{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:34:49Z","timestamp":1787243689437,"version":"build-2736575974"},"reference-count":72,"publisher":"Walter de Gruyter GmbH","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2025-0526_abs_001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Investigations into human performance and health status during long-duration spaceflights are ongoing aboard the International Space Station (ISS) and are critical for planning missions beyond Low Earth Orbit (LEO). This review evaluates the current evidence on point-of-care-testing (POCT) in space, discussing requirements for POCT to support astronaut health during extended deep space missions and the potential for technology transfer to terrestrial healthcare.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-0526_abs_002\">\n                    <jats:title>Contents<\/jats:title>\n                    <jats:p>Microgravity disrupts biochemical and hormonal regulation, leading to reversible homeostatic dysregulation across multiple organ systems in astronauts during spaceflight in LEO. Missions beyond LEO may significantly increase risks of morbidity and mortality in particular for cardiovascular disease. The ability to assess key organ functions by expanding the range of detectable biomarkers on POCTs is crucial for ongoing health monitoring, urgent clinical decisions, and future mission planning. The recent implementation of high-sensitivity cardiac troponin I on POCT will be essential for early identifying myocardial injury and facilitating telemedicine support. Furthermore, the development and use of reference change values (RCV) in space environment, derived from biomarkers measured longitudinally in real-time onboard, will be crucial to differentiate clinically relevant changes in biomarkers levels from alterations induced by microgravity. This approach may overcome the use of traditional cut-off values which are assessed and generally applied under stable terrestrial conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-0526_abs_003\">\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>Clinical laboratory capabilities on the ISS are currently minimal. As missions lengthen, and extend beyond LEO, enhanced POCT is needed. Limited data on POCT performance in space highlight the importance of laboratory professionals\u2019 involvement to ensure high-quality testing and accurate interpretation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2025-0526","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T07:56:26Z","timestamp":1761551786000},"page":"570-581","source":"Crossref","is-referenced-by-count":2,"title":["Point of care testing of biochemical markers for monitoring astronauts during long duration missions in deep space"],"prefix":"10.1515","volume":"64","author":[{"given":"Simona","family":"Ferraro","sequence":"first","affiliation":[{"name":"Pediatric Department , Buzzi Children\u2019s Hospital , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohini","family":"Sengupta","sequence":"additional","affiliation":[{"name":"Department of Laboratory Services , Healthians Labs , Delhi , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3983-8487","authenticated-orcid":false,"given":"Julie","family":"Shaw","sequence":"additional","affiliation":[{"name":"Division of Biochemistry , Eastern Ontario Regional Laboratories Association and Department of Pathology and Laboratory Medicine, The University of Ottawa , Ottawa , ON , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anilkumar","family":"Dave","sequence":"additional","affiliation":[{"name":"Space Economy and Open Innovation, Darwix srl , Venice , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Cheli","sequence":"additional","affiliation":[{"name":"Astronaut Retired; Mission Specialist Space Shuttle Columbia STS-75 , Turin , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Colon","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics , Weill Cornell Medicine , New York , NY , USA"},{"name":"The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine , New York , NY , USA"},{"name":"The World Quant Initiative for Quantitative Prediction, Weill Cornell Medicine , New York , NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianvincenzo","family":"Zuccotti","sequence":"additional","affiliation":[{"name":"Pediatric Department , Buzzi Children\u2019s Hospital , Milan , Italy"},{"name":"Department of Biomedical and Clinical Science , University of Milan , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics , Weill Cornell Medicine , New York , NY , USA"},{"name":"The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine , New York , NY , USA"},{"name":"The World Quant Initiative for Quantitative Prediction, Weill Cornell Medicine , New York , NY , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santica","family":"Marcovina","sequence":"additional","affiliation":[{"name":"Medpace Reference Laboratories , Cincinnati , OH , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"2026021916200381099_j_cclm-2025-0526_ref_001","doi-asserted-by":"crossref","unstructured":"Rea, DJ, Miller, RS, Crucian, BE, Valentine, RW, Cristoforetti, S, Bearg, SB, et al.. Single drop cytometry onboard the International Space Station. Nat Commun 2024;15:2634. https:\/\/doi.org\/10.1038\/s41467-024-46483-6.","DOI":"10.1038\/s41467-024-46483-6"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_002","doi-asserted-by":"crossref","unstructured":"Ferraro, S, Dave, A, Cereda, C, Verduci, E, Marcovina, S, Zuccotti, G. Space research to explore novel biochemical insights on Earth. Clin Chim Acta 2024;558:119673. https:\/\/doi.org\/10.1016\/j.cca.2024.119673.","DOI":"10.1016\/j.cca.2024.119673"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_003","doi-asserted-by":"crossref","unstructured":"Afshinnekoo, E, Scott, RT, MacKay, MJ, Pariset, E, Cekanaviciute, E, Barker, R, et al.. Fundamental biological features of spaceflight: advancing the field to enable deep-space exploration. Cell 2020;183:1162\u201384. https:\/\/doi.org\/10.1016\/j.cell.2020.10.050.","DOI":"10.1016\/j.cell.2020.10.050"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_004","doi-asserted-by":"crossref","unstructured":"Delp, MD, Charvat, JM, Limoli, CL, Globus, RK, Ghosh, P. Apollo lunar astronauts show higher cardiovascular disease mortality: possible deep space radiation effects on the vascular endothelium. Sci Rep 2016;6:29901. https:\/\/doi.org\/10.1038\/srep29901.","DOI":"10.1038\/srep29901"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_005","doi-asserted-by":"crossref","unstructured":"Khine, HW, Steding-Ehrenborg, K, Hastings, JL, Kowal, J, Daniels, JD, Page, RL, et al.. Effects of prolonged spaceflight on atrial size, atrial electrophysiology, and risk of atrial fibrillation. Circ Arrhythm Electrophysiol 2018;11:e005959. https:\/\/doi.org\/10.1161\/circep.117.005959.","DOI":"10.1161\/CIRCEP.117.005959"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_006","doi-asserted-by":"crossref","unstructured":"Aunon-Chancellor, SM, Pattarini, JM, Moll, S, Sargsyan, A. Venous thrombosis during spaceflight. N\u00a0Engl J Med 2020;382:89\u201390. https:\/\/doi.org\/10.1056\/nejmc1905875.","DOI":"10.1056\/NEJMc1905875"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_007","doi-asserted-by":"crossref","unstructured":"Goodenow-Messman, DA, Gokoglu, SA, Kassemi, M, Myers, JGJr. Numerical characterization of astronaut CaOx renal stone incidence rates to quantify in-flight and post-flight relative risk. NPJ Microgravity 2022;8:2. https:\/\/doi.org\/10.1038\/s41526-021-00187-z.","DOI":"10.1038\/s41526-021-00187-z"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_008","doi-asserted-by":"crossref","unstructured":"Rowe, WJ. The Apollo 15 