{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:06:48Z","timestamp":1792530408013,"version":"4.5.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,3,23]],"date-time":"2016-03-23T00:00:00Z","timestamp":1458691200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,3,23]],"date-time":"2016-03-23T00:00:00Z","timestamp":1458691200000},"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>Cornea confocal microscopy (CCM) is a novel non-invasive method to detect small nerve fiber pathology. CCM generally correlates with outcomes of skin biopsies in patients with small fiber pathology. The aim of this study was to quantify the morphology of small nerve fibers of the cornea of patients with fibromyalgia in terms of density, length and branching and further phenotype these patients using standardized quantitative sensory testing (QST). Small fiber pathology was detected in the cornea of 51% of patients: nerve fiber length was significantly decreased in 44% of patients compared to age- and sex-matched reference values; nerve fiber density and branching were significantly decreased in 10% and 28% of patients. The combination of the CCM parameters and sensory tests for central sensitization, (cold pain threshold, mechanical pain threshold, mechanical pain sensitivity, allodynia and\/or windup), yielded four phenotypes of fibromyalgia patients in a subgroup analysis: one group with normal cornea morphology without and with signs of central sensitization and a group with abnormal cornea morphology parameters without and with signs of central sensitization. In conclusion, half of the tested fibromyalgia population demonstrates signs of small fiber pathology as measured by CCM. The four distinct phenotypes suggest possible differences in disease mechanisms and may require different treatment approaches.<\/jats:p>","DOI":"10.1038\/srep23573","type":"journal-article","created":{"date-parts":[[2016,3,23]],"date-time":"2016-03-23T10:10:16Z","timestamp":1458727816000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia"],"prefix":"10.1038","volume":"6","author":[{"given":"Linda","family":"Oudejans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"Niesters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Dahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"van Velzen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,23]]},"reference":[{"key":"BFsrep23573_CR1","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1001\/jama.2014.3266","volume":"311","author":"DJ Clauw","year":"2014","unstructured":"Clauw, D. J. Fibromyalgia: a clinical review. Jama 311, 1547\u20131555, doi: 10.1001\/jama.2014.3266 (2014).","journal-title":"Jama"},{"key":"BFsrep23573_CR2","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/nrrheum.2011.98","volume":"7","author":"T Schmidt-Wilcke","year":"2011","unstructured":"Schmidt-Wilcke, T. & Clauw, D. J. Fibromyalgia: from pathophysiology to therapy. Nature reviews. Rheumatology 7, 518\u2013527, doi: 10.1038\/nrrheum.2011.98 (2011).","journal-title":"Nature reviews. Rheumatology"},{"key":"BFsrep23573_CR3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.pain.2009.03.018","volume":"144","author":"KB Jensen","year":"2009","unstructured":"Jensen, K. B. et al. Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain. Pain 144, 95\u2013100, doi: 10.1016\/j.pain.2009.03.018 (2009).","journal-title":"Pain"},{"key":"BFsrep23573_CR4","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1097\/00002508-199709000-00003","volume":"13","author":"S Lautenbacher","year":"1997","unstructured":"Lautenbacher, S. & Rollman, G. B. Possible deficiencies of pain modulation in fibromyalgia. The Clinical journal of pain 13, 189\u2013196 (1997).","journal-title":"The Clinical journal of pain"},{"key":"BFsrep23573_CR5","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1002\/art.38662","volume":"66","author":"XJ Caro","year":"2014","unstructured":"Caro, X. J. & Winter, E. F. Evidence of abnormal epidermal nerve fiber density in fibromyalgia: clinical and