{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:50:47Z","timestamp":1784224247805,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","doi-asserted-by":"publisher","award":["23K07628"],"award-info":[{"award-number":["23K07628"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Corporation WADOKAI"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Frailty is increasingly recognized as a systemic complication in patients with obstructive pulmonary diseases (OPDs), yet its molecular basis remains unclear. Extracellular vesicles (EVs), which transport small RNAs, may offer mechanistic insight into this comorbidity. This study investigated the association between serum-derived EV small RNAs and frailty in OPD. Sixty-eight patients with OPD were enrolled, and EVs isolated from 29 patients (13 with chronic obstructive pulmonary disease [COPD], four with COPD and asthma, and 12 with asthma; median age 72 years) were analyzed. Based on the Kihon Checklist, patients were classified as frail (n = 11) or non-frail (n = 18). Small RNA sequencing and differential expression analyses were conducted, followed by age-adjusted correlation with physical factors and Ingenuity Pathway Analysis (IPA). A total of 108 small RNAs were differentially expressed between frail and non-frail groups (p &lt; 0.05, fold change &lt; 0.8 or &gt;1.2). IPA linked these RNAs to lung fibrosis and transforming growth factor-beta (TGF-\u03b2) signaling pathways. Eleven small RNAs correlated with lower limb strength, and three\u2014miR-125b-5p, miR-369-3p, and miR-615-3p\u2014emerged as key candidates associated with frailty. These findings suggest that EV-derived small RNAs may contribute to frailty development in OPD through TGF-\u03b2\u2013related molecular mechanisms.<\/jats:p>","DOI":"10.3390\/biom15121663","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T13:03:02Z","timestamp":1764594182000},"page":"1663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Small RNA Profiles of Serum-Derived Extracellular Vesicles in the Comorbid Condition of Frailty and Obstructive Pulmonary Disease: An Observational, Cross-Sectional Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4485-4510","authenticated-orcid":false,"given":"Keiko","family":"Doi","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan"},{"name":"Department of Pulmonology and Gerontology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5475-0806","authenticated-orcid":false,"given":"Tsunahiko","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4368-6586","authenticated-orcid":false,"given":"Naoomi","family":"Tominaga","sequence":"additional","affiliation":[{"name":"Division of Clinical Laboratory Sciences, Department of Nursing and Laboratory Science, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5069-1706","authenticated-orcid":false,"given":"Kenji","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Institute of Gene Research, Yamaguchi University Science Research Center, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4230-0450","authenticated-orcid":false,"given":"Keiji","family":"Oishi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Fukatsu-Chikumoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 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Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8652-2579","authenticated-orcid":false,"given":"Yoriyuki","family":"Murata","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-6132","authenticated-orcid":false,"given":"Maki","family":"Asami-Noyama","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Edakuni","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1339-1031","authenticated-orcid":false,"given":"Tomoyuki","family":"Kakugawa","sequence":"additional","affiliation":[{"name":"Department of Pulmonology and Gerontology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3290-0754","authenticated-orcid":false,"given":"Yoichi","family":"Mizukami","sequence":"additional","affiliation":[{"name":"Institute of Gene Research, Yamaguchi University Science Research Center, 1-1-1 Minami-Kogushi, Ube 755-8505, 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study","volume":"9","author":"Fukuchi","year":"2004","journal-title":"Respirology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Matsunaga, K., Harada, M., Suizu, J., Oishi, K., Asami-Noyama, M., and Hirano, T. (2020). Comorbid conditions in chronic obstructive pulmonary disease: Potential therapeutic targets for unmet needs. J. Clin. Med., 9.","DOI":"10.3390\/jcm9103078"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1177\/1479972316679664","article-title":"Sarcopenia and frailty in chronic respiratory disease","volume":"14","author":"Bone","year":"2017","journal-title":"Chronic Respir. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tarazona-Santabalbina, F.J., Naval, E., De la C\u00e1mara-de las Heras, J.M., Cunha-P\u00e9rez, C., and Vi\u00f1a, J. (2023). Is frailty diagnosis important in patients with COPD? A narrative review of the literature. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20031678"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.jaip.2022.12.043","article-title":"Muscle function in moderate to severe asthma: Association with clinical outcomes and inflammatory markers","volume":"11","author":"Visser","year":"2023","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/ejcn.2017.147","article-title":"Raw BIA variables are predictors of muscle strength in patients with chronic obstructive pulmonary disease","volume":"71","author":"Santaniello","year":"2017","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.2147\/COPD.S178948","article-title":"Measuring and monitoring skeletal muscle function in COPD: Current perspectives","volume":"14","author":"Marklund","year":"2019","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2338248","DOI":"10.1080\/07853890.2024.2338248","article-title":"Multifaceted associations between walking performance, physical fitness, extremity function, health status, and depression in individuals with COPD","volume":"56","author":"Aldhahi","year":"2024","journal-title":"Ann. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"M146","DOI":"10.1093\/gerona\/56.3.M146","article-title":"Frailty in older adults: Evidence for a phenotype","volume":"56","author":"Fried","year":"2001","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101271","DOI":"10.1016\/j.mam.2024.101271","article-title":"Biomarkers of frailty","volume":"97","year":"2024","journal-title":"Mol. Asp. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Picca, A., Calvani, R., Coelho-J\u00fanior, H.J., Marini, F., Landi, F., and Marzetti, E. (2022). Circulating inflammatory, mitochondrial dysfunction, and senescence-related markers in older adults with physical frailty and sarcopenia: A BIOSPHERE exploratory study. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214006"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12967-023-03911-3","article-title":"Evaluation of serum miRNAs expression in frail and robust subjects undergoing multicomponent exercise protocol (VIVIFRAIL)","volume":"21","author":"Agostini","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.devcel.2019.04.011","article-title":"Exosome-mediated metastasis: Communication from a distance","volume":"49","author":"Wortzel","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41580-023-00576-0","article-title":"Context-specific regulation of extracellular vesicle biogenesis and cargo selection","volume":"24","author":"Dixson","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6716","DOI":"10.1038\/ncomms7716","article-title":"Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier","volume":"6","author":"Tominaga","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/nrg2504","article-title":"Small silencing RNAs: An expanding universe","volume":"10","author":"Ghildiyal","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ejim.2023.05.024","article-title":"MiRNA: What clinicians need to know","volume":"113","author":"Venneri","year":"2023","journal-title":"Eur. J. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sassi, F., Tamone, C., and D\u2019Amelio, P. (2018). Vitamin D: Nutrient, hormone, and Immunomodulator. Nutrients, 10.","DOI":"10.3390\/nu10111656"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1002\/jcsm.13364","article-title":"The role of extracellular vesicles in skeletal muscle wasting","volume":"14","author":"Zhang","year":"2023","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e10686","DOI":"10.1002\/jbm4.10686","article-title":"Extracellular vesicles as communicators of senescence in musculoskeletal aging","volume":"6","author":"Alfonzo","year":"2022","journal-title":"JBMR Plus"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/ggi.12543","article-title":"Validity of the Kihon Checklist for assessing frailty status","volume":"16","author":"Satake","year":"2016","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1183\/09031936.05.00034805","article-title":"Standardisation of spirometry","volume":"26","author":"Miller","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.resinv.2014.03.003","article-title":"Clinical Pulmonary Functions Committee of the Japanese Respiratory Society. Reference values for spirometry, including vital capacity, in Japanese adults calculated with the LMS method and compared with previous values","volume":"52","author":"Kubota","year":"2014","journal-title":"Respir. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories (2002). ATS statement: Guidelines for the six-minute walk test. Am. J. Respir. Crit. Care Med., 166, 111\u2013117.","DOI":"10.1164\/ajrccm.166.1.at1102"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1111\/jgs.16132","article-title":"Associations between skeletal muscle and myocardium in aging: A syndrome of \u201ccardio-sarcopenia\u201d?","volume":"67","author":"Keng","year":"2019","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1589\/jpts.32.120","article-title":"Validity and reliability of isometric knee extension muscle strength measurements using a belt-stabilized hand-held dynamometer: A comparison with the measurement using an isokinetic dynamometer in a sitting posture","volume":"32","author":"Hirano","year":"2020","journal-title":"J. Phys. Ther. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.rmed.2018.07.016","article-title":"Nutritional status and pulmonary outcome in children and young people with cystic fibrosis","volume":"142","author":"Papalexopoulou","year":"2018","journal-title":"Respir. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100","DOI":"10.14283\/jfa.2017.45","article-title":"Identifying exosome-derived microRNAs as candidate biomarkers of frailty","volume":"7","author":"Ipson","year":"2018","journal-title":"J. Frailty Aging"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.2147\/COPD.S379774","article-title":"Plasma extracellular vesicle miRNA profiles distinguish chronic obstructive pulmonary disease exacerbations and disease severity","volume":"17","author":"Bowman","year":"2022","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, F., Yang, B., Qiao, J., Bai, L., Li, Z., Sun, W., Liu, Q., Yang, S., and Cui, L. (2023). Serum exosomal microRNA-1258 may as a novel biomarker for the diagnosis of acute exacerbations of chronic obstructive pulmonary disease. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-45592-4"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"eabq2226","DOI":"10.1126\/sciadv.abq2226","article-title":"Small extracellular vesicles from young adipose-derived stem cells prevent frailty, improve health span, and decrease epigenetic age in old mice","volume":"8","author":"Gordevicius","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1007\/s11357-021-00334-0","article-title":"A robust machine learning framework to identify signatures for frailty: A nested case-control study in four aging European cohorts","volume":"43","author":"Walter","year":"2021","journal-title":"GeroScience"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1002\/ijc.24459","article-title":"MicroRNA regulates human vitamin D receptor","volume":"125","author":"Mohri","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ahmad, S., Arora, S., Khan, S., Mohsin, M., Mohan, A., Manda, K., and Syed, M.A. (2021). Vitamin D and its therapeutic relevance in pulmonary diseases. J. Nutr. Biochem., 90.","DOI":"10.1016\/j.jnutbio.2020.108571"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Li, W., and Zheng, Y. (2023). MicroRNAs in extracellular vesicles of Alzheimer\u2019s disease. Cells, 12.","DOI":"10.3390\/cells12101378"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Scalavino, V., Piccinno, E., Valentini, A.M., Schena, N., Armentano, R., Giannelli, G., and Serino, G. (2023). miR-369-3p modulates intestinal inflammatory response via brcc3\/nlrp3 inflammasome axis. Cells, 12.","DOI":"10.3390\/cells12172184"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Scalavino, V., Piccinno, E., Labarile, N., Armentano, R., Giannelli, G., and Serino, G. (2024). Anti-inflammatory effects of mir-369-3p via pde4b in intestinal inflammatory response. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158463"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jphs.2023.12.007","article-title":"Protective effect and regulatory mechanism of salidroside on skin inflammation induced by imiquimod in psoriasis mice","volume":"154","author":"Su","year":"2024","journal-title":"J. Pharmacol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Tao, W., Min, S., Chen, G., He, X., Meng, Y., Li, L., Chen, J., and Li, Y. (2024). Tetramethylpyrazine ameliorates LPS-induced acute lung injury via the miR-369-3p\/DSTN axis. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-70131-0"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3727\/096504018X15215019227688","article-title":"MicroRNA 615\u20133p inhibits the tumor growth and metastasis of NSCLC via inhibiting IGF2","volume":"27","author":"Liu","year":"2019","journal-title":"Oncol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nature09667","article-title":"A critical role for IGF-II in memory consolidation and enhancement","volume":"469","author":"Chen","year":"2011","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.tins.2023.03.007","article-title":"IGF2 in memory, neurodevelopmental disorders, and neurodegenerative diseases","volume":"46","author":"Alberini","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00018-024-05399-6","article-title":"The functions and mechanisms of piRNAs in mediating mammalian spermatogenesis and their applications in reproductive medicine","volume":"81","author":"Du","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"112598","DOI":"10.1016\/j.exger.2024.112598","article-title":"Circulating small non-coding RNA profiling for identification of older adults with low muscle strength and physical performance: A preliminary study","volume":"197","author":"Shin","year":"2024","journal-title":"Exp. Gerontol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/nrm3089","article-title":"PIWI-interacting small RNAs: The vanguard of genome defence","volume":"12","author":"Siomi","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10401","DOI":"10.1080\/21655979.2021.1997078","article-title":"PIWI interacting RNAs perspectives: A new avenues in future cancer investigations","volume":"12","author":"Mokarram","year":"2021","journal-title":"Bioengineered"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Fonseca Cabral, G., Azevedo Dos Santos Pinheiro, J., Vidal, A.F., Santos, S., and Ribeiro-dos-Santos, \u00c2. (2020). piRNAs in gastric cancer: A new approach towards translational research. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062126"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ncrna.2025.01.005","article-title":"Circulating PIWI-interacting RNAs in acute ischemic stroke patients","volume":"11","author":"Toor","year":"2025","journal-title":"Non-Coding RNA Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Hirano, T., Doi, K., Matsunaga, K., Takahashi, S., Donishi, T., Suga, K., Oishi, K., Yasuda, K., Mimura, Y., and Harada, M. (2020). A novel role of growth differentiation factor (GDF)-15 in overlap with sedentary lifestyle and cognitive risk in COPD. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092737"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4133","DOI":"10.1096\/fj.14-254490","article-title":"Diminished skeletal muscle microRNA expression with aging is associated with attenuated muscle plasticity and inhibition of IGF-1 signaling","volume":"28","author":"Rivas","year":"2014","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ding, X.-Q., Ge, P.-C., Liu, Z., Jia, H., Chen, X., An, F.-H., Li, L.-H., Chen, Z.-H., Mao, H.-W., and Li, Z.-Y. (2015). Interaction between microRNA Expression and Classical Risk Factors in the Risk of Coronary Heart Disease. Sci. Rep., 5.","DOI":"10.1038\/srep14925"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Sandau, U.S., Wiedrick, J.T., McFarland, T.J., Galasko, D.R., Fanning, Z., Quinn, J.F., and Saugstad, J.A. (2024). Analysis of the longitudinal stability of human plasma miRNAs and implications for disease biomarkers. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-52681-5"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/12\/1663\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T13:30:30Z","timestamp":1764595830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/12\/1663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,28]]},"references-count":53,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["biom15121663"],"URL":"https:\/\/doi.org\/10.3390\/biom15121663","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,28]]}}}