space syndrome. Circulation 1998;97:119\u201320. https:\/\/doi.org\/10.1161\/01.cir.97.1.119.","DOI":"10.1161\/01.CIR.97.1.119"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_009","doi-asserted-by":"crossref","unstructured":"Cowen, D, Zhang, R, Komorowski, M. Infections in long-duration space missions. Lancet Microbe 2024;5:100875. https:\/\/doi.org\/10.1016\/s2666-5247-24-00098-3.","DOI":"10.1016\/S2666-5247(24)00098-3"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_010","unstructured":"Portable diagnostics technology assessment for space missions. https:\/\/ntrs.nasa.gov\/api\/citations\/20100011008\/downloads\/20100011008.pdf [Accessed 9 December 2024]"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_011","doi-asserted-by":"crossref","unstructured":"Crucian, B, Valentine, R, Calaway, K, Miller, R, Rubins, K, Hopkins, M, et al.. 2021. Spaceflight validation of technology for point-of-care monitoring of peripheral blood WBC and differential in astronauts during space missions. Life Sci Space Res 2021 31:29\u201333. https:\/\/doi.org\/10.1016\/j.lssr.2021.07.003.","DOI":"10.1016\/j.lssr.2021.07.003"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_012","doi-asserted-by":"crossref","unstructured":"Smith, SM, Davis-Street, JE, Fontenot, TB, Lane, HW. Assessment of a portable clinical blood analyzer during space flight. Clin Chem 1997;43:1056\u201365. https:\/\/doi.org\/10.1093\/clinchem\/43.6.1056.","DOI":"10.1093\/clinchem\/43.6.1056"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_013","unstructured":"https:\/\/issnationallab.org\/press-releases\/1drop-diagnostics-leverage-microgravity-improve-medical-diagnostics\/ [Accessed 9 December 2024]."},{"key":"2026021916200381099_j_cclm-2025-0526_ref_014","unstructured":"Beshay, M, Hatch, M, Vu, K, Mudanyali, O, Karlovac, N; 2016. http:\/\/www.intopsys.com\/wpcontent\/uploads\/2016\/02\/NASA-HRP-Conference-2016.pdf [Accessed 9 December 2024]."},{"key":"2026021916200381099_j_cclm-2025-0526_ref_015","doi-asserted-by":"crossref","unstructured":"Han, GR, Goncharov, A, Eryilmaz, M, Ye, S, Palanisamy, B, Ghosh, R, et al.. Machine learning in point-of-care testing: innovations, challenges, and opportunities. Nat Commun 2025;16:3165. https:\/\/doi.org\/10.1038\/s41467-025-58527-6.","DOI":"10.1038\/s41467-025-58527-6"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_016","doi-asserted-by":"crossref","unstructured":"Land, KJ, Boeras, DI, Chen, X-S, Ramsay, AR, Peeling, RW. Reassured diagnostics to inform disease control strategies, strengthen health systems and improve patient outcomes. Nat Microbiol 2019;4:46\u201354. https:\/\/doi.org\/10.1038\/s41564-018-0295-3.","DOI":"10.1038\/s41564-018-0295-3"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_017","unstructured":"CLSI document EP28-A3c\u00a0\u2013\u00a0Defining. Establishing and verifying reference intervals in the clinical laboratory. https:\/\/clsi.org\/shop\/standards\/ep28\/ [Accessed 9 December 2024]."},{"key":"2026021916200381099_j_cclm-2025-0526_ref_018","doi-asserted-by":"crossref","unstructured":"Strangman, GE, Sawyer, A, Fabre, KM, Urquieta, E, Hury, J, Wu, J, et al.. Deep-space applications for point-of-care technologies. Curr Opin Biom Engin 2019;11:45\u201350. https:\/\/doi.org\/10.1016\/j.cobme.2019.08.014.","DOI":"10.1016\/j.cobme.2019.08.014"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_019","doi-asserted-by":"crossref","unstructured":"Roda, A, Mirasoli, M, Guardigli, M, Zangheri, M, Caliceti, C, Calabria, D, et al.. Advanced biosensors for monitoring astronauts\u2019 health during long-duration space missions. Biosens Bioelectron 2018;111:18\u201326. https:\/\/doi.org\/10.1016\/j.bios.2018.03.062.","DOI":"10.1016\/j.bios.2018.03.062"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_020","doi-asserted-by":"crossref","unstructured":"Lewandowski, BE, Schkurko, CM, Miller, RS, Valentine, RW, Calaway, KM, Yang, JD, et al.. Technology modification, development, and demonstrations for future spaceflight medical systems at NASA. Front. Space Technol 2024;5:1384457. https:\/\/www.frontiersin.org\/journals\/spacetechnologies\/articles\/10.3389\/frspt.2024.1384457\/full [Accessed 9 December 2024].","DOI":"10.3389\/frspt.2024.1384457"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_021","unstructured":"https:\/\/www.nasa.gov\/missions\/station\/recycling-in-space-waste-handling-in-a-microgravity-environment-challenge\/ [Accessed 4 July 2025]."