immunologic implications. Arthritis Rheumatol 66, 1945\u20131954, doi: 10.1002\/art.38662 (2014).","journal-title":"Arthritis Rheumatol"},{"key":"BFsrep23573_CR6","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1097\/j.pain.0000000000000285","volume":"156","author":"K Doppler","year":"2015","unstructured":"Doppler, K., Rittner, H. L., Deckart, M. & Sommer, C. Reduced dermal nerve fiber diameter in skin biopsies of patients with fibromyalgia. Pain 156, 2319\u20132325, doi: 10.1097\/j.pain.0000000000000285 (2015).","journal-title":"Pain"},{"key":"BFsrep23573_CR7","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1002\/mus.24156","volume":"49","author":"MP Giannoccaro","year":"2014","unstructured":"Giannoccaro, M. P., Donadio, V., Incensi, A., Avoni, P. & Liguori, R. Small nerve fiber involvement in patients referred for fibromyalgia. Muscle & nerve 49, 757\u2013759, doi: 10.1002\/mus.24156 (2014).","journal-title":"Muscle & nerve"},{"key":"BFsrep23573_CR8","doi-asserted-by":"publisher","first-page":"2310","DOI":"10.1016\/j.pain.2013.06.001","volume":"154","author":"AL Oaklander","year":"2013","unstructured":"Oaklander, A. L., Herzog, Z. D., Downs, H. M. & Klein, M. M. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain 154, 2310\u20132316, doi: 10.1016\/j.pain.2013.06.001 (2013).","journal-title":"Pain"},{"key":"BFsrep23573_CR9","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.semarthrit.2015.03.003","volume":"45","author":"M Ramirez","year":"2015","unstructured":"Ramirez, M. et al. Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy. Seminars in arthritis and rheumatism 45, 214\u2013219, doi: 10.1016\/j.semarthrit.2015.03.003 (2015).","journal-title":"Seminars in arthritis and rheumatism"},{"key":"BFsrep23573_CR10","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.1093\/brain\/awt053","volume":"136","author":"N Uceyler","year":"2013","unstructured":"Uceyler, N. et al. Small fibre pathology in patients with fibromyalgia syndrome. Brain : a journal of neurology 136, 1857\u20131867, doi: 10.1093\/brain\/awt053 (2013).","journal-title":"Brain : a journal of neurology"},{"key":"BFsrep23573_CR11","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1002\/ana.24065","volume":"75","author":"J Serra","year":"2014","unstructured":"Serra, J. et al. Hyperexcitable C nociceptors in fibromyalgia. Annals of neurology 75, 196\u2013208, doi: 10.1002\/ana.24065 (2014).","journal-title":"Annals of neurology"},{"key":"BFsrep23573_CR12","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1097\/j.pain.0000000000000311","volume":"156","author":"DJ Clauw","year":"2015","unstructured":"Clauw, D. J. What is the meaning of \u201csmall fiber neuropathy\u201d in fibromyalgia? Pain 156, 2115\u20132116, doi: 10.1097\/j.pain.0000000000000311 (2015).","journal-title":"Pain"},{"key":"BFsrep23573_CR13","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1016\/j.pain.2013.06.037","volume":"154","author":"N Uceyler","year":"2013","unstructured":"Uceyler, N. & Sommer, C. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain 154, 2569, doi: 10.1016\/j.pain.2013.06.037 (2013).","journal-title":"Pain"},{"key":"BFsrep23573_CR14","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1471-2377-9-13","volume":"9","author":"S Wopking","year":"2009","unstructured":"Wopking, S. et al. Significant difference between three observers in the assessment of intraepidermal nerve fiber density in skin biopsy. BMC Neurol 9, 13, doi: 10.1186\/1471-2377-9-13 (2009).","journal-title":"BMC Neurol"},{"key":"BFsrep23573_CR15","doi-asserted-by":"publisher","first-page":"3646","DOI":"10.2337\/dc13-0193","volume":"36","author":"IN Petropoulos","year":"2013","unstructured":"Petropoulos, I. N. et al. Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes Care 36, 3646\u20133651, doi: 10.2337\/dc13-0193 (2013).","journal-title":"Diabetes Care"},{"key":"BFsrep23573_CR16","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.2337\/dc10-0253","volume":"33","author":"M Tavakoli","year":"2010","unstructured":"Tavakoli, M. et al. Corneal confocal microscopy: a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy. Diabetes Care 33, 1792\u20131797, doi: 10.2337\/dc10-0253 (2010).","journal-title":"Diabetes Care"},{"key":"BFsrep23573_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1142\/S2339547813500039","volume":"1","author":"M Brines","year":"2013","unstructured":"Brines, M. et al. Corneal nerve quantification predicts the severity of symptoms in sarcoidosis patients with painful neuropathy. Technology 1, 1\u20137 (2013).","journal-title":"Technology"},{"key":"BFsrep23573_CR18","doi-asserted-by":"publisher","first-page":"2454","DOI":"10.2337\/db13-1819","volume":"63","author":"D Ziegler","year":"2014","unstructured":"Ziegler, D. et al. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes. Diabetes 63, 2454\u20132463, doi: 10.2337\/db13-1819 (2014).","journal-title":"Diabetes"},{"key":"BFsrep23573_CR19","doi-asserted-by":"publisher","first-page":"838","DOI":"10.2337\/dc14-2311","volume":"38","author":"M Tavakoli","year":"2015","unstructured":"Tavakoli, M. et al. Normative values for corneal nerve morphology assessed using corneal confocal microscopy: a multinational normative data set. Diabetes Care 38, 838\u2013843, doi: 10.2337\/dc14-2311 (2015).","journal-title":"Diabetes Care"},{"key":"BFsrep23573_CR20","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.jpain.2009.02.002","volume":"10","author":"L Arendt-Nielsen","year":"2009","unstructured":"Arendt-Nielsen, L. & Yarnitsky, D. Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera. The journal of pain: official journal of the American Pain Society 10, 556\u2013572, doi: 10.1016\/j.jpain.2009.02.002 (2009).","journal-title":"The journal of pain: official journal of the American Pain Society"},{"key":"BFsrep23573_CR21","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1016\/j.pain.2010.09.030","volume":"152","author":"CJ Woolf","year":"2011","unstructured":"Woolf, C. J. Central sensitization: implications for the diagnosis and treatment of pain. Pain 152, S2\u201315, doi: 10.1016\/j.pain.2010.09.030 (2011).","journal-title":"Pain"},{"key":"BFsrep23573_CR22","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1007\/s00125-003-1086-8","volume":"46","author":"RA Malik","year":"2003","unstructured":"Malik, R. A. et al. Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients. Diabetologia 46, 683\u2013688, doi: 10.1007\/s00125-003-1086-8 (2003).","journal-title":"Diabetologia"},{"key":"BFsrep23573_CR23","doi-asserted-by":"crossref","unstructured":"Tavakoli, M. & Malik, R. A. Corneal confocal microscopy: a novel non-invasive technique to quantify small fibre pathology in peripheral neuropathies. J Vis Exp, doi: 10.3791\/2194 (2011).","DOI":"10.3791\/2194"},{"key":"BFsrep23573_CR24","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1002\/mus.21383","volume":"40","author":"M Tavakoli","year":"2009","unstructured":"Tavakoli, M. et al. Corneal confocal microscopy: a novel noninvasive means to diagnose neuropathy in patients with Fabry disease. Muscle & nerve 40, 976\u2013984, doi: 10.1002\/mus.21383 (2009).","journal-title":"Muscle & nerve"},{"key":"BFsrep23573_CR25","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jns.2014.09.035","volume":"347","author":"ML Kosmidis","year":"2014","unstructured":"Kosmidis, M. L. et al. Reduction of Intraepidermal Nerve Fiber Density (IENFD) in the skin biopsies of patients with fibromyalgia: a controlled study. J Neurol Sci 347, 143\u2013147, doi: 10.1016\/j.jns.2014.09.035 (2014).","journal-title":"J Neurol Sci"},{"key":"BFsrep23573_CR26","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.pain.2008.09.003","volume":"140","author":"S Klauenberg","year":"2008","unstructured":"Klauenberg, S. et al. Depression and changed pain perception: hints for a central disinhibition mechanism. Pain 140, 332\u2013343, doi: 10.1016\/j.pain.2008.09.003 (2008).","journal-title":"Pain"},{"key":"BFsrep23573_CR27","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1097\/AJP.0b013e3182177654","volume":"27","author":"K