Pharmaceutical Research最新文献

{"title":"Development of an In Vitro Permeation Test Framework For Naloxone Hydrochloride Intranasal Spray: Establishing IVIVR for Bioequivalence Assessment.","authors":"Tasmin Ara Sultana, Manar Al-Ghabeish, Steven Chopski, Ross Walenga, Diaa Shakleya, Bryan Newman, Muhammad Ashraf, Ahmed Zidan","doi":"10.1007/s11095-026-04153-w","DOIUrl":"10.1007/s11095-026-04153-w","url":null,"abstract":"<p><strong>Purpose: </strong>Intranasal (IN) naloxone achieves rapid systemic exposure necessary for effective opioid overdose reversal; yet establishing bioequivalence (BE) for fast-acting drug-device combination products remains challenging due to the interplay of formulation attributes, device performance, and nasal physiology. This study developed an in vitro permeation test (IVPT) approach designed to quantitatively relate the nasal permeation behavior of naloxone to its clinical pharmacokinetic (PK) performance through an in vitro-in vivo relationship (IVIVR).</p><p><strong>Methods: </strong>Naloxone hydrochloride (Narcan®, 4 mg/0.1 mL) was deposited onto artificial membranes and EpiAirway™ mucociliary tissues using a controlled aerosol-deposition system (VITROCELL® Cloud Alpha 12). Naloxone permeation was assessed under sink conditions using a validated LC-MS/MS method. Cumulative permeation at 20 and 120 min (F₂₀ and F₁₂₀, respectively) was correlated with clinical maximum plasma concentration (C_max) and area under the curve from time zero to infinity (AUC₀_-∞) to construct IVIVR models, supplemented by exploratory point-to-point in vitro-in vivo extrapolation (IVIVE) using Wagner-Nelson deconvolution.</p><p><strong>Results: </strong>Permeation profiles differed by substrate, with the hydrophilic membranes showing higher dissolution rates and EpiAirway™ tissues demonstrating dose-proportional transport despite lower deposited mass. The tissue-based IVIVR models showed strong linearity (R2 > 0.98) and mean prediction errors within accepted limits (≤ 10%), while artificial membranes consistently overpredicted the systemic exposure. IVIVE analysis further supported close temporal agreement with clinical absorption patterns.</p><p><strong>Conclusion: </strong>These findings indicate that a tissue-based IVPT-IVIVR framework may provide a translational tool for relating in vitro permeation behavior to systemic exposure, supporting its utility in formulation development and BE risk assessment of rapidly acting IN naloxone products.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"3245-3261"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional biological roles of Fusaric acid and its derivatives in the Diverse Kingdoms of Life: Insights from More Than Nine Decades of Research.","authors":"Truong Thanh Tung, Pham Bao Phuong, Dinh Ngoc Minh, Nguyen Cao Huy, Nguyen Phuong Anh, Nguyen Khanh Linh, Nguyen Minh Duc","doi":"10.1007/s11095-026-04209-x","DOIUrl":"10.1007/s11095-026-04209-x","url":null,"abstract":"<p><p>Fusaric acid (5-butylpicolinic) is a mycotoxin produced by Fusarium species as a biological response to external environmental factors. It exhibits hepatotoxicity in humans upon consumption of contaminated agricultural products. The compound was first reported nearly 92 years ago by Yabuta et al. Interestingly, Fusarium spp. can produce this compound in very large amounts, up to 1080 μg per gram of total biomass. However, the primary biological function of fusaric acid is still not fully understood. Numerous studies have attempted to clarify the biological functions of fusaric acid across various species, including virus, fungi, bacteria, mammals, and humans. Several preclinical studies and clinical trials have evaluated its therapeutic potential for human diseases. However, despite these efforts, fusaric acid has not progressed into an approved therapeutic agent, highlighting both its biological complexity and the challenges associated with its clinical development. To date, none of the works have comprehensively enumerated the multifunctional biological roles of fusaric acid and its derivatives. In this review, marking the 90th + anniversary of its discovery, we discuss the most notable roles of fusaric acid across diverse kingdoms of life.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"3011-3034"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical evaluation of the impact of ssDNA cargo length on AAV stability - a case study.","authors":"Jiayi He, Mahsa Azami, Kostika Vangjeli, Sharmin Afroz, Lionel Galibert, Ali Banazadeh, Amr Ali, Tram-Anh Nguyen, Kangwen Deng, Rajeeva Singh, Chen Zhou","doi":"10.1007/s11095-026-04176-3","DOIUrl":"10.1007/s11095-026-04176-3","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate how ssDNA cargo size influences the physicochemical characteristics and stability behavior of AAVX vectors under thermal, chemical, and other accelerated stress conditions.