{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T09:27:32Z","timestamp":1782552452250,"version":"3.54.5"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T00:00:00Z","timestamp":1502755200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T00:00:00Z","timestamp":1502755200000},"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>Aqueous tear-deficient dry eye is a multifactorial chronic disorder in which the lacrimal glands fail to produce enough tears to maintain a healthy ocular surface. The existence of lacrimal gland stem\/progenitor cells was proposed in several species, yet their origin and characteristics are not very clear. Here, we investigated the presence of resident progenitor cells and their regenerative potential in a rabbit model with lacrimal gland main excretory duct ligation-induced injury. The ligation-injured lacrimal glands temporarily decreased in weight and had impaired tear secretion. Protein expression profiles and transcriptional profiles were obtained from injured tissue. Isolated lacrimal gland progenitor cells were tested and characterized by stem cell-related marker evaluation, single cell clonal assay and three-dimensional (3-D) culture. The results of our study indicate that lacrimal glands are capable of tissue repair after duct ligation-induced injury, likely involving resident stem\/progenitor cells and epithelial-mesenchymal transitions. Lacrimal gland progenitor cells isolated from ligated tissue can differentiate in 3-D culture. The results provide further insights into lacrimal gland stem\/progenitor cell physiology and their potential for treating severe cases of tear deficiency.<\/jats:p>","DOI":"10.1038\/s41598-017-08197-2","type":"journal-article","created":{"date-parts":[[2017,8,9]],"date-time":"2017-08-09T15:49:40Z","timestamp":1502293780000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Lacrimal Gland Repair after Short-term Obstruction of Excretory Duct in Rabbits"],"prefix":"10.1038","volume":"7","author":[{"given":"Hui","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Botsford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Yiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,15]]},"reference":[{"key":"8197_CR1","doi-asserted-by":"crossref","unstructured":"Research in dry eye: report of the Research Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf \n                           5, 179\u2013193 (2007).","DOI":"10.1016\/S1542-0124(12)70086-1"},{"key":"8197_CR2","doi-asserted-by":"crossref","unstructured":"Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf \n                           5, 163\u2013178 (2007).","DOI":"10.1016\/S1542-0124(12)70085-X"},{"key":"8197_CR3","doi-asserted-by":"publisher","first-page":"88","DOI":"10.5966\/sctm.2016-0191","volume":"6","author":"A Gromova","year":"2017","unstructured":"Gromova, A. et al. Lacrimal Gland Repair Using Progenitor Cells. Stem Cells Transl Med \n                           6, 88\u201398, doi:10.5966\/sctm.2016-0191 (2017).","journal-title":"Stem Cells Transl Med"},{"key":"8197_CR4","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/nature04372","volume":"439","author":"M Shackleton","year":"2006","unstructured":"Shackleton, M. et al. Generation of a functional mammary gland from a single stem cell. Nature \n                           439, 84\u201388, doi:10.1038\/nature04372 (2006).","journal-title":"Nature"},{"key":"8197_CR5","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1242\/dev.075804","volume":"139","author":"S Afelik","year":"2012","unstructured":"Afelik, S. et al. Notch-mediated patterning and cell fate allocation of pancreatic progenitor cells. Development \n                           139, 1744\u20131753, doi:10.1242\/dev.075804 (2012).","journal-title":"Development"},{"key":"8197_CR6","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1038\/nbt1004","volume":"22","author":"RM Seaberg","year":"2004","unstructured":"Seaberg, R. M. et al. Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol \n                           22, 1115\u20131124, doi:10.1038\/nbt1004 (2004).","journal-title":"Nat Biotechnol"},{"key":"8197_CR7","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1242\/dev.125.10.1921","volume":"125","author":"EC Kordon","year":"1998","unstructured":"Kordon, E. C. & Smith, G. H. An entire functional mammary gland may comprise the progeny from a single cell. Development \n                           125, 1921\u20131930 (1998).","journal-title":"Development"},{"key":"8197_CR8","doi-asserted-by":"publisher","first-page":"2749","DOI":"10.1167\/iovs.11-9025","volume":"53","author":"MA Shatos","year":"2012","unstructured":"Shatos, M. A., Haugaard-Kedstrom, L., Hodges, R. R. & Dartt, D. A. Isolation and characterization of progenitor cells in uninjured, adult rat lacrimal gland. Invest Ophthalmol Vis Sci \n                           53, 2749\u20132759, doi:10.1167\/iovs.11-9025 (2012).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"8197_CR9","doi-asserted-by":"publisher","first-page":"4350","DOI":"10.1167\/iovs.15-16475","volume":"56","author":"P Ackermann","year":"2015","unstructured":"Ackermann, P. et al. Isolation and Investigation of Presumptive Murine Lacrimal Gland Stem Cells. Invest Ophthalmol Vis Sci \n                           56, 4350\u20134363, doi:10.1167\/iovs.15-16475 (2015).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"8197_CR10","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/s00441-011-1271-x","volume":"346","author":"S You","year":"2011","unstructured":"You, S., Tariq, A., Kublin, C. L. & Zoukhri, D. Detection of BrdU-label retaining cells in the lacrimal gland: implications for tissue repair. Cell Tissue Res \n                           346, 317\u2013326, doi:10.1007\/s00441-011-1271-x (2011).","journal-title":"Cell Tissue Res"},{"key":"8197_CR11","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/S0040816602000034","volume":"34","author":"S Takahashi","year":"2002","unstructured":"Takahashi, S. et al. The roles of apoptosis and mitosis in atrophy of the rat sublingual gland. Tissue Cell \n                           34, 297\u2013304 (2002).","journal-title":"Tissue Cell"},{"key":"8197_CR12","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1111\/j.1600-0714.2004.00234.x","volume":"33","author":"S Takahashi","year":"2004","unstructured":"Takahashi, S., Shinzato, K., Domon, T., Yamamoto, T. & Wakita, M. Mitotic proliferation of myoepithelial cells during regeneration of atrophied rat submandibular glands after duct ligation. J Oral Pathol Med \n                           33, 430\u2013434 (2004).","journal-title":"J Oral Pathol Med"},{"key":"8197_CR13","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/S0040-8166(00)80002-6","volume":"32","author":"S Takahashi","year":"2000","unstructured":"Takahashi, S. et al. Apoptosis and mitosis of parenchymal cells in the duct-ligated rat submandibular gland. Tissue Cell \n                           32, 457\u2013463 (2000).","journal-title":"Tissue Cell"},{"key":"8197_CR14","first-page":"50","volume":"23","author":"M Cummins","year":"1994","unstructured":"Cummins, M., Dardick, I., Brown, D. & Burford-Mason, A. Obstructive sialadenitis: a rat model. J Otolaryngol \n                           23, 50\u201356 (1994).","journal-title":"J Otolaryngol"},{"key":"8197_CR15","doi-asserted-by":"crossref","first-page":"G827","DOI":"10.1152\/ajpgi.2000.279.4.G827","volume":"279","author":"CR Scoggins","year":"2000","unstructured":"Scoggins, C. R. et al. p53-dependent acinar cell apoptosis triggers epithelial proliferation in duct-ligated murine pancreas. Am J Physiol Gastrointest Liver Physiol \n                           279, G827\u2013836 (2000).","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"8197_CR16","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1242\/dev.056499","volume":"138","author":"JL Kopp","year":"2011","unstructured":"Kopp, J. L. et al. Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas. Development \n                           138, 653\u2013665, doi:10.1242\/dev.056499 (2011).","journal-title":"Development"},{"key":"8197_CR17","doi-asserted-by":"publisher","first-page":"2708","DOI":"10.1038\/emboj.2013.204","volume":"32","author":"M Huch","year":"2013","unstructured":"Huch, M. et al. Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5\/R-spondin axis. EMBO J \n                           32, 2708\u20132721, doi:10.1038\/emboj.2013.204 (2013).","journal-title":"EMBO J"},{"key":"8197_CR18","first-page":"1267","volume":"18","author":"G Giannelli","year":"2003","unstructured":"Giannelli, G., Quaranta, V. & Antonaci, S. Tissue remodelling in liver diseases. Histol Histopathol \n                           18, 1267\u20131274 (2003).","journal-title":"Histol Histopathol"},{"key":"8197_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1006\/cbir.1994.1001","volume":"18","author":"MR Alison","year":"1994","unstructured":"Alison, M. R. & Sarraf, C. E. The role of growth factors in gastrointestinal cell proliferation. Cell Biol Int \n                           18, 1\u201310, doi:10.1006\/cbir.1994.1001 (1994).","journal-title":"Cell Biol Int"},{"key":"8197_CR20","doi-asserted-by":"crossref","unstructured":"Burgess, K. L. et al. Myoepithelial cells actively proliferate during atrophy of rat parotid gland. Oral Surg Oral Med Oral Pathol Oral Radiol Endod \n                           82, 674\u2013680, doi:S1079-2104(96)80443-4 [pii] (1996).","DOI":"10.1016\/S1079-2104(96)80443-4"},{"key":"8197_CR21","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1034\/j.1600-0714.2003.00043.x","volume":"32","author":"S Takahashi","year":"2003","unstructured":"Takahashi, S., Shinzato, K., Domon, T., Yamamoto, T. & Wakita, M. Proliferation and distribution of myoepithelial cells during atrophy of the rat sublingual gland. J Oral Pathol Med \n                           32, 90\u201394 (2003).","journal-title":"J Oral Pathol Med"},{"key":"8197_CR22","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.diff.2009.11.005","volume":"79","author":"E Cotroneo","year":"2010","unstructured":"Cotroneo, E., Proctor, G. B. & Carpenter, G. H. Regeneration of acinar cells following ligation of rat submandibular gland retraces the embryonic-perinatal pathway of cytodifferentiation. Differentiation \n                           79, 120\u2013130, doi:10.1016\/j.diff.2009.11.005 (2010).","journal-title":"Differentiation"},{"key":"8197_CR23","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.ydbio.2011.02.025","volume":"353","author":"S Arany","year":"2011","unstructured":"Arany, S., Catalan, M. A., Roztocil, E. & Ovitt, C. E. Ascl3 knockout and cell ablation models reveal complexity of salivary gland maintenance and regeneration. Dev Biol \n                           353, 186\u2013193, doi:10.1016\/j.ydbio.2011.02.025 (2011).","journal-title":"Dev Biol"},{"key":"8197_CR24","doi-asserted-by":"publisher","first-page":"4399","DOI":"10.1167\/iovs.08-1730","volume":"49","author":"D Zoukhri","year":"2008","unstructured":"Zoukhri, D., Fix, A., Alroy, J. & Kublin, C. L. Mechanisms of murine lacrimal gland repair after experimentally induced inflammation. Invest Ophthalmol Vis Sci \n                           49, 4399\u20134406, doi:10.1167\/iovs.08-1730 (2008).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"8197_CR25","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/j.exer.2007.01.015","volume":"84","author":"D Zoukhri","year":"2007","unstructured":"Zoukhri, D., Macari, E. & Kublin, C. L. A single injection of interleukin-1 induces reversible aqueous-tear deficiency, lacrimal gland inflammation, and acinar and ductal cell proliferation. Exp Eye Res \n                           84, 894\u2013904, doi:10.1016\/j.exer.2007.01.015 (2007).","journal-title":"Exp Eye Res"},{"key":"8197_CR26","doi-asserted-by":"publisher","first-page":"2792","DOI":"10.1242\/jcs.065268","volume":"123","author":"WC Li","year":"2010","unstructured":"Li, W. C. et al. Activation of pancreatic-duct-derived progenitor cells during pancreas regeneration in adult rats. J Cell Sci \n                           123, 2792\u20132802, doi:10.1242\/jcs.065268 (2010).","journal-title":"J Cell Sci"},{"key":"8197_CR27","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1002\/hep.20063","volume":"39","author":"Y Hisatomi","year":"2004","unstructured":"Hisatomi, Y. et al. Flow cytometric isolation of endodermal progenitors from mouse salivary gland differentiate into hepatic and pancreatic lineages. Hepatology \n                           39, 667\u2013675, doi:10.1002\/hep.20063 (2004).","journal-title":"Hepatology"},{"key":"8197_CR28","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.bbrc.2005.12.031","volume":"340","author":"T Kishi","year":"2006","unstructured":"Kishi, T., Takao, T., Fujita, K. & Taniguchi, H. Clonal proliferation of multipotent stem\/progenitor cells in the neonatal and adult salivary glands. Biochem Biophys Res Commun \n                           340, 544\u2013552, doi:10.1016\/j.bbrc.2005.12.031 (2006).","journal-title":"Biochem Biophys Res Commun"},{"key":"8197_CR29","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1111\/j.1582-4934.2005.tb00359.x","volume":"9","author":"YQ Zhang","year":"2005","unstructured":"Zhang, Y. Q., Kritzik, M. & Sarvetnick, N. Identification and expansion of pancreatic stem\/progenitor cells. J Cell Mol Med \n                           9, 331\u2013344 (2005).","journal-title":"J Cell Mol Med"},{"key":"8197_CR30","doi-asserted-by":"publisher","first-page":"2710","DOI":"10.1167\/iovs.08-2905","volume":"50","author":"N Dong","year":"2009","unstructured":"Dong, N. et al. Abnormal epithelial differentiation and tear film alteration in pinguecula. Invest Ophthalmol Vis Sci \n                           50, 2710\u20132715, doi:10.1167\/iovs.08-2905 (2009).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"8197_CR31","first-page":"1271","volume":"18","author":"S Kobayashi","year":"2012","unstructured":"Kobayashi, S. et al. Characterization of cultivated murine lacrimal gland epithelial cells. Mol Vis \n                           18, 1271\u20131277 (2012).","journal-title":"Mol Vis"},{"key":"8197_CR32","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1089\/ten.tea.2015.0286","volume":"22","author":"H Lin","year":"2016","unstructured":"Lin, H. et al. Three-Dimensional Culture of Functional Adult Rabbit Lacrimal Gland Epithelial Cells on Decellularized Scaffold. Tissue Eng Part A \n                           22, 65\u201374, doi:10.1089\/ten.TEA.2015.0286 (2016).","journal-title":"Tissue Eng Part A"},{"key":"8197_CR33","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1167\/iovs.10-5686","volume":"52","author":"S You","year":"2011","unstructured":"You, S., Kublin, C. L., Avidan, O., Miyasaki, D. & Zoukhri, D. Isolation and propagation of mesenchymal stem cells from the lacrimal gland. Invest Ophthalmol Vis Sci \n                           52, 2087\u20132094, doi:10.1167\/iovs.10-5686 (2011).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"8197_CR34","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/S1542-0124(12)70222-7","volume":"8","author":"JE Schechter","year":"2010","unstructured":"Schechter, J. E., Warren, D. W. & Mircheff, A. K. A Lacrimal Gland is a Lacrimal Gland, But Rodent\u2019s and Rabbit\u2019s Are Not Human. Ocular Surface \n                           8, 111\u2013134 (2010).","journal-title":"Ocular Surface"},{"key":"8197_CR35","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1097\/ICO.0b013e3181f1b0fc","volume":"30","author":"ZY Chen","year":"2011","unstructured":"Chen, Z. Y., Liang, Q. F. & Yu, G. Y. Establishment of a rabbit model for keratoconjunctivitis sicca. Cornea \n                           30, 1024\u20131029, doi:10.1097\/ICO.0b013e3181f1b0fc (2011).","journal-title":"Cornea"},{"key":"8197_CR36","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1111\/j.1582-4934.2008.00297.x","volume":"12","author":"T Kawakita","year":"2008","unstructured":"Kawakita, T., Shimmura, S., Hornia, A., Higa, K. & Tseng, S. C. Stratified epithelial sheets engineered from a single adult murine corneal\/limbal progenitor cell. J Cell Mol Med \n                           12, 1303\u20131316, doi:10.1111\/j.1582-4934.2008.00297.x (2008).","journal-title":"J Cell Mol Med"},{"key":"8197_CR37","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.3109\/02713683.2011.608238","volume":"36","author":"M Pauklin","year":"2011","unstructured":"Pauklin, M., Thomasen, H., Pester, A., Steuhl, K. P. & Meller, D. Expression of pluripotency and multipotency factors in human ocular surface tissues. Curr Eye Res \n                           36, 1086\u20131097, doi:10.3109\/02713683.2011.608238 (2011).","journal-title":"Curr Eye Res"},{"key":"8197_CR38","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1002\/jcp.22215","volume":"225","author":"H