{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:10:05Z","timestamp":1790518205226,"version":"4.1.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"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>Dementia is a major public health issue worldwide and chronic use of benzodiazepine, which is very frequent in northern countries, was found to be a risk factor of dementia. This work aims at evaluating the impact of a reduction in chronic use of benzodiazepine on the future burden of dementia in France. Using estimations of dementia incidence and of benzodiazepine use and nation-wide projections of mortality and population sizes, a Monte Carlo approach based on an illness-death model provided projections of several indicators of dementia burden. With no change in benzodiazepine consumption, the prevalence of dementia between age 65 and 99 in France in 2040 was estimated at 2.16 millions (95% confidence interval (CI) 1.93\u20132.38), with a life expectancy without dementia at 65\u00a0years equal to 25.0\u00a0years (24.7\u201325.3) for women and 23.8\u00a0years (23.5\u201324.2) for men. Assuming a disappearance of chronic use of benzodiazepine in 2020, the prevalence would be reduced by about 6.6% in 2040 and the life expectancy without dementia would increase by 0.99 (0.93\u20131.06) year among women and 0.56 (0.50\u20130.62) among men. To conclude, a modest but significant reduction in future dementia burden could be obtained by applying current recommendation for duration of benzodiazepine use.<\/jats:p>","DOI":"10.1038\/s41598-020-71482-0","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T10:03:02Z","timestamp":1599213782000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impact of benzodiazepine consumption reduction on future burden of dementia"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7727-6625","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Jacqmin-Gadda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1849-223X","authenticated-orcid":false,"given":"Florian","family":"Guillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3615-148X","authenticated-orcid":false,"given":"Cl\u00e9ment","family":"Mathieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-7421","authenticated-orcid":false,"given":"Catherine","family":"Helmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7873-5483","authenticated-orcid":false,"given":"Antoine","family":"Pariente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4875-7814","authenticated-orcid":false,"given":"Pierre","family":"Joly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"key":"71482_CR1","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1016\/S0140-6736(05)67889-0","volume":"366","author":"CP Ferri","year":"2005","unstructured":"Ferri, C. P. et al. Global prevalence of dementia: a Delphi consensus study. Lancet 366, 2112\u20132117 (2005).","journal-title":"Lancet"},{"key":"71482_CR2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jalz.2012.02.001","volume":"8","author":"A Association","year":"2012","unstructured":"Association, A. 2012 Alzheimer\u2019s disease facts and figures. Alzheimers Dement 8, 131\u2013168 (2012).","journal-title":"Alzheimers Dement"},{"key":"71482_CR3","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S1474-4422(16)00062-4","volume":"15","author":"B Winblad","year":"2016","unstructured":"Winblad, B. et al. Defeating Alzheimer\u2019s disease and other dementias: a priority for European science and society. Lancet Neurol. 15, 455\u2013532 (2016).","journal-title":"Lancet Neurol."