{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:23:51Z","timestamp":1768317831807,"version":"3.49.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T00:00:00Z","timestamp":1444262400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T00:00:00Z","timestamp":1444262400000},"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>Antiretroviral therapy has significantly expanded and an increased proportion of patients have switched to second-line regimens in China. We describe the outcomes of second-line therapy among patients having received long-term first-line ART. A prospective follow-up study was conducted in rural areas in China. We compared the virological, immunological outcomes and genotypic drug resistance (DR) profiles before and after regimen switches. A total of 303 patients were enrolled, 283 (93.4%) were retained at 12 months. Of 90 participants with HIV-RNA \u2265\u20091000\u2009copies\/ml before switch, the proportion of viral load (VL)\u2009\u2265\u20091000\u2009copies\/ml at 6 and 12 months was 49.4% and 43.9%, respectively. Of 213 patients with HIV-RNA &lt;\u20091000\u2009copies\/ml before switch, the proportion of VL\u2009\u2265\u20091000\u2009copies\/ml at 6 and 12 months was 4.8% and 6.5%, respectively. The rates of drug resistance to NNRTIs, NRTIs, PIs decreased from 65.5%, 53.3% and 1.1% before regimen switch to 26.8%, 18.3% and 0% at 12 months, respectively. DDI-based initial ART regimens and missing doses in past month were associated with HIV RNA\u2009\u2265\u20091000\u2009copies\/ml at 12 months. The results showed that patients having received long-term first-line ART and experiencing virological failure had good virological outcomes after switching to second-line treatment in China.<\/jats:p>","DOI":"10.1038\/srep14823","type":"journal-article","created":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T09:44:53Z","timestamp":1444297493000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Efficacy and HIV drug resistance profile of second-line ART among patients having received long-term first-line regimens in rural China"],"prefix":"10.1038","volume":"5","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanchao","family":"Yue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shimei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cui","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingjie","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhua","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,10,8]]},"reference":[{"key":"BFsrep14823_CR1","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1093\/eurpub\/ckl062","volume":"16","author":"C Borrell","year":"2006","unstructured":"Borrell, C. et al. AIDS mortality before and after the introduction of highly active antiretroviral therapy: does it vary with socioeconomic group in a country with a National Health System? Eur J Public Health 16, 601\u2013608, 10.1093\/eurpub\/ckl062 (2006).","journal-title":"Eur J Public Health"},{"key":"BFsrep14823_CR2","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1097\/QAI.0b013e3182821821","volume":"62","author":"D Gabillard","year":"2013","unstructured":"Gabillard, D. et al. Mortality, AIDS-morbidity and loss to follow-up by current CD4 cell count among HIV-1-infected adults receiving antiretroviral therapy in Africa and Asia: data from the ANRS 12222 collaboration. J Acquir Immune Defic Syndr 62, 555\u2013561, 10.1097\/QAI.0b013e3182821821 (2013).","journal-title":"J Acquir Immune Defic Syndr"},{"key":"BFsrep14823_CR3","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1097\/QAD.0b013e32802ef30c","volume":"21","author":"VD Lima","year":"2007","unstructured":"Lima, V. D. et al. Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy. AIDS 21, 685\u2013692, 10.1097\/QAD.0b013e32802ef30c (2007).","journal-title":"AIDS"},{"key":"BFsrep14823_CR4","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1016\/S0140-6736(06)69861-9","volume":"368","author":"RD MacArthur","year":"2006","unstructured":"MacArthur, R. D. et al. A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial. Lancet 368, 2125\u20132135, 10.1016\/S0140-6736(06)69861-9 (2006).","journal-title":"Lancet"},{"key":"BFsrep14823_CR5","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1056\/NEJM199912163412501","volume":"341","author":"S Staszewski","year":"1999","unstructured":"Staszewski, S. et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med 341, 1865\u20131873, 10.1056\/NEJM199912163412501 (1999).","journal-title":"N Engl J Med"},{"key":"BFsrep14823_CR6","unstructured":"World Health Organization. WHO HIV drug resistance report 2012. Available at: http:\/\/www.who.int\/hiv\/pub\/drugresistance\/report2012\/en (Accessed: 6th July 2015)."},{"key":"BFsrep14823_CR7","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1086\/590943","volume":"47","author":"R Gupta","year":"2008","unstructured":"Gupta, R., Hill, A., Sawyer, A. W. & Pillay, D. Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: a systematic review of clinical trials. Clin Infect Dis 47, 712\u2013722, 10.1086\/590943 (2008).","journal-title":"Clin Infect Dis"},{"key":"BFsrep14823_CR8","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1016\/S1473-3099(11)70149-9","volume":"11","author":"RL Hamers","year":"2011","unstructured":"Hamers, R. L. et al. HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study. Lancet Infect Dis 11, 750\u2013759, 10.1016\/S1473-3099(11)70149-9 (2011).","journal-title":"Lancet Infect Dis"},{"key":"BFsrep14823_CR9","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1097\/QAD.0b013e3283360976","volume":"24","author":"L Long","year":"2010","unstructured":"Long, L., Fox, M., Sanne, I. & Rosen, S. The high cost of second-line antiretroviral therapy for HIV\/AIDS in South Africa. AIDS 24, 915\u2013919, 10.1097\/QAD.0b013e3283360976 (2010).","journal-title":"AIDS"},{"key":"BFsrep14823_CR10","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1758-2652-14-15","volume":"14","author":"E Hoen","year":"2011","unstructured":"Hoen, E., Berger, J., Calmy, A. & Moon, S. Driving a decade of change: HIV\/AIDS, patents and access to medicines for all. J Int AIDS Soc 14, 15, 10.1186\/1758-2652-14-15 (2011).","journal-title":"J Int AIDS Soc"},{"key":"BFsrep14823_CR11","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1097\/COH.0b013e328333b8c0","volume":"5","author":"MA Boyd","year":"2010","unstructured":"Boyd, M. A. Current and future management of treatment failure in low- and middle-income countries. Curr Opin HIV AIDS 5, 83\u201389, 10.1097\/COH.0b013e328333b8c0 (2010).","journal-title":"Curr Opin HIV AIDS"},{"key":"BFsrep14823_CR12","doi-asserted-by":"publisher","first-page":"241","DOI":"10.7326\/0003-4819-151-4-200908180-00006","volume":"151","author":"F Zhang","year":"2009","unstructured":"Zhang, F. et al. Five-year outcomes of the China National Free Antiretroviral Treatment Program. Ann Intern Med 151, 241\u2013251, W-252, 10.7326\/0003-4819-151-4-200908180-00006 (2009).","journal-title":"Ann Intern Med"},{"key":"BFsrep14823_CR13","unstructured":"NCAIDS, NCSTD, China CDC. Update on the AIDS\/STD epidemic in China and main response in control and prevention in February, 2014. Chin J AIDS STD 3, 145\u2013146 (2014)."