{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:10:56Z","timestamp":1740147056313,"version":"3.37.3"},"reference-count":23,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL151386"],"award-info":[{"award-number":["R01 HL151386"]}],"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":["R01HL155597"],"award-info":[{"award-number":["R01HL155597"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001857, KL2 TR001856, and\/or TL1 TR001858"],"award-info":[{"award-number":["UL1 TR001857, KL2 TR001856, and\/or TL1 TR001858"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32HD071834"],"award-info":[{"award-number":["T32HD071834"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>We have developed a new clinical research approach for the quantification of cellular proliferation in human infants to address unanswered questions about tissue renewal and regeneration. The approach consists of oral <jats:sup>15<\/jats:sup>N-thymidine administration to label cells in S-phase, followed by Multi-isotope Imaging Mass Spectrometry for detection of the incorporated label in cell nuclei. To establish the approach, we performed an observational study to examine uptake and elimination of <jats:sup>15<\/jats:sup>N-thymidine. We compared at-home label administration with in-hospital administration in infants with tetralogy of Fallot, a form of congenital heart disease, and infants with heart failure.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We examined urine samples from 18 infants who received <jats:sup>15<\/jats:sup>N-thymidine (50 mg\/kg body weight) by mouth for five consecutive days. We used Isotope Ratio Mass Spectrometry to determine enrichment of <jats:sup>15<\/jats:sup>N relative to <jats:sup>14<\/jats:sup>N (%) in urine.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results\/findings<\/jats:title>\n<jats:p><jats:sup>15<\/jats:sup>N-thymidine dose administration produced periodic rises of <jats:sup>15<\/jats:sup>N enrichment in urine. Infants with tetralogy of Fallot had a 3.2-fold increase and infants with heart failure had a 4.3-fold increase in mean peak <jats:sup>15<\/jats:sup>N enrichment over baseline. The mean <jats:sup>15<\/jats:sup>N enrichment was not statistically different between the two patient populations (p = 0.103). The time to peak <jats:sup>15<\/jats:sup>N enrichment in tetralogy of Fallot infants was 6.3 \u00b1 1 hr and in infants with heart failure 7.5 \u00b1 2 hr (mean \u00b1 SEM). The duration of significant <jats:sup>15<\/jats:sup>N enrichment after a dose was 18.5 \u00b1 1.7 hr in tetralogy of Fallot and in heart failure 18.2 \u00b1 1.8 hr (mean \u00b1 SEM). The time to peak enrichment and duration of enrichment were also not statistically different (p = 0.617 and p = 0.887).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The presented results support two conclusions of significance for future applications: (1) Demonstration that <jats:sup>15<\/jats:sup>N-thymidine label administration at home is equivalent to in-hospital administration. (2) Two different types of heart disease show no differences in <jats:sup>15<\/jats:sup>N-thymidine absorption and elimination. This enables the comparative analysis of cellular proliferation between different types of heart disease.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0295651","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T18:26:37Z","timestamp":1706207197000},"page":"e0295651","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elimination of 15N-thymidine after oral administration in human infants"],"prefix":"10.1371","volume":"19","author":[{"given":"Niyatie","family":"Ammanamanchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-1634","authenticated-orcid":true,"given":"Jessie","family":"Yester","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita 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