Qi","year":"2010","unstructured":"Qi, H., Zheng, X., Yuan, X., Pflugfelder, S. C. & Li, D. Q. Potential localization of putative stem\/progenitor cells in human bulbar conjunctival epithelium. J Cell Physiol \n                           225, 180\u2013185, doi:10.1002\/jcp.22215 (2010).","journal-title":"J Cell Physiol"},{"key":"8197_CR39","doi-asserted-by":"publisher","first-page":"e87368","DOI":"10.1371\/journal.pone.0087368","volume":"9","author":"H Lin","year":"2014","unstructured":"Lin, H. et al. Air exposure induced characteristics of dry eye in conjunctival tissue culture. PLoS One \n                           9, e87368, doi:10.1371\/journal.pone.0087368 (2014).","journal-title":"PLoS One"},{"key":"8197_CR40","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.exer.2015.11.020","volume":"146","author":"M Hirayama","year":"2016","unstructured":"Hirayama, M., Liu, Y., Kawakita, T., Shimmura, S. & Tsubota, K. Cytokeratin expression in mouse lacrimal gland germ epithelium. Exp Eye Res \n                           146, 54\u201359, doi:10.1016\/j.exer.2015.11.020 (2016).","journal-title":"Exp Eye Res"},{"key":"8197_CR41","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.cell.2008.03.027","volume":"133","author":"SA Mani","year":"2008","unstructured":"Mani, S. A. et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell \n                           133, 704\u2013715, doi:10.1016\/j.cell.2008.03.027 (2008).","journal-title":"Cell"},{"key":"8197_CR42","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1167\/iovs.11-7893","volume":"53","author":"S You","year":"2012","unstructured":"You, S. et al. Role of epithelial-mesenchymal transition in repair of the lacrimal gland after experimentally induced injury. Invest Ophthalmol Vis Sci \n                           53, 126\u2013135, doi:10.1167\/iovs.11-7893 (2012).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"8197_CR43","doi-asserted-by":"publisher","first-page":"38757","DOI":"10.1074\/jbc.M111.244939","volume":"286","author":"JE Oh","year":"2011","unstructured":"Oh, J. E., Kim, R. H., Shin, K. H., Park, N. H. & Kang, M. K. DeltaNp63alpha protein triggers epithelial-mesenchymal transition and confers stem cell properties in normal human keratinocytes. J Biol Chem \n                           286, 38757\u201338767, doi:10.1074\/jbc.M111.244939 (2011).","journal-title":"J Biol Chem"},{"key":"8197_CR44","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1242\/dev.108944","volume":"141","author":"Z Chen","year":"2014","unstructured":"Chen, Z. et al. FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands. Development \n                           141, 2691\u20132701, doi:10.1242\/dev.108944 (2014).","journal-title":"Development"},{"key":"8197_CR45","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1177\/00220345910700100301","volume":"70","author":"D Schwartz-Arad","year":"1991","unstructured":"Schwartz-Arad, D., Michaeli, Y. & Zajicek, G. Compensatory hyperplasia of the rat submandibular gland following unilateral extirpation. J Dent Res \n                           70, 1328\u20131331 (1991).","journal-title":"J Dent Res"},{"key":"8197_CR46","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/path.1711530407","volume":"153","author":"NI Walker","year":"1987","unstructured":"Walker, N. I. & Gobe, G. C. Cell death and cell proliferation during atrophy of the rat parotid gland induced by duct obstruction. J Pathol \n                           153, 333\u2013344, doi:10.1002\/path.1711530407 (1987).","journal-title":"J Pathol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08197-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08197-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08197-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T08:44:49Z","timestamp":1671785089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08197-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,15]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["8197"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-08197-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,15]]},"assertion":[{"value":"17 October 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"8290"}}