Frontiers in drug delivery最新文献

{"title":"Future theranostic strategies: emerging ovarian cancer biomarkers to bridge the gap between diagnosis and treatment","authors":"Weranga Rajapaksha, Riya Khetan, Ian R. D. Johnson, Anton Blencowe, Sanjay Garg, Hugo Albrecht, T. Gillam","doi":"10.3389/fddev.2024.1339936","DOIUrl":"https://doi.org/10.3389/fddev.2024.1339936","url":null,"abstract":"Ovarian cancers are a complex and heterogenic group of malignancies that are difficult to detect, diagnose and treat. Fortunately, considerable knowledge of ovarian cancer specific biomarkers has been generated, that is pertinent to the development of novel theranostic platforms by combining therapies and diagnostics. Genomic and proteomic data has been invaluable in providing critical biomolecular targets for ovarian cancer theranostic approaches. Exploitation of the wealth of biomarker research that has been conducted offers viable targets as beacons for ovarian cancer detection, diagnosis, and therapeutic targeting. These markers can be used in theranostics, a treatment strategy that combines therapy and diagnostics and is common in nuclear medicine, where radionuclides are used for both diagnosis and treatment. The development of theranostics has taken substantial focus in recent years in the battle against ovarian cancer. Yet to date only one theranostic technology has emerged in clinical practice. However, given the wealth of ovarian cancer biomarkers the field is poised to see the emergence of revolutionary disease treatment and monitoring outcomes through their incorporation into the development of theranostic strategies. The future of ovarian cancer treatment is set to enable precise diagnosis, targeted treatment, and vigilant monitoring. This review aims to assess the status of ovarian cancer diagnostic tools and biomarkers in practice, clinical development, or pre-clinical development, highlighting newly emerging theranostic applications.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"31 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139879624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Release of delta-9-tetrahydrocannabinol from polyvinyl alcohol hydrogels and its safe interaction with human skin fibroblasts","authors":"Shujun Cui, Ze Zhang, Denis Rodrigue, François Béland, Mahmoud Rouabhia","doi":"10.3389/fddev.2024.1303812","DOIUrl":"https://doi.org/10.3389/fddev.2024.1303812","url":null,"abstract":"This study aimed to design a THC-rich hydrogel to deliver cannabis derivatives topically. We developed hydrogels using polyvinyl alcohol (PVA) mixed with propylene glycol (PG), vegetable glycerin (VG), or both to facilitate the dissolution of delta-9-tetrahydrocannabinol (THC). The hydrogels showed a brown color, confirming the presence of the cannabinoid. They exhibit a porous structure and better mechanical properties than PVA alone. Indeed, the hydrogel containing PG, VG, or both showed elastic deformation behaviors with lower water content. FTIR analysis demonstrated the presence of THC with two specific peaks at 1,575 and 1,619 cm−1, confirming the presence of THC in the hydrogels. Human dermal fibroblast cultures onto the surface of all hydrogels confirmed the safety of the THC-rich hydrogel as the cell adhesion was comparable to the control (no THC). Furthermore, cells adhering to the hydrogels could proliferate, showing increased cell viability at 48 and 72 h, with a higher proliferation obtained with the THC-rich PVA-PG-VG hydrogels. Such cell behavior could be due to the release of the THC in the culture medium, as demonstrated by ultra-high performance liquid chromatography (UPLC), showing the presence of THC in the culture medium, ranging from 203 to 290 μg after 24 h of incubation of the hydrogels containing PG and VG or both. In comparison, the released THC from the PVA hydrogel was higher, reaching 852 μg. It is interesting to note that the THC release at 24, 48, and 72 h was slower with the hydrogels containing PG, VG, and both, compared to PVA alone. Overall, the present study has designed safe THC-rich PVA-PG-VG hydrogels as a functional delivery system for the topical use of cannabinoids to control tissue diseases, such as inflammation.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"48 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140475811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotechnological innovations in paediatric tuberculosis management: current trends and future prospects","authors":"Taiwo Oreoluwa Ajayi, M. Poka, B. Witika","doi":"10.3389/fddev.2023.1295815","DOIUrl":"https://doi.org/10.3389/fddev.2023.1295815","url":null,"abstract":"Paediatric Tuberculosis (TB) continues to be a major global cause of morbidity and mortality. Children are more prone to contracting TB, which can spread quickly to extrapulmonary infection sites. Although the pathophysiology of the disease, drug pharmacokinetics, and the therapeutic window in children differ from those of adults, the same drugs used to treat adult TB have long been utilised to treat paediatric TB infections. Since many current formulations such as tablets are unsuitable for children due