{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:53:42Z","timestamp":1792166022036,"version":"4.4.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"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>\n                    Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in CTCL cells. KPT-330 reduces cell proliferation, induces G1 cell cycle arrest and apoptosis. RNA-sequencing was used to explore the underlying mechanisms. Genes associated with the cell cycle and the p53 pathway were significantly enriched with KPT-330 treatment. KPT-330 suppressed XPO1 expression, upregulated p53, p21\n                    <jats:sup>WAF1\/Cip1<\/jats:sup>\n                    , and p27\n                    <jats:sup>Kip1<\/jats:sup>\n                    and their nuclear localization, and downregulated anti-apoptotic protein (Survivin). The in vivo efficacy of KPT-330 was investigated using a bioluminescent xenograft mouse model of CTCL. KPT-330 blocked tumor growth and prolonged survival (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0002) compared to controls. These findings support investigating the use of KPT-330 and next-generation XPO1 inhibitors in CTCL.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-59994-5","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T07:02:41Z","timestamp":1713855761000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["XPO1 blockade with KPT-330 promotes apoptosis in cutaneous T-cell lymphoma by activating the p53\u2013p21 and p27 pathways"],"prefix":"10.1038","volume":"14","author":[{"given":"Nitin","family":"Chakravarti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Boles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Burzinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Sindaco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Isabelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"McConnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Porcu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"59994_CR1","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1126\/science.271.5255.1513","volume":"271","author":"D Gorlich","year":"1996","unstructured":"Gorlich, D. & Mattaj, I. W. Nucleocytoplasmic transport. Science 271, 1513\u20131518. https:\/\/doi.org\/10.1126\/science.271.5255.1513 (1996).","journal-title":"Science"},{"key":"59994_CR2","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","volume":"12","author":"D Hanahan","year":"2022","unstructured":"Hanahan, D. Hallmarks of cancer: New dimensions. Cancer Discov. 12, 31\u201346. https:\/\/doi.org\/10.1158\/2159-8290.CD-21-1059 (2022).","journal-title":"Cancer Discov."},{"key":"59994_CR3","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.ceb.2018.01.006","volume":"52","author":"T Cagatay","year":"2018","unstructured":"Cagatay, T. & Chook, Y. M. Karyopherins in cancer. Curr. Opin. Cell Biol. 52, 30\u201342. https:\/\/doi.org\/10.1016\/j.ceb.2018.01.006 (2018).","journal-title":"Curr. Opin. Cell Biol."},{"key":"59994_CR4","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13045-020-00903-4","volume":"13","author":"NG Azizian","year":"2020","unstructured":"Azizian, N. G. & Li, Y. XPO1-dependent nuclear export as a target for cancer therapy. J. Hematol. Oncol. 13, 61. https:\/\/doi.org\/10.1186\/s13045-020-00903-4 (2020).","journal-title":"J. Hematol. Oncol."