{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:33:04Z","timestamp":1789788784812,"version":"4.0.1"},"reference-count":101,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS108779"],"award-info":[{"award-number":["R01 NS108779"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS108779"],"award-info":[{"award-number":["R01 NS108779"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS108779"],"award-info":[{"award-number":["R01 NS108779"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS108779"],"award-info":[{"award-number":["R01 NS108779"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS108779"],"award-info":[{"award-number":["R01 NS108779"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS108779"],"award-info":[{"award-number":["R01 NS108779"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS108779"],"award-info":[{"award-number":["R01 NS108779"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["23POST1019058"],"award-info":[{"award-number":["23POST1019058"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl. Stroke Res."],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1007\/s12975-024-01321-1","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T04:18:01Z","timestamp":1735877881000},"page":"1496-1508","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Escape of Kdm6a from X Chromosome Is Detrimental to Ischemic Brains via IRF5 Signaling"],"prefix":"10.1007","volume":"16","author":[{"given":"Conelius","family":"Ngwa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afzal","family":"Misrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanaka Valli","family":"Manyam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana","family":"Sharmeen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juneyoung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long-Jun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"McCullough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fudong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,3]]},"reference":[{"issue":"3","key":"1321_CR1","doi-asserted-by":"publisher","first-page":"e0058","DOI":"10.5041\/RMMJ.10058","volume":"2","author":"S Balderman","year":"2011","unstructured":"Balderman S, Lichtman MA. A history of the discovery of random X chromosome inactivation in the human female and its significance. Rambam Maimonides Med J. 2011;2(3):e0058.","journal-title":"Rambam Maimonides Med J"},{"issue":"7","key":"1321_CR2","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.18632\/aging.100997","volume":"8","author":"LD McCullough","year":"2016","unstructured":"McCullough LD, et al. Stroke sensitivity in the aged: sex chromosome complement vs. gonadal hormones. Aging (Albany NY). 2016;8(7):1432\u201341.","journal-title":"Aging (Albany NY)"},{"issue":"20","key":"1321_CR3","doi-asserted-by":"publisher","first-page":"e00341-20","DOI":"10.1128\/MCB.00341-20","volume":"40","author":"N Tran","year":"2020","unstructured":"Tran N, Broun A, Ge K. Lysine demethylase KDM6A in differentiation, development, and cancer. Mol Cell Biol. 2020;40(20):e00341-20.","journal-title":"Mol Cell Biol"},{"issue":"4","key":"1321_CR4","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/j.celrep.2013.02.030","volume":"3","author":"NS Outchkourov","year":"2013","unstructured":"Outchkourov NS, et al. Balancing of histone H3K4 methylation states by the Kdm5c\/SMCX histone demethylase modulates promoter and enhancer function. Cell Rep. 2013;3(4):1071\u20139.","journal-title":"Cell Rep"},{"issue":"2","key":"1321_CR5","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/s41431-022-01233-4","volume":"31","author":"E Leonardi","year":"2023","unstructured":"Leonardi E, et al. Expanding the genetics and phenotypic spectrum of lysine-specific demethylase 5C (KDM5C): a report of 13 novel variants. Eur J Hum Genet. 2023;31(2):202\u201315.","journal-title":"Eur J Hum Genet"},{"key":"1321_CR6","doi-asserted-by":"publisher","first-page":"243","DOI":"10.3389\/fncel.2018.00243","volume":"12","author":"M Cheray","year":"2018","unstructured":"Cheray M, Joseph B. Epigenetics control microglia plasticity. Front Cell Neurosci. 2018;12:243.","journal-title":"Front Cell Neurosci"},{"key":"1321_CR7","doi-asserted-by":"publisher","first-page":"6391","DOI":"10.1007\/s12035-016-0149-z","volume":"54","author":"R Patnala","year":"2017","unstructured":"Patnala R, et al. HDAC inhibitor sodium butyrate-mediated epigenetic regulation enhances neuroprotective function of microglia during ischemic stroke. Mol Neurobiol. 2017;54:6391\u2013411.","journal-title":"Mol Neurobiol"},{"key":"1321_CR8","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.697416","volume":"14","author":"M Qiu","year":"2021","unstructured":"Qiu M, Xu E, Zhan L. Epigenetic regulations of microglia\/macrophage polarization in ischemic stroke. Front Mol Neurosci. 