{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T09:43:18Z","timestamp":1767692598567,"version":"3.48.0"},"reference-count":55,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Johns Hopkins University Catalyst Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Testosterone, an androgenic steroid hormone, regulates primary sexual characteristics and influences mood, cognition, social behavior, and sexual function. Deficiency, caused by factors such as aging and genetics, is linked to multiple disease conditions. However, current testosterone therapies are limited by extensive metabolism, poor solubility, and undesirable side effects. To address these limitations, we synthesized a four-armed star PEG-OH-linked testosterone (PEG-T). The in vitro release of testosterone from PEG-T was evaluated in buffer (pH 7.4) and mouse plasma. PEG-T was stable in the buffer, but released testosterone in plasma via esterase-mediated hydrolysis. Pharmacokinetics of testosterone and PEG-T were compared following intraperitoneal (IP) and subcutaneous (SC) administration. Following IP dosing, PEG-T exhibited a ~6-fold improvement in half-life compared to testosterone (1.18 h vs. 0.21 h), and a 54-fold increase in exposure (AUC0-t = 36.0 \u03bcM\u00b7h vs. 0.67 \u03bcM\u00b7h) at equimolar doses; furthermore, following SC dosing, PEG-T showed a 4-fold improvement in both half-life (3.57 h vs. 0.91 h) and plasma exposure (11.5 \u03bcM\u00b7h vs. 3.1 \u03bcM\u00b7h). Additionally, PEG-T showed lower liver and kidney to plasma ratios, which could potentially result in reduced hepatotoxicity and nephrotoxicity. Overall, PEG-T provides sustained release pharmacokinetics, representing a promising candidate for safer testosterone replacement therapy.<\/jats:p>","DOI":"10.3390\/molecules31010198","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:28:57Z","timestamp":1767626937000},"page":"198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Star-PEGylation Strategy to Improve Testosterone Pharmacokinetics"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4551-9191","authenticated-orcid":false,"given":"Chae Bin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6982-3545","authenticated-orcid":false,"given":"Luk\u00e1\u0161","family":"Tenora","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruoning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9382-9800","authenticated-orcid":false,"given":"Arina","family":"Ranjit","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2780-5100","authenticated-orcid":false,"given":"Mark C.","family":"Markowski","sequence":"additional","affiliation":[{"name":"Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-4157","authenticated-orcid":false,"given":"Barbara S.","family":"Slusher","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA"},{"name":"Departments of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4059-2453","authenticated-orcid":false,"given":"Rana","family":"Rais","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA"},{"name":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.juro.2018.03.115","article-title":"Evaluation and Management of Testosterone Deficiency: AUA Guideline","volume":"200","author":"Mulhall","year":"2018","journal-title":"J. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/cge.13432","article-title":"Molecular genetics of hypospadias and cryptorchidism recent developments","volume":"95","author":"Kalfa","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_3","first-page":"3","article-title":"Androgen Receptor Structure, Function and Biology: From Bench to Bedside","volume":"37","author":"Davey","year":"2016","journal-title":"Clin. Biochem. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1530\/eje.1.02306","article-title":"Testosterone and cognitive function: Current clinical evidence of a relationship","volume":"155","author":"Beauchet","year":"2006","journal-title":"Eur. J. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Peterson, M.D., Belakovskiy, A., McGrath, R., and Yarrow, J.F. (2018). Testosterone Deficiency, Weakness, and Multimorbidity in Men. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-24347-6"},{"key":"ref_6","first-page":"3578","article-title":"Testosterone replacement therapy improves mood in hypogonadal men\u2014A clinical research center study","volume":"81","author":"Wang","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1210\/er.2003-0016","article-title":"Testosterone effects on the breast: Implications for testosterone therapy for women","volume":"25","author":"Somboonporn","year":"2004","journal-title":"Endocr. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1212\/01.WNL.0000165995.98986.F1","article-title":"Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment","volume":"64","author":"Cherrier","year":"2005","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.brainres.2005.02.078","article-title":"Effect of testosterone on functional recovery in a castrate male rat stroke model","volume":"1043","author":"Pan","year":"2005","journal-title":"Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"454","DOI":"10.3390\/clinpract13020041","article-title":"Treatment with Testosterone Therapy in Type 2 Diabetic Hypogonadal Adult Males: A Systematic Review and Meta-Analysis","volume":"13","author":"Kumari","year":"2023","journal-title":"Clin. Pract."},{"key":"ref_11","first-page":"21","article-title":"Osteoporosis in male hypogonadism: Responses to androgen substitution differ among men with primary and secondary hypogonadism","volume":"60","author":"Schubert","year":"2003","journal-title":"Horm. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tauchen, J., Jurasek, M., Huml, L., and Rimpelova, S. (2021). Medicinal Use of Testosterone and Related Steroids Revisited. Molecules, 26.","DOI":"10.3390\/molecules26041032"},{"key":"ref_13","first-page":"1591","article-title":"Testosterone treatments: Why, when, and how?","volume":"73","author":"Margo","year":"2006","journal-title":"Am. Fam. Physician"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Carrasquillo, R., Chu, K., and Ramasamy, R. (2018). Novel Therapy for Male Hypogonadism. Curr. Urol. Rep., 19.","DOI":"10.1007\/s11934-018-0816-x"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/BF03189840","article-title":"Absolute bioavailability of testosterone after oral administration of testosterone-undecanoate and testosterone","volume":"11","author":"Tauber","year":"1986","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/ncpuro0650","article-title":"Drug insight: Testosterone preparations","volume":"3","author":"Wu","year":"2006","journal-title":"Nat. Clin. Pract. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1210\/jcem.82.6.3988","article-title":"Testosterone replacement in older hypogonadal men: A 12-month randomized controlled trial","volume":"82","author":"Sih","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_18","first-page":"3469","article-title":"Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men","volume":"84","author":"Dobs","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1046\/j.1365-2265.1997.2521050.x","article-title":"An analysis of testosterone implants for androgen replacement therapy","volume":"47","author":"Handelsman","year":"1997","journal-title":"Clin. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1046\/j.1365-2265.1999.00827.x","article-title":"Extrusion of testosterone pellets: A randomized controlled clinical study","volume":"51","author":"Kelleher","year":"1999","journal-title":"Clin. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1046\/j.1365-2265.2001.01357.x","article-title":"Influence of implantation site and track geometry on the extrusion rate and pharmacology of testosterone implants","volume":"55","author":"Kelleher","year":"2001","journal-title":"Clin. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/978-1-4684-6985-1_35","article-title":"Enzyme-polyethylene glycol adducts: Modified enzymes with unique properties","volume":"Volume 4","author":"Davis","year":"1978","journal-title":"Enzyme Engineering"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1080\/17425247.2016.1182485","article-title":"Polyethylene glycol (PEG): A versatile polymer for pharmaceutical applications","volume":"13","author":"Shegokar","year":"2016","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Webster, R., Elliott, V., Park, B.K., Walker, D., Hankin, M., and Taupin, P. (2009). PEG and PEG conjugates toxicity: Towards an understanding of the toxicity of PEG and its relevance to PEGylated biologicals. PEGylated Protein Drugs: Basic Science and Clinical Applications, Springer.","DOI":"10.1007\/978-3-7643-8679-5_8"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"539","DOI":"10.2165\/00003088-200140070-00005","article-title":"Pegylation: A novel process for modifying pharmacokinetics","volume":"40","author":"Harris","year":"2001","journal-title":"Clin. Pharmacokinet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nrd1033","article-title":"Effect of pegylation on pharmaceuticals","volume":"2","author":"Harris","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Banerjee, S.S., Aher, N., Patil, R., and Khandare, J. (2012). Poly(ethylene glycol)-Prodrug Conjugates: Concept, Design, and Applications. J. Drug Deliv., 2012.","DOI":"10.1155\/2012\/103973"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jconrel.2020.04.039","article-title":"Application of star poly(ethylene glycol) derivatives in drug delivery and controlled release","volume":"323","author":"Zhao","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Machinaga, N., Ashley, G.W., Reid, R., Yamasaki, A., Tanaka, K., Nakamura, K., Yabe, Y., Yoshigae, Y., and Santi, D.V. (2018). A Controlled Release System for Long-Acting Intravitreal Delivery of Small Molecules. Transl. Vis. Sci. Technol., 7.","DOI":"10.1167\/tvst.7.4.21"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1021\/bc700333s","article-title":"Novel prodrugs of SN38 using multiarm poly(ethylene glycol) linkers","volume":"19","author":"Zhao","year":"2008","journal-title":"Bioconjug. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1021\/acs.bioconjchem.7b00770","article-title":"Conjugation with Eight-Arm PEG Markedly Improves the In Vitro Activity and Prolongs the Blood Circulation of Staphylokinase","volume":"29","author":"Qi","year":"2018","journal-title":"Bioconjug. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3979","DOI":"10.1002\/jps.23258","article-title":"Species difference of esterase expression and hydrolase activity in plasma","volume":"101","author":"Bahar","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1210\/en.2014-1664","article-title":"Measurement of testosterone by immunoassays and mass spectrometry in mouse serum, testicular, and ovarian extracts","volume":"156","author":"Handelsman","year":"2015","journal-title":"Endocrinology"},{"key":"ref_34","unstructured":"Behre, H., Wang, C., Handelsman, D., and Nieschlag, E. (2004). Pharmacology of testosterone preparations. Testosterone, Action, Deficiency, Substitution, Springer."