{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T14:37:23Z","timestamp":1762353443262,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T00:00:00Z","timestamp":1705881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Introduction: Multiple factors have been linked with increased risk of anastomotic leak in bowel surgery, including infections, inflammatory bowel disease, patient comorbidities and poor surgical technique. The aim of this study was to investigate the positive effect, if any, of adipose derived mesenchymal stem cells (MSCs) mixed with platelet-rich plasma (PRP) in the healing of bowel anastomoses, in an inflammatory environment after establishment of experimental colitis. Materials and Methods: Thirty-five male Wistar rats were divided into five groups of seven animals: normal controls, colitis controls, PRP, MSCs, and PRP+MSCs. All groups underwent laparotomy, one-cm segmental colectomy and anastomosis in situ. In the colitis group, colectomy was performed at the affected area. Colitis was previously established by transrectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) except for the normal controls. Post-mortem histopathological, tissue hydroxyproline and anastomotic bursting pressure (ABP) assessments were performed. The Mann\u2013Whitney U test was used to assess statistical significance differences between groups. Results: No perioperative mortality was noted. Tissue hydroxyproline and ABP were significantly increased in the group of PRP+MSCs compared to colitis controls (p = 0.0151 and p = 0.0104, respectively). Inflammatory cell infiltration was lower and fibroblast activity higher in PRP+MSCs group, but not statistically significant (p &gt; 0.05). Neoangiogenesis (p = 0.0073) and anastomotic area epithelialization (p = 0.0182) were significantly higher in PRP + MSCs group compared to colitis controls. Discussion: The synergistic effect of the PRP and MSCs is apparently responsible for the improved healing markers in bowel anastomoses even on inflammatory bowel. This gives hope for primary anastomoses and stoma saving in many emergency and\/or elective circumstances, especially in immunocompromised or malnourished patients, even in cases with inflammation or peritonitis. Clinical studies should follow in order to support the clinical application of PRP+MSCs in gastrointestinal anastomoses.<\/jats:p>","DOI":"10.3390\/jpm14010121","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T03:50:22Z","timestamp":1705895422000},"page":"121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Effectiveness of Adipose Tissue-Derived Mesenchymal Stem Cells Mixed with Platelet-Rich Plasma in the Healing of Inflammatory Bowel Anastomoses: A Pre-Clinical Study in Rats"],"prefix":"10.3390","volume":"14","author":[{"given":"Georgios","family":"Geropoulos","sequence":"first","affiliation":[{"name":"2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyriakos","family":"Psarras","sequence":"additional","affiliation":[{"name":"2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3149-6523","authenticated-orcid":false,"given":"Maria","family":"Papaioannou","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasileios","family":"Geropoulos","sequence":"additional","affiliation":[{"name":"2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Argyri","family":"Niti","sequence":"additional","affiliation":[{"name":"Biohellenika Biotechnology Company, 55535 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2920-6945","authenticated-orcid":false,"given":"Christina","family":"Nikolaidou","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Hippokration Hospital, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0669-6980","authenticated-orcid":false,"given":"Georgios","family":"Koimtzis","sequence":"additional","affiliation":[{"name":"2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolaos","family":"Symeonidis","sequence":"additional","affiliation":[{"name":"2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efstathios T.","family":"Pavlidis","sequence":"additional","affiliation":[{"name":"2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios","family":"Koliakos","sequence":"additional","affiliation":[{"name":"Biohellenika Biotechnology Company, 55535 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8141-1412","authenticated-orcid":false,"given":"Theodoros E.","family":"Pavlidis","sequence":"additional","affiliation":[{"name":"2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Galanis","sequence":"additional","affiliation":[{"name":"2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1001\/2013.jamasurg.2","article-title":"Risk factors for anastomotic leakage after anterior resection for rectal cancer","volume":"148","author":"Kang","year":"2013","journal-title":"JAMA Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1097\/01.sla.0000225083.27182.85","article-title":"Anastomotic leaks after intestinal anastomosis: It\u2019s later than you think","volume":"245","author":"Hyman","year":"2007","journal-title":"Ann. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/bjs.9776","article-title":"Systematic review of experimental studies on intestinal anastomosis","volume":"102","author":"Yauw","year":"2015","journal-title":"Br. J. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.21037\/ls.2020.03.07","article-title":"Laparoscopic pancreaticojejunal anastomosis using knotless barbed absorbable sutures are simple, safe and effective: An experience with 34 procedures","volume":"4","author":"Azagra","year":"2020","journal-title":"Laparosc. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00595-018-1726-8","article-title":"Esophagojejunal anastomotic leakage following gastrectomy for gastric cancer","volume":"49","author":"Makuuchi","year":"2019","journal-title":"Surg. Today"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1007\/s00384-019-03358-3","article-title":"A positive proximal resection margin is associated with anastomotic complications following primary ileocaecal resection for Crohn\u2019s disease","volume":"34","author":"Garofalo","year":"2019","journal-title":"Int. J. Colorectal. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1308\/rcsann.2018.0126","article-title":"The incidence of stoma related morbidity\u2014A systematic review of randomised controlled trials","volume":"100","author":"Malik","year":"2018","journal-title":"Ann. R Coll. Surg. Engl."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1177\/0963689717721515","article-title":"Adipose-Derived Mesenchymal Stromal Cells Improve the Healing of Colonic Anastomoses Following High Dose of Irradiation Through Anti-Inflammatory and Angiogenic Processes","volume":"26","author":"Demarquay","year":"2017","journal-title":"Cell Transpl."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/scrt30","article-title":"Topical delivery of mesenchymal stem cells and their function in wounds","volume":"1","author":"Sorrell","year":"2010","journal-title":"Stem. Cell Res Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1634\/stemcells.2007-0226","article-title":"Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis","volume":"25","author":"Wu","year":"2007","journal-title":"Stem Cells"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mazini, L., Rochette, L., Admou, B., Amal, S., and Malka, G. (2020). Hopes and limits of adipose-derived stem cells (ADSCs) and mesenchymal stem cells (MSCs) in wound healing. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041306"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Trevor, L.V., Riches-Suman, K., Mahajan, A.L., and Thornton, M.J. (2020). Adipose tissue: A source of stem cells with potential for regenerative therapies for wound healing. J. Clin. Med., 9.","DOI":"10.3390\/jcm9072161"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1634\/stemcells.2008-0178","article-title":"IFATS Collection: Human Adipose-Derived Stem Cells Seeded on a Silk Fibroin-Chitosan Scaffold Enhance Wound Repair in a Murine Soft Tissue Injury Model","volume":"27","author":"Altman","year":"2009","journal-title":"Stem Cells"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"32993","DOI":"10.1038\/srep32993","article-title":"Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts","volume":"6","author":"Hu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"\u00d6zc\u0327ay, N., \u00d6zdemir, H., and Besim, H. (2018). Role of platelet-rich fibrin on intestinal anastomosis wound healing in a rat. Biomed. Mater., 13.","DOI":"10.1088\/1748-605X\/aab8e1"},{"key":"ref_16","first-page":"CD009072","article-title":"Pathogen- reduced platelets for the prevention of bleeding","volume":"7","author":"Estcourt","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/BF02723005","article-title":"Regulation of fibroblast proliferation in three- dimensional collagen gel matrix","volume":"32","author":"Mio","year":"1996","journal-title":"In Vitro Cell Dev. Biol. Anim."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.4240\/wjgs.v13.i12.1736","article-title":"Platelet rich plasma effectiveness in bowel anastomoses: A systematic review","volume":"13","author":"Geropoulos","year":"2021","journal-title":"World J. Gastrointest. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.amsu.2016.07.019","article-title":"The TNBS-induced colitis animal model: An overview","volume":"11","author":"Antoniou","year":"2016","journal-title":"Ann. Med. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0002-9610(92)90255-P","article-title":"Effect of cronic corticosteroid and vitamin A on the healing of intestinal anastomoses","volume":"163","author":"Philips","year":"1992","journal-title":"Am. J. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/BF02234744","article-title":"Microscopic analysis of anastomotic healing in the intestine of normal and diabetic rats","volume":"44","author":"Verhofstad","year":"2001","journal-title":"Dis. Colon Rectum."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"848","DOI":"10.28982\/josam.875206","article-title":"Early enteral nutrition with L-glutamine improves anastomotic healing in rats administered hyperthermic intraperitoneal chemotherapy with cisplatin and 5-FU","volume":"5","author":"Erten","year":"2021","journal-title":"J. Surg. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Cohen, J., and A power primer (2023, December 24). In Methodological Issues and Strategies in Clinical Research; Kazdin, A.E., Ed.; 2016, 279\u2013284. Available online: https:\/\/psycnet.apa.org\/record\/2015-32022-018.","DOI":"10.1037\/14805-018"},{"key":"ref_24","first-page":"131","article-title":"Clinical review: Healing in gastrointestinal anastomoses, part I","volume":"26","author":"Thompson","year":"2006","journal-title":"Microsurg. Off. J. Int. Microsurg. Soc. Eur. Fed. Soc. Microsurg."},{"key":"ref_25","first-page":"137","article-title":"Clinical review: Healing in gastrointestinal anastomoses, part II","volume":"26","author":"Enestvedt","year":"2006","journal-title":"Microsurg. Off. J. Int. Microsurg. Soc. Eur. Fed. Soc. Microsurg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0039-6109(05)70567-3","article-title":"Healing in other tissues","volume":"77","author":"Mast","year":"1997","journal-title":"Surg. Clin. North. Am."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1136\/gut.32.12.1482","article-title":"Postoperative changes in collagen synthesis in intestinal anastomoses of the rat: Differences between small and large bowel","volume":"32","author":"Martens","year":"1991","journal-title":"Gut"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.jss.2010.06.036","article-title":"Heparin-binding EGF- like growth factor promotes intestinal anastomotic healing","volume":"171","author":"Radulescu","year":"2011","journal-title":"J. Surg. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jss.2013.10.013","article-title":"Growth factors and gastrointestinal anastomotic healing","volume":"187","author":"Rijcken","year":"2014","journal-title":"J. Surg. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s13287-023-03438-w","article-title":"Mesenchymal stem cells shift the pro-inflammatory phenotype of neutrophils to ameliorate acute lung injury","volume":"14","author":"Feng","year":"2023","journal-title":"Stem Cell Res Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"154","DOI":"10.4266\/acc.2018.00619","article-title":"Anti-inflammatory role of mesenchymal stem cells in an acute lung injury mouse model","volume":"33","author":"Huh","year":"2018","journal-title":"Acute Crit. Care."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1159\/000526603","article-title":"Stem Cell Therapies for Gastrointestinal Anastomotic Healing: A Systematic Review and Meta-Analysis on Results from Animal Studies","volume":"63","author":"Gaitanidis","year":"2022","journal-title":"Eur. Surg. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.surg.2019.07.023","article-title":"Protective effect of adipose tissue\u2013derived mesenchymal stromal cells in an experimental model of high-risk colonic anastomosis","volume":"166","author":"Alvarenga","year":"2019","journal-title":"Surgery"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1007\/s10350-005-0052-6","article-title":"A phase I clinical trial of the treatment of Crohn\u2019s fistula by adipose mesenchymal stem cell transplantation","volume":"48","author":"Herreros","year":"2005","journal-title":"Dis. Colon. Rectum."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/S0140-6736(16)31203-X","article-title":"Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn\u2019s disease: A phase 3 randomised, double-blind controlled trial","volume":"388","author":"Colombel","year":"2016","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-021-02454-y","article-title":"Adipose mesenchymal stem cells combined with platelet-rich plasma accelerate diabetic wound healing by modulating the Notch pathway","volume":"12","author":"Ebrahim","year":"2021","journal-title":"Stem. Cell Res. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.2217\/rme-2020-0040","article-title":"Combination of preconditioned adipose-derived mesenchymal stem cells and platelet-rich plasma improves the repair of osteoarthritis in rat","volume":"15","author":"Ahmad","year":"2020","journal-title":"Regen Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1177\/1553350612458544","article-title":"Breast Reconstruction with Autologous Fat Graft Mixed with Platelet-Rich Plasma","volume":"20","author":"Gentile","year":"2013","journal-title":"Surg. Innov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S538","DOI":"10.1097\/01.CCM.0000081436.09826.A4","article-title":"Repair of full-thickness bowel injury","volume":"31","author":"Witte","year":"2003","journal-title":"Crit. Care. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"212","DOI":"10.4252\/wjsc.v10.i12.212","article-title":"Platelet-rich plasma enhances adipose-derived stem cell-mediated angiogenesis in a mouse ischemic hindlimb model","volume":"10","author":"Chen","year":"2018","journal-title":"World J. Stem. Cells."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.jviscsurg.2014.10.004","article-title":"Anastomotic leakage after gastrointestinal surgery: Diagnosis and management","volume":"151","author":"Girard","year":"2014","journal-title":"J. Visc. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kawai, M., Sakamoto, K., Honjo, K., Okazawa, Y., Takahashi, R., Kawano, S., Munakata, S., Sugimoto, K., Ishiyama, S., and Takahashi, M. (2022). Benefits and risks of diverting stoma creation during rectal cancer surgery. Ann. Coloproctol., Epub ahead of print.","DOI":"10.3393\/ac.2022.00353.0050"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1016\/j.cgh.2022.06.030","article-title":"Global Hospitalization Trends for Crohn\u2019s Disease and Ulcerative Colitis in the 21st Century: A Systematic Review with Temporal Analyses","volume":"21","author":"Buie","year":"2023","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1053\/j.gastro.2018.12.033","article-title":"Epidemiology, Pathophysiology, and Treatment of Diverticulitis","volume":"156","author":"Strate","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"283","DOI":"10.51821\/85.2.9527","article-title":"Clinical features and risk factors for ischemic colitis in young and middle-aged patients","volume":"85","author":"Cai","year":"2022","journal-title":"Acta. Gastroenterol. Belg."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Selvaraj, V., and Alsamman, M.A. (2022). Antibiotic-Associated Diarrhea Beyond C. Difficile: A Scoping Review. Brown Hosp. Med., 2.","DOI":"10.56305\/001c.39745"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"888962","DOI":"10.3389\/fonc.2022.888962","article-title":"Research progress on the mechanism of radiation enteritis","volume":"12","author":"Fan","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Gentile, P., Scioli, M.G., Bielli, A., De Angelis, B., De Sio, C., De Fazio, D., Ceccarelli, G., Trivisonno, A., Orlandi, A., and Cervelli, V. (2019). Platelet-rich plasma and micrografts enriched with autologous human follicle mesenchymal stem cells improve hair re-growth in androgenetic alopecia. biomolecular pathway analysis and clinical evaluation. Biomedicines, 7.","DOI":"10.3390\/biomedicines7020027"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-020-02095-7","article-title":"Efficacy of stem cells therapy for Crohn\u2019s fistula: A meta-analysis and systematic review","volume":"12","author":"Cao","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/cyto.a.23242","article-title":"Isolation, cultivation, and characterization of human mesenchymal stem cells","volume":"93","author":"Mushahary","year":"2018","journal-title":"Cytom. Part A"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4161\/org.6.1.10019","article-title":"Isolating adipose-derived mesenchymal stem cells from lipoaspirate blood and saline fraction","volume":"6","author":"Francis","year":"2010","journal-title":"Organogenesis"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/14\/1\/121\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:46:54Z","timestamp":1760104014000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/14\/1\/121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,22]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["jpm14010121"],"URL":"https:\/\/doi.org\/10.3390\/jpm14010121","relation":{},"ISSN":["2075-4426"],"issn-type":[{"type":"electronic","value":"2075-4426"}],"subject":[],"published":{"date-parts":[[2024,1,22]]}}}