2021;14: 697416.","journal-title":"Front Mol Neurosci"},{"key":"1321_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13148-018-0549-1","volume":"10","author":"Q Kong","year":"2018","unstructured":"Kong Q, et al. HDAC4 in ischemic stroke: mechanisms and therapeutic potential. Clin Epigenetics. 2018;10:1\u20139.","journal-title":"Clin Epigenetics"},{"issue":"1","key":"1321_CR10","doi-asserted-by":"publisher","first-page":"89","DOI":"10.3390\/genes11010089","volume":"11","author":"R Stanzione","year":"2020","unstructured":"Stanzione R, et al. Pathogenesis of ischemic stroke: role of epigenetic mechanisms. Genes (Basel). 2020;11(1):89.","journal-title":"Genes (Basel)"},{"key":"1321_CR11","doi-asserted-by":"publisher","first-page":"175628641877181","DOI":"10.1177\/1756286418771815","volume":"11","author":"GY Ng","year":"2018","unstructured":"Ng GY, et al. Epigenetic regulation of inflammation in stroke. Ther Adv Neurol Disord. 2018;11:1756286418771815.","journal-title":"Ther Adv Neurol Disord"},{"issue":"6432","key":"1321_CR12","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1126\/science.aau5870","volume":"363","author":"M Batie","year":"2019","unstructured":"Batie M, et al. Hypoxia induces rapid changes to histone methylation and reprograms chromatin. Science. 2019;363(6432):1222\u20136.","journal-title":"Science"},{"issue":"11","key":"1321_CR13","doi-asserted-by":"publisher","first-page":"3320","DOI":"10.1161\/STROKEAHA.120.029951","volume":"51","author":"Y Luo","year":"2020","unstructured":"Luo Y, et al. Inhibition of EZH2 (enhancer of zeste homolog 2) attenuates neuroinflammation via H3k27me3\/SOCS3\/TRAF6\/NF-\u03baB (trimethylation of histone 3 lysine 27\/suppressor of cytokine signaling 3\/tumor necrosis factor receptor family 6\/nuclear factor-\u03baB) in a rat model of subarachnoid hemorrhage. Stroke. 2020;51(11):3320\u201331.","journal-title":"Stroke"},{"issue":"6","key":"1321_CR14","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1038\/sj.embor.7400686","volume":"7","author":"AB Brinkman","year":"2006","unstructured":"Brinkman AB, et al. Histone modification patterns associated with the human X chromosome. EMBO Rep. 2006;7(6):628\u201334.","journal-title":"EMBO Rep"},{"issue":"1","key":"1321_CR15","doi-asserted-by":"publisher","first-page":"10794","DOI":"10.1038\/s41598-017-11044-z","volume":"7","author":"JC Moreira de Mello","year":"2017","unstructured":"Moreira de Mello JC, et al. Early X chromosome inactivation during human preimplantation development revealed by single-cell RNA-sequencing. Sci Rep. 2017;7(1):10794.","journal-title":"Sci Rep."},{"issue":"15","key":"1321_CR16","doi-asserted-by":"publisher","first-page":"2514","DOI":"10.1016\/j.febslet.2014.06.023","volume":"588","author":"R Chalign\u00e9","year":"2014","unstructured":"Chalign\u00e9 R, Heard E. X-chromosome inactivation in development and cancer. FEBS Lett. 2014;588(15):2514\u201322.","journal-title":"FEBS Lett"},{"issue":"12","key":"1321_CR17","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1038\/nrm3231","volume":"12","author":"JT Lee","year":"2011","unstructured":"Lee JT. Gracefully ageing at 50, X-chromosome inactivation becomes a paradigm for RNA and chromatin control. Nat Rev Mol Cell Biol. 2011;12(12):815\u201326.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"5","key":"1321_CR18","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1038\/ng.349","volume":"41","author":"G van Haaften","year":"2009","unstructured":"van Haaften G, et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet. 2009;41(5):521\u20133.","journal-title":"Nat Genet"},{"issue":"1","key":"1321_CR19","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.molcel.2013.10.030","volume":"53","author":"KJ Ferrari","year":"2014","unstructured":"Ferrari KJ, et al. Polycomb-dependent H3K27me1 and H3K27me2 regulate active transcription and enhancer fidelity. Mol Cell. 2014;53(1):49\u201362.","journal-title":"Mol Cell"},{"issue":"1","key":"1321_CR20","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13072-018-0193-1","volume":"11","author":"K Kim","year":"2018","unstructured":"Kim K, et al. H3K27me1 is essential for MMP-9-dependent H3N-terminal tail proteolysis during osteoclastogenesis. Epigenetics Chromatin. 2018;11(1):23.","journal-title":"Epigenetics Chromatin"},{"issue":"1","key":"1321_CR21","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s13578-023-01017-3","volume":"13","author":"Y Yu","year":"2023","unstructured":"Yu Y, et al. H3K27me3-H3K4me1 transition at bivalent promoters instructs lineage specification in development. Cell Biosci. 