to difficulty swallowing and risk of choking, adult medications are frequently used by breaking or crushing tablets to obtain a paediatric dose. This can result in inaccurate dosing due to pharmacokinetic differences in children which could subsequently lead to sub-therapeutic or toxic systemic concentrations. In addition, many of the medications used in the treatment of TB and most medicines in general, have a profoundly unpleasant taste to children causing them to reject and spit out medication which contributes to challenges with adherence, ultimately leading to treatment failure. The aforementioned demonstrates a huge need for the development of novel drug delivery formulations that are paediatric-friendly and address the limitations of current dosage forms. This review discusses the currently available oral paediatric formulations, recent developments of novel oral drug delivery systems studied to overcome the current problems associated with the treatment of tuberculosis in paediatrics and provides potential direction for future research through nanotechnology by using a SWOT analysis.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"32 22","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139445249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of Oxytocin (OT)-elicited reductions of body weight gain and adiposity in male diet-induced obese rats.","authors":"Melise M Edwards, Ha K Nguyen, Andrew D Dodson, Adam J Herbertson, Mackenzie K Honeycutt, Jared D Slattery, June R Rambousek, Edison Tsui, Tami Wolden-Hanson, Tomasz A Wietecha, James L Graham, Geronimo P Tapia, Carl L Sikkema, Kevin D O'Brien, Thomas O Mundinger, Elaine R Peskind, Vitaly Ryu, Peter J Havel, Arshad M Khan, Gerald J Taborsky, James E Blevins","doi":"10.3389/fddev.2024.1497746","DOIUrl":"10.3389/fddev.2024.1497746","url":null,"abstract":"<p><p>Recent studies indicate that central administration of oxytocin (OT) reduces body weight (BW) in high fat diet-induced obese (DIO) rodents by reducing energy intake and increasing energy expenditure (EE). Previous studies in our lab have shown that administration of OT into the fourth ventricle (4V; hindbrain) elicits weight loss and stimulates interscapular brown adipose tissue temperature (T_IBAT) in DIO rats. We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of IBAT contributes to its ability to activate BAT and reduce BW in DIO rats. To test this, we determined the effect of disrupting SNS activation of IBAT on OT-elicited stimulation of T_IBAT and reduction of BW in DIO rats. We first confirmed that bilateral surgical SNS denervation to IBAT was successful based on having achieved ≥ 60% reduction in IBAT norepinephrine (NE) content from DIO rats. NE content was selectively reduced in IBAT by 94.7 ± 2.7, 96.8 ± 1.8 and 85.9 ± 6.1% (<i>P</i><0.05) at 1, 6 and 7-weeks post-denervation, respectively, and was unchanged in liver or inguinal white adipose tissue. We then measured the impact of bilateral surgical SNS denervation to IBAT on the ability of acute 4V OT (1, 5 μg) to stimulate T_IBAT in DIO rats. We found that the high dose of 4V OT (5 μg) stimulated T_IBAT similarly between sham and denervated rats (<i>P</i>=NS) and that the effects of 4V OT to stimulate T_IBAT did not require beta-3 adrenergic receptor signaling. We subsequently measured the effect of bilateral surgical denervation of IBAT on the effect of chronic 4V OT (16 nmol/day) or vehicle infusion to reduce BW, adiposity, and energy intake in DIO rats. Chronic 4V OT reduced BW gain by -7.2 ± 9.6 g and -14.1 ± 8.8 g in sham and denervated rats (<i>P</i><0.05 vs vehicle treatment), respectively, and this effect was similar between groups (<i>P</i>=NS). These effects were associated with reductions in adiposity and energy intake (<i>P</i><0.05). Collectively, these findings support the hypothesis that sympathetic innervation of IBAT is not required for central OT to increase BAT thermogenesis and reduce BW gain and adiposity in male DIO rats.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biodistribution of the saponin-based adjuvant Matrix-M™ following intramuscular injection in mice","authors":"Cecilia Carnrot, Berit Carow, Anna-Karin E. Palm, Eray Akpinar, Per-Henrik Helgesson, Ingrid Lekberg Osterman, Emelie Bringeland, Bryant Foreman, Nita Patel, Johan Bankefors, Louis Fries, Linda Stertman","doi":"10.3389/fddev.2023.1279710","DOIUrl":"https://doi.org/10.3389/fddev.2023.1279710","url":null,"abstract":"Novel adjuvants are extensively utilized in the development of safe and effective vaccines against emerging pathogens. Matrix-M™ adjuvant is a saponin-based adjuvant used in several active clinical development programs and in widespread use in the COVID-19 vaccine NVX-CoV2373. Here, we conducted a biodistribution study to better understand the mechanism of action and safety profile for Matrix-M™ adjuvant. Radiolabeled saponins or cholesterol were incorporated into Matrix-A™ particles, which represent 85% of Matrix-M™. Labeled Matrix-M™ adjuvant was given to mice by intramuscular injection with or without SARS-CoV-2 Spike protein. Radioactivity of the adjuvant components was quantified in local