{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:30:49Z","timestamp":1790760649205,"version":"4.1.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T00:00:00Z","timestamp":1492473600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T00:00:00Z","timestamp":1492473600000},"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>\n                  <jats:p>Atrophy patterns on MRI can reliably predict three neuropathological subtypes of Alzheimer\u2019s disease (AD): typical, limbic-predominant, or hippocampal-sparing. A method to enable their investigation in the clinical routine is still lacking. We aimed to (1) validate the combined use of visual rating scales for identification of AD subtypes; (2) characterise these subtypes at baseline and over two years; and (3) investigate how atrophy patterns and non-memory cognitive domains contribute to memory impairment. AD patients were classified as either typical AD (n\u2009=\u2009100), limbic-predominant (n\u2009=\u200933), or hippocampal-sparing (n\u2009=\u200935) by using the Scheltens\u2019 scale for medial temporal lobe atrophy (MTA), the Koedam\u2019s scale for posterior atrophy (PA), and the Pasquier\u2019s global cortical atrophy scale for frontal atrophy (GCA-F). A fourth group with no atrophy was also identified (n\u2009=\u200930). 230 healthy controls were also included. There was great overlap among subtypes in demographic, clinical, and cognitive variables. Memory performance was more dependent on non-memory cognitive functions in hippocampal-sparing and the no atrophy group. Hippocampal-sparing and the no atrophy group showed less aggressive disease progression. Visual rating scales can be used to identify distinct AD subtypes. Recognizing AD heterogeneity is important and visual rating scales may facilitate investigation of AD heterogeneity in clinical routine.<\/jats:p>","DOI":"10.1038\/srep46263","type":"journal-article","created":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T07:20:24Z","timestamp":1492500024000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":209,"title":["Distinct subtypes of Alzheimer\u2019s disease based on patterns of brain atrophy: longitudinal trajectories and clinical applications"],"prefix":"10.1038","volume":"7","author":[{"given":"Daniel","family":"Ferreira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00eb","family":"Verhagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Andr\u00e9s","family":"Hern\u00e1ndez-Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Cavallin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Jie","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urban","family":"Ekman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J-Sebastian","family":"Muehlboeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Barroso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars-Olof","family":"Wahlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Westman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,18]]},"reference":[{"key":"BFsrep46263_CR1","doi-asserted-by":"publisher","first-page":"1936","DOI":"10.1212\/WNL.0000000000001003","volume":"83","author":"Y Noh","year":"2014","unstructured":"Noh, Y. et al. Anatomical heterogeneity of Alzheimer disease: based on cortical thickness on MRIs. Neurology 83, 1936\u20131944 (2014).","journal-title":"Neurology"},{"key":"BFsrep46263_CR2","doi-asserted-by":"crossref","unstructured":"Varol, E., Sotiras, A. & Davatzikos, C. HYDRA: revealing heterogeneity of imaging and genetic patterns through a multiple max-margin discriminative analysis framework. Neuroimage pii: S1053-8119(16)00150-6. doi: 10.1016\/j.neuroimage.2016.02.041 (2016).","DOI":"10.1016\/j.neuroimage.2016.02.041"},{"key":"BFsrep46263_CR3","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1136\/jnnp-2014-309582","volume":"87","author":"NME Scheltens","year":"2016","unstructured":"Scheltens, N. M. E. et al. The identification of cognitive subtypes in Alzheimer\u2019s disease dementia using latent class analysis. J. Neurol. Neurosurg. Psychiatry 87, 235\u2013243 (2016).