2023;13(1):66.","journal-title":"Cell Biosci"},{"issue":"6","key":"1321_CR22","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/j.molcel.2014.02.032","volume":"53","author":"J Cheng","year":"2014","unstructured":"Cheng J, et al. A role for H3K4 monomethylation in gene repression and partitioning of chromatin readers. Mol Cell. 2014;53(6):979\u201392.","journal-title":"Mol Cell"},{"key":"1321_CR23","doi-asserted-by":"publisher","first-page":"937875","DOI":"10.3389\/fcell.2022.937875","volume":"10","author":"LE Cabrera Zapata","year":"2022","unstructured":"Cabrera Zapata LE, Cambiasso MJ, Arevalo MA. Epigenetic modifier Kdm6a\/Utx controls the specification of hypothalamic neuronal subtypes in a sex-dependent manner. Front Cell Dev Biol. 2022;10:937875.","journal-title":"Front Cell Dev Biol."},{"key":"1321_CR24","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.jaut.2017.02.007","volume":"80","author":"X Li","year":"2017","unstructured":"Li X, et al. Demethylase Kdm6a epigenetically promotes IL-6 and IFN-\u03b2 production in macrophages. J Autoimmun. 2017;80:85\u201394.","journal-title":"J Autoimmun"},{"issue":"11","key":"1321_CR25","doi-asserted-by":"publisher","first-page":"5688","DOI":"10.1172\/JCI140223","volume":"130","author":"JC Link","year":"2020","unstructured":"Link JC, et al. X chromosome dosage of histone demethylase KDM5C determines sex differences in adiposity. J Clin Invest. 2020;130(11):5688\u2013702.","journal-title":"J Clin Invest"},{"issue":"3","key":"1321_CR26","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1073\/pnas.1914742117","volume":"117","author":"A Al Mamun","year":"2020","unstructured":"Al Mamun A, et al. Microglial IRF5-IRF4 regulatory axis regulates neuroinflammation after cerebral ischemia and impacts stroke outcomes. Proc Natl Acad Sci U S A. 2020;117(3):1742\u201352.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"15","key":"1321_CR27","doi-asserted-by":"publisher","first-page":"6047","DOI":"10.18632\/aging.204216","volume":"14","author":"C Ngwa","year":"2022","unstructured":"Ngwa C, et al. Regulation of microglial activation in stroke in aged mice: a translational study. Aging (Albany NY). 2022;14(15):6047\u201365.","journal-title":"Aging (Albany NY)"},{"issue":"5","key":"1321_CR28","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1007\/s12975-022-01070-z","volume":"14","author":"S Qi","year":"2023","unstructured":"Qi S, et al. X, but not Y, chromosomal complement contributes to stroke sensitivity in aged animals. Transl Stroke Res. 2023;14(5):776\u201389.","journal-title":"Transl Stroke Res"},{"issue":"1","key":"1321_CR29","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s12974-021-02120-3","volume":"18","author":"S Qi","year":"2021","unstructured":"Qi S, et al. X chromosome escapee genes are involved in ischemic sexual dimorphism through epigenetic modification of inflammatory signals. J Neuroinflammation. 2021;18(1):70.","journal-title":"J Neuroinflammation"},{"issue":"10","key":"1321_CR30","doi-asserted-by":"publisher","first-page":"3362","DOI":"10.1161\/STROKEAHA.120.032374","volume":"52","author":"A Al Mamun","year":"2021","unstructured":"Al Mamun A, et al. Neuronal CD200 signaling is protective in the acute phase of ischemic stroke. Stroke. 2021;52(10):3362\u201373.","journal-title":"Stroke"},{"issue":"1","key":"1321_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jneumeth.2008.12.028","volume":"179","author":"F Liu","year":"2009","unstructured":"Liu F, Schafer DP, McCullough LD. TTC, fluoro-Jade B and NeuN staining confirm evolving phases of infarction induced by middle cerebral artery occlusion. J Neurosci Methods. 2009;179(1):1\u20138.","journal-title":"J Neurosci Methods"},{"key":"1321_CR32","doi-asserted-by":"publisher","first-page":"110864","DOI":"10.1016\/j.brainresbull.2023.110864","volume":"207","author":"A Misrani","year":"2024","unstructured":"Misrani A, et al. Brain endothelial CD200 signaling protects brain against ischemic damage. Brain Res Bull. 2024;207:110864.","journal-title":"Brain Res Bull"},{"issue":"2","key":"1321_CR33","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3390\/cells10020276","volume":"10","author":"C Ngwa","year":"2021","unstructured":"Ngwa C, et al. Phosphorylation of microglial IRF5 and IRF4 by IRAK4 regulates inflammatory responses to ischemia. Cells. 2021;10(2):276.","journal-title":"Cells"},{"key":"1321_CR34","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/978-1-4939-8994-2_9","volume":"1916","author":"AK Kraeuter","year":"2019","unstructured":"Kraeuter AK, Guest PC, Sarnyai Z. The open field test for measuring locomotor activity and anxiety-like behavior. Methods Mol Biol. 2019;1916:99\u2013103.","journal-title":"Methods Mol Biol"},{"issue":"3","key":"1321_CR35","first-page":"233","volume":"1","author":"OA Meyer","year":"1979","unstructured":"Meyer OA, et al. A method for the routine assessment of fore-and hindlimb grip strength of rats and mice. Neurobehav Toxicol. 