{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T01:18:51Z","timestamp":1775092731746,"version":"3.50.1"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T00:00:00Z","timestamp":1729296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T00:00:00Z","timestamp":1729296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"FCT fellowship","award":["SFRH\/BD\/145767\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145767\/2019"]}]},{"name":"FCT fellowship","award":["SFRH\/BD\/116780\/2016"],"award-info":[{"award-number":["SFRH\/BD\/116780\/2016"]}]},{"name":"H2020  Marie Sklodowska-Curie grant agreement","award":["No. 813453"],"award-info":[{"award-number":["No. 813453"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-75582-z","type":"journal-article","created":{"date-parts":[[2024,10,19]],"date-time":"2024-10-19T13:02:17Z","timestamp":1729342937000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Oxygen control in bioreactor drives high yield production of functional hiPSC-like hepatocytes for advanced liver disease modelling"],"prefix":"10.1038","volume":"14","author":[{"given":"Pedro","family":"Vicente","sequence":"first","affiliation":[]},{"given":"Joana I.","family":"Almeida","sequence":"additional","affiliation":[]},{"given":"In\u00eas E.","family":"Crespo","sequence":"additional","affiliation":[]},{"given":"Nikolaus","family":"Virgolini","sequence":"additional","affiliation":[]},{"given":"In\u00eas A.","family":"Isidro","sequence":"additional","affiliation":[]},{"given":"Maria Er\u00e9ndira","family":"Calleja-Cervantes","sequence":"additional","affiliation":[]},{"given":"Juan R.","family":"Rodriguez-Madoz","sequence":"additional","affiliation":[]},{"given":"Felipe","family":"Prosper","sequence":"additional","affiliation":[]},{"given":"Paula M.","family":"Alves","sequence":"additional","affiliation":[]},{"given":"Margarida","family":"Serra","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,10,19]]},"reference":[{"key":"75582_CR1","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.jhep.2018.09.014","volume":"70","author":"SK Asrani","year":"2019","unstructured":"Asrani, S. K., Devarbhavi, H., Eaton, J. & Kamath, P. S. Burden of liver diseases in the world. J. Hepatol.70, 151\u2013171 (2019).","journal-title":"J. Hepatol."},{"key":"75582_CR2","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.cgh.2016.07.020","volume":"15","author":"M Stepanova","year":"2017","unstructured":"Stepanova, M. et al. Direct and indirect economic burden of chronic liver disease in the United States. Clin. Gastroenterol. Hepatol.15, 759-766e5 (2017).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"75582_CR3","doi-asserted-by":"crossref","unstructured":"Heydari, Z. et al. Tissue engineering in liver regenerative medicine: Insights into novel translational technologies. Cells9, 304 (2020).","DOI":"10.3390\/cells9020304"},{"key":"75582_CR4","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.stem.2023.03.013","volume":"30","author":"Y Wang","year":"2023","unstructured":"Wang, Y. et al. Reversal of liver failure using a bioartificial liver device implanted with clinical-grade human-induced hepatocytes. Cell. Stem Cell.30, 617\u2013631e8 (2023).","journal-title":"Cell. Stem Cell."},{"key":"75582_CR5","doi-asserted-by":"crossref","unstructured":"Lee, J. H. et al. Establishment of a serum-free hepatocyte cryopreservation process for the development of an off-the-shelf bioartificial liver system. Bioengineering9, 738 (2022).","DOI":"10.3390\/bioengineering9120738"},{"key":"75582_CR6","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.scr.2012.06.004","volume":"9","author":"Y Yu","year":"2012","unstructured":"Yu, Y. et al. Hepatocyte-like cells differentiated from human induced pluripotent stem cells: Relevance to cellular therapies. Stem Cell. Res.9, 196\u2013207 (2012).","journal-title":"Stem Cell. Res."},{"key":"75582_CR7","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1007\/s10565-017-9383-z","volume":"33","author":"X Gao","year":"2017","unstructured":"Gao, X. & Liu, Y. A transcriptomic study suggesting human iPSC-derived hepatocytes potentially offer a better in vitro model of hepatotoxicity than most hepatoma cell lines. Cell. Biol. Toxicol.33, 407\u2013421 (2017).","journal-title":"Cell. Biol. Toxicol."