{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T16:11:29Z","timestamp":1765901489455,"version":"3.48.0"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cVictor Babes\u201d University of Medicine and Pharmacy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Pregnancy represents a unique physiological state marked by extensive metabolic adaptations, particularly in lipid pathways essential for maternal adjustments, fetal development, and postpartum recovery. This study aimed to explore these changes through untargeted lipidomic profiling. Methods: This observational, comparative, non-interventional clinical study included 107 women, of which 65 were in the third trimester of pregnancy (mean age 27.9 \u00b1 5 years) and 42 were in the early postpartum period (\u22647 days, mean age 28.9 \u00b1 5.9 years). Inclusion criteria were singleton, term pregnancies (37\u201341 weeks) with neonates weighing &gt; 2500 g and no associated pregnancy-related pathologies; exclusion criteria included multiple gestation, use of lipid-altering medications, maternal age &gt; 40 years, or diagnosed pregnancy complications. Plasma samples were analyzed using High-Performance Liquid Chromatography\u2013Quadrupole Time-Of-Flight\u2013Electrospray Ionization (positive mode)\u2013Mass Spectrometry, data were processed with MetaboAnalyst 6.0 using multivariate and univariate analyses (Partial Least Squares\u2013Discriminant Analysis, Volcano Plot, Random Forest, Receiver Operating Characteristic analysis), with statistical significance set at p &lt; 0.05. Results: Multivariate analysis demonstrated a clear separation between groups with high predictive accuracy as reflected by strong classification metrics (Accuracy = 0.90, R2 = 0.75, Q2 = 0.68). Several discriminative lipids were consistently identified across statistical models, including 2-Methoxyestrone (AUC = 0.861), Eicosanedioic acid (AUC = 0.854), and Pregnenolone sulfate (AUC = 0.843). These biomarkers were further categorized into five major lipid classes: steroid hormones, long-chain fatty acids, lysophospholipids, ceramides\/sphingolipids, and glycerolipids. Conclusions: Untargeted lipidomic profiling revealed distinct metabolic signatures that differentiate late pregnancy from early post-partum states. The identification of robust lipid biomarkers with high discriminative performance highlights their potential utility in maternal health monitoring, obstetric risk assessment, and postpartum recovery surveillance.<\/jats:p>","DOI":"10.3390\/metabo15120798","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T15:41:12Z","timestamp":1765899672000},"page":"798","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-Targeted Plasma Lipidomic Profiling in Late Pregnancy and Early Postpartum Stages: An Observational Comparative Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Alexandra","family":"Traila","sequence":"first","affiliation":[{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"},{"name":"Department of Obstetrics and Gynecology, County Emergency Hospital, 220056 Drobeta Turnu Severin, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6793-5361","authenticated-orcid":false,"given":"Simona-Alina","family":"Abu-Awwad","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"},{"name":"Clinic of Obstetrics and Gynecology, \u201cPius Brinzeu\u201d County Clinical Emergency Hospital, 300723 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen-Ioana","family":"Marta","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"},{"name":"Clinic of Obstetrics and Gynecology, \u201cPius Brinzeu\u201d County Clinical Emergency Hospital, 300723 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5899-5851","authenticated-orcid":false,"given":"Manuela Violeta","family":"Bacanoiu","sequence":"additional","affiliation":[{"name":"Sport Medicine and Physiotherapy Department, University of Craiova Romania, 200500 Craiova, Romania"},{"name":"Department of Laboratory Medicine, County Clinical Emergency Hospital of Craiova, 200642 Craiova, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anca Laura","family":"Maghiari","sequence":"additional","affiliation":[{"name":"Department I\u2014Discipline of Anatomy and Embryology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6185-0960","authenticated-orcid":false,"given":"Ahmed","family":"Abu-Awwad","sequence":"additional","affiliation":[{"name":"Department XV\u2014Discipline of Orthopedics\u2014Traumatology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania"},{"name":"Research Center University Professor Doctor Teodor \u0218ora, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius Lucian","family":"Craina","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"},{"name":"Clinic of Obstetrics and Gynecology, \u201cPius Brinzeu\u201d County Clinical Emergency Hospital, 300723 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","unstructured":"Kepley, J.M., Bates, K., and Mohiuddin, S.S. (2025, September 05). Physiology, Maternal Changes, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK539766\/."