1979;1(3):233\u20136.","journal-title":"Neurobehav Toxicol"},{"issue":"1","key":"1321_CR36","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/0091-3057(78)90131-4","volume":"8","author":"PA Cabe","year":"1978","unstructured":"Cabe PA, et al. A simple recording grip strength device. Pharmacol Biochem Behav. 1978;8(1):101\u20132.","journal-title":"Pharmacol Biochem Behav"},{"issue":"1\u20132","key":"1321_CR37","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/0165-0270(95)00049-6","volume":"62","author":"JP Smith","year":"1995","unstructured":"Smith JP, et al. Quantitative measurement of muscle strength in the mouse. J Neurosci Methods. 1995;62(1\u20132):15\u20139.","journal-title":"J Neurosci Methods"},{"issue":"7968","key":"1321_CR38","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/s41586-023-06084-7","volume":"619","author":"AS Agustinus","year":"2023","unstructured":"Agustinus AS, et al. Epigenetic dysregulation from chromosomal transit in micronuclei. Nature. 2023;619(7968):176\u201383.","journal-title":"Nature"},{"issue":"1","key":"1321_CR39","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1038\/s41467-022-29730-6","volume":"13","author":"R Franklin","year":"2022","unstructured":"Franklin R, et al. Regulation of chromatin accessibility by the histone chaperone CAF-1 sustains lineage fidelity. Nat Commun. 2022;13(1):2350.","journal-title":"Nat Commun"},{"issue":"6","key":"1321_CR40","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1002\/eji.200424898","volume":"34","author":"E Barnes","year":"2004","unstructured":"Barnes E, et al. Ultra-sensitive class I tetramer analysis reveals previously undetectable populations of antiviral CD8+ T cells. Eur J Immunol. 2004;34(6):1570\u20137.","journal-title":"Eur J Immunol"},{"key":"1321_CR41","doi-asserted-by":"publisher","first-page":"e21856","DOI":"10.7554\/eLife.21856","volume":"6","author":"PJ Skene","year":"2017","unstructured":"Skene PJ, Henikoff S. An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. Elife. 2017;6:e21856.","journal-title":"Elife"},{"key":"1321_CR42","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1007\/s12975-023-01172-2","volume":"15","author":"C Ngwa","year":"2023","unstructured":"Ngwa C, et al. Central IRF4\/5 signaling are critical for microglial activation and impact on stroke outcomes. Transl Stroke Res. 2023;15:831\u201343.","journal-title":"Transl Stroke Res"},{"key":"1321_CR43","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3389\/fncel.2020.00198","volume":"14","author":"AM Jurga","year":"2020","unstructured":"Jurga AM, Paleczna M, Kuter KZ. Overview of general and discriminating markers of differential microglia phenotypes. Front Cell Neurosci. 2020;14:198.","journal-title":"Front Cell Neurosci"},{"key":"1321_CR44","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.abb.2019.05.011","volume":"669","author":"E Butturini","year":"2019","unstructured":"Butturini E, et al. STAT1 drives M1 microglia activation and neuroinflammation under hypoxia. Arch Biochem Biophys. 2019;669:22\u201330.","journal-title":"Arch Biochem Biophys"},{"issue":"7","key":"1321_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0111-4","volume":"50","author":"E Bok","year":"2018","unstructured":"Bok E, et al. Modulation of M1\/M2 polarization by capsaicin contributes to the survival of dopaminergic neurons in the lipopolysaccharide-lesioned substantia nigra in vivo. Exp Mol Med. 2018;50(7):1\u201314.","journal-title":"Exp Mol Med"},{"key":"1321_CR46","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1159\/000333606","volume":"30","author":"P Decavel","year":"2012","unstructured":"Decavel P, Vuillier F, Moulin T. Lenticulostriate infarction. Front Neurol Neurosci. 2012;30:115\u20139.","journal-title":"Front Neurol Neurosci"},{"issue":"1","key":"1321_CR47","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s13148-023-01549-y","volume":"15","author":"Y Liu","year":"2023","unstructured":"Liu Y, et al. The inactive X chromosome accumulates widespread epigenetic variability with age. Clin Epigenetics. 2023;15(1):135.","journal-title":"Clin Epigenetics"},{"issue":"1","key":"1321_CR48","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/s10577-023-09717-9","volume":"31","author":"P Juchniewicz","year":"2023","unstructured":"Juchniewicz P, et al. X-chromosome inactivation patterns depend on age and tissue but not conception method in humans. Chromosome Res. 2023;31(1):4.","journal-title":"Chromosome Res"},{"key":"1321_CR49","doi-asserted-by":"publisher","first-page":"219","DOI":"10.3389\/fcell.2019.00219","volume":"7","author":"H Fang","year":"2019","unstructured":"Fang H, Disteche CM, Berletch JB. X inactivation and escape: epigenetic and structural features. Front Cell Dev Biol. 2019;7:219.","journal-title":"Front Cell Dev Biol"},{"issue":"2","key":"1321_CR50","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s00439-011-1011-z","volume":"130","author":"JB Berletch","year":"2011","unstructured":"Berletch JB, et al. Genes that escape from X inactivation. Hum Genet. 