{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:08:15Z","timestamp":1789718895556,"version":"4.0.1"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["1030856"],"award-info":[{"award-number":["1030856"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["916512"],"award-info":[{"award-number":["916512"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DGE 1632976"],"award-info":[{"award-number":["DGE 1632976"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2211966"],"award-info":[{"award-number":["2211966"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003181","name":"National Niemann-Pick Disease Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003181","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["RO1HL165193"],"award-info":[{"award-number":["RO1HL165193"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL140239-01"],"award-info":[{"award-number":["R01HL140239-01"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD008988"],"award-info":[{"award-number":["HD008988"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Biomed Eng"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cholesterol is a vital component of the cell membrane and plays an essential role in mediating integral membrane protein function. Altered cholesterol regulation has been implicated in neurological diseases that are associated with blood\u2013brain barrier breakdown. However, the role of brain barrier function in inherited disorders of cholesterol metabolism, such as Niemann-Pick disease C1 (NP-C1), remains unclear. In this study, we determined how cholesterol depletion with U18666A, a chemical inhibitor of NPC1 protein, as well as with the cholesterol-depleting agent methyl-\u03b2 cyclodextrin (M\u03b2CD), impacted brain endothelial cell barrier function. We hypothesized that cholesterol depletion would decrease barrier integrity by disrupting tight junction protein continuity. To test this hypothesis, we differentiated human-induced pluripotent stem cells into brain microvascular endothelial cells (hiBMECs). We then assessed barrier integrity by quantifying trans-endothelial electrical resistance (TEER), small fluorescent molecule permeability, and tight junction continuity and protein levels. We now show that U18666A-treated hiBMECs demonstrated a 75% decrease in TEER and 9-fold increase in sodium fluorescein permeability. Similar trends were observed for hiBMECs treated with M\u03b2CD, which showed significantly lowered TEER (93% decrease) and increased sodium fluorescein permeability (20-fold higher). We also observed decreased continuity of the tight junction proteins occludin (13% lower) and claudin-5 (8% lower) as well as a 53% decrease in claudin-5 protein with U18666A treatment. Co-treating U18666A-treated hiBMECs with hydroxypropyl-\u03b2 cyclodextrin (HP\u03b2CD), which releases lysosomal cholesterol, prevented these changes. Together, our results demonstrate that cholesterol is vital for hiBMEC barrier function and tight junction continuity. This study highlights the potential of therapeutics targeted to brain endothelium in NP-C1 and other cholesterol metabolism disorders.<\/jats:p>","DOI":"10.1007\/s10439-025-03841-9","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T16:45:13Z","timestamp":1758127513000},"page":"3222-3236","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cholesterol Depletion with U18666A and Methyl-\u03b2 Cyclodextrin Increased Small Molecule Permeability Across Brain Microvascular Endothelial Cells"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7378-6399","authenticated-orcid":false,"given":"Bilal","family":"Moiz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana Alpizar","family":"Vargas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken D.","family":"Brandon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurneet","family":"Sangha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callie","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan","family":"Pepper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Walls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristin","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Stroka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forbes D.","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2462-2122","authenticated-orcid":false,"given":"Alisa Morss","family":"Clyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"3841_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-8118-9-23","author":"AC Luissint","year":"2012","unstructured":"Luissint, A. C., C. Artus, F. Glacial, K. Ganeshamoorthy, and P. O. Couraud. Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation. Fluids Barriers CNS. 2012. https:\/\/doi.org\/10.1186\/2045-8118-9-23.","journal-title":"Fluids Barriers CNS"},{"key":"3841_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/S12987-020-00230-3","author":"H Kadry","year":"2020","unstructured":"Kadry, H., B. Noorani, and L. Cucullo. A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS. 2020. https:\/\/doi.org\/10.1186\/S12987-020-00230-3.","journal-title":"Fluids Barriers CNS"},{"key":"3841_CR3","doi-asserted-by":"publisher","first-page":"C343","DOI":"10.1152\/AJPCELL.00095.2018","volume":"315","author":"W Abdullahi","year":"2018","unstructured":"Abdullahi, W., D. Tripathi, and P. T. Ronaldson. Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection. Am. J. Physiol. Cell Physiol. 315:C343\u2013C356, 2018. https:\/\/doi.org\/10.1152\/AJPCELL.00095.2018.","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"3841_CR4","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1750-1172-5-16","volume":"5","author":"MT Vanier","year":"2010","unstructured":"Vanier, M. T. Niemann-pick disease type C. Orphanet J. Rare Dis. 5:16, 2010. https:\/\/doi.org\/10.1186\/1750-1172-5-16.","journal-title":"Orphanet J. Rare Dis."},{"key":"3841_CR5","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/S0022-2275(20)31487-5","volume":"43","author":"WS Garver","year":"2002","unstructured":"Garver, W. S., K. Krishnan, J. R. Gallagos, M. Michikawa, G. A. Francis, and R. A. Heidenreich. Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae. J. Lipid Res. 43:579\u2013589, 2002.","journal-title":"J. Lipid Res."},{"key":"3841_CR6","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.cca.2013.11.026","volume":"429","author":"X-HH Yu","year":"2014","unstructured":"Yu, X.-H.H., N. Jiang, P.-B.B. Yao, X.-L.L. Zheng, F. S. Cayabyab, and C.-K.K. Tang. NPC1, intracellular cholesterol trafficking and atherosclerosis. Clin. Chim. Acta. 429:69\u201375, 2014. https:\/\/doi.org\/10.1016\/j.cca.2013.11.026.","journal-title":"Clin. Chim. Acta"},{"key":"3841_CR7","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.mehy.2014.08.025","volume":"83","author":"N Kresojevi\u0107","year":"2014","unstructured":"Kresojevi\u0107, N., V. Dobri\u010di\u0107, M. Svetel, and V. Kosti\u0107. Mutations in Niemann Pick type C gene are risk factor for Alzheimer\u2019s disease. Med. Hypotheses. 83:559\u2013562, 2014. https:\/\/doi.org\/10.1016\/j.mehy.2014.08.025.","journal-title":"Med. Hypotheses"},{"key":"3841_CR8","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.15252\/embr.201439225","volume":"15","author":"MG Mart\u00edn","year":"2014","unstructured":"Mart\u00edn, M. G., F. Pfrieger, and C. G. Dotti. Cholesterol in brain disease: sometimes determinant and frequently implicated. EMBO Rep. 15:1036\u20131052, 2014. https:\/\/doi.org\/10.15252\/embr.201439225.","journal-title":"EMBO Rep."},{"key":"3841_CR9","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1093\/hmg\/ddw367","volume":"26","author":"RJ Chandler","year":"2017","unstructured":"Chandler, R. J., I. M. Williams, A. L. Gibson, C. D. Davidson, A. A. Incao, B. T. Hubbard, F. D. Porter, W. J. Pavan, and C. P. Venditti. Systemic AAV9 gene therapy improves the lifespan of mice with Niemann-Pick disease, type C1. Hum. Mol. Genet. 26:52\u201364, 2017. https:\/\/doi.org\/10.1093\/hmg\/ddw367.","journal-title":"Hum. Mol. Genet."},{"key":"3841_CR10","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1042\/BJ20041377","volume":"387","author":"D Lambert","year":"2005","unstructured":"Lambert, D., C. A. O\u2019Neill, and P. J. Padfield. Depletion of Caco-2 cell cholesterol disrupts barrier function by altering the detergent solubility and distribution of specific tight-junction proteins. Biochem. J. 387:553\u2013560, 2005. https:\/\/doi.org\/10.1042\/BJ20041377.","journal-title":"Biochem. J."},{"key":"3841_CR11","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1159\/000107533","volume":"20","author":"D Lambert","year":"2007","unstructured":"Lambert, D., C. A. O\u2019Neill, and P. J. Padfield. Methyl-beta-cyclodextrin increases permeability of Caco-2 cell monolayers by displacing specific claudins from cholesterol rich domains associated with tight junctions. Cell Physiol. Biochem. 20:495\u2013506, 2007. https:\/\/doi.org\/10.1159\/000107533.","journal-title":"Cell Physiol. Biochem."},{"key":"3841_CR12","doi-asserted-by":"publisher","first-page":"2373","DOI":"10.1083\/jcb.201711042","volume":"217","author":"K Shigetomi","year":"2018","unstructured":"Shigetomi, K., Y. Ono, T. Inai, and J. Ikenouchi. Adherens junctions influence tight junction formation via changes in membrane lipid composition. J. Cell Biol. 217:2373\u20132381, 2018. https:\/\/doi.org\/10.1083\/jcb.201711042.","journal-title":"J. Cell Biol."