},{"key":"2026021916200381099_j_cclm-2025-0526_ref_022","unstructured":"https:\/\/www.nasa.gov\/artemis-accords\/ [Accessed 4 July 2025]."},{"key":"2026021916200381099_j_cclm-2025-0526_ref_023","unstructured":"https:\/\/science.nasa.gov\/learn\/basics-of-space-flight\/chapter11-4\/#:\u223c:text=Passive%20thermal%20control%20is%20obtained,spacecraft%20from%20excess%20solar%20heating [Accessed 4 July 2025]."},{"key":"2026021916200381099_j_cclm-2025-0526_ref_024","doi-asserted-by":"crossref","unstructured":"Dobney, W, Mols, L, Mistry, D, Tabury, K, Baselet, B, Baatout, S. Evaluation of deep space exploration risks and mitigations against radiation and microgravity. Front Nucl Med 2023;3:1225034. https:\/\/doi.org\/10.3389\/fnume.2023.1225034.","DOI":"10.3389\/fnume.2023.1225034"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_025","doi-asserted-by":"crossref","unstructured":"Fogtman, A, Baatout, S, Baselet, B, Berger, T, Hellweg, CE, Jiggens, P, et al.. Towards sustainable human space exploration\u00a0\u2013\u00a0priorities for radiation research to quantify and mitigate radiation risks. Npj Microgravity 2023;9:8. https:\/\/doi.org\/10.1038\/s41526-023-00262-7.","DOI":"10.1038\/s41526-023-00262-7"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_026","doi-asserted-by":"crossref","unstructured":"Patel, S. The effects of microgravity and space radiation on cardiovascular health: from low-Earth orbit and beyond. Int J Cardiol Heart Vasc 2020;30:100595. https:\/\/doi.org\/10.1016\/j.ijcha.2020.100595.","DOI":"10.1016\/j.ijcha.2020.100595"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_027","doi-asserted-by":"crossref","unstructured":"Mircea, AA, Pistritu, DV, Fortner, A, Tanca, A, Liehn, EA, Bucur, O. Space travel: the radiation and microgravity effects on the cardiovascular system. Int J Mol Sci 2024;25:11812. https:\/\/doi.org\/10.3390\/ijms252111812.","DOI":"10.3390\/ijms252111812"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_028","doi-asserted-by":"crossref","unstructured":"Khera, A, Budoff, MJ, O\u2019Donnell, CJ, Ayers, CA, Locke, J, de Lemos, JA, et al.. Astronaut cardiovascular health and risk modification (Astro-CHARM) coronary calcium atherosclerotic cardiovascular disease risk calculator. Circulation 2018;138:1819\u201327. https:\/\/doi.org\/10.1161\/circulationaha.118.033505.","DOI":"10.1161\/CIRCULATIONAHA.118.033505"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_029","doi-asserted-by":"crossref","unstructured":"Charvat, JM, Leonard, D, Barlow, CE, DeFina, LF, Willis, BL, Lee, SMC, et al.. Long-term cardiovascular risk in astronauts: comparing NASA mission astronauts with a healthy cohort from the cooper Center longitudinal Study. Mayo Clin Proc 2022;97:1237\u201346. https:\/\/doi.org\/10.1016\/j.mayocp.2022.04.003.","DOI":"10.1016\/j.mayocp.2022.04.003"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_030","doi-asserted-by":"crossref","unstructured":"Ade, CJ, Broxterman, RM, Charvat, JM, Barstow, TJ. Incidence rate of cardiovascular disease end points in the national Aeronautics and Space Administration Astronaut Corps. J\u00a0Am Heart Assoc 2017;6:e005564. https:\/\/doi.org\/10.1161\/jaha.117.005564.","DOI":"10.1161\/JAHA.117.005564"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_031","doi-asserted-by":"crossref","unstructured":"Gallo, C, Ridolfi, L, Scarsoglio, S. Cardiovascular deconditioning during long-term spaceflight through multiscale modeling. NPJ Microgravity 2020;6:27. https:\/\/doi.org\/10.1038\/s41526-020-00117-5.","DOI":"10.1038\/s41526-020-00117-5"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_032","unstructured":"Cl\u00e9ment, G. Fundamentals of space medicine, 2nd ed. Springer; 2011. https:\/\/link.springer.com\/book\/10.1007\/978-1-4419-9905-4 [Accessed 9 December 2024]."