2011;130(2):237\u201345.","journal-title":"Hum Genet"},{"issue":"2","key":"1321_CR51","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1111\/ejn.13778","volume":"47","author":"A Al Mamun","year":"2018","unstructured":"Al Mamun A, et al. Interferon regulatory factor 4\/5 signaling impacts on microglial activation after ischemic stroke in mice. Eur J Neurosci. 2018;47(2):140\u20139.","journal-title":"Eur J Neurosci"},{"issue":"11","key":"1321_CR52","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1038\/aps.2017.122","volume":"38","author":"S-C Zhao","year":"2017","unstructured":"Zhao S-C, et al. Age-related differences in interferon regulatory factor-4 and -5 signaling in ischemic brains of mice. Acta Pharmacol Sin. 2017;38(11):1425\u201334.","journal-title":"Acta Pharmacol Sin"},{"issue":"2","key":"1321_CR53","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.genm.2012.02.002","volume":"9","author":"S Sealy-Jefferson","year":"2012","unstructured":"Sealy-Jefferson S, et al. Age-and ethnic-specific sex differences in stroke risk. Gend Med. 2012;9(2):121\u20138.","journal-title":"Gend Med"},{"issue":"4","key":"1321_CR54","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1161\/STROKEAHA.108.542894","volume":"40","author":"RE Petrea","year":"2009","unstructured":"Petrea RE, et al. Gender differences in stroke incidence and poststroke disability in the Framingham heart study. Stroke. 2009;40(4):1032\u20137.","journal-title":"Stroke"},{"issue":"5","key":"1321_CR55","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/S1043-2760(03)00076-6","volume":"14","author":"LD McCullough","year":"2003","unstructured":"McCullough LD, Hurn PD. Estrogen and ischemic neuroprotection: an integrated view. Trends Endocrinol Metab. 2003;14(5):228\u201335.","journal-title":"Trends Endocrinol Metab"},{"issue":"2","key":"1321_CR56","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/jcbfm.2014.186","volume":"35","author":"B Manwani","year":"2015","unstructured":"Manwani B, et al. Sex differences in ischemic stroke sensitivity are influenced by gonadal hormones, not by sex chromosome complement. J Cereb Blood Flow Metab. 2015;35(2):221\u20139.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"3","key":"1321_CR57","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1093\/cvr\/cvu064","volume":"102","author":"J Li","year":"2014","unstructured":"Li J, et al. The number of X chromosomes influences protection from cardiac ischaemia\/reperfusion injury in mice: one X is better than two. Cardiovasc Res. 2014;102(3):375\u201384.","journal-title":"Cardiovasc Res"},{"issue":"5","key":"1321_CR58","doi-asserted-by":"publisher","first-page":"e1002709","DOI":"10.1371\/journal.pgen.1002709","volume":"8","author":"X Chen","year":"2012","unstructured":"Chen X, et al. The number of x chromosomes causes sex differences in adiposity in mice. PLoS Genet. 2012;8(5):e1002709.","journal-title":"PLoS Genet"},{"issue":"1","key":"1321_CR59","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1186\/s12974-022-02652-2","volume":"19","author":"KE Ronning","year":"2022","unstructured":"Ronning KE, Karlen SJ, Burns ME. Structural and functional distinctions of co-resident microglia and monocyte-derived macrophages after retinal degeneration. J Neuroinflammation. 2022;19(1):299.","journal-title":"J Neuroinflammation"},{"issue":"4","key":"1321_CR60","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.immuni.2018.10.005","volume":"49","author":"M Guilliams","year":"2018","unstructured":"Guilliams M, Mildner A, Yona S. Developmental and functional heterogeneity of monocytes. Immunity. 2018;49(4):595\u2013613.","journal-title":"Immunity"},{"key":"1321_CR61","doi-asserted-by":"publisher","first-page":"831747","DOI":"10.3389\/fncel.2022.831747","volume":"16","author":"AV Manjally","year":"2022","unstructured":"Manjally AV, Tay TL. Attack of the clones: microglia in health and disease. Front Cell Neurosci. 2022;16:831747.","journal-title":"Front Cell Neurosci"},{"issue":"2","key":"1321_CR62","doi-asserted-by":"publisher","first-page":"e1010556","DOI":"10.1371\/journal.pgen.1010556","volume":"19","author":"A Zito","year":"2023","unstructured":"Zito A, et al. Escape from X-inactivation in twins exhibits intra- and inter-individual variability across tissues and is heritable. PLoS Genet. 