},{"key":"59994_CR5","doi-asserted-by":"publisher","first-page":"82144","DOI":"10.18632\/oncotarget.19285","volume":"8","author":"AS Azmi","year":"2017","unstructured":"Azmi, A. S. et al. Exportin 1 (XPO1) inhibition leads to restoration of tumor suppressor miR-145 and consequent suppression of pancreatic cancer cell proliferation and migration. Oncotarget 8, 82144\u201382155. https:\/\/doi.org\/10.18632\/oncotarget.19285 (2017).","journal-title":"Oncotarget"},{"key":"59994_CR6","doi-asserted-by":"publisher","first-page":"2875","DOI":"10.1038\/s41375-020-0958-y","volume":"34","author":"B Nachmias","year":"2020","unstructured":"Nachmias, B. & Schimmer, A. D. Targeting nuclear import and export in hematological malignancies. Leukemia 34, 2875\u20132886. https:\/\/doi.org\/10.1038\/s41375-020-0958-y (2020).","journal-title":"Leukemia"},{"key":"59994_CR7","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s41572-021-00296-9","volume":"7","author":"R Dummer","year":"2021","unstructured":"Dummer, R. et al. Cutaneous T cell lymphoma. Nat. Rev. Dis. Primers 7, 61. https:\/\/doi.org\/10.1038\/s41572-021-00296-9 (2021).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"59994_CR8","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1007\/s10637-022-01250-6","volume":"40","author":"C Ishikawa","year":"2022","unstructured":"Ishikawa, C. & Mori, N. Exportin-1 is critical for cell proliferation and survival in adult T cell leukemia. Invest. New Drugs 40, 718\u2013727. https:\/\/doi.org\/10.1007\/s10637-022-01250-6 (2022).","journal-title":"Invest. New Drugs"},{"key":"59994_CR9","doi-asserted-by":"publisher","first-page":"113180","DOI":"10.1016\/j.yexcr.2022.113180","volume":"416","author":"D Nie","year":"2022","unstructured":"Nie, D. et al. Prognostic and therapeutic significance of XPO1 in T-cell lymphoma. Exp. Cell Res. 416, 113180. https:\/\/doi.org\/10.1016\/j.yexcr.2022.113180 (2022).","journal-title":"Exp. Cell Res."},{"key":"59994_CR10","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/j.bcp.2011.12.016","volume":"83","author":"JG Turner","year":"2012","unstructured":"Turner, J. G., Dawson, J. & Sullivan, D. M. Nuclear export of proteins and drug resistance in cancer. Biochem. Pharmacol. 83, 1021\u20131032. https:\/\/doi.org\/10.1016\/j.bcp.2011.12.016 (2012).","journal-title":"Biochem. Pharmacol."},{"key":"59994_CR11","doi-asserted-by":"publisher","first-page":"6","DOI":"10.21037\/sci.2019.02.03","volume":"6","author":"AY Wang","year":"2019","unstructured":"Wang, A. Y. & Liu, H. The past, present, and future of CRM1\/XPO1 inhibitors. Stem Cell Investig 6, 6. https:\/\/doi.org\/10.21037\/sci.2019.02.03 (2019).","journal-title":"Stem Cell Investig"},{"key":"59994_CR12","doi-asserted-by":"publisher","first-page":"16010","DOI":"10.1038\/sigtrans.2016.10","volume":"1","author":"Q Sun","year":"2016","unstructured":"Sun, Q. et al. Inhibiting cancer cell hallmark features through nuclear export inhibition. Signal Transduct. Target Ther 1, 16010. https:\/\/doi.org\/10.1038\/sigtrans.2016.10 (2016).","journal-title":"Signal Transduct. Target Ther"},{"key":"59994_CR13","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41571-020-00442-4","volume":"18","author":"AS Azmi","year":"2021","unstructured":"Azmi, A. S., Uddin, M. H. & Mohammad, R. M. The nuclear export protein XPO1\u2014From biology to targeted therapy. Nat. Rev. Cli.n Oncol. 18, 152\u2013169. https:\/\/doi.org\/10.1038\/s41571-020-00442-4 (2021).","journal-title":"Nat. Rev. Cli.n Oncol."