},{"key":"BFsrep14823_CR14","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/S1473-3099(11)70097-4","volume":"11","author":"F Zhang","year":"2011","unstructured":"Zhang, F. et al. Effect of earlier initiation of antiretroviral treatment and increased treatment coverage on HIV-related mortality in China: a national observational cohort study. Lancet Infect Dis 11, 516\u2013524, 10.1016\/S1473-3099(11)70097-4 (2011).","journal-title":"Lancet Infect Dis"},{"key":"BFsrep14823_CR15","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1086\/590945","volume":"47","author":"F Zhang","year":"2008","unstructured":"Zhang, F. et al. The effect of highly active antiretroviral therapy on mortality among HIV-infected former plasma donors in China. Clin Infect Dis 47, 825\u2013833, 10.1086\/590945 (2008).","journal-title":"Clin Infect Dis"},{"key":"BFsrep14823_CR16","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1097\/QAD.0b013e3283611931","volume":"27","author":"L Liao","year":"2013","unstructured":"Liao, L. et al. Impact of HIV drug resistance on virologic and immunologic failure and mortality in a cohort of patients on antiretroviral therapy in China. AIDS 27, 1815\u20131824, 10.1097\/QAD.0b013e3283611931 (2013).","journal-title":"AIDS"},{"key":"BFsrep14823_CR17","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1097\/01.aids.0000233577.33973.fa","volume":"20","author":"HZ Qian","year":"2006","unstructured":"Qian, H. Z. et al. Co-infection with HIV and hepatitis C virus in former plasma\/blood donors: challenge for patient care in rural China. AIDS 20, 1429\u20131435, 10.1097\/01.aids.0000233577.33973.fa (2006).","journal-title":"AIDS"},{"key":"BFsrep14823_CR18","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1111\/j.1365-3156.2009.02445.x","volume":"15","author":"O Keiser","year":"2010","unstructured":"Keiser, O. et al. Mortality after failure of antiretroviral therapy in sub-Saharan Africa. Trop Med Int Health 15, 251\u2013258 10.1111\/j.1365-3156.2009.02445.x (2010).","journal-title":"Trop Med Int Health"},{"key":"BFsrep14823_CR19","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1089\/aid.2009.0125","volume":"26","author":"K Siripassorn","year":"2010","unstructured":"Siripassorn, K. et al. Effectiveness of boosted protease inhibitor-based regimens in HIV type 1-infected patients who experienced virological failure with NNRTI-based antiretroviral therapy in a resource-limited setting. AIDS Res Hum Retroviruses 26, 139\u2013148, 10.1089\/aid.2009.0125 (2010).","journal-title":"AIDS Res Hum Retroviruses"},{"key":"BFsrep14823_CR20","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1093\/infdis\/jis261","volume":"205","author":"KC Sigaloff","year":"2012","unstructured":"Sigaloff, K. C. et al. Second-line antiretroviral treatment successfully resuppresses drug-resistant HIV-1 after first-line failure: prospective cohort in Sub-Saharan Africa. J Infect Dis 205, 1739\u20131744, 10.1093\/infdis\/jis261 (2012).","journal-title":"J Infect Dis"},{"key":"BFsrep14823_CR21","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1097\/QAD.0b013e328351f5b2","volume":"26","author":"O Ajose","year":"2012","unstructured":"Ajose, O., Mookerjee, S., Mills, E. J., Boulle, A. & Ford, N. Treatment outcomes of patients on second-line antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis. AIDS 26, 929\u2013938, 10.1097\/QAD.0b013e328351f5b2 (2012).","journal-title":"AIDS"},{"key":"BFsrep14823_CR22","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3851\/IMP2329","volume":"18","author":"L Waters","year":"2013","unstructured":"Waters, L. et al. Second-line protease inhibitor-based antiretroviral therapy after non-nucleoside reverse transcriptase inhibitor failure: the effect of a nucleoside backbone. Antivir Ther 18, 213\u2013219, 10.3851\/IMP2329 (2013).","journal-title":"Antivir Ther"},{"key":"BFsrep14823_CR23","doi-asserted-by":"crossref","unstructured":"DART Virology Group and Trial Team. Virological response to a triple nucleoside\/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa. AIDS 20, 1391\u20131399, 10.1097\/01.aids.0000233572.59522.45 (2006).","DOI":"10.1097\/01.aids.0000233572.59522.45"},{"key":"BFsrep14823_CR24","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1016\/S0140-6736(06)68580-2","volume":"367","author":"L Ferradini","year":"2006","unstructured":"Ferradini, L. et al. Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment. Lancet 367, 1335\u20131342, 10.1016\/S0140-6736(06)68580-2 (2006).","journal-title":"Lancet"},{"key":"BFsrep14823_CR25","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1086\/587109","volume":"46","author":"VC Marconi","year":"2008","unstructured":"Marconi, V. C. et al. Prevalence of HIV-1 drug resistance after failure of a first highly active antiretroviral therapy regimen in KwaZulu Natal, South Africa. Clin Infect Dis 46, 1589\u20131597, 10.1086\/587109 (2008).","journal-title":"Clin Infect Dis"},{"key":"BFsrep14823_CR26","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1177\/135965350601100709","volume":"11","author":"F Maggiolo","year":"2006","unstructured":"Maggiolo, F. et al. The effect of HIV-1 resistance mutations after first-line virological failure on the possibility to sequence antiretroviral drugs in second-line regimens. Antivir Ther 11, 923\u2013929 (2006).","journal-title":"Antivir Ther"},{"key":"BFsrep14823_CR27","doi-asserted-by":"publisher","first-page":"e47289","DOI":"10.1371\/journal.pone.0047289","volume":"7","author":"X He","year":"2012","unstructured":"He, X. et al. A comprehensive mapping of HIV-1 genotypes in various risk groups and regions across China based on a nationwide molecular epidemiologic survey. PLoS One 7, e47289, 10.1371\/journal.pone.0047289 (2012).","journal-title":"PLoS One"},{"key":"BFsrep14823_CR28","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1097\/QAD.0b013e328351430d","volume":"26","author":"Z Li","year":"2012","unstructured":"Li Z. et al. Tracing the origin and history of HIV-1 subtype B\u2019 epidemic by near full-length genome analyses. AIDS 26, 877\u2013884, 10.1097\/QAD.0b013e328351430d (2012).","journal-title":"AIDS"},{"key":"BFsrep14823_CR29","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1086\/381784","volume":"189","author":"MD Miller","year":"2004","unstructured":"Miller, M. D. et al. Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients. J Infect Dis 189, 837\u2013846, 10.1086\/381784 (2004).","journal-title":"J Infect Dis"},{"key":"BFsrep14823_CR30","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1111\/j.1468-1293.2010.00825.x","volume":"11","author":"MC Hosseinipour","year":"2010","unstructured":"Hosseinipour, M. C. et al. Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline. HIV Med 11, 510\u2013518, 10.1111\/j.1468-1293.2010.00825.x (2010).","journal-title":"HIV Med"},{"key":"BFsrep14823_CR31","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1097\/QAI.0b013e318227fc34","volume":"58","author":"KC Sigaloff","year":"2011","unstructured":"Sigaloff, K. C. et al. Unnecessary antiretroviral treatment switches and accumulation of HIV resistance mutations; two arguments for viral load monitoring in Africa. J Acquir Immune Defic Syndr 58, 23\u201331, 10.1097\/QAI.0b013e318227fc34 (2011).","journal-title":"J Acquir Immune Defic Syndr"},{"key":"BFsrep14823_CR32","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1128\/AAC.48.1.172-175.2004","volume":"48","author":"V Joly","year":"2004","unstructured":"Joly, V. et al. Evolution of human immunodeficiency virus type 1 (HIV-1) resistance mutations in nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1-infected patients switched to antiretroviral therapy without NNRTIs. Antimicrob Agents Chemother 48, 172\u2013175, 10.1128\/AAC.48.1.172-175.2004 (2004).","journal-title":"Antimicrob Agents Chemother"},{"key":"BFsrep14823_CR33","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1093\/jac\/dkq338","volume":"65","author":"HT Xu","year":"2010","unstructured":"Xu, H. T., Oliveira, M., Quan, Y., Bar-Magen, T. & Wainberg, M. A. Differential impact of the HIV-1 non-nucleoside reverse transcriptase inhibitor mutations K103N and M230L on viral replication and enzyme function. J Antimicrob Chemother 65, 2291\u20132299, 10.1093\/jac\/dkq338 (2010).","journal-title":"J Antimicrob Chemother"},{"key":"BFsrep14823_CR34","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1001\/jama.2010.980","volume":"304","author":"M