},{"key":"3841_CR13","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/J.BRAINRES.2019.03.024","volume":"1715","author":"M At\u0131\u015f","year":"2019","unstructured":"At\u0131\u015f, M., U. Akcan, C. U\u011fur Y\u0131lmaz, N. Orhan, P. D\u00fczg\u00fcn, U. Deniz Ceylan, N. Ar\u0131can, S. Karah\u00fcseyino\u011flu, G. Nur \u015eahin, B. Ah\u0131shal\u0131, and M. Kaya. Effects of methyl-beta-cyclodextrin on blood-brain barrier permeability in angiotensin II-induced hypertensive rats. Brain Res. 1715:148\u2013155, 2019. https:\/\/doi.org\/10.1016\/J.BRAINRES.2019.03.024.","journal-title":"Brain Res."},{"key":"3841_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/S40169-016-0106-5","volume":"5","author":"V Ribas","year":"2016","unstructured":"Ribas, V., C. Garc\u00eda-Ruiz, and J. C. Fern\u00e1ndez-Checa. Mitochondria, cholesterol and cancer cell metabolism. Clin. Transl. Med. 5:1\u201324, 2016. https:\/\/doi.org\/10.1186\/S40169-016-0106-5.","journal-title":"Clin. Transl. Med."},{"key":"3841_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2022.159266","author":"NM Fenton","year":"2023","unstructured":"Fenton, N. M., T. B. Nguyen, L. J. Sharpe, and A. J. Brown. Refining sugar\u2019s involvement in cholesterol synthesis. Biochim. Biophys. Acta Mol. Cell. Biol. Lipids. 2023. https:\/\/doi.org\/10.1016\/j.bbalip.2022.159266.","journal-title":"Biochim. Biophys. Acta Mol. Cell. Biol. Lipids"},{"key":"3841_CR16","doi-asserted-by":"publisher","first-page":"5483","DOI":"10.1021\/ACS.BIOCHEM.6B00342","volume":"55","author":"NMFSA Cerqueira","year":"2016","unstructured":"Cerqueira, N. M. F. S. A., E. F. Oliveira, D. S. Gesto, D. Santos-Martins, C. Moreira, H. N. Moorthy, M. J. Ramos, and P. A. Fernandes. Cholesterol biosynthesis: a mechanistic overview. Biochemistry. 55:5483\u20135506, 2016. https:\/\/doi.org\/10.1021\/ACS.BIOCHEM.6B00342.","journal-title":"Biochemistry"},{"key":"3841_CR17","doi-asserted-by":"publisher","first-page":"106769","DOI":"10.1016\/J.NBD.2024.106769","volume":"204","author":"B Moiz","year":"2025","unstructured":"Moiz, B., M. Walls, V. Alpizar Vargas, A. Addepalli, C. Weber, A. Li, G. Sriram, and A. M. Clyne. Instationary metabolic flux analysis reveals that NPC1 inhibition increases glycolysis and decreases mitochondrial metabolism in brain microvascular endothelial cells. Neurobiol. Dis. 204:106769, 2025. https:\/\/doi.org\/10.1016\/J.NBD.2024.106769.","journal-title":"Neurobiol. Dis."},{"key":"3841_CR18","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1083\/JCB.200711165","volume":"181","author":"L Shen","year":"2008","unstructured":"Shen, L., C. R. Weber, and J. R. Turner. The tight junction protein complex undergoes rapid and continuous molecular remodeling at steady state. J. Cell Biol. 181:683, 2008. https:\/\/doi.org\/10.1083\/JCB.200711165.","journal-title":"J. Cell Biol."},{"key":"3841_CR19","doi-asserted-by":"publisher","DOI":"10.3389\/FPHYS.2017.00794","author":"LM JanssenDuijghuijsen","year":"2017","unstructured":"JanssenDuijghuijsen, L. M., S. Grefte, V. C. J. de Boer, L. Zeper, D. A. M. van Dartel, I. van der Stelt, M. Bekkenkamp-Grovenstein, K. van Norren, H. J. Wichers, and J. Keijer. Mitochondrial ATP depletion disrupts Caco-2 monolayer integrity and internalizes claudin 7. Front. Physiol. 2017. https:\/\/doi.org\/10.3389\/FPHYS.2017.00794.","journal-title":"Front. Physiol."},{"key":"3841_CR20","doi-asserted-by":"publisher","DOI":"10.1096\/FJ.202001634R","author":"A Ziogas","year":"2021","unstructured":"Ziogas, A., M. S. Sajib, J. H. Lim, T. C. Alves, A. Das, A. Witt, E. Hagag, N. Androulaki, S. Grossklaus, M. Gerlach, T. Noll, T. Grinenko, P. Mirtschink, G. Hajishengallis, T. Chavakis, C. M. Mikelis, and D. Sprott. Glycolysis is integral to histamine-induced endothelial hyperpermeability. FASEB J. 2021. https:\/\/doi.org\/10.1096\/FJ.202001634R.","journal-title":"FASEB J."},{"key":"3841_CR21","doi-asserted-by":"publisher","DOI":"10.7554\/ELIFE.12177","author":"F Lu","year":"2015","unstructured":"Lu, F., Q. Liang, L. Abi-Mosleh, A. Das, J. K. de Brabander, J. L. Goldstein, and M. S. Brown. Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection. Elife. 2015. https:\/\/doi.org\/10.7554\/ELIFE.12177.","journal-title":"Elife"},{"key":"3841_CR22","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1126\/SCIENCE.1151526","volume":"318","author":"J Yu","year":"2007","unstructured":"Yu, J., M. A. Vodyanik, K. Smuga-Otto, J. Antosiewicz-Bourget, J. L. Frane, S. Tian, J. Nie, G. A. Jonsdottir, V. Ruotti, R. Stewart, I. I. Slukvin, and J. A. Thomson. Induced pluripotent stem cell lines derived from human somatic cells. Science. 