},{"key":"59994_CR14","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-022-04247-z","author":"JR Landes","year":"2022","unstructured":"Landes, J. R. et al. The efficacy of selinexor (KPT-330), an XPO1 inhibitor, on non-hematologic cancers: A comprehensive review. J. Cancer Res. Clin. Oncol. https:\/\/doi.org\/10.1007\/s00432-022-04247-z (2022).","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"59994_CR15","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14010087","author":"A Sochacka-Cwikla","year":"2021","unstructured":"Sochacka-Cwikla, A., Maczynski, M. & Regiec, A. FDA-approved drugs for hematological malignancies-the last decade review. Cancers (Basel) https:\/\/doi.org\/10.3390\/cancers14010087 (2021).","journal-title":"Cancers (Basel)"},{"key":"59994_CR16","doi-asserted-by":"publisher","first-page":"D587","DOI":"10.1093\/nar\/gkac963","volume":"51","author":"M Kanehisa","year":"2023","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M. & Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 51, D587\u2013D592. https:\/\/doi.org\/10.1093\/nar\/gkac963 (2023).","journal-title":"Nucleic Acids Res."},{"key":"59994_CR17","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27\u201330. https:\/\/doi.org\/10.1093\/nar\/28.1.27 (2000).","journal-title":"Nucleic Acids Res."},{"key":"59994_CR18","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1158\/1078-0432.CCR-14-2249","volume":"21","author":"S Jain","year":"2015","unstructured":"Jain, S. et al. Preclinical pharmacologic evaluation of pralatrexate and romidepsin confirms potent synergy of the combination in a murine model of human T-cell lymphoma. Clin. Cancer Res. 21, 2096\u20132106. https:\/\/doi.org\/10.1158\/1078-0432.CCR-14-2249 (2015).","journal-title":"Clin. Cancer Res."},{"key":"59994_CR19","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1158\/1535-7163.MCT-21-0370","volume":"20","author":"KF Handley","year":"2021","unstructured":"Handley, K. F. et al. Rational combination of CRM1 inhibitor selinexor and olaparib shows synergy in ovarian cancer cell lines and mouse models. Mol. Cancer Ther. 20, 2352\u20132361. https:\/\/doi.org\/10.1158\/1535-7163.MCT-21-0370 (2021).","journal-title":"Mol. Cancer Ther."},{"key":"59994_CR20","doi-asserted-by":"publisher","first-page":"3307","DOI":"10.1158\/1078-0432.CCR-20-4929","volume":"27","author":"EK Seymour","year":"2021","unstructured":"Seymour, E. K. et al. Selinexor in combination with R-CHOP for frontline treatment of non-hodgkin lymphoma: Results of a phase I study. Clin. Cancer Res. 27, 3307\u20133316. https:\/\/doi.org\/10.1158\/1078-0432.CCR-20-4929 (2021).","journal-title":"Clin. Cancer Res."},{"key":"59994_CR21","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/s41419-019-1627-9","volume":"10","author":"ZC Zhu","year":"2019","unstructured":"Zhu, Z. C., Liu, J. W., Yang, C., Zhao, M. & Xiong, Z. Q. XPO1 inhibitor KPT-330 synergizes with Bcl-xL inhibitor to induce cancer cell apoptosis by perturbing rRNA processing and Mcl-1 protein synthesis. Cell Death Dis. 10, 395. https:\/\/doi.org\/10.1038\/s41419-019-1627-9 (2019).","journal-title":"Cell Death Dis."},{"key":"59994_CR22","doi-asserted-by":"publisher","first-page":"3338","DOI":"10.1038\/sj.onc.1207456","volume":"23","author":"B Scheijen","year":"2004","unstructured":"Scheijen, B., Ngo, H. T., Kang, H. & Griffin, J. D. FLT3 receptors with internal tandem duplications promote cell viability and proliferation by signaling through Foxo proteins. Oncogene 23, 3338\u20133349. https:\/\/doi.org\/10.1038\/sj.onc.1207456 (2004).","journal-title":"Oncogene"},{"key":"59994_CR23","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/s41375-021-01483-z","volume":"36","author":"SK Balasubramanian","year":"2022","unstructured":"Balasubramanian, S. K., Azmi, A. S. & Maciejewski, J. Selective inhibition of nuclear export: A promising approach in the shifting treatment paradigms for hematological neoplasms. Leukemia 36, 601\u2013612. https:\/\/doi.org\/10.1038\/s41375-021-01483-z (2022).","journal-title":"Leukemia"},{"key":"59994_CR24","doi-asserted-by":"publisher","first-page":"e0224305","DOI":"10.1371\/journal.pone.0224305","volume":"14","author":"IM Talaat","year":"2019","unstructured":"Talaat, I. M. et