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"BFsrep46263_CR4","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/S1474-4422(11)70156-9","volume":"10","author":"ME Murray","year":"2011","unstructured":"Murray, M. E. et al. Neuropathologically defined subtypes of Alzheimer\u2019s disease with distinct clinical characteristics: a retrospective study. Lancet. Neurol. 10, 785\u201396 (2011).","journal-title":"Lancet. Neurol."},{"key":"BFsrep46263_CR5","doi-asserted-by":"publisher","first-page":"651","DOI":"10.3233\/JAD-140261","volume":"42","author":"J Peter","year":"2014","unstructured":"Peter, J. et al. Subgroups of Alzheimer\u2019s disease: stability of empirical clusters over time. J. Alzheimers. Dis. 42, 651\u2013661 (2014).","journal-title":"J. Alzheimers. Dis."},{"key":"BFsrep46263_CR6","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","volume":"7","author":"GM McKhann","year":"2011","unstructured":"McKhann, G. M. et al. The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimers. Dement. 7, 263\u2013269 (2011).","journal-title":"Alzheimers. Dement."},{"key":"BFsrep46263_CR7","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1111\/joim.12199","volume":"275","author":"JC Morris","year":"2014","unstructured":"Morris, J. C. et al. Harmonized diagnostic criteria for Alzheimer\u2019s disease: recommendations. J. Intern. Med. 275, 204\u2013213 (2014).","journal-title":"J. Intern. Med."},{"key":"BFsrep46263_CR8","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/S1474-4422(10)70223-4","volume":"9","author":"B Dubois","year":"2010","unstructured":"Dubois, B. et al. Revising the definition of Alzheimer\u2019s disease: a new lexicon. Lancet Neurol. 9, 1118\u20131127 (2010).","journal-title":"Lancet Neurol"},{"key":"BFsrep46263_CR9","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1016\/S1474-4422(12)70200-4","volume":"11","author":"JL Whitwell","year":"2012","unstructured":"Whitwell, J. L. et al. Neuroimaging correlates of pathologically defined subtypes of Alzheimer\u2019s disease: a case-control study. Lancet. Neurol. 11, 868\u2013877 (2012).","journal-title":"Lancet. Neurol."},{"key":"BFsrep46263_CR10","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1016\/j.neurobiolaging.2009.10.012","volume":"32","author":"JL Whitwell","year":"2011","unstructured":"Whitwell, J. L. et al. Temporoparietal atrophy: a marker of AD pathology independent of clinical diagnosis. Neurobiol. Aging 32, 1531\u20131541 (2011).","journal-title":"Neurobiol. Aging"},{"key":"BFsrep46263_CR11","doi-asserted-by":"publisher","first-page":"e0142756","DOI":"10.1371\/journal.pone.0142756","volume":"10","author":"MS Byun","year":"2015","unstructured":"Byun, M. S. et al. Heterogeneity of regional brain atrophy patterns associated with distinct progression rates in Alzheimer\u2019s disease. PLoS One 10, e0142756 (2015).","journal-title":"PLoS One"},{"key":"BFsrep46263_CR12","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/j.nic.2005.09.008","volume":"15","author":"SG Mueller","year":"2005","unstructured":"Mueller, S. G. et al. The Alzheimer\u2019s disease neuroimaging initiative. Neuroimaging Clin. N. Am. 15, 869\u2013877 (2005).","journal-title":"Neuroimaging Clin. N. Am."},{"key":"BFsrep46263_CR13","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1002\/jmri.21049","volume":"27","author":"CR Jack","year":"2008","unstructured":"Jack, C. R. et al. The Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI): MRI methods. J. Magn. Reson. Imaging 27, 685\u2013991 (2008).","journal-title":"J. Magn. Reson. Imaging"},{"key":"BFsrep46263_CR14","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.neuroimage.2006.06.010","volume":"33","author":"A Shiino","year":"2006","unstructured":"Shiino, A. et al. Four subgroups of Alzheimer\u2019s disease based on patterns of atrophy using VBM and a unique pattern for early onset disease. Neuroimage 33, 17\u201326 (2006).","journal-title":"Neuroimage"},{"key":"BFsrep46263_CR15","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.dadm.2015.11.008","volume":"2","author":"J