318:1917\u20131920, 2007. https:\/\/doi.org\/10.1126\/SCIENCE.1151526.","journal-title":"Science"},{"key":"3841_CR23","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1111\/JNC.15532","volume":"159","author":"EH Neal","year":"2021","unstructured":"Neal, E. H., K. A. Katdare, Y. Shi, N. A. Marinelli, K. A. Hagerla, and E. S. Lippmann. Influence of basal media composition on barrier fidelity within human pluripotent stem cell-derived blood-brain barrier models. J. Neurochem. 159:980\u2013991, 2021. https:\/\/doi.org\/10.1111\/JNC.15532.","journal-title":"J. Neurochem."},{"key":"3841_CR24","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.stemcr.2019.05.008","volume":"12","author":"EH Neal","year":"2019","unstructured":"Neal, E. H., N. A. Marinelli, Y. Shi, P. M. McClatchey, K. M. Balotin, D. R. Gullett, K. A. Hagerla, A. B. Bowman, K. C. Ess, J. P. Wikswo, and E. S. Lippmann. A simplified, fully defined differentiation scheme for producing blood-brain barrier endothelial cells from human iPSCs. Stem Cell Rep. 12:1380\u20131388, 2019. https:\/\/doi.org\/10.1016\/j.stemcr.2019.05.008.","journal-title":"Stem Cell Rep."},{"key":"3841_CR25","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1016\/j.bbalip.2019.04.002","volume":"1864","author":"N Hammond","year":"2019","unstructured":"Hammond, N., A. B. Munkacsi, and S. L. Sturley. The complexity of a monogenic neurodegenerative disease: more than two decades of therapeutic driven research into Niemann-Pick type C disease. Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 1864:1109\u20131123, 2019. https:\/\/doi.org\/10.1016\/j.bbalip.2019.04.002.","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"3841_CR26","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/1750-1172-9-64","volume":"9","author":"K Kwiatkowska","year":"2014","unstructured":"Kwiatkowska, K., E. Marsza\u0142ek-Sadowska, G. Traczyk, P. Koprowski, M. Musielak, A. \u0141ugowska, M. Kulma, A. Grzelczyk, and A. Sobota. Visualization of cholesterol deposits in lysosomes of Niemann-Pick type C fibroblasts using recombinant perfringolysin O. Orphanet J. Rare Dis. 9:64, 2014. https:\/\/doi.org\/10.1186\/1750-1172-9-64.","journal-title":"Orphanet J. Rare Dis."},{"key":"3841_CR27","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/978-1-4939-9136-5_11l","volume":"1949","author":"LP Wilhelm","year":"2019","unstructured":"Wilhelm, L. P., L. Voilquin, T. Kobayashi, C. Tomasetto, and F. Alpy. Intracellular and plasma membrane cholesterol labeling and quantification using filipin and GFP-D4. Methods Mol. Biol. 1949:137\u2013152, 2019. https:\/\/doi.org\/10.1007\/978-1-4939-9136-5_11l.","journal-title":"Methods Mol. Biol."},{"key":"3841_CR28","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.ymeth.2015.10.016","volume":"101","author":"MJ Stebbins","year":"2016","unstructured":"Stebbins, M. J., H. K. Wilson, S. G. Canfield, T. Qian, S. P. Palecek, and E. V. Shusta. Differentiation and characterization of human pluripotent stem cell-derived brain microvascular endothelial cells. Methods. 101:93\u2013102, 2016. https:\/\/doi.org\/10.1016\/j.ymeth.2015.10.016.","journal-title":"Methods"},{"key":"3841_CR29","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1007\/s10439-019-02266-5","volume":"47","author":"KM Gray","year":"2019","unstructured":"Gray, K. M., D. B. Katz, E. G. Brown, and K. M. Stroka. Quantitative phenotyping of cell-cell junctions to evaluate ZO-1 presentation in brain endothelial cells. Ann. Biomed. Eng. 47:1675\u20131687, 2019. https:\/\/doi.org\/10.1007\/s10439-019-02266-5.","journal-title":"Ann. Biomed. Eng."},{"key":"3841_CR30","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1177\/2211068214561025","volume":"20","author":"B Srinivasan","year":"2015","unstructured":"Srinivasan, B., A. R. Kolli, M. B. Esch, H. E. Abaci, M. L. Shuler, and J. J. Hickman. TEER measurement techniques for in vitro barrier model systems. J. Lab. Autom. 20:107\u2013126, 2015. https:\/\/doi.org\/10.1177\/2211068214561025.","journal-title":"J. Lab. Autom."},{"key":"3841_CR31","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1007\/S00418-021-02026-4","volume":"156","author":"K Felix","year":"2021","unstructured":"Felix, K., S. Tobias, H. Jan, S. Nicolas, and M. Michael. Measurements of transepithelial electrical resistance (TEER) are affected by junctional length in immature epithelial monolayers. Histochem. Cell Biol. 156:609, 2021. https:\/\/doi.org\/10.1007\/S00418-021-02026-4.","journal-title":"Histochem. Cell Biol."