al. Potential role for microRNA-16 (miR-16) and microRNA-93 (miR-93) in diagnosis and prediction of disease progression in mycosis fungoides in Egyptian patients. PLoS One 14, e0224305. https:\/\/doi.org\/10.1371\/journal.pone.0224305 (2019).","journal-title":"PLoS One"},{"key":"59994_CR25","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1038\/jid.2010.86","volume":"130","author":"C Zhang","year":"2010","unstructured":"Zhang, C. et al. Curcumin selectively induces apoptosis in cutaneous T-cell lymphoma cell lines and patients\u2019 PBMCs: Potential role for STAT-3 and NF-kappaB signaling. J. Invest. Dermatol. 130, 2110\u20132119. https:\/\/doi.org\/10.1038\/jid.2010.86 (2010).","journal-title":"J. Invest. Dermatol."},{"key":"59994_CR26","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1038\/sj.embor.7400824","volume":"7","author":"SK Knauer","year":"2006","unstructured":"Knauer, S. K., Bier, C., Habtemichael, N. & Stauber, R. H. The Survivin-Crm1 interaction is essential for chromosomal passenger complex localization and function. EMBO Rep. 7, 1259\u20131265. https:\/\/doi.org\/10.1038\/sj.embor.7400824 (2006).","journal-title":"EMBO Rep."},{"key":"59994_CR27","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/nrc968","volume":"3","author":"DC Altieri","year":"2003","unstructured":"Altieri, D. C. Validating survivin as a cancer therapeutic target. Nat. Rev. Cancer 3, 46\u201354. https:\/\/doi.org\/10.1038\/nrc968 (2003).","journal-title":"Nat. Rev. Cancer"},{"key":"59994_CR28","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nrc2293","volume":"8","author":"DC Altieri","year":"2008","unstructured":"Altieri, D. C. Survivin, cancer networks and pathway-directed drug discovery. Nat. Rev. Cancer 8, 61\u201370. https:\/\/doi.org\/10.1038\/nrc2293 (2008).","journal-title":"Nat. Rev. Cancer"},{"key":"59994_CR29","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.canlet.2012.03.005","volume":"332","author":"DC Altieri","year":"2013","unstructured":"Altieri, D. C. Targeting survivin in cancer. Cancer Lett. 332, 225\u2013228. https:\/\/doi.org\/10.1016\/j.canlet.2012.03.005 (2013).","journal-title":"Cancer Lett."},{"key":"59994_CR30","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.1038\/jid.2008.138","volume":"128","author":"C Zhang","year":"2008","unstructured":"Zhang, C. et al. Avicin D selectively induces apoptosis and downregulates p-STAT-3, bcl-2, and survivin in cutaneous T-cell lymphoma cells. J. Invest. Dermatol. 128, 2728\u20132735. https:\/\/doi.org\/10.1038\/jid.2008.138 (2008).","journal-title":"J. Invest. Dermatol."},{"key":"59994_CR31","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1046\/j.1523-1747.1998.00167.x","volume":"110","author":"G Li","year":"1998","unstructured":"Li, G. et al. Overexpression of p53 protein in cutaneous T cell lymphoma: Relationship to large cell transformation and disease progression. J. Invest. Dermatol 110, 767\u2013770. https:\/\/doi.org\/10.1046\/j.1523-1747.1998.00167.x (1998).","journal-title":"J. Invest. Dermatol"},{"key":"59994_CR32","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s13045-021-01169-0","volume":"14","author":"J Hu","year":"2021","unstructured":"Hu, J. et al. Targeting mutant p53 for cancer therapy: direct and indirect strategies. J. Hematol. Oncol. 14, 157. https:\/\/doi.org\/10.1186\/s13045-021-01169-0 (2021).","journal-title":"J. Hematol. Oncol."