},{"key":"ref_2","unstructured":"Wild, R., and Feingold, K.R. (2025, September 05). Effect of Pregnancy on Lipid Metabolism and Lipoprotein Levels, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK498654\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/epirev\/mxt006","article-title":"Pregnancy characteristics and women\u2019s future cardiovascular health: An underused opportunity to improve women\u2019s health?","volume":"36","author":"Fraser","year":"2014","journal-title":"Epidemiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Blaauwendraad, S.M., Wahab, R.J., van Rijn, B.B., Koletzko, B., Jaddoe, V.W.V., and Gaillard, R. (2022). Associations of Early Pregnancy Metabolite Profiles with Gestational Blood Pressure Development. Metabolites, 12.","DOI":"10.3390\/metabo12121169"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1177\/1933719108316908","article-title":"Detection and Identification of Novel Metabolomic Biomarkers in Preeclampsia","volume":"15","author":"Kenny","year":"2008","journal-title":"Reprod. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/aogs.14505","article-title":"Metabolic profiling of pregnancies complicated by preeclampsia: A longitudinal study","volume":"102","author":"Skytte","year":"2023","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15829","DOI":"10.1038\/s41598-024-65947-9","article-title":"Plasma metabolites are altered before and after diagnosis of preeclampsia or fetal growth restriction","volume":"14","author":"Bartho","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16142","DOI":"10.1038\/s41598-020-72852-4","article-title":"Metabolomic biomarkers in midtrimester maternal plasma can accurately predict the development of preeclampsia","volume":"10","author":"Lee","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e15320","DOI":"10.1097\/MD.0000000000015320","article-title":"Maternal lipid profiles in women with and without gestational diabetes mellitus","volume":"98","author":"Wang","year":"2019","journal-title":"Medicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.cca.2021.02.023","article-title":"Plasma metabolites, especially lipid metabolites, are altered in pregnant women with gestational diabetes mellitus","volume":"517","author":"Zhan","year":"2021","journal-title":"Clin. Chim. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"O\u2019Neill, K., Alexander, J., Azuma, R., Xiao, R., Snyder, N.W., Mesaros, C.A., Blair, I.A., and Pinney, S.E. (2018). Gestational Diabetes Alters the Metabolomic Profile in 2nd Trimester Amniotic Fluid in a Sex-Specific Manner. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092696"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1093\/ajcn\/nqab242","article-title":"Plasma lipidomics in early pregnancy and risk of gestational diabetes mellitus: A prospective nested case-control study in Chinese women","volume":"114","author":"Wang","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10800","DOI":"10.1038\/s41598-024-61119-x","article-title":"The association between pregnancy levels of blood lipids and the risk of preterm birth","volume":"14","author":"Lv","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8115","DOI":"10.1038\/s41598-021-87472-9","article-title":"Maternal lipidomic signatures in relation to spontaneous preterm birth and large-for-gestational age neonates","volume":"11","author":"Aung","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11306-020-1639-6","article-title":"Association between phospholipid metabolism in plasma and spontaneous preterm birth: A discovery lipidomic analysis in the Cork pregnancy cohort","volume":"16","author":"Morillon","year":"2020","journal-title":"Metabolomics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"179827","DOI":"10.1155\/2012\/179827","article-title":"Regulation of nutrient transport across the placenta","volume":"2012","author":"Lager","year":"2012","journal-title":"J. Pregnancy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104881","DOI":"10.1016\/j.ebiom.2023.104881","article-title":"Longitudinal lipidomic profiles during pregnancy and associations with neonatal anthropometry: Findings from a multiracial cohort","volume":"98","author":"Song","year":"2023","journal-title":"EBioMedicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e72779","DOI":"10.7554\/eLife.72779","article-title":"Ontogeny of circulating lipid metabolism in pregnancy and early childhood\u2013a longitudinal population study","volume":"11","author":"Burugupalli","year":"2022","journal-title":"eLife"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Chen, L., Mir, S.A., Bendt, A.K., Chua, E.W.L., Narasimhan, K., Tan, K.M.