},{"key":"3841_CR32","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1091\/mbc.E07-12-1215","volume":"19","author":"T Katsuno","year":"2008","unstructured":"Katsuno, T., K. Umeda, T. Matsui, M. Hata, A. Tamura, M. Itoh, K. Takeuchi, T. Fujimori, Y.-I. Nabeshima, T. Noda, S. Tsukita, and S. Tsukita. Deficiency of Zonula Occludens-1 causes embryonic lethal phenotype associated with defected yolk sac angiogenesis and apoptosis of embryonic cells. Mol. Biol. Cell. 19:2465\u20132475, 2008. https:\/\/doi.org\/10.1091\/mbc.E07-12-1215.","journal-title":"Mol. Biol. Cell."},{"key":"3841_CR33","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1128\/MCB.06029-11","volume":"32","author":"PM Cummins","year":"2012","unstructured":"Cummins, P. M. Occludin: one protein, many forms. Mol. Cell Biol. 32:242, 2012. https:\/\/doi.org\/10.1128\/MCB.06029-11.","journal-title":"Mol. Cell Biol."},{"key":"3841_CR34","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s12987-019-0123-z","volume":"5","author":"C Greene","year":"2019","unstructured":"Greene, C., N. Hanley, and M. Campbell. Claudin-5: gatekeeper of neurological function. Fluids Barriers CNS. 5:35, 2019. https:\/\/doi.org\/10.1186\/s12987-019-0123-z.","journal-title":"Fluids Barriers CNS"},{"key":"3841_CR35","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1083\/jcb.200302070","volume":"161","author":"T Nitta","year":"2003","unstructured":"Nitta, T., M. Hata, S. Gotoh, Y. Seo, H. Sasaki, N. Hashimoto, M. Furuse, and S. Tsukita. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J. Cell Biol. 161:653\u2013660, 2003. https:\/\/doi.org\/10.1083\/jcb.200302070.","journal-title":"J. Cell Biol."},{"key":"3841_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2020.108725","volume":"164","author":"CM Ramirez","year":"2020","unstructured":"Ramirez, C. M., A. M. Taylor, A. M. Lopez, J. J. Repa, and S. D. Turley. Delineation of metabolic responses of Npc1\u2212\/\u2212nih mice lacking the cholesterol-esterifying enzyme SOAT2 to acute treatment with 2-hydroxypropyl-\u03b2-cyclodextrin. Steroids.164:108725, 2020. https:\/\/doi.org\/10.1016\/j.steroids.2020.108725.","journal-title":"Steroids"},{"key":"3841_CR37","doi-asserted-by":"publisher","first-page":"6231","DOI":"10.2174\/1381612823666171019164220","volume":"23","author":"P Calias","year":"2017","unstructured":"Calias, P. 2-Hydroxypropyl-\u03b2-cyclodextrins and the Blood-Brain Barrier: Considerations for Niemann-Pick Disease Type C1. Curr. Pharm. Des. 23:6231, 2017. https:\/\/doi.org\/10.2174\/1381612823666171019164220.","journal-title":"Curr. Pharm. Des."},{"key":"3841_CR38","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.1016\/S0140-6736(17)31465-4","volume":"390","author":"DS Ory","year":"2017","unstructured":"Ory, D. S., E. A. Ottinger, N. Y. Farhat, K. A. King, X. Jiang, L. Weissfeld, E. Berry-Kravis, C. D. Davidson, S. Bianconi, L. A. Keener, R. Rao, A. Soldatos, R. Sidhu, K. A. Walters, X. Xu, A. Thurm, B. Solomon, W. J. Pavan, B. N. Machielse, M. Kao, S. A. Silber, J. C. McKew, C. C. Brewer, C. H. Vite, S. U. Walkley, C. P. Austin, and F. D. Porter. Intrathecal 2-hydroxypropyl-\u03b2-cyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1\u20132 trial. Lancet. 390:1758\u20131768, 2017. https:\/\/doi.org\/10.1016\/S0140-6736(17)31465-4.","journal-title":"Lancet"},{"key":"3841_CR39","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.2174\/1570159X16666180222164809","volume":"16","author":"W Li","year":"2018","unstructured":"Li, W., Z. Chen, I. Chin, Z. Chen, and H. Dai. The role of VE-cadherin in blood-brain barrier integrity under central nervous system pathological conditions. Curr. Neuropharmacol. 16:1375\u20131384, 2018. https:\/\/doi.org\/10.2174\/1570159X16666180222164809.","journal-title":"Curr. Neuropharmacol."},{"key":"3841_CR40","doi-asserted-by":"publisher","DOI":"10.1096\/FJ.202201623RR","volume":"37","author":"R Lugano","year":"2023","unstructured":"Lugano, R., K. Vemuri, S. Barbera, M. Orlandini, E. Dejana, L. Claesson-Welsh, and A. Dimberg. CD93 maintains endothelial barrier function by limiting the phosphorylation and turnover of VE-cadherin. FASEB J.37:e22894, 2023. https:\/\/doi.org\/10.1096\/FJ.202201623RR.","journal-title":"FASEB J."},{"key":"3841_CR41","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/BF02529879","volume":"31","author":"M Liza","year":"1996","unstructured":"Liza, M., J. R. Romero, Y. Chico, O. Fresnedo, and B. Ochoa. Application of 2-hydroxypropyl-\u03b2-cyclodextrin in the assay of acyl-CoA:Cholesterol acyltransferase and neutral and acid cholesterol ester hydrolases. Lipids. 