{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T01:36:11Z","timestamp":1766367371815,"version":"3.48.0"},"reference-count":45,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Hypertrophic scars (HS) are a fibrotic proliferative disorder that results from an abnormal wound healing process, presenting significant challenges for clinical intervention. The primary characteristics of HS include excessive collagen deposition and angiogenesis. In recent years, the study of mesenchymal stem cells (MSCs) and their derived exosomes has emerged as a prominent area of research within the academic community. However, the therapeutic application of MSCs is impeded by several challenges, including immune rejection, sourcing limitations, ethical dilemmas, and difficulties related to the scalability of exosome production. Cell-free adipose extract (CEFAE), a novel bioproduct derived from adipose tissue, is rich in various active protein factors that are essential for MSCs and their exosomes. CEFAE presents several advantages, including low immunogenicity, non-tumorigenicity, and a high degree of clinical safety. However, the application of CEFAE in the prevention and treatment of scar formation has not been adequately validated through experimental studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This research established a rabbit ear scar model, establishing a control group, a low-concentration CEFAE group (L-CEFAE), and a high-concentration CEFAE group (H-CEFAE) to evaluate wound treatment. Observations of scar changes were conducted at 14 and 28 days post-treatment, supplemented by histological and immunohistochemical analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Histological analysis revealed that the H-CEFAE group achieved optimal outcomes, with the lowest collagen deposition, thinnest epidermal\/dermal thickness, and the most orderly collagen alignment. Furthermore, the formation of new blood vessels in the H-CEFAE group showed a significant reduction over time, resulting in decreased blood supply, which is beneficial for suppressing scar tissue development. Quantification of COL I, COL III, and vascular endothelial growth factor also supports these results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings indicated that high-concentration CEFAE has a beneficial preventive and therapeutic effect on scar proliferation. Furthermore, the study explored the potential mechanisms by which CEFAE inhibits scar proliferation, thereby providing novel therapeutic strategies for the prevention and management of clinical scars.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/med-2025-1249","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T08:00:36Z","timestamp":1755849636000},"source":"Crossref","is-referenced-by-count":0,"title":["Cell-free adipose extract inhibits hypertrophic scar formation through collagen remodeling and antiangiogenesis"],"prefix":"10.1515","volume":"20","author":[{"given":"Junchao","family":"Sun","sequence":"first","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University , Weifang , China"},{"name":"Department of Burns and Wound Repair, Weifang People\u2019s Hospital, Shandong Second Medical University , Weifang , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University , Weifang , China"},{"name":"Department of Burns and Wound Repair, Weifang People\u2019s Hospital, Shandong Second Medical University , Weifang , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhoujiang","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University , Weifang , China"},{"name":"Department of Burns and Wound Repair, Weifang People\u2019s Hospital, Shandong Second Medical University , Weifang , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shudong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Burns and Wound Repair, Weifang People\u2019s Hospital, Shandong Second Medical University , Weifang , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Burns and Wound Repair, Weifang People\u2019s Hospital, Shandong Second Medical University , Weifang , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"2025122201303422558_j_med-2025-1249_ref_001","unstructured":"Mbiine R, Wayengera M, Kiwanuka N, Munabi I, Muwonge H, Nakanwagi C, et al. Autologous adipose-derived stromal vascular fraction (SVF) in scar treatment among patients with keloids and hypertrophic scars: a systematic review and meta-analysis of current practices and outcomes. Am J Stem Cell. 2023;12(5):98\u2013111."