Hwang","year":"2015","unstructured":"Hwang, J. et al. Prediction of Alzheimer\u2019s disease pathophysiology based on cortical thickness patterns. Alzheimer\u2019s Dement. (Amst) 2, 58\u201367 (2015).","journal-title":"Alzheimer\u2019s Dement. (Amst)"},{"key":"BFsrep46263_CR16","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1017\/S1355617709991160","volume":"16","author":"JE Davidson","year":"2010","unstructured":"Davidson, J. E. et al. An exploration of cognitive subgroups in Alzheimer\u2019s disease. J. Int. Neuropsychol. Soc. 16, 233\u2013243 (2010).","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"BFsrep46263_CR17","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.cortex.2005.11.002","volume":"44","author":"CL Stopford","year":"2008","unstructured":"Stopford, C. L., Snowden, J. S., Thompson, J. C. & Neary, D. Variability in cognitive presentation of Alzheimer\u2019s disease. Cortex 44, 185\u2013195 (2008).","journal-title":"Cortex"},{"key":"BFsrep46263_CR18","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1093\/brain\/aww005","volume":"139","author":"L Harper","year":"2016","unstructured":"Harper, L. et al. MRI visual rating scales in the diagnosis of dementia: evaluation in 184 post-mortem confirmed cases. Brain 139, 1211\u20131225 (2016).","journal-title":"Brain"},{"key":"BFsrep46263_CR19","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/joim.12358","volume":"278","author":"D Ferreira","year":"2015","unstructured":"Ferreira, D. et al. Practical cut-offs for visual rating scales of medial temporal, frontal, and posterior atrophy in Alzheimer\u2019s disease and mild cognitive impairment. J. Intern. Med. 278, 277\u2013290 (2015).","journal-title":"J. Intern. Med."},{"key":"BFsrep46263_CR20","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1159\/000448394","volume":"42","author":"D Ferreira","year":"2016","unstructured":"Ferreira, D. et al. Electroencephalography is a good complement to currently established dementia biomarkers. Dement. Geriatr. Cogn. Disord. 42, 80\u201392 (2016).","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"BFsrep46263_CR21","doi-asserted-by":"publisher","first-page":"313","DOI":"10.3233\/JAD-132306","volume":"41","author":"WM van der Flier","year":"2014","unstructured":"van der Flier, W. M. et al. Optimizing patient care and research: the Amsterdam Dementia Cohort. J. Alzheimers. Dis. 41, 313\u2013327 (2014).","journal-title":"J. Alzheimers. Dis."},{"key":"BFsrep46263_CR22","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1111\/joim.12176","volume":"275","author":"LA van de Pol","year":"2014","unstructured":"van de Pol, L. A. & Scheltens, P. Medial temporal lobe atrophy scores translated to clinical practice: editorial comment on \u2018influence of age, disease onset and ApoE4 on visual medial temporal lobe atrophy cut-offs\u2019. J. Intern. Med. 275, 331\u2013333 (2014).","journal-title":"J. Intern. Med."},{"key":"BFsrep46263_CR23","doi-asserted-by":"publisher","first-page":"2618","DOI":"10.1007\/s00330-011-2205-4","volume":"21","author":"EL Koedam","year":"2011","unstructured":"Koedam, E. L. et al. Visual assessment of posterior atrophy development of a MRI rating scale. Eur. Radiol. 21, 2618\u20132625 (2011).","journal-title":"Eur. Radiol"},{"key":"BFsrep46263_CR24","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1159\/000117417","volume":"37","author":"P Scheltens","year":"1997","unstructured":"Scheltens, P., Pasquier, F., Weerts, J., Barkhof, F. & Leys, D. Qualitative assessment of cerebral atrophy on MRI: inter- and intra-observer reproducibility in dementia and normal aging. Eur. Neurol. 37, 95\u201399 (1997).","journal-title":"Eur. Neurol."},{"key":"BFsrep46263_CR25","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1007\/s00330-015-4101-9","volume":"26","author":"D Ferreira","year":"2015","unstructured":"Ferreira, D. et al. Quantitative validation of a visual rating scale for frontal atrophy: associations with clinical status, APOE e4, CSF biomarkers and cognition. Eur. Radiol. 