and systemic tissues at seven timepoints over a period of 1–168 h. The highest saponin levels were found at the 1-h timepoint at the injection site, in the draining (iliac) lymph nodes, and in urine. Saponins were rapidly cleared from these tissues, reaching very low levels by 48–72 h. Systemically, saponins were found at low levels in the plasma, kidneys, liver, and bone marrow, and were barely detectable in other investigated tissues. Cholesterol was also found at high levels at the injection site and in the draining lymph nodes. These levels declined rapidly at first, then plateaued at 24–48 h. Radiolabeled cholesterol was found at very low levels in other tissues at the earliest timepoints, until increasing and stabilizing after the 24-h timepoint, indicating entry into the endogenous cholesterol recycling pool. This study demonstrates a rapid distribution of Matrix-M™ adjuvant from the injection site to the draining lymph nodes, thus excluding a depot effect as central to the mechanism of action for this adjuvant. The diverging clearance patterns for saponins and cholesterol are suggestive of at least partial disassembly of the Matrix-particles, which has implications for the downstream effects of Matrix-M™ adjuvant on adaptive immune responses. Systemic exposure to toxicologically relevant tissues is very low.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"18 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135589356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mannose-functionalization of reconstituted high-density lipoprotein nanoparticles improves payload delivery and enhances M2-to-M1 phenotype reprogramming of RAW 264.7 macrophages polarized by B16-F10 melanoma cells","authors":"Akpedje S. Dossou, Morgan E. Mantsch, Nirupama Sabnis, Rance E. Berg, Rafal Fudala, Andras G. Lacko","doi":"10.3389/fddev.2023.1281066","DOIUrl":"https://doi.org/10.3389/fddev.2023.1281066","url":null,"abstract":"The targeting and conversion of the immunosuppressive (M2) tumor-associated macrophages (TAMs) to an immunostimulatory (M1) phenotype can induce tumor regression in advanced melanoma. We have previously characterized and reported the ability of reconstituted high-density lipoprotein nanoparticles (rHDL NPs) functionalized with DSPE-PEG-mannose (DPM) to deliver payload to macrophages. Herein, we investigate the modulation of macrophage phenotype and payload delivery mechanisms of the rHDL-DPM NPs in RAW 264.7 murine macrophages exposed to the conditioned medium (CM) from murine B16-F10 melanoma cells. The rHDL-DPM NPs loaded with the Stimulator of Interferon genes agonist, DMXAA, reduced protein levels of M2 markers. Through the mannose moiety, the rHDL-DPM-DMXAA NPs enhanced the production of interferon β and CXCL10 compared to the free DMXAA in the B16-F10 CM-educated RAW 264.7 macrophages. Compared to their non-mannosylated counterpart, the rHDL-DPM NPs delivered their payload more efficiently to the B16-F10 CM-educated RAW 264.7 macrophages. Mechanistically, both the scavenger receptor type B class 1 (SR-B1) and the mannose receptor (CD206) facilitated payload delivery to the macrophages via endocytic and non-endocytic mechanisms. Finally, the CM from rHDL-DPM-DMXAA NPs -treated macrophages enhanced paclitaxel (paclitaxel)-mediated cytotoxicity in B16-F10 cells. Together, these in vitro findings demonstrate the potential of the mannose-functionalized rHDL NPs in improving the targeting of M2-like TAMs and treatment outcomes when combined with immunotherapy or PTX in B16-F10 melanoma in vivo models.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135265840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontiers in hepatic drug delivery-grand challenges","authors":"José M. Lanao","doi":"10.3389/fddev.2023.1265446","DOIUrl":"https://doi.org/10.3389/fddev.2023.1265446","url":null,"abstract":"SPECIALTY GRAND CHALLENGE article Front. Drug Deliv., 20 October 2023Sec. Hepatic Drug Delivery Volume 3 - 2023 | https://doi.org/10.3389/fddev.2023.1265446","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"86 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135570278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a depot formulation with an in situ non-lamellar liquid crystal-forming system with phospholipids","authors":"Hiroaki Todo, Rina Niki, Akie Okada, Ibuki Narita, Kazuya Inamura, Ayu Ito, Shoko Itakura, Ichiro Hijikuro, Kenji Sugibayashi","doi":"10.3389/fddev.2023.1270584","DOIUrl":"https://doi.org/10.3389/fddev.2023.1270584","url":null,"abstract":"Non-lamellar liquid crystal (NLLC) structures have gained increasing attention for the controlled release of entrapped drugs. In the present study, an in situ NLLC structure-forming depot formulation through contact with water was developed using a ternary mixture system of soya phosphatidyl choline (SPC), 1, 2-dioleoyl- sn -glycero-3-phosphoglycerol sodium salt (DOPG), and sorbitan trioleate (Span 85), and the long-term release of an entrapped model drug, leuprolide acetate (LA), was investigated using evaluation of in vitro release and in vivo blood concentration–time profiles. Polarized images and small angle X-ray