic nervous system function in geriatric hypertension. Hypertension 55, 1217\u20131223 (2010).","journal-title":"Hypertension"},{"key":"BFsrep11249_CR27","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1111\/j.1365-2826.2005.01392.x","volume":"18","author":"S Heindl","year":"2006","unstructured":"Heindl, S. et al. Acute effects of aldosterone on the autonomic nervous system and the baroreflex function in healthy humans. Journal of neuroendocrinology 18, 115\u2013121, 10.1111\/j.1365-2826.2005.01392.x (2006).","journal-title":"Journal of neuroendocrinology"},{"key":"BFsrep11249_CR28","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/0165-1838(94)00159-H","volume":"52","author":"M Munakata","year":"1995","unstructured":"Munakata, M. et al. Normal sympathetic vasomotor and cardiac parasympathetic activities in patients with primary aldosteronism: assessment by spectral analysis. Journal of the autonomic nervous system 52, 213\u2013223 (1995).","journal-title":"Journal of the autonomic nervous system"},{"key":"BFsrep11249_CR29","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1463-1326.2012.01669.x","volume":"15","author":"RE Maser","year":"2013","unstructured":"Maser, R. E., Lenhard, M. J., Kolm, P. & Edwards, D. G. Direct renin inhibition improves parasympathetic function in diabetes. Diabetes, obesity & metabolism 15, 28\u201334 (2013).","journal-title":"Diabetes, obesity & metabolism"},{"key":"BFsrep11249_CR30","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1097\/00004872-199512010-00025","volume":"13","author":"M Munakata","year":"1995","unstructured":"Munakata, M. et al. Increased gain in baroreceptor-heart rate reflex in patients with primary aldosteronism. J Hypertens 13, 1648\u20131653 (1995).","journal-title":"J Hypertens"},{"key":"BFsrep11249_CR31","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1161\/HYPERTENSIONAHA.107.095448","volume":"50","author":"C Catena","year":"2007","unstructured":"Catena, C. et al. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension 50, 911\u2013918 (2007).","journal-title":"Hypertension"},{"key":"BFsrep11249_CR32","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1038\/ajh.2008.243","volume":"21","author":"B Strauch","year":"2008","unstructured":"Strauch, B. et al. Adrenalectomy improves arterial stiffness in primary aldosteronism. Am J Hypertens 21, 1086\u20131092 (2008).","journal-title":"Am J Hypertens"},{"key":"BFsrep11249_CR33","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.recesp.2012.07.025","volume":"66","author":"M Abad-Cardiel","year":"2013","unstructured":"Abad-Cardiel, M. et al. Hypertension caused by primary hyperaldosteronism: increased heart damage and cardiovascular risk. Revista espanola de cardiologia 66, 47\u201352 (2013).","journal-title":"Revista espanola de cardiologia"},{"key":"BFsrep11249_CR34","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1177\/1470320310391329","volume":"12","author":"CC Kuo","year":"2011","unstructured":"Kuo, C. C. et al. Verification and evaluation of aldosteronism demographics in the Taiwan Primary Aldosteronism Investigation Group (TAIPAI Group). J Renin Angiotensin Aldosterone Syst 12, 348\u2013357 (2011).","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"key":"BFsrep11249_CR35","doi-asserted-by":"crossref","first-page":"294594","DOI":"10.1155\/2013\/294594","volume":"2013","author":"CS Hung","year":"2013","unstructured":"Hung, C. S. et al. Twenty-four-hour urinary aldosterone predicts inappropriate left ventricular mass index in patients with primary aldosteronism. The Scientific World Journal 2013, 294594 (2013).","journal-title":"The Scientific World Journal"},{"key":"BFsrep11249_CR36","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ultrasmedbio.2012.08.023","volume":"39","author":"HH Lee","year":"2013","unstructured":"Lee, H. H. et al. Myocardial ultrasound tissue characterization of patients with primary aldosteronism. Ultrasound in medicine & biology 39, 54\u201361 (2013).","journal-title":"Ultrasound in medicine & biology"},{"key":"BFsrep11249_CR37","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1161\/01.CIR.91.7.1918","volume":"91","author":"E Vanoli","year":"1995","unstructured":"Vanoli, E. et al. Heart rate variability during specific sleep stages. A comparison of healthy subjects with patients after myocardial infarction. Circulation 91, 1918\u20131922 (1995).","journal-title":"Circulation"},{"key":"BFsrep11249_CR38","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1063\/1.166141","volume":"5","author":"CK Peng","year":"1995","unstructured":"Peng, C. K., Havlin, S., Stanley, H. E. & Goldberger, A. L. Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series. Chaos 5, 82\u201387 (1995).","journal-title":"Chaos"},{"key":"BFsrep11249_CR39","doi-asserted-by":"crossref","first-page":"H2039","DOI":"10.1152\/ajpheart.2000.278.6.H2039","volume":"278","author":"JS Richman","year":"2000","unstructured":"Richman, J. S. & Moorman, J. R. Physiological time-series analysis using approximate entropy and sample entropy. American journal of physiology. Heart and circulatory physiology 278, H2039\u20132049 (2000).","journal-title":"Heart and circulatory physiology"},{"key":"BFsrep11249_CR40","doi-asserted-by":"crossref","first-page":"14889","DOI":"10.1073\/pnas.0701020104","volume":"104","author":"Z Wu","year":"2007","unstructured":"Wu, Z., Huang, N. E., Long, S. R. & Peng, C. K. On the trend, detrending and variability of nonlinear and nonstationary time series. Proceedings of the National Academy of Sciences of the United States of America 104, 14889\u201314894 (2007).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"BFsrep11249_CR41","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1142\/S1793536909000035","volume":"1","author":"CK Peng","year":"2009","unstructured":"Peng, C. K., Costa, M. & Goldberger, A. L. Adaptive Data Analysis of Complex Fluctuations in Physiologic Time Series. Advances in adaptive data analysis 1, 61\u201370 (2009).","journal-title":"Advances in adaptive data analysis"},{"key":"BFsrep11249_CR42","doi-asserted-by":"crossref","first-page":"061924","DOI":"10.1103\/PhysRevE.79.061924","volume":"79","author":"MT Lo","year":"2009","unstructured":"Lo, M. T., Novak, V., Peng, C. K., Liu, Y. & Hu, K. Nonlinear phase interaction between nonstationary signals: a comparison study of methods based on Hilbert-Huang and Fourier transforms. Physical review. E, Statistical, nonlinear and soft matter physics 79, 061924 (2009).","journal-title":"Physical review. E, Statistical, nonlinear and soft matter physics"},{"key":"BFsrep11249_CR43","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.cca.2011.02.018","volume":"412","author":"VC Wu","year":"2011","unstructured":"Wu, V. C. et al. Kidney impairment in primary aldosteronism. Clin Chim Acta 412, 1319\u20131325 (2011).","journal-title":"Clin Chim Acta"},{"key":"BFsrep11249_CR44","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.2967\/jnumed.109.064873","volume":"50","author":"RF Yen","year":"2009","unstructured":"Yen, R. F. et al. 131I-6beta-iodomethyl-19-norcholesterol SPECT\/CT for primary aldosteronism patients with inconclusive adrenal venous sampling and CT results. J Nucl Med 50, 1631\u20131637 (2009).","journal-title":"J Nucl Med"},{"key":"BFsrep11249_CR45","first-page":"111","volume":"26","author":"VC Wu","year":"2012","unstructured":"Wu, V. C. et al. Diagnosis and Management of Primary Aldosteronism. Acta Nephrologica 26, 111\u2013120 (2012).","journal-title":"Acta Nephrologica"},{"key":"BFsrep11249_CR46","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1161\/01.CIR.55.4.613","volume":"55","author":"RB Devereux","year":"1977","unstructured":"Devereux, R. B. & Reichek, N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation 55, 613\u2013618 (1977).","journal-title":"Circulation"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep11249","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep11249.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep11249.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T01:21:09Z","timestamp":1748568069000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep11249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,18]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,9,1]]}},"alternative-id":["BFsrep11249"],"URL":"https:\/\/doi.org\/10.1038\/srep11249","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,18]]},"assertion":[{"value":"17 December 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2015","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":"11249"}}