31:323\u2013329, 1996. https:\/\/doi.org\/10.1007\/BF02529879.","journal-title":"Lipids"},{"key":"3841_CR42","doi-asserted-by":"publisher","DOI":"10.1063\/5.0035610","author":"CM Weber","year":"2021","unstructured":"Weber, C. M., and A. M. Clyne. Sex differences in the blood-brain barrier and neurodegenerative diseases. APL Bioeng. 2021. https:\/\/doi.org\/10.1063\/5.0035610.","journal-title":"APL Bioeng."},{"key":"3841_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-44548-1.00145-5","author":"AF Louis-Jacques","year":"2020","unstructured":"Louis-Jacques, A. F., A. O. Odibo, and R. J. Bradshaw. Smith\u2013Lemli\u2013Opitz syndrome. Obstetric Imaging Fetal Diagn. Care. 2020. https:\/\/doi.org\/10.1016\/B978-0-323-44548-1.00145-5.","journal-title":"Obstetric Imaging Fetal Diagn. Care"},{"key":"3841_CR44","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1021\/acs.jpcb.8b09535","volume":"123","author":"N Rajagopal","year":"2019","unstructured":"Rajagopal, N., F. J. Irudayanathan, and S. Nangia. Palmitoylation of Claudin-5 proteins influences their lipid domain affinity and tight junction assembly at the blood-brain barrier interface. J. Phys. Chem. B. 123:983\u2013993, 2019. https:\/\/doi.org\/10.1021\/acs.jpcb.8b09535.","journal-title":"J. Phys. Chem. B"},{"key":"3841_CR45","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.yexcr.2009.10.020","volume":"316","author":"E Casas","year":"2010","unstructured":"Casas, E., C. Barron, S. A. Francis, J. M. McCormack, K. M. McCarthy, E. E. Schneeberger, and R. D. Lynch. Cholesterol efflux stimulates metalloproteinase-mediated cleavage of occludin and release of extracellular membrane particles containing its C-terminal fragments. Exp. Cell Res. 316:353\u2013365, 2010. https:\/\/doi.org\/10.1016\/j.yexcr.2009.10.020.","journal-title":"Exp. Cell Res."},{"key":"3841_CR46","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1002\/JGM.1211","volume":"10","author":"M Campbell","year":"2008","unstructured":"Campbell, M., A. S. Kiang, P. F. Kenna, C. Kerskens, C. Blau, L. O\u2019Dwyer, A. Tivnan, J. A. Kelly, B. Brankin, G. J. Farrar, and P. Hyumphries. RNAi-mediated reversible opening of the blood-brain barrier. J. Gene Med. 10:930\u2013947, 2008. https:\/\/doi.org\/10.1002\/JGM.1211.","journal-title":"J. Gene Med."},{"key":"3841_CR47","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1500472","author":"J Keaney","year":"2015","unstructured":"Keaney, J., D. M. Walsh, T. O\u2019Malley, N. Hudson, D. E. Crosbie, T. Loftus, F. Sheehan, J. McDaid, M. M. Humphries, J. J. Callanan, F. M. Brett, M. A. Farrell, P. Humphries, and M. Campbell. Autoregulated paracellular clearance of amyloid-\u03b2 across the blood-brain barrier. Sci. Adv. 2015. https:\/\/doi.org\/10.1126\/sciadv.1500472.","journal-title":"Sci. Adv."},{"key":"3841_CR48","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1093\/hmg\/ddy112","volume":"27","author":"A Cougnoux","year":"2018","unstructured":"Cougnoux, A., R. A. Drummond, A. L. Collar, J. R. Iben, A. Salman, H. Westgarth, C. A. Wassif, N. X. Cawley, N. Y. Farhat, K. Ozato, M. S. Lionakis, and F. D. Porter. Microglia activation in Niemann-Pick disease, type C1 is amendable to therapeutic intervention. Hum. Mol. Genet. 27:2076\u20132089, 2018. https:\/\/doi.org\/10.1093\/hmg\/ddy112.","journal-title":"Hum. Mol. Genet."},{"key":"3841_CR49","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/7628037","author":"L Yao","year":"2018","unstructured":"Yao, L., X. Xue, P. Yu, Y. Ni, and F. Chen. Evans blue dye: a revisit of its applications in biomedicine. Contrast Media Mol. Imaging. 2018. https:\/\/doi.org\/10.1155\/2018\/7628037.","journal-title":"Contrast Media Mol. Imaging"},{"key":"3841_CR50","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/J.BBAMEM.2013.07.018","volume":"1838","author":"BP Head","year":"2014","unstructured":"Head, B. P., H. H. Patel, and P. A. Insel. Interaction of membrane\/lipid rafts with the cytoskeleton: impact on signaling and function: membrane\/lipid rafts, mediators of cytoskeletal arrangement and cell signaling. Biochim. et Biophys. Acta Biomembr. 1838:532\u2013545, 2014. https:\/\/doi.org\/10.1016\/J.BBAMEM.2013.07.018.","journal-title":"Biochim. et Biophys. Acta Biomembr."},{"key":"3841_CR51","doi-asserted-by":"publisher","first-page":"18992","DOI":"10.1073\/PNAS.0609009103","volume":"103","author":"BF Lillemeier","year":"2006","unstructured":"Lillemeier, B. F., J. R. Pfeiffer, Z. Surviladze, B. S. Wilson, and M. M. Davis. Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton. Proc. Natl. Acad. Sci. USA. 103:18992\u201318997, 2006. https:\/\/doi.org\/10.1073\/PNAS.0609009103.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"3841_CR52","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1242\/JCS.001370","volume":"120","author":"M Sun","year":"2007","unstructured":"Sun, M., N. Northup, F. Marga, T. Huber, F. J. Byfield, I. Levitan, and G. Forgacs. The effect of cellular cholesterol on membrane-cytoskeleton adhesion. J. Cell Sci. 120:2223\u20132231, 2007. https:\/\/doi.org\/10.1242\/JCS.001370.","journal-title":"J. Cell Sci."},{"key":"3841_CR53","doi-asserted-by":"publisher","DOI":"10.3389\/FPHYS.2012.00426","author":"Z Hong","year":"2012","unstructured":"Hong, Z., M. C. Staiculescu, P. Hampel, I. Levitan, and G. Forgacs. How cholesterol regulates endothelial biomechanics. Front. Physiol. 2012. https:\/\/doi.org\/10.3389\/FPHYS.2012.00426.","journal-title":"Front. Physiol."},{"key":"3841_CR54","doi-asserted-by":"publisher","first-page":"3336","DOI":"10.1529\/biophysj.104.040634","volume":"87","author":"FJ Byfield","year":"2004","unstructured":"Byfield, F. J., H. Aranda-Espinoza, V. G. Romanenko, G. H. Rothblat, and I. Levitan. Cholesterol depletion increases membrane stiffness of aortic endothelial cells. Biophys. J. 87:3336\u20133343, 2004. https:\/\/doi.org\/10.1529\/biophysj.104.040634.","journal-title":"Biophys. J."},{"key":"3841_CR55","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/S00232-022-00263-9","volume":"255","author":"FT Doole","year":"2022","unstructured":"Doole, F. T., T. Kumarage, R. Ashkar, and M. F. Brown. Cholesterol stiffening of lipid membranes. J. Membr. Biol. 255:385\u2013405, 2022. https:\/\/doi.org\/10.1007\/S00232-022-00263-9.","journal-title":"J. Membr. Biol."},{"key":"3841_CR56","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/J.CSBJ.2014.09.007","volume":"11","author":"A Rosenhouse-Dantsker","year":"2014","unstructured":"Rosenhouse-Dantsker, A., Y. Epshtein, and I. Levitan. Interplay between lipid modulators of Kir2 channels: cholesterol and PIP2. Comput. Struct. Biotechnol. J. 11:131\u2013137, 2014. https:\/\/doi.org\/10.1016\/J.CSBJ.2014.09.007.","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"3841_CR57","doi-asserted-by":"publisher","first-page":"13964","DOI":"10.1073\/PNAS.2336102100\/ASSET\/18C1BBB8-B462-4543-B8B8-7F96F1C9DC53\/ASSETS\/GRAPHIC\/PQ2336102005.JPEG","volume":"100","author":"J Kwik","year":"2003","unstructured":"Kwik, J., S. Boyle, D. Fooksman, L. Margolis, M. P. Sheetz, and M. Edidin. Membrane cholesterol, lateral mobility, and the phosphatidylinositol 4,5-bisphosphate-dependent organization of cell actin. Proc. Natl. Acad. Sci. USA. 100:13964\u201313969, 2003. https:\/\/doi.org\/10.1073\/PNAS.2336102100\/ASSET\/18C1BBB8-B462-4543-B8B8-7F96F1C9DC53\/ASSETS\/GRAPHIC\/PQ2336102005.JPEG.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"3841_CR58","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1146\/ANNUREV.PHYSIOL.65.092101.142517","volume":"65","author":"HL Yin","year":"2003","unstructured":"Yin, H. L., and P. A. Janmey. Phosphoinositide regulation of the actin cytoskeleton. Annu. Rev. Physiol. 65:761\u2013789, 2003. https:\/\/doi.org\/10.1146\/ANNUREV.PHYSIOL.65.092101.142517.","journal-title":"Annu. Rev. Physiol."},{"key":"3841_CR59","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/S0092-8674(00)81560-3","volume":"100","author":"D Raucher","year":"2000","unstructured":"Raucher, D., T. Stauffer, W. Chen, K. Shen, S. Guo, J. D. York, M. P. Sheetz, and T. Meyer. Phosphatidylinositol 4,5-bisphosphate functions as a second messenger that regulates cytoskeleton-plasma membrane adhesion. Cell. 100:221\u2013228, 2000. https:\/\/doi.org\/10.1016\/S0092-8674(00)81560-3.","journal-title":"Cell"},{"key":"3841_CR60","doi-asserted-by":"publisher","first-page":"29745","DOI":"10.1074\/jbc.273.45.29745","volume":"273","author":"AS Fanning","year":"1998","unstructured":"Fanning, A. S., B. J. Jameson, L. A. Jesaitis, and J. M. Anderson. The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J. Biol. Chem. 273:29745\u201329753, 1998. https:\/\/doi.org\/10.1074\/jbc.273.45.29745.","journal-title":"J. Biol. Chem."