},{"key":"2025122201303422558_j_med-2025-1249_ref_002","doi-asserted-by":"crossref","unstructured":"Neelon J, Yau I, Carlsson AH, Smithson SB, Varon DE, Chan CK, et al. Topical application of anti-inflammatory agents on burn wounds and their effect on healing. Burns. 2024;50(9):107290.","DOI":"10.1016\/j.burns.2024.107290"},{"key":"2025122201303422558_j_med-2025-1249_ref_003","doi-asserted-by":"crossref","unstructured":"Chen D, Li Q, Zhang H, Kou F, Li Q, Lyu C, et al. Traditional Chinese medicine for hypertrophic scars-A review of the therapeutic methods and potential effects. Front Pharmacol. 2022;13:1025602.","DOI":"10.3389\/fphar.2022.1025602"},{"key":"2025122201303422558_j_med-2025-1249_ref_004","doi-asserted-by":"crossref","unstructured":"Agrawal A, Ding J, Agrawal B, Kwan PO, Tredget EE. Stimulation of toll-like receptor pathways by burn eschar tissue as a possible mechanism for hypertrophic scarring. Wound Repair Regen. 2021;29(5):810\u20139.","DOI":"10.1111\/wrr.12940"},{"key":"2025122201303422558_j_med-2025-1249_ref_005","doi-asserted-by":"crossref","unstructured":"Yuan B, Yu J, Dong J, Mao Z, Wang X. Bacteria in hypertrophic scars promote scar formation through HSBP1-mediated autophagy. Wound Repair Regen. 2025;33(1):e13253.","DOI":"10.1111\/wrr.13253"},{"key":"2025122201303422558_j_med-2025-1249_ref_006","doi-asserted-by":"crossref","unstructured":"Xu R, Yang E, Liang H, Luo S, Liu Y, Khoong Y, et al. ALKBH5-mediated m(6)A demethylation ameliorates extracellular matrix deposition in cutaneous pathological fibrosis. Clin Transl Med. 2024;14(9):e70016.","DOI":"10.1002\/ctm2.70016"},{"key":"2025122201303422558_j_med-2025-1249_ref_007","doi-asserted-by":"crossref","unstructured":"Kim SH, Oh JM, Roh H, Lee KW, Lee JH, Lee WJ. Zinc-Alpha-2-glycoprotein peptide downregulates type I and III collagen expression via suppression of TGF-beta and p-Smad 2\/3 pathway in keloid fibroblasts and rat incisional model. Tissue Eng Regen Med. 2024;21(7):1079\u201392.","DOI":"10.1007\/s13770-024-00664-y"},{"key":"2025122201303422558_j_med-2025-1249_ref_008","doi-asserted-by":"crossref","unstructured":"Zhou X, Ye H, Wang X, Sun J, Tu J, Lv J. Ursolic acid inhibits human dermal fibroblasts hyperproliferation, migration, and collagen deposition induced by TGF-beta via regulating the Smad2\/3 pathway. Gene. 2023;867:147367.","DOI":"10.1016\/j.gene.2023.147367"},{"key":"2025122201303422558_j_med-2025-1249_ref_009","doi-asserted-by":"crossref","unstructured":"Liu C, Zhang H, Cui X, Wang S, Zhou Q. The effects of Shikonin on the hypertrophic scar of rabbit ears via the TLR4\/NF-kappaB signaling pathway. Cell Mol Biol (Noisy-le-grand). 2023;69(9):161\u20136.","DOI":"10.14715\/cmb\/2023.69.9.24"},{"key":"2025122201303422558_j_med-2025-1249_ref_010","doi-asserted-by":"crossref","unstructured":"Han F, Wang K, Shen K, Wang J, Han S, Hu D, et al. Extracellular vesicles from Lactobacillus druckerii inhibit hypertrophic scar fibrosis. J Nanobiotechnology. 2023;21(1):113.","DOI":"10.1186\/s12951-023-01861-y"},{"key":"2025122201303422558_j_med-2025-1249_ref_011","doi-asserted-by":"crossref","unstructured":"Gili N, Micallef Stafrace K, Laybats F, Mifsud T. The role of extracorporeal shock wave therapy in keloids and hypertrophic scars: a systematic review. Cureus. 2024;16(10):e71869.","DOI":"10.7759\/cureus.71869"},{"key":"2025122201303422558_j_med-2025-1249_ref_012","unstructured":"Bailey J, Schwehr M, Beattie A. Management of keloids and hypertrophic scars. Am Fam Physician. 