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.3748\/wjg.v28.i26.3071","article-title":"Anabolic androgenic steroid-induced liver injury: An update","volume":"28","author":"Petrovic","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1111\/j.1523-1755.2004.00497.x","article-title":"Testosterone promotes apoptotic damage in human renal tubular cells","volume":"65","author":"Verzola","year":"2004","journal-title":"Kidney Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1177\/193229681300700128","article-title":"Insulin depot formation in subcutaneous tissue","volume":"7","author":"Jockel","year":"2013","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jconrel.2014.03.011","article-title":"Improving the outcomes of biopharmaceutical delivery via the subcutaneous route by understanding the chemical, physical and physiological properties of the subcutaneous injection site","volume":"182","author":"Kinnunen","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1210\/clinem\/dgab772","article-title":"Testosterone Therapy with Subcutaneous Injections: A Safe, Practical, and Reasonable Option","volume":"107","author":"Figueiredo","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1046\/j.1365-2265.1999.00881.x","article-title":"Repeated intramuscular injections of testosterone undecanoate for substitution therapy in hypogonadal men","volume":"51","author":"Nieschlag","year":"1999","journal-title":"Clin. Endocrinol."},{"key":"ref_41","first-page":"4500","article-title":"Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men","volume":"85","author":"Swerdloff","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1743-6109.2005.20231.x","article-title":"Comparison of the steady-state pharmacokinetics, metabolism, and variability of a transdermal testosterone patch versus a transdermal testosterone gel in hypogonadal men","volume":"2","author":"Mazer","year":"2005","journal-title":"J. Sex Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1365-2265.1996.tb02061.x","article-title":"Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men","volume":"45","author":"Jockenhovel","year":"1996","journal-title":"Clin. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1111\/j.1365-2265.1985.tb00161.x","article-title":"Testosterone replacement in hypogonadal men: Effects on obstructive sleep apnoea, respiratory drives, and sleep","volume":"22","author":"Matsumoto","year":"1985","journal-title":"Clin. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1210\/jc.2003-030236","article-title":"The short-term effects of high-dose testosterone on sleep, breathing, and function in older men","volume":"88","author":"Liu","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/s41443-022-00585-1","article-title":"Occurrence of pulmonary oil microembolism (POME) with intramuscular testosterone undecanoate injection: Literature review","volume":"35","author":"Adam","year":"2023","journal-title":"Int. J. Impot. Res."},{"key":"ref_47","first-page":"1843","article-title":"Subcutaneous administration of testosterone. A pilot study report","volume":"27","author":"Almahrezi","year":"2006","journal-title":"Saudi Med. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2146\/ajhp170160","article-title":"Pharmacokinetics, safety, and patient acceptability of subcutaneous versus intramuscular testosterone injection for gender-affirming therapy: A pilot study","volume":"75","author":"Wilson","year":"2018","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/sm2.80","article-title":"Pharmacokinetic Profile of Subcutaneous Testosterone Enanthate Delivered via a Novel, Prefilled Single-Use Autoinjector: A Phase II Study","volume":"3","author":"Kaminetsky","year":"2015","journal-title":"Sex Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1210\/js.2019-00134","article-title":"Pharmacokinetics and Acceptability of Subcutaneous Injection of Testosterone Undecanoate","volume":"3","author":"Turner","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1002\/jps.22098","article-title":"In vivo absorption of steroidal hormones from smart polymer based delivery systems","volume":"99","author":"Chen","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1295\/polymj.14.941","article-title":"In Vivo Release of Testosterone from Hydrophobic\u2013Hydrophilic Copolymer Composites in Long Term Delivery Systems","volume":"14","author":"Yoshida","year":"1982","journal-title":"Polym. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ijbiomac.2014.08.001","article-title":"Pharmacokinetic evaluation of testosterone-loaded nanocapsules in rats","volume":"72","author":"Jana","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Rais, R., Lemberg, K.M., Tenora, L., Arwood, M.L., Pal, A., Alt, J., Wu, Y., Lam, J., Aguilar, J.M.H., and Zhao, L. (2022). Discovery of DRP-104, a tumor-targeted metabolic inhibitor prodrug. Sci. Adv., 8.","DOI":"10.1126\/sciadv.abq5925"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.clinms.2018.11.005","article-title":"Comparison of four clinically validated testosterone LC-MS\/MS assays: Harmonization is an attainable goal","volume":"11","author":"French","year":"2019","journal-title":"Clin. Mass Spectrom."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/1\/198\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T09:40:36Z","timestamp":1767692436000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/1\/198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["molecules31010198"],"URL":"https:\/\/doi.org\/10.3390\/molecules31010198","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2026,1,5]]}}}