},{"key":"2026021916200381099_j_cclm-2025-0526_ref_033","doi-asserted-by":"crossref","unstructured":"McDermott, M, Kimenai, D, Anand, A, Huang, Z, Houston, A, McDermott, M, et al.. Adoption of high-sensitivity cardiac troponin for risk stratification of patients with suspected myocardial infarction: a multicentre cohort study. Lancet Reg Health Eur 2024;43:100960. https:\/\/doi.org\/10.1016\/j.lanepe.2024.100960.","DOI":"10.1016\/j.lanepe.2024.100960"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_034","doi-asserted-by":"crossref","unstructured":"Horwich, TB, Patel, J, MacLellan, WR, Fonarow, GC. Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation 2003;108:833\u20138. https:\/\/doi.org\/10.1161\/01.cir.0000084543.79097.34.","DOI":"10.1161\/01.CIR.0000084543.79097.34"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_035","doi-asserted-by":"crossref","unstructured":"Shibata, S, Wakeham, DJ, Thomas, JD, Abdullah, SM, Platts, S, Bungo, MW, et al.. Cardiac effects of long-duration space flight. J\u00a0Am Coll Cardiol 2023;82:674\u201384. https:\/\/doi.org\/10.1016\/j.jacc.2023.05.058.","DOI":"10.1016\/j.jacc.2023.05.058"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_036","doi-asserted-by":"crossref","unstructured":"Welsh, P, Preiss, D, Hayward, C, Shah, ASV, McAllister, D, Briggs, A, et al.. Cardiac troponin T and troponin I in the general population. Circulation 2019;139:2754\u201364. https:\/\/doi.org\/10.1161\/circulationaha.118.038529.","DOI":"10.1161\/CIRCULATIONAHA.118.038529"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_037","doi-asserted-by":"crossref","unstructured":"Toprak, B, Solleder, H, Di Carluccio, E, Greenslade, JH, Parsonage, WA, Schulz, K, et al.. Artificial Intelligence in Suspected Myocardial Infarction Study (ARTEMIS) group. Diagnostic accuracy of a machine learning algorithm using point-of-care high-sensitivity cardiac troponin I for rapid rule-out of myocardial infarction: a retrospective study. Lancet Digit Health 2024;6:e729\u201338. https:\/\/doi.org\/10.1016\/s2589-7500-24-00191-2.","DOI":"10.1016\/S2589-7500(24)00191-2"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_038","doi-asserted-by":"crossref","unstructured":"Frings-Meuthen, P, Luchitskaya, E, Jordan, J, Tank, J, Lichtinghagen, R, Smith, SM, et al.. Natriuretic peptide resetting in astronauts. Circulation 2020;141:1593\u20135. https:\/\/doi.org\/10.1161\/circulationaha.119.044203.","DOI":"10.1161\/CIRCULATIONAHA.119.044203"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_039","doi-asserted-by":"crossref","unstructured":"Olde Engberink, RHG, van Oosten, PJ, Weber, T, Tabury, K, Baatout, S, Siew, K, et al.. The kidney, volume homeostasis and osmoregulation in space: current perspective and knowledge gaps. NPJ Microgravity 2023;9:29. https:\/\/doi.org\/10.1038\/s41526-023-00268-1.","DOI":"10.1038\/s41526-023-00268-1"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_040","doi-asserted-by":"crossref","unstructured":"Michel, L, Mincu, RI, Mahabadi, AA, Settelmeier, S, Al-Rashid, F, Rassaf, T, et al.. Troponins and brain natriuretic peptides for the prediction of cardiotoxicity in cancer patients: a meta-analysis. Eur J Heart Fail 2020;22:350\u201361. https:\/\/doi.org\/10.1002\/ejhf.1631.","DOI":"10.1002\/ejhf.1631"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_041","doi-asserted-by":"crossref","unstructured":"Li, J, Wagar, EA, Meng, QH. Comprehensive