2024;110(6):605\u201311."},{"key":"2025122201303422558_j_med-2025-1249_ref_013","doi-asserted-by":"crossref","unstructured":"Cao LL, Yang ZG, Qi WH, Zhang H, Bi Y, Shan Y, et al. A preliminary study on ultrasound techniques applied to evaluate the curative effect of botulinum toxin type a in hypertrophic scars. Heliyon. 2024;10(15):e34723.","DOI":"10.1016\/j.heliyon.2024.e34723"},{"key":"2025122201303422558_j_med-2025-1249_ref_014","doi-asserted-by":"crossref","unstructured":"Rimmer SN, Chandy RJ, Khan D, Feldman SR. Recurrence rates in the treatment of keloids and hypertrophic scars with intralesional triamcinolone combined with other intralesional agents. Arch Dermatol Res. 2023;315(10):2757\u201367.","DOI":"10.1007\/s00403-023-02662-x"},{"key":"2025122201303422558_j_med-2025-1249_ref_015","doi-asserted-by":"crossref","unstructured":"Luo XY, Wu XG, Xu AE, Song XZ, Peng JZ. The combination of the mini-punch technique and photodynamic therapy for the treatment of mandibular keloids and hypertrophic scars. Dermatol Surg. 2022;48(12):1294\u20138.","DOI":"10.1097\/DSS.0000000000003621"},{"key":"2025122201303422558_j_med-2025-1249_ref_016","doi-asserted-by":"crossref","unstructured":"Wang Y, Zhou X. Exosomes and microRNAs: insights into their roles in thermal-induced skin injury, wound healing and scarring. Mol Genet Genomics. 2024;299(1):89.","DOI":"10.1007\/s00438-024-02183-w"},{"key":"2025122201303422558_j_med-2025-1249_ref_017","doi-asserted-by":"crossref","unstructured":"Sierra-Sanchez A, Montero-Vilchez T, Quinones-Vico MI, Sanchez-Diaz M, Arias-Santiago S. Current advanced therapies based on human mesenchymal stem cells for skin diseases. Front Cell Dev Biol. 2021;9:643125.","DOI":"10.3389\/fcell.2021.643125"},{"key":"2025122201303422558_j_med-2025-1249_ref_018","doi-asserted-by":"crossref","unstructured":"Xu C, Zhang H, Yang C, Wang Y, Wang K, Wang R, et al. miR-125b-5p delivered by adipose-derived stem cell exosomes alleviates hypertrophic scarring by suppressing Smad2. Burn Trauma. 2024;12:tkad064.","DOI":"10.1093\/burnst\/tkad064"},{"key":"2025122201303422558_j_med-2025-1249_ref_019","doi-asserted-by":"crossref","unstructured":"Jafarzadeh A, PourMohammad A, Goodarzi A. A systematic review of the efficacy, safety and satisfaction of regenerative medicine treatments, including platelet-rich plasma, stromal vascular fraction and stem cell-conditioned medium for hypertrophic scars and keloids. Int Wound J. 2024;21(4):e14557.","DOI":"10.1111\/iwj.14557"},{"key":"2025122201303422558_j_med-2025-1249_ref_020","doi-asserted-by":"crossref","unstructured":"Yuan R, Dai X, Li Y, Li C, Liu L. Exosomes from miR-29a-modified adipose-derived mesenchymal stem cells reduce excessive scar formation by inhibiting TGF-beta2\/Smad3 signaling. Mol Med Rep. 2021;24(5):758.","DOI":"10.3892\/mmr.2021.12398"},{"key":"2025122201303422558_j_med-2025-1249_ref_021","doi-asserted-by":"crossref","unstructured":"Zhang T. Hepatocyte growth factor-modified adipose-derived mesenchymal stem cells inhibit human hypertrophic scar fibroblast activation. J Cosmet Dermatol. 2024;23(12):4268\u201376.","DOI":"10.1111\/jocd.16509"},{"key":"2025122201303422558_j_med-2025-1249_ref_022","doi-asserted-by":"crossref","unstructured":"Zahorec P, Sarkozyova N, Ferancikova N, Bukovcan P, Danisovic L, Bohac M, et al. Autologous mesenchymal stem cells application in post-burn scars treatment: a preliminary study. Cell Tissue Bank. 2021;22(1):39\u201346.","DOI":"10.1007\/s10561-020-09862-z"},{"key":"2025122201303422558_j_med-2025-1249_ref_023","doi-asserted-by":"crossref","unstructured":"Bojanic C, To K, Hatoum A, Shea J, Seah KTM, Khan W, et al. Mesenchymal stem cell therapy in hypertrophic and keloid scars. Cell Tissue Res. 2021;383(3):915\u201330.","DOI":"10.1007\/s00441-020-03361-z"},{"key":"2025122201303422558_j_med-2025-1249_ref_024","doi-asserted-by":"crossref","unstructured":"Zhang