scattering analysis were used to confirm the presence of NLLC structures by contacting the prepared formulation with water. In addition, LA release and blood concentration–time profiles were investigated using in vitro and in vivo experiments, respectively. In situ NLLC constructed formulations by contacting water were achieved using a ternary mixture of SPC, DOPG, and Span 85. In particular, negative curvature was increased with an increase in the amount of Span 85 in the formulation, and an Fd3m structure was obtained with a sustained release of LA. A maintained blood concentration of LA over 21 days was confirmed by subcutaneous ( s.c. ) administration of the formulation. No retained administered formulation at the injection site was confirmed 28 days after administration without any signs of irritation, inflammation, or other apparent toxicity confirmed by visual observation. This result may be helpful for the development of a lipid-based formulation of peptides and proteins with sustained drug release.","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"73 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135731760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelium dynamics differ in time and space when exposed to the permeation enhancers penetramax and EGTA. A head-to-head mechanistic comparison.","authors":"D A Panou, S F Pedersen, M Kristensen, H M Nielsen","doi":"10.3389/fddev.2023.1221628","DOIUrl":"10.3389/fddev.2023.1221628","url":null,"abstract":"<p><p>Absorption of therapeutic peptides like glucagon-like peptide or insulin for diabetes therapy upon oral administration is highly restricted by the tight junction (TJ) proteins interconnecting the cells comprising the intestinal epithelium. An approach to improve transepithelial permeation of such biopharmaceuticals via the paracellular pathway is to use functional excipients, which transiently modulate the TJs. Here, we investigated the membrane-interacting peptide, penetramax, and the divalent cation chelator, ethylene glycol tetraacetic acid (EGTA) at different concentrations, to reveal and compare their cellular modes of action when increasing the transepithelial permeation of drug macromolecules. The epithelial integrity was studied in real time along with dextran permeation across differentiated epithelial Caco-2 cell monolayers. TJ protein expression and cytoskeleton organization were investigated during and after exposure to penetramax or EGTA. Based on orthogonal methods, we show that penetramax acts by a mechanism that immediately and transiently widens the paracellular space, resulting in size selective permeant passage and with subsequent reconstitution of the epithelium. At the same time, the expression and organization of different TJ proteins are modulated reversibly. In contrast, the effect of EGTA on modulating the paracellular space is slower and TJ protein unspecific, and without clear permeant size selectivity. Overall, these data provide in-depth insights for understanding intestinal barrier dynamics of importance when evaluating new or existing excipients for oral delivery of biopharmaceuticals, such as peptide therapeutics.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":"1 1","pages":"1221628"},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41878996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid-based oral formulation in capsules to improve the delivery of poorly water-soluble drugs.","authors":"Popat Mohite, Sudarshan Singh, Anil Pawar, Adinath Sangale, Bhupendra G Prajapati","doi":"10.3389/fddev.2023.1232012","DOIUrl":"10.3389/fddev.2023.1232012","url":null,"abstract":"<p><p>Poorly water-soluble drugs demonstrate significant challenge in pharmaceutical development, which is linked to their limited oral bioavailability and therapeutic efficacy. To overcome these limitations, lipid-based formulations have emerged as a promising approach to enhance the delivery of such drugs. Moreover, encapsulation within capsules to provide a convenient dosage form for oral administration. The encapsulation techniques are optimized to ensure uniform drug content and efficient encapsulation efficiency. Several investigations demonstrated that the lipid-based formulations in capsules significantly improved the solubility and dissolution rate of poorly water-soluble drugs compared to non-lipid formulations. Additionally, the encapsulation of lipid-based formulations protected the drug against degradation and improved its stability. Overall, incorporating lipid-based formulations in capsules represents a promising strategy for enhancing the delivery of poorly water-soluble drugs with improvement in solubility, dissolution, stability, and bioavailability, overcoming the challenges associated with these challenging drug molecules. The review focussed a brief on utilization of lipids in capsule form to improve therapeutic efficacy of poorly soluble, dissolution and bioavailability of drugs.</p>","PeriodicalId":73079,"journal":{"name":"Frontiers in drug delivery","volume":" ","pages":"1232012"},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44556155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}