},{"key":"71482_CR4","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.jalz.2016.07.152","volume":"13","author":"V Bellou","year":"2017","unstructured":"Bellou, V. et al. Systematic evaluation of the associations between environmental risk factors and dementia: an umbrella review of systematic reviews and meta-analyses. Alzheimers Dement 13, 406\u2013418 (2017).","journal-title":"Alzheimers Dement"},{"key":"71482_CR5","doi-asserted-by":"crossref","first-page":"e49113","DOI":"10.1371\/journal.pone.0049113","volume":"7","author":"PL Chen","year":"2012","unstructured":"Chen, P. L., Lee, W. J., Sun, W. Z., Oyang, Y. J. & Fuh, J. L. Risk of dementia in patients with insomnia and long-term use of hypnotics: a population-based retrospective cohort study. PLoS ONE 7, e49113 (2012).","journal-title":"PLoS ONE"},{"key":"71482_CR6","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/S0895-4356(01)00453-X","volume":"55","author":"R Lagnaoui","year":"2002","unstructured":"Lagnaoui, R. et al. Benzodiazepine use and risk of dementia: a nested case-control study. J. Clin. Epidemiol. 55, 314\u2013318 (2002).","journal-title":"J. Clin. Epidemiol."},{"key":"71482_CR7","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1097\/JGP.0b013e3181a65210","volume":"17","author":"CS Wu","year":"2009","unstructured":"Wu, C. S., Wang, S. C., Chang, I. S. & Lin, K. M. The association between dementia and long-term use of benzodiazepine in the elderly: nested case-control study using claims data. Am. J. Geriatr. Psychiatry 17, 614\u2013620 (2009).","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"71482_CR8","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1136\/jech-2011-200314","volume":"66","author":"J Gallacher","year":"2012","unstructured":"Gallacher, J. et al. Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS). J. Epidemiol. Community Health 66, 869\u2013873 (2012).","journal-title":"J. Epidemiol. Community Health"},{"key":"71482_CR9","doi-asserted-by":"crossref","first-page":"e6231","DOI":"10.1136\/bmj.e6231","volume":"345","author":"S Billioti de Gage","year":"2012","unstructured":"Billioti de Gage, S. et al. Benzodiazepine use and risk of dementia: prospective population based study. BMJ 345, e6231 (2012).","journal-title":"BMJ"},{"key":"71482_CR10","doi-asserted-by":"crossref","first-page":"g5205","DOI":"10.1136\/bmj.g5205","volume":"349","author":"S Billioti de Gage","year":"2014","unstructured":"Billioti de Gage, S. et al. Benzodiazepine use and risk of Alzheimer\u2019s disease: case-control study. BMJ 349, g5205 (2014).","journal-title":"BMJ"},{"key":"71482_CR11","doi-asserted-by":"crossref","first-page":"801","DOI":"10.3233\/JAD-151006","volume":"54","author":"W Gomm","year":"2016","unstructured":"Gomm, W. et al. Regular benzodiazepine and Z-substance use and risk of dementia: an analysis of German claims data. J. Alzheimers Dis. 54, 801\u2013808 (2016).","journal-title":"J. Alzheimers Dis."},{"key":"71482_CR12","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.jalz.2015.10.006","volume":"12","author":"D Shash","year":"2016","unstructured":"Shash, D. et al. Benzodiazepine, psychotropic medication, and dementia: a population-based cohort study. Alzheimers Dement. 12, 604\u2013613 (2016).","journal-title":"Alzheimers Dement."},{"key":"71482_CR13","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/acps.12909","volume":"138","author":"VTH Taipanen","year":"2018","unstructured":"Taipanen, V. T. H., Tanskanen, A., Tiihonen, J., Hartikainen, S. & Tolppanen, A. M. The risk of Alzheimer\u2019s disease associated with benzodiazepines and related drugs: a nested case-control study. Acta Psychiatr. Scand. 138, 91\u2013100 (2018).","journal-title":"Acta Psychiatr. Scand."},{"issue":"1","key":"71482_CR14","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s12877-019-1280-2","volume":"19","author":"CM Grossi","year":"2019","unstructured":"Grossi, C. M. et al. Anticholinergic and benzodiazepine medication use and risk of incident dementia: a UK cohort study. BMC Geriatr. 19(1), 276 (2019).","journal-title":"BMC Geriatr."