},{"key":"3841_CR61","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.devcel.2020.07.022","volume":"54","author":"B Belardi","year":"2020","unstructured":"Belardi, B., T. Hamkins-Indik, A. R. Harris, J. Kim, K. Xu, and D. A. Fletcher. A weak link with actin organizes tight junctions to control epithelial permeability. Dev Cell. 54:792-804.e7, 2020. https:\/\/doi.org\/10.1016\/j.devcel.2020.07.022.","journal-title":"Dev Cell"},{"key":"3841_CR62","doi-asserted-by":"publisher","DOI":"10.3389\/FNINS.2015.00023\/PDF","volume":"9","author":"I Allaman","year":"2015","unstructured":"Allaman, I., M. B\u00e9langer, and P. J. Magistretti. Methylglyoxal, the dark side of glycolysis. Front Neurosci.9:123680, 2015. https:\/\/doi.org\/10.3389\/FNINS.2015.00023\/PDF.","journal-title":"Front Neurosci"},{"key":"3841_CR63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/S12987-023-00477-6","volume":"20","author":"E Berends","year":"2023","unstructured":"Berends, E., R. J. van Oostenbrugge, S. Foulquier, and C. G. Schalkwijk. Methylglyoxal, a highly reactive dicarbonyl compound, as a threat for blood brain barrier integrity. Fluids Barriers CNS. 20:1\u201315, 2023. https:\/\/doi.org\/10.1186\/S12987-023-00477-6.","journal-title":"Fluids Barriers CNS"},{"key":"3841_CR64","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1097\/SHK.0000000000001983","volume":"58","author":"M Fan","year":"2022","unstructured":"Fan, M., K. Yang, X. Wang, X. Zhang, J. Xu, F. Tu, P. S. Gill, T. Ha, D. L. Williams, and C. Li. Lactate impairs vascular permeability by inhibiting HSPA12B expression via GPR81-dependent signaling in sepsis. Shock. 58:304\u2013312, 2022. https:\/\/doi.org\/10.1097\/SHK.0000000000001983.","journal-title":"Shock"},{"key":"3841_CR65","doi-asserted-by":"publisher","first-page":"8965","DOI":"10.1126\/SCIADV.ABM8965\/SUPPL_FILE\/SCIADV.ABM8965_SM.PDF","volume":"8","author":"K Yang","year":"2022","unstructured":"Yang, K., M. Fan, X. Wang, J. Xu, Y. Wang, P. S. Gill, T. Ha, L. Liu, J. V. Hall, D. L. Williams, and C. Li. Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis. Sci. Adv. 8:8965, 2022. https:\/\/doi.org\/10.1126\/SCIADV.ABM8965\/SUPPL_FILE\/SCIADV.ABM8965_SM.PDF.","journal-title":"Sci. Adv."},{"key":"3841_CR66","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1042\/BCJ20160679","volume":"474","author":"R Gangwar","year":"2017","unstructured":"Gangwar, R., A. S. Meena, P. K. Shukla, A. S. Nagaraja, P. L. Dorniak, S. Pallikuth, C. M. Waters, A. Sood, and R. Rao. Calcium-mediated oxidative stress: a common mechanism in tight junction disruption by different types of cellular stress. Biochem. J. 474:731\u2013749, 2017. https:\/\/doi.org\/10.1042\/BCJ20160679.","journal-title":"Biochem. J."},{"key":"3841_CR67","doi-asserted-by":"publisher","DOI":"10.1038\/S41419-018-1056-1","author":"A Singhal","year":"2018","unstructured":"Singhal, A., L. Szente, J. E. K. Hildreth, and B. Song. Hydroxypropyl-beta and -gamma cyclodextrins rescue cholesterol accumulation in Niemann-Pick C1 mutant cell via lysosome-associated membrane protein 1. Cell Death Dis. 2018. https:\/\/doi.org\/10.1038\/S41419-018-1056-1.","journal-title":"Cell Death Dis."},{"key":"3841_CR68","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1007\/s11745-009-3305-7","volume":"44","author":"RJ Cenedella","year":"2009","unstructured":"Cenedella, R. J. Cholesterol synthesis inhibitor U18666A and the role of sterol metabolism and trafficking in numerous pathophysiological processes. Lipids. 44:477\u2013487, 2009. https:\/\/doi.org\/10.1007\/s11745-009-3305-7.","journal-title":"Lipids"},{"key":"3841_CR69","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1111\/jnc.13923","volume":"140","author":"SG Canfield","year":"2017","unstructured":"Canfield, S. G., M. J. Stebbins, B. S. Morales, S. W. Asai, G. D. Vatine, C. N. Svendsen, S. P. Palecek, and E. V. Shusta. An isogenic blood\u2013brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells. J. Neurochem. 140:874\u2013888, 2017. https:\/\/doi.org\/10.1111\/jnc.13923.","journal-title":"J. Neurochem."}],"container-title":["Annals of Biomedical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10439-025-03841-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10439-025-03841-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10439-025-03841-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:02:42Z","timestamp":1761868962000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10439-025-03841-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":69,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["3841"],"URL":"https:\/\/doi.org\/10.1007\/s10439-025-03841-9","relation":{},"ISSN":["0090-6964","1573-9686"],"issn-type":[{"value":"0090-6964","type":"print"},{"value":"1573-9686","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,17]]},"assertion":[{"value":"30 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2025","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 have no competing interests to declare that are relevant to the content of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}