},{"key":"59994_CR33","doi-asserted-by":"publisher","first-page":"3275","DOI":"10.1182\/blood-2021-151373","volume":"138","author":"JT Baeten","year":"2021","unstructured":"Baeten, J. T., Chan, I. C. C., Link, D. C. & Bolton, K. L. Effects of PARP inhibitor therapy on p53-deficient hematopoietic stem and progenitor cell fitness. Blood 138, 3275\u20133275. https:\/\/doi.org\/10.1182\/blood-2021-151373 (2021).","journal-title":"Blood"},{"key":"59994_CR34","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1002\/emmm.201200228","volume":"4","author":"M Jemaa","year":"2012","unstructured":"Jemaa, M. et al. Selective killing of p53-deficient cancer cells by SP600125. EMBO Mol. Med. 4, 500\u2013514. https:\/\/doi.org\/10.1002\/emmm.201200228 (2012).","journal-title":"EMBO Mol. Med."},{"key":"59994_CR35","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.cell.2012.04.026","volume":"149","author":"T Li","year":"2012","unstructured":"Li, T. et al. Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence. Cell 149, 1269\u20131283. https:\/\/doi.org\/10.1016\/j.cell.2012.04.026 (2012).","journal-title":"Cell"},{"key":"59994_CR36","doi-asserted-by":"publisher","first-page":"95981","DOI":"10.18632\/oncotarget.21619","volume":"8","author":"E Netchiporouk","year":"2017","unstructured":"Netchiporouk, E. et al. Analysis of CTCL cell lines reveals important differences between mycosis fungoides\/Sezary syndrome versus HTLV-1(+) leukemic cell lines. Oncotarget 8, 95981\u201395998. https:\/\/doi.org\/10.18632\/oncotarget.21619 (2017).","journal-title":"Oncotarget"},{"key":"59994_CR37","doi-asserted-by":"publisher","first-page":"3502","DOI":"10.1002\/jcb.23296","volume":"112","author":"J Cmielova","year":"2011","unstructured":"Cmielova, J. & Rezacova, M. p21Cip1\/Waf1 protein and its function based on a subcellular localization [corrected]. J. Cell Biochem. 112, 3502\u20133506. https:\/\/doi.org\/10.1002\/jcb.23296 (2011).","journal-title":"J. Cell Biochem."},{"key":"59994_CR38","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41408-021-00409-3","volume":"11","author":"E Boons","year":"2021","unstructured":"Boons, E. et al. XPO1 inhibitors represent a novel therapeutic option in Adult T-cell Leukemia, triggering p53-mediated caspase-dependent apoptosis. Blood Cancer J. 11, 27. https:\/\/doi.org\/10.1038\/s41408-021-00409-3 (2021).","journal-title":"Blood Cancer J."},{"key":"59994_CR39","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1182\/blood-2023-182553","volume":"142","author":"K Ding","year":"2023","unstructured":"Ding, K. et al. High rates of remission with the initial treatment of oral selinexor plus CHOP for newly diagnosed peripheral T-cell lymphoma (PTCL): Clinical outcomes analysis of a multi-center phase II study in China. Blood 142, 1696\u20131696. https:\/\/doi.org\/10.1182\/blood-2023-182553 (2023).","journal-title":"Blood"},{"key":"59994_CR40","doi-asserted-by":"publisher","first-page":"3637","DOI":"10.1182\/bloodadvances.2023009807","volume":"7","author":"C Isabelle","year":"2023","unstructured":"Isabelle, C. et al. Preclinical evaluation of anti-CD38 therapy in mature T-cell neoplasms. Blood Adv. 7, 3637\u20133641. https:\/\/doi.org\/10.1182\/bloodadvances.2023009807 (2023).","journal-title":"Blood Adv."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-59994-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-59994-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-59994-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T07:04:59Z","timestamp":1713855899000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-59994-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,23]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["59994"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-59994-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,23]]},"assertion":[{"value":"18 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2024","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":"9305"}}