X, Jiang X, Deng H, Yu G, Yang N, Al Mamun A, et al. Engineering exosomes from fibroblast growth factor 1 pre-conditioned adipose-derived stem cells promote ischemic skin flaps survival by activating autophagy. Mater Today Bio. 2024;29:101314.","DOI":"10.1016\/j.mtbio.2024.101314"},{"key":"2025122201303422558_j_med-2025-1249_ref_025","doi-asserted-by":"crossref","unstructured":"Miller LN, Walters AE, Denninger JK, Hanson MA, Marshall AH, Johantges AC, et al. Neural stem and progenitor cells support and protect adult hippocampal function via vascular endothelial growth factor secretion. Mol Psychiatry. 2025;30(5):2152\u201367.","DOI":"10.1038\/s41380-024-02827-8"},{"key":"2025122201303422558_j_med-2025-1249_ref_026","doi-asserted-by":"crossref","unstructured":"Jung SI, Choi SH, Kim JW, Lim J, Rim YA, Ju JH. The effect of nerve growth factor on cartilage fibrosis and hypertrophy during in vitro chondrogenesis using induced pluripotent stem cells. Int J Stem Cell. 2025;18(1):59\u201371.","DOI":"10.15283\/ijsc24097"},{"key":"2025122201303422558_j_med-2025-1249_ref_027","doi-asserted-by":"crossref","unstructured":"Gong C, Xia C, Liu L. Exosomes derived from epidermal growth factor-like domain protein 6-preconditioned mesenchymal stem cells for diabetic wound healing. Regen Ther. 2024;26:932\u201340.","DOI":"10.1016\/j.reth.2024.09.009"},{"key":"2025122201303422558_j_med-2025-1249_ref_028","doi-asserted-by":"crossref","unstructured":"Chen QH, Zhang Y, Gu X, Yang PL, Yuan J, Yu LN, et al. Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor. World J Stem Cell. 2024;16(8):811\u201323.","DOI":"10.4252\/wjsc.v16.i8.811"},{"key":"2025122201303422558_j_med-2025-1249_ref_029","doi-asserted-by":"crossref","unstructured":"Yang T, Zhao F, Zhao J, Geng J, Shao C, Liu J, et al. Negatively charged bladder acellular matrix loaded with positively charged adipose-derived mesenchymal stem cell-derived small extracellular vesicles for bladder tissue engineering. J Control Release. 2023;364:718\u201333.","DOI":"10.1016\/j.jconrel.2023.10.048"},{"key":"2025122201303422558_j_med-2025-1249_ref_030","doi-asserted-by":"crossref","unstructured":"Sood R, Shergill S, Singh J, Sharma E, Ridhi G. Treatment of gingival class I or class II recession using subepithelial connective tissue graft and acellular dermal matrix allograft. Bioinformation. 2022;18(9):801\u20136.","DOI":"10.6026\/97320630018801"},{"key":"2025122201303422558_j_med-2025-1249_ref_031","doi-asserted-by":"crossref","unstructured":"Mihalecko J, Bohac M, Danisovic L, Koller J, Varga I, Kuniakova M. Acellular dermal matrix in plastic and reconstructive surgery. Physiol Res. 2022;71(Suppl 1):S51\u20137.","DOI":"10.33549\/physiolres.935045"},{"key":"2025122201303422558_j_med-2025-1249_ref_032","doi-asserted-by":"crossref","unstructured":"Wang Y, Xu Y, Zhou G, Liu Y, Cao Y. Biological evaluation of acellular cartilaginous and dermal matrixes as tissue engineering scaffolds for cartilage regeneration. Front Cell Dev Biol. 2020;8:624337.","DOI":"10.3389\/fcell.2020.624337"},{"key":"2025122201303422558_j_med-2025-1249_ref_033","doi-asserted-by":"crossref","unstructured":"Jia Z, Kang B, Cai Y, Chen C, Yu Z, Li W, et al. Cell-free fat extract attenuates osteoarthritis via chondrocytes regeneration and macrophages immunomodulation. Stem Cell Res Ther. 2022;13(1):133.","DOI":"10.1186\/s13287-022-02813-3"},{"key":"2025122201303422558_j_med-2025-1249_ref_034","doi-asserted-by":"crossref","unstructured":"Liu M, Zhang D, Zhou X, Duan J, Hu Y, Zhang W, et al. Cell-free fat extract improves ovarian function and fertility in mice with premature ovarian insufficiency. Stem Cell Res Ther. 2022;13(1):320.","DOI":"10.1186\/s13287-022-03012-w"},{"key":"2025122201303422558_j_med-2025-1249_ref_035","doi-asserted-by":"crossref","unstructured":"Xu M, Du J, Cui J, Zhang S, Zhang S, Deng M, et al. Cell-free fat extract prevents tail suspension-induced bone loss by inhibiting osteocyte apoptosis. Front Bioeng Biotechnol. 