Pujades-Rodriguez","year":"2010","unstructured":"Pujades-Rodriguez, M., Balkan, S., Arnould, L., Brinkhof, M. A. & Calmy, A. Treatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries. JAMA 304, 303\u2013312, 10.1001\/jama.2010.980 (2010).","journal-title":"JAMA"},{"key":"BFsrep14823_CR35","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1089\/AID.2012.0164","volume":"28","author":"X Wang","year":"2012","unstructured":"Wang, X. et al. Short communication: emerging transmitted HIV type 1 drug resistance mutations among patients prior to start of first-line antiretroviral therapy in middle and low prevalence sites in China. AIDS Res Hum Retroviruses 28, 1637\u20131639, 10.1089\/AID.2012.0164 (2012).","journal-title":"AIDS Res Hum Retroviruses"},{"key":"BFsrep14823_CR36","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1086\/649215","volume":"50","author":"Y Ma","year":"2010","unstructured":"Ma, Y. et al. Predictors of virologic failure in HIV-1-infected adults receiving first-line antiretroviral therapy in 8 provinces in China. Clin Infect Dis 50, 264\u2013271, 10.1086\/649215 (2010).","journal-title":"Clin Infect Dis"},{"key":"BFsrep14823_CR37","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1111\/j.1365-3156.2010.02621.x","volume":"15","author":"Y Ruan","year":"2010","unstructured":"Ruan, Y. et al. Virologic outcomes of first-line HAART and associated factors among Chinese patients with HIV in three sentinel antiretroviral treatment sites. Trop Med Int Health 15, 1357\u20131363, 10.1111\/j.1365-3156.2010.02621.x (2010).","journal-title":"Trop Med Int Health"},{"key":"BFsrep14823_CR38","doi-asserted-by":"publisher","first-page":"103","DOI":"10.2174\/157016211795569122","volume":"9","author":"X Wang","year":"2011","unstructured":"Wang, X. et al. Factors associated with HIV virologic failure among patients on HAART for one year at three sentinel surveillance sites in China. Curr HIV Res 9, 103\u2013111, 10.2174\/157016211795569122 (2011).","journal-title":"Curr HIV Res"},{"key":"BFsrep14823_CR39","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1097\/QAD.0b013e328011e691","volume":"21","author":"RW Shafer","year":"2007","unstructured":"Shafer, R. W. et al. HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance. AIDS 21, 215\u2013223, 10.1097\/QAD.0b013e328011e691 (2007).","journal-title":"AIDS"},{"key":"BFsrep14823_CR40","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.1086\/503914","volume":"42","author":"TF Liu","year":"2006","unstructured":"Liu, T. F. & Shafer, R. W. Web resources for HIV type 1 genotypic-resistance test interpretation. Clin Infect Dis 42, 1608\u20131618, 10.1086\/503914 (2006).","journal-title":"Clin Infect Dis"},{"key":"BFsrep14823_CR41","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1089\/aid.2006.0196","volume":"23","author":"P Zhong","year":"2007","unstructured":"Zhong, P. et al. Genetic diversity and drug resistance of human immunodeficiency virus type 1 (HIV-1) strains circulating in Shanghai. AIDS Res Hum Retroviruses 23, 847\u2013856, 10.1089\/aid.2006.0196 (2007).","journal-title":"AIDS Res Hum Retroviruses"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep14823.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep14823","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep14823.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T16:04:15Z","timestamp":1672934655000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep14823"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,8]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,12,7]]}},"alternative-id":["BFsrep14823"],"URL":"https:\/\/doi.org\/10.1038\/srep14823","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,8]]},"assertion":[{"value":"12 September 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 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":"14823"}}