},{"key":"75582_CR8","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.dmpk.2016.10.408","volume":"32","author":"K Takayama","year":"2017","unstructured":"Takayama, K. & Mizuguchi, H. Generation of human pluripotent stem cell-derived hepatocyte-like cells for drug toxicity screening. Drug Metab. Pharmacokinet.32, 12\u201320 (2017).","journal-title":"Drug Metab. Pharmacokinet."},{"key":"75582_CR9","doi-asserted-by":"crossref","unstructured":"Blaszkiewicz, J. & Duncan, S. A. Advancements in disease modeling and drug discovery using iPSC-derived hepatocyte-like cells. Genes (Basel)13, 573 (2022).","DOI":"10.3390\/genes13040573"},{"key":"75582_CR10","doi-asserted-by":"crossref","unstructured":"Corbett, J. L. & Duncan, S. A. iPSC-derived hepatocytes as a platform for disease modeling and drug discovery. Front. Med. (Lausanne)6, 265 (2019).","DOI":"10.3389\/fmed.2019.00265"},{"key":"75582_CR11","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1002\/hep.25871","volume":"56","author":"MA Cayo","year":"2012","unstructured":"Cayo, M. A. et al. JD induced pluripotent stem cell\u2013derived hepatocytes faithfully recapitulate the pathophysiology of familial hypercholesterolemia. Hepatology. 56, 2163\u20132171 (2012).","journal-title":"Hepatology"},{"key":"75582_CR12","doi-asserted-by":"publisher","first-page":"bio055087","DOI":"10.1242\/bio.055087","volume":"9","author":"I Gurevich","year":"2020","unstructured":"Gurevich, I. et al. iPSC-derived hepatocytes generated from NASH donors provide a valuable platform for disease modeling and drug discovery. Biol. Open.9, bio055087 (2020).","journal-title":"Biol. Open."},{"key":"75582_CR13","doi-asserted-by":"publisher","first-page":"101467","DOI":"10.1016\/j.scr.2019.101467","volume":"38","author":"J Est\u00e8ve","year":"2019","unstructured":"Est\u00e8ve, J. et al. Generation of induced pluripotent stem cells-derived hepatocyte-like cells for ex vivo gene therapy of primary hyperoxaluria type 1. Stem Cell. Res.38, 101467 (2019).","journal-title":"Stem Cell. Res."},{"key":"75582_CR14","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/nrneph.2012.113","volume":"8","author":"B Hoppe","year":"2012","unstructured":"Hoppe, B. An update on primary hyperoxaluria. Nat. Rev. Nephrol.8, 467\u2013475 (2012).","journal-title":"Nat. Rev. Nephrol."},{"key":"75582_CR15","doi-asserted-by":"publisher","first-page":"101626","DOI":"10.1016\/j.scr.2019.101626","volume":"41","author":"R Martinez-Turrillas","year":"2019","unstructured":"Martinez-Turrillas, R. et al. Generation of an induced pluripotent stem cell line (CIMAi001-A) from a compound heterozygous primary hyperoxaluria type I (PH1) patient carrying p.G170R and p.R122* mutations in the AGXT gene. Stem Cell. Res.41, 101626 (2019).","journal-title":"Stem Cell. Res."},{"key":"75582_CR16","doi-asserted-by":"publisher","first-page":"1G41","DOI":"10.1002\/9780470151808.sc01g04s26","volume":"26","author":"SK Mallanna","year":"2013","unstructured":"Mallanna, S. K. & Duncan, S. A. Differentiation of hepatocytes from pluripotent stem cells. Curr. Protoc. Stem Cell. Biol.26, 1G41\u20131G413 (2013).","journal-title":"Curr. Protoc. Stem Cell. Biol."},{"key":"75582_CR17","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1002\/hep.23354","volume":"51","author":"K Si-tayeb","year":"2010","unstructured":"Si-tayeb, K. et al. Highly efficient generation of human hepatocyte\u2013like cells from induced pluripotent stem cells. Hepatology51, 297\u2013305 (2010).","journal-title":"Hepatology"},{"key":"75582_CR18","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.bbrc.2018.01.186","volume":"496","author":"T Yamashita","year":"2018","unstructured":"Yamashita, T., Takayama, K., Sakurai, F. & Mizuguchi, H. Billion-scale production of hepatocyte-like cells from human induced pluripotent stem cells. Biochem. Biophys. Res. Commun.496, 1269\u20131275 (2018).