assessment of biotin interference in immunoassays. Clin Chim Acta 2018;487:293\u20138. https:\/\/doi.org\/10.1016\/j.cca.2018.10.013.","DOI":"10.1016\/j.cca.2018.10.013"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_042","doi-asserted-by":"crossref","unstructured":"Eggers, KM, Hammarsten, O, Lindahl, B. Differences between high-sensitivity cardiac troponin T and I in stable populations: underlying causes and clinical implications. Clin Chem Lab Med 2022;61:380\u20137. https:\/\/doi.org\/10.1515\/cclm-2022-0778.","DOI":"10.1515\/cclm-2022-0778"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_043","doi-asserted-by":"crossref","unstructured":"Garmany, A, Yamada, S, Park, S, Terzic, A. Plasma biomarkers of first all-civilian space flight to the international space station. Mayo Clin Proc 2024;99:1523\u20135. https:\/\/doi.org\/10.1016\/j.mayocp.2024.05.024.","DOI":"10.1016\/j.mayocp.2024.05.024"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_044","doi-asserted-by":"crossref","unstructured":"Stavnichuk, M, Mikolajewicz, N, Corlett, T, Morris, M, Komarova, SV. A systematic review and meta-analysis of bone loss in space travelers. NPJ Microgravity 2020;6:13. https:\/\/doi.org\/10.1038\/s41526-020-0103-2.","DOI":"10.1038\/s41526-020-0103-2"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_045","doi-asserted-by":"crossref","unstructured":"Garrett-Bakelman, FE, Darshi, M, Green, SJ, Gur, RC, Lin, L, Macias, BR, et al.. The NASA Twins Study: a multidimensional analysis of a year-long human spaceflight. Science 2019;364:eaau8650. https:\/\/doi.org\/10.1126\/science.aau8650.","DOI":"10.1126\/science.aau8650"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_046","doi-asserted-by":"crossref","unstructured":"Smith, SM, Heer, MA, Shackelford, LC, Sibonga, JD, Ploutz-Snyder, L, Zwart, SR. Benefits for bone from resistance exercise and nutrition in long-duration spaceflight: evidence from biochemistry and densitometry. J\u00a0Bone Miner Res 2012;27:1896\u2013906. https:\/\/doi.org\/10.1002\/jbmr.1647.","DOI":"10.1002\/jbmr.1647"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_047","doi-asserted-by":"crossref","unstructured":"Braga, F, Ferraro, S, Mozzi, R, Dolci, A, Panteghini, M. Biological variation of neuroendocrine tumor markers chromogranin A and neuron-specific enolase. Clin Biochem 2013;46:148\u201351. https:\/\/doi.org\/10.1016\/j.clinbiochem.2012.09.005.","DOI":"10.1016\/j.clinbiochem.2012.09.005"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_048","doi-asserted-by":"crossref","unstructured":"Matom\u00e4ki, P, Kainulainen, H, Kyr\u00f6l\u00e4inen, H. Corrected whole blood biomarkers\u00a0\u2013\u00a0the equation of Dill and Costill revisited. Phys Rep 2018;6:e13749. https:\/\/doi.org\/10.14814\/phy2.13749.","DOI":"10.14814\/phy2.13749"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_049","doi-asserted-by":"crossref","unstructured":"White, NJ, Wenthe, A. Managing hemostasis in space. Arterioscler Thromb Vasc Biol 2023;43:2079\u201387. https:\/\/doi.org\/10.1161\/atvbaha.123.318783.","DOI":"10.1161\/ATVBAHA.123.318783"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_050","doi-asserted-by":"crossref","unstructured":"Kunz, H, Quiriarte, H, Simpson, RJ, Ploutz-Snyder, R, McMonigal, K, Sams, C, et al.. Alterations in hematologic indices during long-duration spaceflight. BMC Hematol 2017;17:12. https:\/\/doi.org\/10.1186\/s12878-017-0083-y.","DOI":"10.1186\/s12878-017-0083-y"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_051","doi-asserted-by":"crossref","unstructured":"Smith, SM. Red blood cell and iron metabolism during space flight. Nutrition 2002;18:864\u20136. https:\/\/doi.org\/10.1016\/s0899-9007-02-00912-7.","DOI":"10.1016\/S0899-9007(02)00912-7"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_052","unstructured":"Olivari, M. Space technology transfers and their commercialisation. Organisation for Economic Co-operation and Development (OECD) science, technology, and industry policy papers. https:\/\/www.oecd.org\/en\/publications\/space-technology-transfers-and-their-commercialisation_0e78ff9f-en.html [Accessed 9 July 2025]."