</p><p><strong>Methods: </strong>AAVX vectors with differing ssDNA cargo length (i.e. 2.8 kb and 4.6 kb) were analyzed under manufacturing-relevant, storage-related, and accelerated stress conditions using complementary analytical methods to assess capsid stability, genome integrity, potency, and capsid chemical modifications.</p><p><strong>Results: </strong>Thermal and chemical denaturation experiments showed similar capsid unfolding across the cargo sizes tested. Under accelerated thermal stress (40°C), the shorter-genome vector showed less ssDNA release and better preservation of capsid and genome titers than the longer-genome vector. Fragmentation of encapsulated ssDNA was also observed for the shorter cargo. Capsid chemical modifications, including asparagine deamidation and aspartic acid isomerization, increased markedly at 40°C.</p><p><strong>Conclusions: </strong>These findings provide a case-study view of how cargo size can affect AAV stability readouts in a condition-dependent behavior and highlight the value of multi-attribute characterization for evaluating AAV vector stability. In addition, our results also suggest that suggest that, under the conditions tested for AAVX, the same capsid may be useful for evaluating vector stability with different genome sizes.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"3263-3272"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrostatic Interactions Guide the Detrimental Effect of Oleic Acid on Monoclonal Antibody Stability.","authors":"Jiayi He, Jing Song, Jingtao Zhang, Katelyn J Smith","doi":"10.1007/s11095-026-04160-x","DOIUrl":"10.1007/s11095-026-04160-x","url":null,"abstract":"<p><p>PURPOSE OR OBJECTIVE: To investigate how polysorbate 80 (PS-80) hydrolysis byproducts, especially oleic acid, affect monoclonal antibody (mAb) stability and contribute to protein particle formation.</p><p><strong>Methods: </strong>The study evaluated oleic acid-associated protein particle formation using microflow imaging (MFI), Scanning Electron Microscopy-Energy Dispersive X-ray spectroscopy (SEM-EDX), field-flow fractionation (FFF), and Fourier Transform Infrared (FT-IR) particle characterization. The proposed electrostatic interaction mechanism was examined by varying ionic strength with saline and arginine, adjusting pH, and considering mAb isoelectric points.</p><p><strong>Results: </strong>Oleic acid was associated with the formation of proteinaceous particles. The data supported the idea that oleic acid induces mAb aggregation through electrostatic interactions. Oleic acid-induced protein aggregate formation was reversible in the presence of additional salt, suggesting that increased ionic strength disrupts the charged interactions driving aggregation.</p><p><strong>Conclusions: </strong>PS-80 degradation byproducts, particularly oleic acid, can promote reversible mAb aggregation and particle formation through electrostatic interactions. These findings improve understanding of particle formation in protein formulations and may help guide buffer selection, ionic strength, pH optimization, and prediction of stability in intravenous solutions such as saline.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"3287-3298"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On-Demand Hospital Manufacturing of Baclofen Lozenges Using Pharmaceutical 3D Printing.","authors":"Daniel Grandal-Gonzalez, Carlos Bendicho-Lavilla, Eduardo Diaz-Torres, Rocio Sanin-Fontela, María L Couce, María José de Castro-López, Isabel Gonzalez-Alvarez, Marta Gonzalez-Alvarez, Alejandro Ruiz-Picazo, Marival Bermejo, Pedro Garcia-Salom, Abdul W Basit, Carmen Alvarez-Lorenzo, Alvaro Goyanes","doi":"10.1007/s11095-026-04164-7","DOIUrl":"10.1007/s11095-026-04164-7","url":null,"abstract":"<p><strong>Purpose: </strong>Dysphagia in neurological patients complicates oral drug administration. Manual preparation of lozenges/troches lacks precision and scalability. This study investigates the feasibility of implementing a pharmaceutical 3D printer in a hospital pharmacy for the automated production of personalized baclofen troches.</p><p><strong>Methods: </strong>Baclofen troches were manufactured in a hospital pharmacy setting, both manually and via pharmaceutical 3D printer. Quality was evaluated using Process Analytical Technologies (PAT). Performance was assessed through European Pharmacopoeia (EP) tests for drug content, mass uniformity, in vitro dissolution, disintegration, and a six-month stability study.</p><p><strong>Results: </strong>Printed troches complied with all EP acceptance criteria for drug content and mass uniformity, whereas manual formulations failed, particularly at the lowest dose. Printed troches demonstrated immediate drug release, consistent quality across batches, and remained stable for six months. 3D printing showed superior precision over traditional manual compounding.</p><p><strong>Conclusions: </strong>This research describes the first successful implementation of an automated blister-filling workflow using a pharmaceutical 3D printer within a hospital pharmacy setting, spanning from manufacturing and dispensing to direct patient administration. The automated approach provides a significant advancement in personalized medicine, ensuring safer, more accurate, and efficient treatment options for patients with specific needs like dysphagia.