2023;19(2):e1010556.","journal-title":"PLoS Genet"},{"issue":"16","key":"1321_CR63","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1016\/j.devcel.2022.07.007","volume":"57","author":"JM Werner","year":"2022","unstructured":"Werner JM, et al. Variability of cross-tissue X-chromosome inactivation characterizes timing of human embryonic lineage specification events. Dev Cell. 2022;57(16):1995-2008.e5.","journal-title":"Dev Cell"},{"issue":"1","key":"1321_CR64","doi-asserted-by":"publisher","first-page":"4326","DOI":"10.1038\/s41598-021-83702-2","volume":"11","author":"J Mengel-From","year":"2021","unstructured":"Mengel-From J, et al. Skewness of X-chromosome inactivation increases with age and varies across birth cohorts in elderly Danish women. Sci Rep. 2021;11(1):4326.","journal-title":"Sci Rep"},{"key":"1321_CR65","doi-asserted-by":"publisher","first-page":"e78263","DOI":"10.7554\/eLife.78263","volume":"11","author":"AL Roberts","year":"2022","unstructured":"Roberts AL, et al. Age acquired skewed X chromosome inactivation is associated with adverse health outcomes in humans. Elife. 2022;11:e78263.","journal-title":"Elife"},{"issue":"3","key":"1321_CR66","doi-asserted-by":"publisher","first-page":"A160","DOI":"10.1289\/ehp.114-a160","volume":"114","author":"B Weinhold","year":"2006","unstructured":"Weinhold B. Epigenetics: the science of change. Environ Health Perspect. 2006;114(3):A160\u20137.","journal-title":"Environ Health Perspect"},{"issue":"3","key":"1321_CR67","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/cr.2011.22","volume":"21","author":"AJ Bannister","year":"2011","unstructured":"Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381\u201395.","journal-title":"Cell Res"},{"issue":"2","key":"1321_CR68","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/nrg3863","volume":"16","author":"D Holoch","year":"2015","unstructured":"Holoch D, Moazed D. RNA-mediated epigenetic regulation of gene expression. Nat Rev Genet. 2015;16(2):71\u201384.","journal-title":"Nat Rev Genet"},{"issue":"11","key":"1321_CR69","doi-asserted-by":"publisher","first-page":"2000","DOI":"10.1177\/0271678X221116192","volume":"42","author":"KC Morris-Blanco","year":"2022","unstructured":"Morris-Blanco KC, et al. Epigenetic mechanisms and potential therapeutic targets in stroke. J Cereb Blood Flow Metab. 2022;42(11):2000\u201316.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"5","key":"1321_CR70","doi-asserted-by":"publisher","first-page":"105690","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.105690","volume":"30","author":"A Kumar","year":"2021","unstructured":"Kumar A, et al. Epigenetics mechanisms in ischemic stroke: a promising avenue? J Stroke Cerebrovasc Dis. 2021;30(5):105690.","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"1321_CR71","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/978-1-61779-376-9_6","volume-title":"Transcriptional Regulation: Methods and Protocols","author":"P Gade","year":"2012","unstructured":"Gade P, Kalvakolanu DV. Chromatin immunoprecipitation assay as a tool for analyzing transcription factor activity. In: Transcriptional Regulation: Methods and Protocols. New York: Springer; 2012. p. 85\u2013104."},{"issue":"1","key":"1321_CR72","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1038\/s41467-019-09982-5","volume":"10","author":"HS Kaya-Okur","year":"2019","unstructured":"Kaya-Okur HS, et al. CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat Commun. 2019;10(1):1930.","journal-title":"Nat Commun"},{"key":"1321_CR73","doi-asserted-by":"publisher","first-page":"102745","DOI":"10.1016\/j.bcmd.2023.102745","volume":"101","author":"M Salma","year":"2023","unstructured":"Salma M, et al. High-throughput methods for the analysis of transcription factors and chromatin modifications: low input, single cell and spatial genomic technologies. Blood Cells Mol Dis. 2023;101:102745.","journal-title":"Blood Cells Mol Dis"},{"issue":"8","key":"1321_CR74","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nrm4029","volume":"16","author":"C Mozzetta","year":"2015","unstructured":"Mozzetta C, et al. Sound of silence: the properties and functions of repressive Lys methyltransferases. Nat Rev Mol Cell Biol. 2015;16(8):499\u2013513.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"4","key":"1321_CR75","doi-asserted-by":"publisher","first-page":"e12772","DOI":"10.1111\/acel.12772","volume":"17","author":"E Cuy\u00e0s","year":"2018","unstructured":"Cuy\u00e0s E, et al. Metformin directly targets the H3K27me3 demethylase KDM6A\/UTX. Aging Cell. 2018;17(4):e12772.","journal-title":"Aging Cell"},{"issue":"1","key":"1321_CR76","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41420-022-01284-y","volume":"8","author":"M Xiao","year":"2022","unstructured":"Xiao M, et al. Elevated histone demethylase KDM5C increases recurrent miscarriage risk by preventing trophoblast proliferation and invasion. Cell Death Discov. 