Blumenstiel","year":"2011","unstructured":"Blumenstiel, K. et al. Quantitative sensory testing profiles in chronic back pain are distinct from those in fibromyalgia. The Clinical journal of pain 27, 682\u2013690, doi: 10.1097\/AJP.0b013e3182177654 (2011).","journal-title":"The Clinical journal of pain"},{"key":"BFsrep23573_CR28","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.pain.2006.01.041","volume":"123","author":"R Rolke","year":"2006","unstructured":"Rolke, R. et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 123, 231\u2013243, doi: 10.1016\/j.pain.2006.01.041 (2006).","journal-title":"Pain"},{"key":"BFsrep23573_CR29","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.pain.2006.04.011","volume":"124","author":"PM Lang","year":"2006","unstructured":"Lang, P. M. et al. Sensory neuropathy and signs of central sensitization in patients with peripheral arterial disease. Pain 124, 190\u2013200, doi: 10.1016\/j.pain.2006.04.011 (2006).","journal-title":"Pain"},{"key":"BFsrep23573_CR30","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1002\/acr.20140","volume":"62","author":"F Wolfe","year":"2010","unstructured":"Wolfe, F. et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis care & research 62, 600\u2013610, doi: 10.1002\/acr.20140 (2010).","journal-title":"Arthritis care & research"},{"key":"BFsrep23573_CR31","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1002\/art.10893","volume":"48","author":"JA Desmeules","year":"2003","unstructured":"Desmeules, J. A. et al. Neurophysiologic evidence for a central sensitization in patients with fibromyalgia. Arthritis and rheumatism 48, 1420\u20131429, doi: 10.1002\/art.10893 (2003).","journal-title":"Arthritis and rheumatism"},{"key":"BFsrep23573_CR32","doi-asserted-by":"publisher","first-page":"R134","DOI":"10.1186\/ar3072","volume":"12","author":"N Fayed","year":"2010","unstructured":"Fayed, N. et al. Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate\/glutamine, inositol, choline and N-acetylaspartate. Arthritis research & therapy 12, R134, doi: 10.1186\/ar3072 (2010).","journal-title":"Arthritis research & therapy"},{"key":"BFsrep23573_CR33","doi-asserted-by":"publisher","first-page":"3146","DOI":"10.1002\/art.24849","volume":"60","author":"RE Harris","year":"2009","unstructured":"Harris, R. E. et al. Elevated insular glutamate in fibromyalgia is associated with experimental pain. Arthritis and rheumatism 60, 3146\u20133152, doi: 10.1002\/art.24849 (2009).","journal-title":"Arthritis and rheumatism"},{"key":"BFsrep23573_CR34","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.berh.2011.02.003","volume":"25","author":"RH Gracely","year":"2011","unstructured":"Gracely, R. H. & Ambrose, K. R. Neuroimaging of fibromyalgia. Best practice & research. Clinical rheumatology 25, 271\u2013284, doi: 10.1016\/j.berh.2011.02.003 (2011).","journal-title":"Best practice & research. Clinical rheumatology"},{"key":"BFsrep23573_CR35","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/1744-8069-8-32","volume":"8","author":"KB Jensen","year":"2012","unstructured":"Jensen, K. B. et al. Patients with fibromyalgia display less functional connectivity in the brain\u2019s pain inhibitory network. Molecular pain 8, 32, doi: 10.1186\/1744-8069-8-32 (2012).","journal-title":"Molecular pain"},{"key":"BFsrep23573_CR36","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1186\/s13075-014-0425-0","volume":"16","author":"V Napadow","year":"2014","unstructured":"Napadow, V. & Harris, R. E. What has functional connectivity and chemical neuroimaging in fibromyalgia taught us about the mechanisms and management of \u2018centralized\u2019 pain? Arthritis research & therapy 16, 425 (2014).","journal-title":"Arthritis research & therapy"},{"key":"BFsrep23573_CR37","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.berh.2015.04.024","volume":"29","author":"DJ Clauw","year":"2015","unstructured":"Clauw, D. J. Diagnosing and treating chronic musculoskeletal pain