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"75582_CR19","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.biomaterials.2018.01.005","volume":"159","author":"Z Heidariyan","year":"2018","unstructured":"Heidariyan, Z. et al. Efficient and cost-effective generation of hepatocyte-like cells through microparticle-mediated delivery of growth factors in a 3D culture of human pluripotent stem cells. Biomaterials159, 174\u2013188 (2018).","journal-title":"Biomaterials"},{"key":"75582_CR20","doi-asserted-by":"crossref","unstructured":"Sivertsson, L., Synnergren, J. & Jensen, J. Hepatic differentiation and maturation of human embryonic stem cells cultured in a perfused three-dimensional bioreactor. Stem Cells Dev. 22, 581-594 (2013).","DOI":"10.1089\/scd.2012.0202"},{"key":"75582_CR21","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.bpg.2017.03.003","volume":"31","author":"J Willemse","year":"2017","unstructured":"Willemse, J., Lieshout, R., van der Laan, L. J. W. & Verstegen, M. M. A. from organoids to organs: Bioengineering liver grafts from hepatic stem cells and matrix. Best Pract. Res. Clin. Gastroenterol.31, 151\u2013159 (2017).","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"75582_CR22","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.redox.2017.01.012","volume":"11","author":"T Kietzmann","year":"2017","unstructured":"Kietzmann, T. Metabolic zonation of the liver: The oxygen gradient revisited. Redox Biol.11, 622\u2013630 (2017).","journal-title":"Redox Biol."},{"key":"75582_CR23","doi-asserted-by":"publisher","first-page":"3739","DOI":"10.1002\/bit.27521","volume":"117","author":"Z Farzaneh","year":"2020","unstructured":"Farzaneh, Z. et al. Dissolved oxygen concentration regulates human hepatic organoid formation from pluripotent stem cells in a fully controlled bioreactor. Biotechnol. Bioeng.117, 3739\u20133756 (2020).","journal-title":"Biotechnol. Bioeng."},{"key":"75582_CR24","doi-asserted-by":"publisher","first-page":"2987","DOI":"10.1002\/jcp.22651","volume":"226","author":"JB Lillegard","year":"2011","unstructured":"Lillegard, J. B. et al. Normal atmospheric oxygen tension and the use of antioxidants improve hepatocyte spheroid viability and function. J. Cell. Physiol.226, 2987\u20132996 (2011).","journal-title":"J. Cell. Physiol."},{"key":"75582_CR25","doi-asserted-by":"crossref","unstructured":"Turner, K. J. et al. The hypoxia-inducible genes VEGF and CA9 are differentially regulated in superficial vs invasive bladder cancer. Br J Cancer. 9, 1276\u20131282 (2002).","DOI":"10.1038\/sj.bjc.6600215"},{"key":"75582_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/emm.2004.1","volume":"36","author":"JW Lee","year":"2004","unstructured":"Lee, J. W., Bae, S. H., Jeong, J. W., Kim, S. H. & Kim, K. W. Hypoxia-inducible factor (HIF-1)\u03b1: Its protein stability and biological functions. Exp. Mol. Med.36, 1\u201312 (2004).","journal-title":"Exp. Mol. Med."},{"key":"75582_CR27","doi-asserted-by":"crossref","unstructured":"Morel, Y. & Barouki, R. Repression of Gene expression by oxidative stress. Biochem. J.342, 481\u2013496 (1999).","DOI":"10.1042\/bj3420481"},{"key":"75582_CR28","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.semcdb.2019.10.007","volume":"100","author":"M Ozaki","year":"2020","unstructured":"Ozaki, M. Cellular and molecular mechanisms of liver regeneration: Proliferation, growth, death and protection of hepatocytes. Semin Cell. Dev. Biol.100, 62\u201373 (2020).","journal-title":"Semin Cell. Dev. Biol."},{"key":"75582_CR29","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1111\/j.1523-1755.2004.00842.x","volume":"66","author":"G Rumsby","year":"2004","unstructured":"Rumsby, G., Williams, E. & Coulter-Mackie, M. Evaluation of mutation screening as a first line test for the diagnosis of the primary hyperoxalurias. Kidney Int.66, 959\u2013963 (2004).","journal-title":"Kidney Int."},{"key":"75582_CR30","doi-asserted-by":"publisher","first-page":"3610","DOI":"10.1002\/bit.27751","volume":"118","author":"IA Isidro","year":"2021","unstructured":"Isidro, I. A. et al. Online monitoring of hiPSC expansion and hepatic differentiation in 3D culture by dielectric spectroscopy. Biotechnol. Bioeng.118, 3610\u20133617 (2021).","journal-title":"Biotechnol. Bioeng."},{"key":"75582_CR31","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jbiotec.2014.01.025","volume":"174","author":"Y Park","year":"2014","unstructured":"Park, Y., Chen, Y., Ordovas, L. & Verfaillie, C. M. Hepatic differentiation of human embryonic stem cells on microcarriers. J. Biotechnol.174, 39\u201348 (2014).","journal-title":"J. Biotechnol."