26, 2597\u20132610 (2015).","journal-title":"Eur. Radiol"},{"key":"BFsrep46263_CR26","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2307\/2529310","volume":"33","author":"J Landis","year":"1977","unstructured":"Landis, J. & Koch, G. The measurement of observer agreement for categorical data. Biometrics 33, 159\u2013174 (1977).","journal-title":"Biometrics"},{"key":"BFsrep46263_CR27","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/S1474-4422(10)70306-9","volume":"10","author":"WM van der Flier","year":"2011","unstructured":"van der Flier, W. M., Pijnenburg, Y. Al, Fox, N. C. & Scheltens, P. Early-onset versus late-onset Alzheimer\u2019s disease: the case of the missing APOE \u025b4 allele. Lancet Neurol. 10, 280\u2013288 (2011).","journal-title":"Lancet Neurol."},{"key":"BFsrep46263_CR28","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S1474-4422(12)70209-0","volume":"11","author":"GG Kovacs","year":"2012","unstructured":"Kovacs, G. G. Clinical stratification of subtypes of Alzheimer\u2019s disease. Lancet. Neurol. 11, 839\u2013841 (2012).","journal-title":"Lancet. Neurol."},{"key":"BFsrep46263_CR29","doi-asserted-by":"publisher","first-page":"625","DOI":"10.3233\/JAD-160366","volume":"55","author":"A Rivero-Santana","year":"2016","unstructured":"Rivero-Santana, A. et al. Cerebrospinal fluid biomarkers for the differential diagnosis between Alzheimer\u2019s disease and frontotemporal lobar degeneration: systematic review, HSROC analysis, and confounding factors. J. Alzheimer\u2019s Dis. 55, 625\u2013644. (2016).","journal-title":"J. Alzheimer\u2019s Dis"},{"key":"BFsrep46263_CR30","unstructured":"Wechsler, D. Wechsler Memory Scale - Third Edition. Technical Manual. (The Psychological Corporation, 1997)."},{"key":"BFsrep46263_CR31","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3389\/fninf.2013.00049","volume":"7","author":"J-S Muehlboeck","year":"2014","unstructured":"Muehlboeck, J.-S., Westman, E. & Simmons, A. TheHiveDB image data management and analysis framework. Front. Neuroinform. 7, 49 (2014).","journal-title":"Front. Neuroinform"},{"key":"BFsrep46263_CR32","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1016\/j.neurobiolaging.2013.10.095","volume":"35","author":"D Ferreira","year":"2014","unstructured":"Ferreira, D. et al. Cognitive decline is mediated by gray matter changes during middle age. Neurobiol. Aging 35, 1086\u20131094 (2014).","journal-title":"Neurobiol. Aging"},{"key":"BFsrep46263_CR33","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1136\/jnnp.55.10.967","volume":"55","author":"P Scheltens","year":"1992","unstructured":"Scheltens, P. et al. Atrophy of medial temporal lobes on MRI in \u2018probable\u2019 Alzheimer\u2019s disease and normal ageing: diagnostic value and neuropsychological correlates. J. Neurol. Neurosurg. Psychiatry 55, 967\u2013972 (1992).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"BFsrep46263_CR34","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1159\/000442443","volume":"16","author":"C Orellana","year":"2016","unstructured":"Orellana, C. et al. Measuring global brain atrophy with the brain volume\/cerebrospinal fluid index: normative values, cut-offs and clinical associations. Neurodegener. Dis. 16, 77\u201386 (2016).","journal-title":"Neurodegener. Dis."},{"key":"BFsrep46263_CR35","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.jalz.2015.06.1886","volume":"12","author":"J Ramirez","year":"2016","unstructured":"Ramirez, J., McNeely, A. A., Scott, C. J. M., Masellis, M. & Black, S. E. White matter hyperintensity burden in elderly cohort studies. The Sunnybrook Dementia Study, Alzheimer\u2019s Disease Neuroimaging Initiative, and Three-City Study. Alzheimers Dement. 12, 203\u2013210 (2016).","journal-title":"Alzheimers Dement."