2022;8(1):495.","journal-title":"Cell Death Discov"},{"issue":"5","key":"1321_CR77","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1038\/s41418-020-00694-8","volume":"28","author":"J Chen","year":"2021","unstructured":"Chen J, et al. Kdm6a suppresses the alternative activation of macrophages and impairs energy expenditure in obesity. Cell Death Differ. 2021;28(5):1688\u2013704.","journal-title":"Cell Death Differ"},{"issue":"1","key":"1321_CR78","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s13148-022-01305-8","volume":"14","author":"J Abu-Hanna","year":"2022","unstructured":"Abu-Hanna J, et al. Therapeutic potential of inhibiting histone 3 lysine 27 demethylases: a review of the literature. Clin Epigenetics. 2022;14(1):98.","journal-title":"Clin Epigenetics"},{"issue":"3","key":"1321_CR79","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/s41375-023-01810-6","volume":"37","author":"ML Trempenau","year":"2023","unstructured":"Trempenau ML, et al. The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes. Leukemia. 2023;37(3):593\u2013605.","journal-title":"Leukemia"},{"key":"1321_CR80","doi-asserted-by":"publisher","first-page":"906662","DOI":"10.3389\/fgene.2022.906662","volume":"13","author":"E Pavlenko","year":"2022","unstructured":"Pavlenko E, et al. Functions and interactions of mammalian KDM5 demethylases. Front Genet. 2022;13:906662.","journal-title":"Front Genet"},{"issue":"3","key":"1321_CR81","doi-asserted-by":"publisher","first-page":"e292","DOI":"10.1002\/mco2.292","volume":"4","author":"R Liu","year":"2023","unstructured":"Liu R, et al. Post-translational modifications of histones: mechanisms, biological functions, and therapeutic targets. MedComm (2020). 2023;4(3):e292.","journal-title":"MedComm (2020)"},{"issue":"7779","key":"1321_CR82","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/s41586-019-1678-1","volume":"574","author":"D Zhang","year":"2019","unstructured":"Zhang D, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019;574(7779):575\u201380.","journal-title":"Nature"},{"issue":"4","key":"1321_CR83","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","volume":"128","author":"T Kouzarides","year":"2007","unstructured":"Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693\u2013705.","journal-title":"Cell"},{"key":"1321_CR84","doi-asserted-by":"publisher","first-page":"106409","DOI":"10.1016\/j.bioorg.2023.106409","volume":"133","author":"LJ Chen","year":"2023","unstructured":"Chen LJ, et al. The role of lysine-specific demethylase 6A (KDM6A) in tumorigenesis and its therapeutic potentials in cancer therapy. Bioorg Chem. 2023;133:106409.","journal-title":"Bioorg Chem"},{"issue":"6765","key":"1321_CR85","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/47412","volume":"403","author":"BD Strahl","year":"2000","unstructured":"Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403(6765):41\u20135.","journal-title":"Nature"},{"key":"1321_CR86","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-021-02120-3","volume":"18","author":"S Qi","year":"2021","unstructured":"Qi S, et al. X chromosome escapee genes are involved in ischemic sexual dimorphism through epigenetic modification of inflammatory signals. J Neuroinflammation. 2021;18:1\u201316.","journal-title":"J Neuroinflammation"},{"issue":"1","key":"1321_CR87","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/npp.2012.134","volume":"38","author":"J-Y Hwang","year":"2013","unstructured":"Hwang J-Y, Aromolaran KA, Zukin RS. Epigenetic mechanisms in stroke and epilepsy. Neuropsychopharmacology. 2013;38(1):167\u201382.","journal-title":"Neuropsychopharmacology"},{"issue":"6","key":"1321_CR88","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/s41582-018-0002-2","volume":"14","author":"J-C Baron","year":"2018","unstructured":"Baron J-C. Protecting the ischaemic penumbra as an adjunct to thrombectomy for acute stroke. Nat Rev Neurol. 2018;14(6):325\u201337.","journal-title":"Nat Rev Neurol"},{"issue":"1","key":"1321_CR89","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/s41420-023-01489-9","volume":"9","author":"L Qu","year":"2023","unstructured":"Qu L, et al. Histone demethylases in the regulation of immunity and inflammation. Cell Death Discov. 2023;9(1):188.","journal-title":"Cell Death Discov"},{"issue":"5","key":"1321_CR90","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1586\/14789450.2015.1084231","volume":"12","author":"\u00d6 \u00d6nder","year":"2015","unstructured":"\u00d6nder \u00d6, et al. Progress in epigenetic histone modification analysis by mass spectrometry for clinical investigations. Expert Rev Proteomics. 2015;12(5):499\u2013517.","journal-title":"Expert Rev Proteomics"},{"issue":"47","key":"1321_CR91","doi-asserted-by":"publisher","first-page":"18439","DOI":"10.1073\/pnas.0707292104","volume":"104","author":"S Hong","year":"2007","unstructured":"Hong S, et al. Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. Proc Natl Acad Sci. 2007;104(47):18439\u201344.","journal-title":"Proc Natl Acad Sci"},{"issue":"4","key":"1321_CR92","doi-asserted-by":"publisher","first-page":"e173","DOI":"10.1002\/mco2.173","volume":"3","author":"S Zhang","year":"2022","unstructured":"Zhang S, et al. Targeting epigenetic regulators for inflammation: mechanisms and intervention therapy. MedComm (2020). 2022;3(4):e173.","journal-title":"MedComm (2020)"},{"issue":"1","key":"1321_CR93","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/s42003-020-1001-6","volume":"3","author":"CN Vallianatos","year":"2020","unstructured":"Vallianatos CN, et al. Mutually suppressive roles of KMT2A and KDM5C in behaviour, neuronal structure, and histone H3K4 methylation. Commun Biol. 2020;3(1):278.","journal-title":"Commun Biol"},{"key":"1321_CR94","doi-asserted-by":"publisher","first-page":"110748","DOI":"10.1016\/j.brainresbull.2023.110748","volume":"202","author":"MR Fazazi","year":"2023","unstructured":"Fazazi MR, et al. The X-linked histone demethylases KDM5C and KDM6A as regulators of T cell-driven autoimmunity in the central nervous system. Brain Res Bull. 2023;202:110748.","journal-title":"Brain Res Bull"},{"issue":"1","key":"1321_CR95","doi-asserted-by":"publisher","first-page":"e85","DOI":"10.1002\/cpmb.85","volume":"126","author":"SJ Hainer","year":"2019","unstructured":"Hainer SJ, Fazzio TG. High-resolution chromatin profiling using CUT&RUN. Curr Protoc Mol Biol. 2019;126(1):e85.","journal-title":"Curr Protoc Mol Biol"},{"key":"1321_CR96","doi-asserted-by":"publisher","first-page":"746068","DOI":"10.1155\/2013\/746068","volume":"2013","author":"RA Taylor","year":"2013","unstructured":"Taylor RA, Sansing LH. Microglial responses after ischemic stroke and intracerebral hemorrhage. Clin Dev Immunol. 2013;2013:746068.","journal-title":"Clin Dev Immunol"},{"issue":"5","key":"1321_CR97","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1161\/STROKEAHA.108.534503","volume":"40","author":"M Gelderblom","year":"2009","unstructured":"Gelderblom M, et al. Temporal and spatial dynamics of cerebral immune cell accumulation in stroke. Stroke. 2009;40(5):1849\u201357.","journal-title":"Stroke"},{"issue":"1\u20132","key":"1321_CR98","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/S0006-8993(02)02292-8","volume":"932","author":"SL Stevens","year":"2002","unstructured":"Stevens SL, et al. The use of flow cytometry to evaluate temporal changes in inflammatory cells following focal cerebral ischemia in mice. Brain Res. 2002;932(1\u20132):110\u20139.","journal-title":"Brain Res"},{"key":"1321_CR99","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41420-020-0273-4","volume":"6","author":"X Yang","year":"2020","unstructured":"Yang X, et al. Zoledronic acid regulates the synthesis and secretion of IL-1\u03b2 through histone methylation in macrophages. Cell Death Discov. 2020;6:47.","journal-title":"Cell Death Discov"},{"key":"1321_CR100","doi-asserted-by":"publisher","unstructured":"Corbin AL, Gomez-Vazquez M, Berthold DL, Attar M, Arnold IC, Powrie FM, Sansom SN, Udalova IA. IRF5 guides monocytes toward an inflammatory CD11c+ macrophage phenotype and promotes intestinal inflammation. Sci Immunol. 2020;5(47):eaax6085.\u00a0https:\/\/doi.org\/10.1126\/sciimmunol.aax6085.","DOI":"10.1126\/sciimmunol.aax6085"},{"issue":"7","key":"1321_CR101","doi-asserted-by":"publisher","first-page":"3741","DOI":"10.4049\/jimmunol.1201162","volume":"189","author":"L Yang","year":"2012","unstructured":"Yang L, et al. Monocytes from Irf5-\/-mice have an intrinsic defect in their response to pristane-induced lupus. J Immunol. 2012;189(7):3741\u201350.","journal-title":"J Immunol"}],"container-title":["Translational Stroke Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12975-024-01321-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12975-024-01321-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12975-024-01321-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T05:14:49Z","timestamp":1757135689000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12975-024-01321-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,3]]},"references-count":101,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["1321"],"URL":"https:\/\/doi.org\/10.1007\/s12975-024-01321-1","relation":{},"ISSN":["1868-4483","1868-601X"],"issn-type":[{"value":"1868-4483","type":"print"},{"value":"1868-601X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,3]]},"assertion":[{"value":"7 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All studies were conducted in accordance with NIH guidelines for the care and use of laboratory animals and approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Texas Health Science Center at Houston McGovern Medical School.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}