},{"key":"2026021916200381099_j_cclm-2025-0526_ref_053","doi-asserted-by":"crossref","unstructured":"Wilde, JH, Sun, YY, Simpson, SR, Hill, ER, Fu, Z, Bian, EJ, et al.. A positron emission tomography tracer for the imaging of oxidative stress in the central nervous system. Nat Biomed Eng 2025;9:716\u201329. https:\/\/doi.org\/10.1038\/s41551-025-01362-3.","DOI":"10.1038\/s41551-025-01362-3"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_054","doi-asserted-by":"crossref","unstructured":"Scarpa, J, Parazynski, S, Strangman, G. Space exploration as a catalyst for medical innovations. Front Med 2023;10:1226531. https:\/\/doi.org\/10.3389\/fmed.2023.1226531.","DOI":"10.3389\/fmed.2023.1226531"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_055","unstructured":"Zimmerman, MS, Carswell Smith, AG, Sable, CA, Echko, MM, Wilner, LB, Olsen, HE; Congenital Heart Disease Collaborators (GBD), et al.. Global, regional, and national burden of congenital heart disease, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Child Adolesc Health. 2020;4:185\u2013200, https:\/\/doi.org\/10.1016\/s2352-4642-19-30402-x."},{"key":"2026021916200381099_j_cclm-2025-0526_ref_056","doi-asserted-by":"crossref","unstructured":"Ferraro, S, Biganzoli, E, Mannarino, S, Lanzoni, M, Zuccotti, G, Plebani, M, et al.. High-sensitivity cardiac troponin and the management of congenital heart disease in newborns and infants. Clin Chem 2024;70:486\u201396. https:\/\/doi.org\/10.1093\/clinchem\/hvad215.","DOI":"10.1093\/clinchem\/hvad215"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_057","doi-asserted-by":"crossref","unstructured":"Cheng, SPS, Heo, K, Joos, E, Vervoort, D, Joharifard, S. Barriers to accessing congenital heart surgery in Low- and middle-income countries: a systematic review. World J Pediatr Congenit Heart Surg 2024;15:94\u2013103. https:\/\/doi.org\/10.1177\/21501351231204328.","DOI":"10.1177\/21501351231204328"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_058","unstructured":"https:\/\/www.asc-csa.gc.ca\/eng\/iss\/bio-analyzer.asp [Accessed 4 July 2025]"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_059","doi-asserted-by":"crossref","unstructured":"McIntyre, ABR, Rizzardi, L, Yu, AM, Alexander, N, Rosen, GL, Botkin, DJ, et al.. Nanopore sequencing in microgravity. NPJ Microgravity 2016;2:16035. https:\/\/doi.org\/10.1038\/npjmgrav.2016.35.","DOI":"10.1038\/npjmgrav.2016.35"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_060","doi-asserted-by":"crossref","unstructured":"Castro-Wallace, SL, Chiu, CY, John, KK, Stahl, SE, Rubins, KH, McIntyre, ABR, et al.. Nanopore DNA sequencing and genome assembly on the international space station. Sci Rep 2017;7:18022. https:\/\/doi.org\/10.1038\/s41598-017-18364-0.","DOI":"10.1038\/s41598-017-18364-0"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_061","doi-asserted-by":"crossref","unstructured":"Overbey, EG, Kim, J, Tierney, BT, Park, J, Houerbi, N, Lucaci, AG, et al.. The space omics and medical atlas (SOMA) and international astronaut biobank. Nature 2024;632:1145\u201354. https:\/\/doi.org\/10.1038\/s41586-024-07639-y.","DOI":"10.1038\/s41586-024-07639-y"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_062","doi-asserted-by":"crossref","unstructured":"Mason, CE, Green, J, Adamopoulos, KI, Afshin, EE, Baechle, JJ, Basner, M, et al.. A second space age spanning omics, platforms, and medicine across orbits. Nature 2024;632:995\u20131008. https:\/\/doi.org\/10.1038\/s41586-024-07586-8.","DOI":"10.1038\/s41586-024-07586-8"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_063","doi-asserted-by":"crossref","unstructured":"Jones, CW, Overbey, EG, Lacombe, J, Ecker, AJ, Meydan, C, Ryon, K, et al.. Molecular and physiological changes in the SpaceX Inspiration4 civilian crew. Nature 2024;632:1155\u201364. https:\/\/doi.org\/10.1038\/s41586-024-07648-x.","DOI":"10.1038\/s41586-024-07648-x"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_064","doi-asserted-by":"crossref","unstructured":"Kim, J, Tierney, BT, Overbey, EG, Dantas, E, Fuentealba, M, Park, J, et al.. Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight. Nat Commun 2024;15:4954. https:\/\/doi.org\/10.1038\/s41467-024-49211-2.","DOI":"10.1038\/s41467-024-49211-2"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_065","doi-asserted-by":"crossref","unstructured":"Tierney, BT, Kim, J, Overbey, EG, Ryon, KA, Foox, J, Sierra, MA, et al.. Longitudinal multi-omics analysis of host microbiome architecture and immune responses during short-term spaceflight. Nat Microbiol 2024;9:1661\u201375. https:\/\/doi.org\/10.1038\/s41564-024-01635-8.","DOI":"10.1038\/s41564-024-01635-8"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_066","doi-asserted-by":"crossref","unstructured":"Park, J, Overbey, EG, Narayanan, SA, Kim, J, Tierney, BT, Damle, N, et al.. Spatial multi-omics of human skin reveals KRAS and inflammatory responses to spaceflight. Nat Commun 2024;15:4773. https:\/\/doi.org\/10.1038\/s41467-024-48625-2.","DOI":"10.1038\/s41467-024-48625-2"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_067","doi-asserted-by":"crossref","unstructured":"Houerbi, N, Kim, J, Overbey, EG, Batra, R, Schweickart, A, Patras, L, et al.. Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight. Nat Commun 2024;15:4862. https:\/\/doi.org\/10.1038\/s41467-024-48841-w.","DOI":"10.1038\/s41467-024-48841-w"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_068","doi-asserted-by":"crossref","unstructured":"Grigorev, K, Nelson, TM, Overbey, EG, Houerbi, N, Kim, J, Najjar, D, et al.. Direct RNA sequencing of astronaut blood reveals spaceflight-associated m6A increases and hematopoietic transcriptional responses. Nat Commun 2024;15:4950. https:\/\/doi.org\/10.1038\/s41467-024-48929-3.","DOI":"10.1038\/s41467-024-48929-3"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_069","doi-asserted-by":"crossref","unstructured":"Garcia-Medina, JS, Sienkiewicz, K, Narayanan, SA, Overbey, EG, Grigorev, K, Ryon, KA, et al.. Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight. Precis Clin Med 2024;7:pbae007. https:\/\/doi.org\/10.1093\/pcmedi\/pbae007.","DOI":"10.21203\/rs.3.rs-2928049\/v1"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_070","unstructured":"https:\/\/etd.gsfc.nasa.gov\/our-work\/lunar-gnss-receiver-experiment-lugre\/ [Accessed 4 July 2025]"},{"key":"2026021916200381099_j_cclm-2025-0526_ref_071","unstructured":"https:\/\/www.axiomspace.com\/missions\/ax3 [Accessed4 July 2025]."},{"key":"2026021916200381099_j_cclm-2025-0526_ref_072","doi-asserted-by":"crossref","unstructured":"Asachi, P, Ghanem, G, Burton, J, Aintablian, H, Chiem, A. Utility of ultrasound in managing acute medical conditions in space: a scoping review. Ultrasound J 2023;15:47. https:\/\/doi.org\/10.1186\/s13089-023-00349-y.","DOI":"10.1186\/s13089-023-00349-y"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0526\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0526\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T16:22:24Z","timestamp":1771518144000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0526\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":72,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9,29]]},"published-print":{"date-parts":[[2026,2,24]]}},"alternative-id":["10.1515\/cclm-2025-0526"],"URL":"https:\/\/doi.org\/10.1515\/cclm-2025-0526","relation":{},"ISSN":["1434-6621","1437-4331"],"issn-type":[{"value":"1434-6621","type":"print"},{"value":"1437-4331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,28]]}}}