-L., Loy, S.L., Tan, K.H., Shek, L.P., and Chan, J. (2023). Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: A preconception and longitudinal cohort study. BMC Med., 21.","DOI":"10.1186\/s12916-023-02740-x"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Handelman, S.K., Romero, R., Tarca, A.L., Pacora, P., Ingram, B., Maymon, E., Chaiworapongsa, T., Hassan, S.S., and Erez, O. (2019). The plasma metabolome of women in early pregnancy differs from that of non-pregnant women. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224682"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ando.2016.04.023","article-title":"Evolution of steroids during pregnancy: Maternal, placental and fetal synthesis","volume":"77","author":"Morel","year":"2016","journal-title":"Ann. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Orczyk-Pawilowicz, M., Jawien, E., Deja, S., Hirnle, L., Zabek, A., and Mlynarz, P. (2016). Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152740"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"67.e1\u201367.e21","DOI":"10.1016\/j.ajog.2017.02.037","article-title":"The maternal plasma proteome changes as a function of gestational age in normal pregnancy: A longitudinal study","volume":"217","author":"Romero","year":"2017","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mitro, S.D., Wu, J., Rahman, M.L., Cao, Y., Zhu, Y., Chen, Z., Chen, L., Li, M., Hinkle, S.N., and Bremer, A.A. (2021). Longitudinal Plasma Metabolomics Profile in Pregnancy\u2014A Study in an Ethnically Diverse U.S. Pregnancy Cohort. Nutrients, 13.","DOI":"10.3390\/nu13093080"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"591","DOI":"10.2147\/IJWH.S314469","article-title":"Postpartum Metabolism: How Does It Change from Pregnancy and What Are the Potential Implications?","volume":"13","author":"Tinius","year":"2021","journal-title":"Int. J. Womens Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105666","DOI":"10.1016\/j.isci.2022.105666","article-title":"Plasma metabolic disturbances during pregnancy and postpartum in women with depression","volume":"25","author":"Yu","year":"2022","journal-title":"iScience"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"World Medical Association (2013). World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chen, Y., Li, E.M., and Xu, L.Y. (2022). Guide to Metabolomics Analysis: A Bioinformatics Workflow. Metabolites, 12.","DOI":"10.3390\/metabo12040357"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Antonelli, J., Claggett, B.L., Henglin, M., Kim, A., Ovsak, G., Kim, N., Deng, K., Rao, K., Tyagi, O., and Watrous, J.D. (2019). Statistical Workflow for Feature Selection in Human Metabolomics Data. Metabolites, 9.","DOI":"10.3390\/metabo9070143"},{"key":"ref_30","first-page":"298183","article-title":"Random forest in clinical metabolomics for phenotypic discrimination and biomarker selection","volume":"2013","author":"Chen","year":"2013","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kumar, N., Hoque, M.A., and Sugimoto, M. (2018). Robust volcano plot: Identification of differential metabolites in the presence of outliers. BMC Bioinform., 19.","DOI":"10.1186\/s12859-018-2117-2"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-4939-7643-0_7","article-title":"LC-MS untargeted analysis","volume":"1738","author":"Want","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1080\/09513590.2018.1564742","article-title":"Steroid hormones and pregnancy","volume":"35","author":"Halhali","year":"2019","journal-title":"Gynecol. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Duttaroy, A.K., and Basak, S. (2021). Maternal Fatty Acid Metabolism in Pregnancy and Its Consequences in the Feto-Placental Development. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.787848"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/aji.12239","article-title":"Emerging roles for lysophospholipid mediators in pregnancy","volume":"72","author":"Nagamatsu","year":"2014","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"106670","DOI":"10.1016\/j.prostaglandins.2022.106670","article-title":"Lysophosphatidic acid production from lysophosphatidylcholine by lysophospholipase D activity of autotaxin in plasma of women with normal and adverse pregnancies","volume":"163","author":"Tsutsumi","year":"2022","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110041","DOI":"10.1016\/j.cellsig.2021.110041","article-title":"Physiological and pathological functions of sphingolipids in pregnancy","volume":"85","author":"Fakhr","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lantzanaki, M., Vavilis, T., Harizopoulou, V.C., Bili, H., Goulis, D.G., and Vavilis, D. (2023). Ceramides during Pregnancy and Obstetrical Adverse Outcomes. Metabolites, 13.","DOI":"10.3390\/metabo13111136"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Saadat, N., Aguate, F., Nowak, A.L., Hyer, S., Lin, A.B., Decot, H., Koch, H., Walker, D.S., Lydic, T., and Padmanabhan, V. (2024). Changes in Lipid Profiles with the Progression of Pregnancy in Black Women. J. Clin. Med., 13.","DOI":"10.3390\/jcm13102795"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Lai, M., Piro, A.L., Alexeeff, S.E., Allalou, A., R\u00f6st, H.L., Dai, F.F., Wheeler, M.B., and Gunderson, E.P. (2021). Intensive lactation among women with recent gestational diabetes significantly alters the early postpartum circulating lipid profile: The SWIFT study. BMC Med., 19.","DOI":"10.1186\/s12916-021-02095-1"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/0002-9378(70)90447-3","article-title":"The Effect of Pregnenolone Sulfate on Uterine Contractility","volume":"108","author":"Scommegna","year":"1970","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_42","unstructured":"Hinoroni, A., Kazuyoshi, U., and Shinji, N. (2021). Pregnenolone Sulfate. Handbook of Hormones, Academic Press. [2nd ed.]. Subchapter 124A."},{"key":"ref_43","unstructured":"Pasqualini, J.R., and Kincl, F.A. (1985). Biosynthesis and Metabolism of Pregnenolone, 17-Hydroxypregnenolone and Its Sulfates. Hormones in the Fetus, Elsevier Ltd.. Chapter 2.2."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hashimoto, M., and Hossain, S. (2018). Fatty Acids: From Membrane Ingredients to Signaling Molecules. Biochemistry and Health Benefits of Fatty Acids, IntechOpen.","DOI":"10.5772\/intechopen.80430"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Klemetti, M.M., Alahari, S., Post, M., and Caniggia, I. (2023). Distinct Changes in Placental Ceramide Metabolism Characterize Type 1 and 2 Diabetic Pregnancies with Fetal Macrosomia or Preeclampsia. Biomedicines, 11.","DOI":"10.3390\/biomedicines11030932"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/1389201015666140330192345","article-title":"Lipid metabolism during pregnancy and its implications for fetal growth","volume":"15","author":"Herrera","year":"2014","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.placenta.2018.05.011","article-title":"Altered maternal and placental lipid metabolism and fetal fat development in obesity: Current knowledge and advances in non-invasive assessment","volume":"69","author":"Delhaes","year":"2018","journal-title":"Placenta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"607","DOI":"10.5603\/GP.2019.0105","article-title":"Early potential metabolic biomarkers of primary postpartum haemorrhage based on serum metabolomics","volume":"90","author":"Chen","year":"2019","journal-title":"Ginekol. Pol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Troisi, J., Symes, S.J.K., Lombardi, M., Cavallo, P., Colucci, A., Scala, G., Adair, D.C., Guida, M., and Richards, S.M. (2023). Placental Metabolomics of Fetal Growth Restriction. Metabolites, 13.","DOI":"10.3390\/metabo13020235"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Birchenall, K.A., Welsh, G.I., and L\u00f3pez Bernal, A. (2019). Metabolite Changes in Maternal and Fetal Plasma Following Spontaneous Labour at Term in Humans Using Untargeted Metabolomics Analysis: A Pilot Study. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16091527"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/12\/798\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T15:45:21Z","timestamp":1765899921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/12\/798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,16]]},"references-count":50,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["metabo15120798"],"URL":"https:\/\/doi.org\/10.3390\/metabo15120798","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,16]]}}}