},{"key":"75582_CR32","doi-asserted-by":"crossref","unstructured":"Fisher, R. A. & Strom, S. C. Human hepatocyte transplantation: Worldwide results. Transplantation82, 441-9 (2006).","DOI":"10.1097\/01.tp.0000231689.44266.ac"},{"key":"75582_CR33","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1159\/000493162","volume":"205","author":"S Fathollahipour","year":"2018","unstructured":"Fathollahipour, S., Patil, P. S. & Leipzig, N. D. Oxygen regulation in development: Lessons from embryogenesis towards tissue engineering. Cells Tissues Organs.205, 350\u2013371 (2018).","journal-title":"Cells Tissues Organs."},{"key":"75582_CR34","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/j.bbrc.2011.11.111","volume":"417","author":"H Shimada","year":"2012","unstructured":"Shimada, H., Hashimoto, Y., Nakada, A., Shigeno, K. & Nakamura, T. Accelerated generation of human induced pluripotent stem cells with retroviral transduction and chemical inhibitors under physiological hypoxia. Biochem. Biophys. Res. Commun.417, 659\u2013664 (2012).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"75582_CR35","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.bej.2013.02.012","volume":"74","author":"T Katsuda","year":"2013","unstructured":"Katsuda, T., Teratani, T., Chowdhury, M. M., Ochiya, T. & Sakai, Y. Hypoxia efficiently induces differentiation of mouse embryonic stem cells into endodermal and hepatic progenitor cells. Biochem. Eng. J.74, 95\u2013101 (2013).","journal-title":"Biochem. Eng. J."},{"key":"75582_CR36","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s12079-018-0456-4","volume":"12","author":"M van Wenum","year":"2018","unstructured":"van Wenum, M. et al. Oxygen drives hepatocyte differentiation and phenotype stability in liver cell lines. J. Cell. Commun. Signal.12, 575\u2013588 (2018).","journal-title":"J. Cell. Commun. Signal."},{"key":"75582_CR37","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.stemcr.2018.06.015","volume":"11","author":"H Ayabe","year":"2018","unstructured":"Ayabe, H. et al. Optimal hypoxia regulates human iPSC-derived liver bud differentiation through intercellular TGFB signaling. Stem Cell. Rep.11, 306\u2013316 (2018).","journal-title":"Stem Cell. Rep."},{"key":"75582_CR38","doi-asserted-by":"publisher","first-page":"5923","DOI":"10.1038\/s41598-017-06433-3","volume":"7","author":"R Guo","year":"2017","unstructured":"Guo, R., Xu, X., Lu, Y. & Xie, X. Physiological oxygen tension reduces hepatocyte dedifferentiation in in vitro culture. Sci. Rep.7, 5923 (2017).","journal-title":"Sci. Rep."},{"key":"75582_CR39","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.scr.2015.12.014","volume":"16","author":"N Zapata-Linares","year":"2016","unstructured":"Zapata-Linares, N. et al. Generation and characterization of human iPSC lines derived from a primary hyperoxaluria type I patient with p.I244T mutation. Stem Cell. Res.16, 116\u2013119 (2016).","journal-title":"Stem Cell. Res."},{"key":"75582_CR40","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1080\/14728214.2018.1552940","volume":"23","author":"A Weigert","year":"2018","unstructured":"Weigert, A., Martin-Higueras, C. & Hoppe, B. Novel therapeutic approaches in primary hyperoxaluria. Expert Opin. Emerg. Drugs23, 349\u2013357 (2018).","journal-title":"Expert Opin. Emerg. Drugs"},{"key":"75582_CR41","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1056\/NEJMoa2031054","volume":"384","author":"H Frangoul","year":"2021","unstructured":"Frangoul, H. et al. CRISPR-Cas9 gene editing for sickle cell disease and \u03b2-Thalassemia. N. Engl. J. Med.384, 252\u2013260 (2021).","journal-title":"N. Engl. J. Med."},{"key":"75582_CR42","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/d41587-023-00016-6","volume":"42","author":"C Sheridan","year":"2023","unstructured":"Sheridan, C. The world\u2019s first CRISPR therapy is approved: Who will receive it?. Nat. Biotechnol.42, 3\u20134 (2023).","journal-title":"Nat. Biotechnol."