2022;10:818572.","DOI":"10.3389\/fbioe.2022.818572"},{"key":"2025122201303422558_j_med-2025-1249_ref_036","doi-asserted-by":"crossref","unstructured":"Cai Y, Jia Z, Zhang Y, Kang B, Chen C, Liu W, et al. Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia. Stem Cell Res Ther. 2023;14(1):219.","DOI":"10.1186\/s13287-023-03398-1"},{"key":"2025122201303422558_j_med-2025-1249_ref_037","doi-asserted-by":"crossref","unstructured":"Xu B, Zhou M, Liu M, Wang Z, Duan J, Li W, et al. Bioactive injectable and self-healing hydrogel via cell-free fat extract for endometrial regeneration. Small. 2023;19(30):e2300481.","DOI":"10.1002\/smll.202300481"},{"key":"2025122201303422558_j_med-2025-1249_ref_038","doi-asserted-by":"crossref","unstructured":"Li D, Li Q, Xu T, Guo X, Tang H, Wang W, et al. Pro-vasculogenic Fibers by PDA-Mediated Surface Functionalization Using Cell-Free Fat Extract (CEFFE). Biomacromolecules. 2024;25(3):1550\u201362.","DOI":"10.1021\/acs.biomac.3c01124"},{"key":"2025122201303422558_j_med-2025-1249_ref_039","doi-asserted-by":"crossref","unstructured":"Liu M, Li W, Zhou X, Zhou M, Zhang W, Liu Q, et al. Cell-free fat extract improves ovarian function and fertility in mice with advanced age. Front Endocrinol (Lausanne). 2022;13:912648.","DOI":"10.3389\/fendo.2022.912648"},{"key":"2025122201303422558_j_med-2025-1249_ref_040","unstructured":"Wu D, Li X, Wang X, Wang D. Cell-free fat extract protects septic lethality via restraining NLRP3 inflammasome activation. Am J Transl Res. 2022;14(7):5201\u201314."},{"key":"2025122201303422558_j_med-2025-1249_ref_041","doi-asserted-by":"crossref","unstructured":"Zhang L, Hu C, Xu W, Wu D, Lei S. Advances in wound repair and regeneration: Systematic comparison of cell free fat extract and platelet rich plasma. Front Chem. 2022;10:1089277.","DOI":"10.3389\/fchem.2022.1089277"},{"key":"2025122201303422558_j_med-2025-1249_ref_042","doi-asserted-by":"crossref","unstructured":"Kan T, Ran Z, Sun L, Jiang X, Hou L, Yang Y, et al. Cell-free fat extract-loaded microneedles attenuate inflammation-induced apoptosis and mitochondrial damage in tendinopathy. Mater Today Bio. 2023;22:100738.","DOI":"10.1016\/j.mtbio.2023.100738"},{"key":"2025122201303422558_j_med-2025-1249_ref_043","doi-asserted-by":"crossref","unstructured":"Ding J, Wei C, Xu Y, Dai W, Chen R. 3D printing of Ceffe-infused scaffolds for tailored nipple-like cartilage development. BMC Biotechnol. 2024;24(1):25.","DOI":"10.1186\/s12896-024-00848-3"},{"key":"2025122201303422558_j_med-2025-1249_ref_044","doi-asserted-by":"crossref","unstructured":"Li D, Xu T, Wang X, Xiao Q, Zhang W, Li F, et al. Enhanced osteo-angiogenic coupling by a bioactive cell-free fat extract (CEFFE) delivered through electrospun fibers. J Mater Chem B. 2025;13(3):1100\u201317.","DOI":"10.1039\/D4TB01394H"},{"key":"2025122201303422558_j_med-2025-1249_ref_045","doi-asserted-by":"crossref","unstructured":"Li G, Han Q, Lu P, Zhang L, Zhang Y, Chen S, et al. Construction of dual-biofunctionalized chitosan\/collagen scaffolds for simultaneous neovascularization and nerve regeneration. Research (Wash D C). 2020 Aug;2020:2603048. 10.34133\/2020\/2603048.","DOI":"10.34133\/2020\/2603048"}],"container-title":["Open Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/med-2025-1249\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/med-2025-1249\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T01:31:45Z","timestamp":1766367105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/med-2025-1249\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,9]]},"published-print":{"date-parts":[[2025,1,9]]}},"alternative-id":["10.1515\/med-2025-1249"],"URL":"https:\/\/doi.org\/10.1515\/med-2025-1249","relation":{},"ISSN":["2391-5463"],"issn-type":[{"type":"electronic","value":"2391-5463"}],"subject":[],"published":{"date-parts":[[2025,1,1]]},"article-number":"20251249"}}