{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:05:20Z","timestamp":1790791520945,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002738","name":"Assistance Publique\u2014H\u00f4pitaux de Paris (D\u00e9l\u00e9gation \u00e0 la Recherche Clinique et \u00e0 l\u2019Innovation)","doi-asserted-by":"publisher","award":["F101H1"],"award-info":[{"award-number":["F101H1"]}],"id":[{"id":"10.13039\/501100002738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Despite conventional treatment combining complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy, residual microscopic peritoneal metastases (mPM) may persist as the cause of peritoneal recurrence in 60% of patients. Therefore, there is a real need to specifically target these mPM to definitively eradicate any traces of the disease and improve patient survival. Therapeutic targeting method, such as photodynamic therapy, would be a promising method for such a purpose. Folate receptor alpha (FR\u03b1), as it is specifically overexpressed by cancer cells from various origins, including ovarian cancer cells, is a good target to address photosensitizing molecules. The aim of this study was to determine FR\u03b1 expression by residual mPM after complete macroscopic CRS in patients with advanced high-grade serous ovarian cancer (HGSOC). A prospective study conducted between 1 June 2018 and 10 July 2019 in a single referent center accredited by the European Society of Gynecological Oncology for advanced EOC surgical management. Consecutive patients presenting with advanced HGSOC and eligible for complete macroscopic CRS were included. Up to 13 peritoneal biopsies were taken from macroscopically healthy peritoneum at the end of CRS and examined for the presence of mPM. In case of detection of mPM, a systematic search for RF\u03b1 expression by immunohistochemistry was performed. Twenty-six patients were included and 26.9% presented mPM. In the subgroup of patients with mPM, FR\u03b1 expression was positive on diagnostic biopsy before neoadjuvant chemotherapy for 67% of patients, on macroscopic peritoneal metastases for 86% of patients, and on mPM for 75% of patients. In the subgroup of patients with no mPM, FR\u03b1 expression was found on diagnostic biopsy before neoadjuvant chemotherapy in 29% of patients and on macroscopic peritoneal metastases in 78% of patients. FR\u03b1 is well expressed by patients with or without mPM after complete macroscopic CRS in patients with advanced HGSOC. In addition to conventional cytoreductive surgery, the use of a therapeutic targeting method, such as photodynamic therapy, by addressing photosensitizing molecules that specifically target FR\u03b1 may be studied.<\/jats:p>","DOI":"10.3390\/ph15081034","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T21:30:34Z","timestamp":1661203834000},"page":"1034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Residual Microscopic Peritoneal Metastases after Macroscopic Complete Cytoreductive Surgery for Advanced High-Grade Serous Ovarian Carcinoma: A Target for Folate Receptor Targeted Photodynamic Therapy?"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2949-9146","authenticated-orcid":false,"given":"Morgane","family":"Moinard","sequence":"first","affiliation":[{"name":"Laboratoire des R\u00e9actions et G\u00e9nie des Proc\u00e9d\u00e9s (LRGP), CNRS-Universit\u00e9 de Lorraine, 1 rue Grandville, 54000 Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Augustin","sequence":"additional","affiliation":[{"name":"AP-HP, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Department of Pathology, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Carrier","sequence":"additional","affiliation":[{"name":"Department of Gynecological and Breast Surgery and Oncology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Da Ma\u00efa","sequence":"additional","affiliation":[{"name":"AP-HP, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Department of Pathology, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alix","family":"Penel","sequence":"additional","affiliation":[{"name":"AP-HP, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Centre de Pharmaco-\u00e9pid\u00e9miologie de l\u2019APHP (CEPHEPI), 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9mie","family":"Belghiti","sequence":"additional","affiliation":[{"name":"Department of Gynecological and Breast Surgery and