},{"key":"71482_CR15","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1176\/appi.ajp.2019.19030315","volume":"177","author":"M Osler","year":"2020","unstructured":"Osler, M. & J\u00f8rgensen, M. B. Associations of benzodiazepines, Z-drugs, and other anxiolytics with subsequent dementia in patients with affective disorders: a nationwide cohort and nested case-control study. Am. J. Psychiatry 177, 497\u2013505 (2020).","journal-title":"Am. J. Psychiatry"},{"key":"71482_CR16","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1159\/000454881","volume":"47","author":"MM Islam","year":"2016","unstructured":"Islam, M. M. et al. Benzodiazepine use and risk of dementia in the elderly population: a systematic review and meta-analysis. Neuroepidemiology 47, 181\u2013191 (2016).","journal-title":"Neuroepidemiology"},{"key":"71482_CR17","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s40263-018-0535-3","volume":"32","author":"R Penninkilampi","year":"2018","unstructured":"Penninkilampi, R. & Eslick, G. D. A systematic review and meta-analysis of the risk of dementia associated with benzodiazepine use, after controlling for protopathic bias. CNS Drugs 32, 485\u2013497 (2018).","journal-title":"CNS Drugs"},{"issue":"1","key":"71482_CR18","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3988\/jcn.2019.15.1.9","volume":"15","author":"Q He","year":"2019","unstructured":"He, Q., Chen, X., Wu, T., Li, L. & Fei, X. Risk of dementia in long-term benzodiazepine users: evidence from a meta-analysis of observational studies. J. Clin. Neurol. 15(1), 9\u201319 (2019).","journal-title":"J. Clin. Neurol."},{"key":"71482_CR19","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1517\/14740338.2015.1014796","volume":"14","author":"S Billioti de Gage","year":"2015","unstructured":"Billioti de Gage, S., Pariente, A. & B\u00e9gaud, B. Is there really a link between benzodiazepine use and the risk of dementia?. Expert Opin. Drug Saf. 14, 733\u2013747 (2015).","journal-title":"Expert Opin. Drug Saf."},{"key":"71482_CR20","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3109\/13651500903447810","volume":"14","author":"J Donoghue","year":"2010","unstructured":"Donoghue, J. & Lader, M. Usage of benzodiazepines: a review. Int. J. Psychiatry Clin. Pract. 14, 78\u201387 (2010).","journal-title":"Int. J. Psychiatry Clin. Pract."},{"key":"71482_CR21","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1001\/jamapsychiatry.2014.1763","volume":"72","author":"M Olfson","year":"2015","unstructured":"Olfson, M., King, M. & Schoenbaum, M. Benzodiazepine use in the United States. JAMA Psychiatry 72, 136\u2013142 (2015).","journal-title":"JAMA Psychiatry"},{"key":"71482_CR22","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.eurpsy.2015.09.003","volume":"30","author":"TA Kurko","year":"2015","unstructured":"Kurko, T. A. et al. Long-term use of benzodiazepines: definitions, prevalence and usage patterns\u2014a systematic review of register-based studies. Eur. Psychiatry 30, 1037\u20131047 (2015).","journal-title":"Eur. Psychiatry"},{"key":"71482_CR23","doi-asserted-by":"crossref","first-page":"61","DOI":"10.2165\/00002512-200825010-00007","volume":"25","author":"A Pariente","year":"2008","unstructured":"Pariente, A. et al. Benzodiazepines and injurious falls in community dwelling elders. Drugs Aging 25, 61\u201370 (2008).","journal-title":"Drugs Aging"},{"key":"71482_CR24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1541-0420.2012.01827.x","volume":"69","author":"P Joly","year":"2013","unstructured":"Joly, P. et al. Prevalence projections of chronic diseases and impact of public health intervention. Biometrics 69, 109\u2013117 (2013).","journal-title":"Biometrics"},{"key":"71482_CR25","doi-asserted-by":"crossref","first-page":"j2856","DOI":"10.1136\/bmj.j2856","volume":"358","author":"S Ahmadi-Abhari","year":"2017","unstructured":"Ahmadi-Abhari, S. et al. Temporal trend in dementia incidence since 2002 and projections for prevalence in England and Wales to 2040: modelling study. BMJ 358, j2856 (2017).","journal-title":"BMJ"},{"key":"71482_CR26","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jalz.2017.10.009","volume":"14","author":"R Brookmeyer","year":"2018","unstructured":"Brookmeyer, R., Abdalla, N., Kawas, C. H. & Corrada, M. M. Forecasting the prevalence of preclinical and clinical Alzheimer\u2019s disease in the United States. Alzheimers Dement. 