},{"key":"75582_CR43","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.stemcr.2015.02.021","volume":"4","author":"AA Wilson","year":"2015","unstructured":"Wilson, A. A. et al. Emergence of a stage-dependent Human Liver Disease signature with Directed differentiation of Alpha-1 antitrypsin-deficient iPS cells. Stem Cell. Rep.4, 873\u2013885 (2015).","journal-title":"Stem Cell. Rep."},{"key":"75582_CR44","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1002\/hep.27712","volume":"61","author":"S Li","year":"2015","unstructured":"Li, S. et al. Valproic acid-induced hepatotoxicity in alpers syndrome is associated with mitochondrial permeability transition pore opening-dependent apoptotic sensitivity in an induced pluripotent stem cell model. Hepatology61, 1730\u20131739 (2015).","journal-title":"Hepatology"},{"key":"75582_CR45","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.jhep.2019.03.031","volume":"71","author":"AW Overeem","year":"2019","unstructured":"Overeem, A. W. et al. Pluripotent stem cell-derived bile canaliculi-forming hepatocytes to study genetic liver diseases involving hepatocyte polarity. J. Hepatol.71, 344\u2013356 (2019).","journal-title":"J. Hepatol."},{"key":"75582_CR46","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.1242\/dev.114215","volume":"142","author":"M Gordillo","year":"2015","unstructured":"Gordillo, M., Evans, T. & Gouon-Evans, V. Orchestrating liver development. Development142, 2094\u20132108 (2015).","journal-title":"Development"},{"key":"75582_CR47","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.bbrc.2015.12.007","volume":"469","author":"D Nakamori","year":"2016","unstructured":"Nakamori, D. et al. Hepatic maturation of human iPS cell-derived hepatocyte-like cells by ATF5, c\/EBP\u03b1, and PROX1 transduction. Biochem. Biophys. Res. Commun.469, 424\u2013429 (2016).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"75582_CR48","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1007\/s12015-015-9621-9","volume":"12","author":"A Asplund","year":"2016","unstructured":"Asplund, A. et al. One standardized differentiation Procedure robustly generates homogenous hepatocyte cultures displaying metabolic diversity from a large panel of human pluripotent stem cells. Stem Cell. Rev. Rep.12, 90\u2013104 (2016).","journal-title":"Stem Cell. Rev. Rep."},{"key":"75582_CR49","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jbiotec.2017.01.004","volume":"246","author":"B Abecasis","year":"2017","unstructured":"Abecasis, B. et al. Expansion of 3D human induced pluripotent stem cell aggregates in bioreactors: Bioprocess intensification and scaling-up approaches. J. Biotechnol.246, 81\u201393 (2017).","journal-title":"J. Biotechnol."},{"key":"75582_CR50","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1007\/s12015-014-9533-0","volume":"10","author":"C Correia","year":"2014","unstructured":"Correia, C. et al. Combining hypoxia and bioreactor hydrodynamics boosts induced pluripotent stem cell differentiation towards cardiomyocytes. Stem Cell. Rev. Rep.10, 786\u2013801 (2014).","journal-title":"Stem Cell. Rev. Rep."},{"key":"75582_CR51","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1002\/bit.22920","volume":"108","author":"RM Tost\u00f5es","year":"2011","unstructured":"Tost\u00f5es, R. M. et al. Perfusion of 3D encapsulated hepatocytes\u2014A synergistic effect enhancing long-term functionality in bioreactors. Biotechnol. Bioeng.108, 41\u201349 (2011).","journal-title":"Biotechnol. Bioeng."},{"key":"75582_CR52","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real- time quantitative PCR and the 2 \u2013 \u2206\u2206CT method. Methods25, 402\u2013408 (2001).","journal-title":"Methods"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75582-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75582-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75582-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T17:11:08Z","timestamp":1729617068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-75582-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,19]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["75582"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-75582-z","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,19]]},"assertion":[{"value":"15 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}],"article-number":"24599"}}