Oncology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Nikpayam","sequence":"additional","affiliation":[{"name":"Department of Gynecological and Breast Surgery and Oncology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mentine","family":"Gonthier","sequence":"additional","affiliation":[{"name":"Department of Gynecological and Breast Surgery and Oncology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffroy","family":"Canlorbe","sequence":"additional","affiliation":[{"name":"Department of Gynecological and Breast Surgery and Oncology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, 75013 Paris, France"},{"name":"Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Sorbonne University, INSERM UMR_S_938, 75020 Paris, France"},{"name":"Institut Universitaire de Canc\u00e9rologie (IUC), Sorbonne University, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8776-1632","authenticated-orcid":false,"given":"Samir","family":"Acherar","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie-Physique Macromol\u00e9culaire (LCPM), CNRS-Universit\u00e9 de Lorraine, 54000 Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadira","family":"Delhem","sequence":"additional","affiliation":[{"name":"INSERM, CHU-Lille, U1189-ONCO-THAI\u2014Assisted Laser Therapy and Immunotherapy for Oncology, University of Lille, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7659-3864","authenticated-orcid":false,"given":"C\u00e9line","family":"Frochot","sequence":"additional","affiliation":[{"name":"Laboratoire des R\u00e9actions et G\u00e9nie des Proc\u00e9d\u00e9s (LRGP), CNRS-Universit\u00e9 de Lorraine, 1 rue Grandville, 54000 Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Uzan","sequence":"additional","affiliation":[{"name":"Department of Gynecological and Breast Surgery and Oncology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, 75013 Paris, France"},{"name":"Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Sorbonne University, INSERM UMR_S_938, 75020 Paris, France"},{"name":"Institut Universitaire de Canc\u00e9rologie (IUC), Sorbonne University, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6855-9754","authenticated-orcid":false,"given":"Henri","family":"Aza\u00efs","sequence":"additional","affiliation":[{"name":"Department of Gynecological and Breast Surgery and Oncology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1016\/S0140-6736(13)62146-7","article-title":"Ovarian Cancer","volume":"384","author":"Jayson","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.ygyno.2013.05.040","article-title":"Survival Impact of Complete Cytoreduction to No Gross Residual Disease for Advanced-Stage Ovarian Cancer: A Meta-Analysis","volume":"130","author":"Chang","year":"2013","journal-title":"Gynecol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1093\/annonc\/mdu116","article-title":"Optimal Treatment of Early-Stage Ovarian Cancer","volume":"25","author":"Collinson","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_4","first-page":"CD008765","article-title":"Surgical cytoreduction for recurrent epithelial ovarian cancer","volume":"2013","author":"Lopes","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102","DOI":"10.4251\/wjgo.v2.i2.102","article-title":"Peritoneal Carcinosis of Ovarian Origin","volume":"2","author":"Fagotti","year":"2010","journal-title":"World J. Gastrointest. Oncol. WJGO"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.suronc.2017.01.001","article-title":"Dealing with Microscopic Peritoneal Metastases of Epithelial Ovarian Cancer. A Surgical Challenge","volume":"26","author":"Estevez","year":"2017","journal-title":"Surg. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ygyno.2006.07.004","article-title":"\u201cOptimal\u201d Cytoreduction for Advanced Epithelial Ovarian Cancer: A Commentary","volume":"103","author":"Eisenkop","year":"2006","journal-title":"Gynecol. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S88","DOI":"10.1016\/S0959-8049(11)70152-6","article-title":"Primary Surgery or Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery in Advanced Ovarian Cancer","volume":"47","author":"Vergote","year":"2011","journal-title":"Eur. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ygyno.2012.02.024","article-title":"Evolution of Surgical Treatment Paradigms for Advanced-Stage Ovarian Cancer: Redefining \u2018Optimal\u2019 Residual Disease","volume":"125","author":"Chang","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1245\/s10434-012-2446-8","article-title":"Impact of Complete Cytoreduction Leaving No Gross Residual Disease Associated with Radical Cytoreductive Surgical Procedures on Survival in Advanced Ovarian Cancer","volume":"19","author":"Chang","year":"2012","journal-title":"Ann. Surg. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1200\/JCO.2002.20.5.1248","article-title":"Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: A meta-analysis","volume":"20","author":"Bristow","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1002\/cncr.24149","article-title":"Role of Surgical Outcome as Prognostic Factor in Advanced Epithelial Ovarian Cancer: A Combined Exploratory Analysis of 3 Prospectively Randomized Phase 3 Multicenter Trials: By the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d\u2019Investigateurs Nationaux Pour Les Etudes Des Cancers de l\u2019Ovaire (GINECO)","volume":"115","author":"Reuss","year":"2009","journal-title":"Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ygyno.2009.03.018","article-title":"Improved Progression-Free and Overall Survival in Advanced Ovarian Cancer as a Result of a Change in Surgical Paradigm","volume":"114","author":"Chi","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_14","first-page":"CD007565","article-title":"Optimal primary surgical treatment for advanced epithelial ovarian cancer","volume":"2011","author":"Elattar","year":"2011","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Aza\u00efs, H., Vignion-Dewalle, A.-S., Carrier, M., Augustin, J., Da Ma\u00efa, E., Penel, A., Belghiti, J., Nikpayam, M., Gonthier, C., and Ziane, L. (2020). Microscopic Peritoneal Residual Disease after Complete Macroscopic Cytoreductive Surgery for Advanced High Grade Serous Ovarian Cancer. J. Clin. Med. JCM, 10.","DOI":"10.3390\/jcm10010041"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.2217\/fon-2017-0253","article-title":"Image-Guided Surgery in Gynecologic Oncology","volume":"13","author":"Canlorbe","year":"2017","journal-title":"Future Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/0360-3016(93)90066-5","article-title":"Phase I Study of Debulking Surgery and Photodynamic Therapy for Disseminated Intraperitoneal Tumors","volume":"25","author":"Delaney","year":"1993","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1158\/1078-0432.CCR-05-1625","article-title":"A Phase II Trial of Intraperitoneal Photodynamic Therapy for Patients with Peritoneal Carcinomatosis and Sarcomatosis","volume":"12","author":"Hahn","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s10434-001-0065-x","article-title":"Phase II Trial of Debulking Surgery and Photodynamic Therapy for Disseminated Intraperitoneal Tumors","volume":"8","author":"Hendren","year":"2001","journal-title":"Ann. Surg. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5464","DOI":"10.1158\/1078-0432.CCR-06-0953","article-title":"Photofrin Uptake in the Tumor and Normal Tissues of Patients Receiving Intraperitoneal Photodynamic Therapy","volume":"12","author":"Hahn","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_21","first-page":"493","article-title":"Intraperitoneal Photodynamic Therapy","volume":"134","author":"Cengel","year":"2007","journal-title":"Cancer Treat. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.biopha.2018.07.049","article-title":"Photodynamic Therapy\u2014Mechanisms, Photosensitizers and Combinations","volume":"106","author":"Kwiatkowski","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1016\/j.bmc.2005.02.025","article-title":"Design, Synthesis, and Biological Evaluation of Folic Acid Targeted Tetraphenylporphyrin as Novel Photosensitizers for Selective Photodynamic Therapy","volume":"13","author":"Schneider","year":"2005","journal-title":"Bioorg. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ab.2004.12.026","article-title":"Folate Receptor Expression in Carcinomas and Normal Tissues Determined by a Quantitative Radioligand Binding Assay","volume":"338","author":"Parker","year":"2005","journal-title":"Anal. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1021\/ar7000815","article-title":"Discovery and Development of Folic-Acid-Based Receptor Targeting for Imaging and Therapy of Cancer and Inflammatory Diseases","volume":"41","author":"Low","year":"2008","journal-title":"Acc. Chem. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.2174\/0929867322666150729113912","article-title":"The Interest of Folic Acid in Targeted Photodynamic Therapy","volume":"22","author":"Stallivieri","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4394","DOI":"10.1021\/acsabm.1c00151","article-title":"Ru(II) Polypyridine Complex Functionalized Mesoporous Silica Nanoparticles as Photosensitizers for Cancer Targeted Photodynamic Therapy","volume":"4","author":"Karges","year":"2021","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111755","DOI":"10.1016\/j.colsurfb.2021.111755","article-title":"Folate-Targeted Pluronic-Chitosan Nanocapsules Loaded with IR780 for near-Infrared Fluorescence Imaging and Photothermal-Photodynamic Therapy of Ovarian Cancer","volume":"203","author":"Potara","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1039\/C9BM02081K","article-title":"A Nanosystem Loaded with Perfluorohexane and Rose Bengal Coupled Upconversion Nanoparticles for Multimodal Imaging and Synergetic Chemo-Photodynamic Therapy of Cancer","volume":"8","author":"Wang","year":"2020","journal-title":"Biomater. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bazyli\u0144ska, U., Kulbacka, J., and Chodaczek, G. (2019). Nanoemulsion Structural Design in Co-Encapsulation of Hybrid Multifunctional Agents: Influence of the Smart PLGA Polymers on the Nanosystem-Enhanced Delivery and Electro-Photodynamic Treatment. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11080405"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1111\/cas.13605","article-title":"Hypocrellin B-Loaded, Folate-Conjugated Polymeric Micelle for Intraperitoneal Targeting of Ovarian Cancer in Vitro and in Vivo","volume":"109","author":"Li","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"37943","DOI":"10.1039\/C5RA05125H","article-title":"Conducting Polymer Nanoparticles for Targeted Cancer Therapy","volume":"5","author":"Doshi","year":"2015","journal-title":"RSC Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.pdpdt.2015.07.005","article-title":"Assessment of the Specificity of a New Folate-Targeted Photosensitizer for Peritoneal Metastasis of Epithelial Ovarian Cancer to Enable Intraperitoneal Photodynamic Therapy. A Preclinical Study","volume":"13","author":"Schmitt","year":"2016","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Baydoun, M., Moral\u00e8s, O., Frochot, C., Ludovic, C., Leroux, B., Thecua, E., Ziane, L., Grabarz, A., Kumar, A., and de Schutter, C. (2020). Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties. J. Clin. Med. JCM, 9.","DOI":"10.3390\/jcm9041185"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijgo.2013.10.001","article-title":"Classification for Cancer of the Ovary, Fallopian Tube, and Peritoneum","volume":"124","author":"Prat","year":"2014","journal-title":"Int. J. Gynecol. Obstet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1097\/GCO.0b013e32831f8f32","article-title":"Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for the Treatment of Advanced Primary and Recurrent Ovarian Cancer","volume":"21","author":"Sugarbaker","year":"2009","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"642.e1","DOI":"10.1016\/j.ajog.2008.06.052","article-title":"Prospective Validation of a Laparoscopic Predictive Model for Optimal Cytoreduction in Advanced Ovarian Carcinoma","volume":"199","author":"Fagotti","year":"2008","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.jogoh.2019.03.018","article-title":"Management of Epithelial Cancer of the Ovary, Fallopian Tube, Primary Peritoneum. Long Text of the Joint French Clinical Practice Guidelines Issued by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY, Endorsed by INCa. (Part 2: Systemic, Intraperitoneal Treatment, Elderly Patients, Fertility Preservation, Follow-Up)","volume":"48","author":"Lavoue","year":"2019","journal-title":"J. Gynecol. Obstet. Hum. Reprod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1056\/NEJMoa1808424","article-title":"A Randomized Trial of Lymphadenectomy in Patients with Advanced Ovarian Neoplasms","volume":"380","author":"Harter","year":"2019","journal-title":"N. Engl. J. Med."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/8\/1034\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:13:33Z","timestamp":1760141613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/8\/1034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,22]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ph15081034"],"URL":"https:\/\/doi.org\/10.3390\/ph15081034","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,22]]}}}