14, 121\u2013129 (2018).","journal-title":"Alzheimers Dement."},{"key":"71482_CR27","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.2105\/AJPH.88.9.1337","volume":"88","author":"R Brookmeyer","year":"1998","unstructured":"Brookmeyer, R., Gray, S. & Kawas, C. Projections of Alzheimer\u2019s disease in the United States and the public health impact of delaying disease onset. Am. J. Public Health 88, 1337\u20131342 (1998).","journal-title":"Am. J. Public Health"},{"key":"71482_CR28","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jalz.2007.04.381","volume":"3","author":"R Brookmeyer","year":"2007","unstructured":"Brookmeyer, R., Johnson, E., Ziegler-Graham, K. & Arrighi, H. M. Forecasting the global burden of Alzheimer\u2019s disease. Alzheimers Dement. 3, 186\u2013191 (2007).","journal-title":"Alzheimers Dement."},{"key":"71482_CR29","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1468-1331.2009.02783.x","volume":"17","author":"T Mura","year":"2010","unstructured":"Mura, T., Dartigues, J. F. & Berr, C. How many dementia cases in France and Europe? Alternative projections and scenarios 2010\u20132050. Eur. J. Neurol. 17, 252\u2013259 (2010).","journal-title":"Eur. J. Neurol."},{"key":"71482_CR30","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s10654-013-9818-7","volume":"28","author":"H Jacqmin-Gadda","year":"2013","unstructured":"Jacqmin-Gadda, H. et al. 20-Year prevalence projections for dementia and impact of preventive policy about risk factors. Eur. J. Epidemiol. 28, 493\u2013502 (2013).","journal-title":"Eur. J. Epidemiol."},{"key":"71482_CR31","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1177\/0962280216631360","volume":"27","author":"M Wanneveich","year":"2018","unstructured":"Wanneveich, M., Jacqmin-Gadda, H., Dartigues, J. F. & Joly, P. Impact of intervention targeting risk factors on chronic disease burden. Stat. Methods Med. Res. 27, 414\u2013427 (2018).","journal-title":"Stat. Methods Med. Res."},{"key":"71482_CR32","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1097\/EDE.0b013e31822708b5","volume":"22","author":"MC Power","year":"2011","unstructured":"Power, M. C. et al. The association between blood pressure and incident Alzheimer disease: a systematic review and meta-analysis. Epidemiology. 22, 646\u2013659 (2011).","journal-title":"Epidemiology."},{"key":"71482_CR33","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3233\/JAD-2012-120802","volume":"32","author":"AM Tolppanen","year":"2012","unstructured":"Tolppanen, A. M., Solomon, A., Soininen, H. & Kivipelto, M. Midlife vascular risk factors and Alzheimer\u2019s disease: evidence from epidemiological studies. J. Alzheimers Dis. 32, 531\u2013540 (2012).","journal-title":"J. Alzheimers Dis."},{"issue":"suppl 1","key":"71482_CR34","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1159\/000110955","volume":"11","author":"J Dartigues","year":"1992","unstructured":"Dartigues, J. et al. The paquid epidemiological program on brain ageing. Neuroepidemiology 11(suppl 1), 14\u201318. https:\/\/doi.org\/10.1159\/000110955 (1992).","journal-title":"Neuroepidemiology"},{"issue":"6","key":"71482_CR35","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.revmed.2014.11.009","volume":"36","author":"G Moulis","year":"2015","unstructured":"Moulis, G. et al. French health insurance databases: what interest for medical research?. La Revue de m\u00e9decine interne 36(6), 411\u2013417 (2015).","journal-title":"La Revue de m\u00e9decine interne"},{"key":"71482_CR36","doi-asserted-by":"crossref","first-page":"686","DOI":"10.2105\/AJPH.2016.303061","volume":"106","author":"MA Bachhuber","year":"2016","unstructured":"Bachhuber, M. A., Hennessy, S., Cunningham, C. O. & Starrels, J. L. Increasing benzodiazepine prescriptions and overdose mortality in the United States, 1996\u20132013. Am. J. Public Health 106, 686\u2013688 (2016).","journal-title":"Am. J. Public Health"},{"key":"71482_CR37","unstructured":"Blanpain, N. & Buisson, G. Projections de population 2013\u20132070 pour la France (Insee, 2016)."