based on the underlying mechanism(s). Best Pract Res Cl Rh 29, 6\u201319, doi: 10.1016\/j.berh.2015.04.024 (2015).","journal-title":"Best Pract Res Cl Rh"},{"key":"BFsrep23573_CR38","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.berh.2015.04.018","volume":"29","author":"JN Ablin","year":"2015","unstructured":"Ablin, J. N. & Buskila, D. Update on the genetics of the fibromyalgia syndrome. Best practice & research. Clinical rheumatology 29, 20\u201328, doi: 10.1016\/j.berh.2015.04.018 (2015).","journal-title":"Best practice & research. Clinical rheumatology"},{"key":"BFsrep23573_CR39","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.jpain.2013.10.004","volume":"15","author":"J Desmeules","year":"2014","unstructured":"Desmeules, J. et al. Central pain sensitization, COMT Val158Met polymorphism and emotional factors in fibromyalgia. The journal of pain : official journal of the American Pain Society 15, 129\u2013135, doi: 10.1016\/j.jpain.2013.10.004 (2014).","journal-title":"The journal of pain : official journal of the American Pain Society"},{"key":"BFsrep23573_CR40","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.2119\/molmed.2012.00332","volume":"18","author":"L Heij","year":"2012","unstructured":"Heij, L. et al. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med 18, 1430\u20131436, doi: 10.2119\/molmed.2012.00332 (2012).","journal-title":"Mol Med"},{"key":"BFsrep23573_CR41","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1002\/art.1780330203","volume":"33","author":"F Wolfe","year":"1990","unstructured":"Wolfe, F. et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheumatol 33, 160\u2013172 (1990).","journal-title":"Arthritis Rheumatol"},{"key":"BFsrep23573_CR42","doi-asserted-by":"crossref","unstructured":"Chen, X. et al. Small Nerve Fiber Quantification in the Diagnosis of Diabetic Sensorimotor Polyneuropathy: Comparing Corneal Confocal Microscopy With Intraepidermal Nerve Fiber Density. Diabetes Care, doi: 10.2337\/dc14-2422 (2015).","DOI":"10.2337\/dc14-2422"},{"key":"BFsrep23573_CR43","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1167\/iovs.13-13787","volume":"55","author":"IN Petropoulos","year":"2014","unstructured":"Petropoulos, I. N. et al. Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy. Investigative ophthalmology & visual science 55, 2071\u20132078, doi: 10.1167\/iovs.13-13787 (2014).","journal-title":"Investigative ophthalmology & visual science"},{"key":"BFsrep23573_CR44","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.rmed.2010.09.014","volume":"105","author":"E Hoitsma","year":"2011","unstructured":"Hoitsma, E., De Vries, J. & Drent, M. The small fiber neuropathy screening list: Construction and cross-validation in sarcoidosis. Respiratory medicine 105, 95\u2013100, doi: 10.1016\/j.rmed.2010.09.014 (2011).","journal-title":"Respiratory medicine"},{"key":"BFsrep23573_CR45","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.pain.2010.07.026","volume":"151","author":"W Magerl","year":"2010","unstructured":"Magerl, W. et al. Reference data for quantitative sensory testing (QST): refined stratification for age and a novel method for statistical comparison of group data. Pain 151, 598\u2013605, doi: 10.1016\/j.pain.2010.07.026 (2010).","journal-title":"Pain"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep23573","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep23573.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep23573.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T18:55:01Z","timestamp":1672858501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep23573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,23]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,7,26]]}},"alternative-id":["BFsrep23573"],"URL":"https:\/\/doi.org\/10.1038\/srep23573","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,23]]},"assertion":[{"value":"24 December 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2016","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":"23573"}}