},{"key":"BFsrep46263_CR36","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1001\/archneur.1975.00490510088009","volume":"32","author":"VC Hachinski","year":"1975","unstructured":"Hachinski, V. C. et al. Cerebral blood flow in dementia. Arch Neurol 32, 632\u2013637 (1975).","journal-title":"Arch Neurol"},{"key":"BFsrep46263_CR37","doi-asserted-by":"publisher","first-page":"2412","DOI":"10.1212\/WNL.43.11.2412-a","volume":"43","author":"JC Morris","year":"1993","unstructured":"Morris, J. C. The Clinical Dementia Rating (CDR): current vision and scoring rules Neurology. Neurology 43, 2412\u20132414 (1993).","journal-title":"Neurology"},{"key":"BFsrep46263_CR38","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","volume":"12","author":"MF Folstein","year":"1975","unstructured":"Folstein, M. F., Folstein, S. E. & McHugh, P. R. Mini-mental- state. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189\u2013198 (1975).","journal-title":"J. Psychiatr. Res."},{"key":"BFsrep46263_CR39","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1093\/geronj\/37.3.323","volume":"37","author":"RI Pfeffer","year":"1982","unstructured":"Pfeffer, R. I., Kurosaki, T. T., Harrah, C. H., Chance, J. M. & Filos, S. Measurement of functional activities in older adults in the community. J. Gerontol. 37, 323\u2013329 (1982).","journal-title":"J. Gerontol."},{"key":"BFsrep46263_CR40","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1300\/J018v05n01_09","volume":"5","author":"J Sheikh","year":"1986","unstructured":"Sheikh, J. & Yesavage, J. Geriatric Depression Scale (GDS): recent evidence and development of a shorter version. Clin Gerontol 5, 165\u2013173 (1986).","journal-title":"Clin Gerontol"},{"key":"BFsrep46263_CR41","unstructured":"Schmidt, M. Rey Auditory Verbal Learning Test: A Handbook. (Western Psychological Services, 1996)."},{"key":"BFsrep46263_CR42","doi-asserted-by":"publisher","first-page":"271","DOI":"10.2466\/pms.1958.8.3.271","volume":"8","author":"R Reitan","year":"1958","unstructured":"Reitan, R. Validity of the trail making test as an indicator of organic brain damage. Percept. Mot. Skills 8, 271\u2013276 (1958).","journal-title":"Percept. Mot. Skills"},{"key":"BFsrep46263_CR43","doi-asserted-by":"crossref","unstructured":"Wechsler, D. Wechsler Adult Intelligence Scale - Administration and Scoring Manual, Third Edition. (The Psychological Corporation, San Antonio, TX., 1997).","DOI":"10.1037\/t49755-000"},{"key":"BFsrep46263_CR44","unstructured":"Kaplan, E., Goodglass, H. & Weintraub, S. Boston Naming Test. (Lea & Febiger, 1983)."},{"key":"BFsrep46263_CR45","unstructured":"Benton, A., Hamsher, K. & Sivan, A. Multilingual Aphasia Examination- Second Edition. (AJA Associates, University of Iowa., 1989)."},{"key":"BFsrep46263_CR46","unstructured":"Goodglass, H. & Kaplan, E. The Assessment Of Aphasia And Related Disorders. (Lea & Febiger., 1983)."},{"key":"BFsrep46263_CR47","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1002\/sim.4780090710","volume":"9","author":"Y Hochberg","year":"1990","unstructured":"Hochberg, Y. & Benjamin, Y. More powerful procedures for multiple significance testing. Stat. Med. 9, 811\u2013818 (1990).","journal-title":"Stat. Med."},{"key":"BFsrep46263_CR48","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.bbr.2016.05.061","volume":"311","author":"D Ferreira","year":"2016","unstructured":"Ferreira, D. et al. Different reserve proxies confer overlapping and unique endurance to cortical thinning in healthy middle-aged adults. Behav. Brain Res. 311, 375\u2013383 (2016).","journal-title":"Behav. Brain Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep46263.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep46263","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/srep46263","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/srep46263.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T18:15:29Z","timestamp":1671819329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep46263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,18]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,5,3]]}},"alternative-id":["BFsrep46263"],"URL":"https:\/\/doi.org\/10.1038\/srep46263","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,18]]},"assertion":[{"value":"6 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"46263"}}