},{"key":"71482_CR38","unstructured":"Mathieu, C. et al. A. Excess of all-cause mortality associated with benzodiazepine use: a cohort study. Submitted."},{"key":"71482_CR39","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/biostatistics\/3.3.433","volume":"3","author":"P Joly","year":"2002","unstructured":"Joly, P., Commenges, D., Helmer, C. & Letenneur, L. A penalized likelihood approach for an illness-death model with interval-censored data: application to age-specific incidence of dementia. Biostatistics. 3, 433\u2013443 (2002).","journal-title":"Biostatistics."},{"key":"71482_CR40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v079.i07","volume":"79","author":"C Touraine","year":"2017","unstructured":"Touraine, C., Gerds, T. A. & Joly, P. The SmoothHazard package for R: Fitting regression models to interval-censored observations of illness-death models. J. Stat. Softw. 79, 1\u201322 (2017).","journal-title":"J. Stat. Softw."},{"key":"71482_CR41","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1093\/aje\/kwy234","volume":"188","author":"FJ Wolters","year":"2019","unstructured":"Wolters, F. J. et al. Life expectancy with and without dementia: a population-based study of dementia burden and preventive potential. Am J Epidemiol. 188, 372\u2013381 (2019).","journal-title":"Am J Epidemiol."},{"key":"71482_CR42","volume-title":"Modern epidemiology","author":"KJ Rothman","year":"2008","unstructured":"Rothman, K. J., Greenland, S. & Lash, T. L. Modern epidemiology (Lippincott Williams & Wilkins, Philadelphia, 2008)."},{"key":"71482_CR43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40263-015-0305-4","volume":"30","author":"A Pariente","year":"2016","unstructured":"Pariente, A., Billioti de Gage, S., Moore, N. & B\u00e9gaud, B. The benzodiazepine-dementia disorders link: current state of knowledge. CNS Drugs 30, 1\u20137 (2016).","journal-title":"CNS Drugs"},{"key":"71482_CR44","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s40268-017-0207-7","volume":"17","author":"J Brandt","year":"2017","unstructured":"Brandt, J. & Leong, C. Benzodiazepines and Z-drugs: an updated review of major adverse outcomes reported on in epidemiologic research. Drugs R&D 17, 493\u2013507 (2017).","journal-title":"Drugs R&D"},{"key":"71482_CR45","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1177\/1533317514524813","volume":"29","author":"RR Tampi","year":"2014","unstructured":"Tampi, R. R. & Tampi, D. J. Efficacy and tolerability of benzodiazepines for the treatment of behavioral and psychological symptoms of dementia: a systematic review of randomized controlled trials. Am. J. Alzheimer\u2019s Dis. Other Dement. 29, 565\u2013574 (2014).","journal-title":"Am. J. Alzheimer\u2019s Dis. Other Dement."},{"issue":"4","key":"71482_CR46","doi-asserted-by":"crossref","first-page":"e203630","DOI":"10.1001\/jamanetworkopen.2020.3630","volume":"3","author":"A Rubino","year":"2020","unstructured":"Rubino, A. et al. Association of the US food and drug administration antipsychotic drug boxed warning with medication use and health outcomes in elderly patients with dementia. JAMA Netw. Open 3(4), e203630\u2013e203630 (2020).","journal-title":"JAMA Netw. Open"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71482-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71482-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71482-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T19:15:29Z","timestamp":1670354129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71482-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,4]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["71482"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-71482-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,4]]},"assertion":[{"value":"24 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14666"}}