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"3411-3425"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosurfactant-Based Interventions for Improving Lung Function and Controlling Inflammation.","authors":"Nathalia Marton Sant'Ana, Paula Rezende-Teixeira","doi":"10.1007/s11095-026-04202-4","DOIUrl":"10.1007/s11095-026-04202-4","url":null,"abstract":"<p><p>Biosurfactants are promising biotechnological compounds for respiratory diseases due to their ability to act as antimicrobials, antivirals, and anti-inflammatories, as well as their capacity to reduce pulmonary surface tension. In vitro evidence shows that molecules such as surfactin, rhamnolipids, sophorolipids, and MELs can partially mimic natural pulmonary surfactant, promote alveolar stabilization, and improve respiratory mechanics. Furthermore, these compounds modulate essential inflammatory pathways, including NF-κB, MAPK, and inflammasomes (NLRP3 and AIM2), leading to decreased production of the pro-inflammatory cytokines IL-1β, TNF-α, and IL-6. Activity against Pseudomonas aeruginosa, Staphylococcus aureus, Mycobacterium tuberculosis, respiratory fungi, and enveloped viruses support their use as therapeutic agents in infectious or inflammatory conditions of the respiratory tract. Despite their potential, several challenges persist, particularly the high production costs, difficulties in structural standardization, the limited stability of inhalable forms, and the lack of clinical trials evaluating safety and efficacy in humans. The development of more advanced disease prediction models, such as pulmonary organoids and \"lung-on-a-chip\" systems, emerges as an essential path for translational evaluation. Thus, although many obstacles remain, this body of evidence demonstrates that biosurfactants represent an innovative and promising platform for improving lung function or modulating inflammatory processes in various respiratory diseases.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"3035-3056"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Solution to Sublimation: Thermodynamic Evaluation of Iproniazid Multicomponent Crystals for Robust Pharmaceutical Solid Form Development.","authors":"Ksenia V Drozd, Anna G Ramazanova, Liudmila E Shmukler, German L Perlovich","doi":"10.1007/s11095-026-04177-2","DOIUrl":"10.1007/s11095-026-04177-2","url":null,"abstract":"<p><strong>Purpose: </strong>To comprehensively characterize the solution and sublimation thermodynamics of 1:1 multicomponent crystals of the antidepressant drug iproniazid (IPN) with six positional isomers of dihydroxybenzoic acid (DHBA) in acetonitrile, and to establish structure-thermodynamic relationships guiding coformer selection in pharmaceutical development.</p><p><strong>Methods: </strong>Temperature-dependent solubilities were measured over 293.15-313.15 K using the shake-flask method. Activity coefficients were derived via the Schrӧder-van Laar equations. Standard formation thermodynamic parameters were calculated from solubility data. Sublimation parameters were indirectly evaluated using a thermodynamic cycle linking dissolution, solvation, and sublimation.</p><p><strong>Results: </strong>Activity coefficients showed positive deviations from ideality for most compounds, while 25DHBA and 35DHBA exhibited negative deviations, indicating favorable solute-solvent interactions. All stable systems formed spontaneously through an enthalpy-driven mechanism. Sublimation enthalpies were highly endothermic (233.2-266.5 kJ·mol^-1) and correlated with the calculated total lattice energies, providing a quantitative measure of crystal lattice strength relevant to pharmaceutical processing and storage.</p><p><strong>Conclusions: </strong>Positional isomerism of the DHBA coformer governs the thermodynamic stability of IPN multicomponent crystals through a balance of intra- and intermolecular interactions. The integrated thermodynamic cycle approach offers an experimentally accessible framework for evaluating sublimation parameters, providing practical guidance for coformer selection, solid form screening, and predicting physical stability in pharmaceutical development.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"3333-3347"},"PeriodicalIF":4.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing a Fixed and Freely Rotating Capsule in a Dry Powder Inhaler Under Realistic Breathing Conditions.","authors":"Karan Shrivastava, Ajit Kumar, Somashekhar S Hiremath, Agisilaos Kourmatzis, Gajendra Singh","doi":"10.1007/s11095-026-04184-3","DOIUrl":"https://doi.org/10.1007/s11095-026-04184-3","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the performance of a capsule-based dry powder inhaler (DPI) under two device configurations - free-axis and fixed-axis capsule rotation - across steady-state and transient inhalation profiles.</p><p><strong>Method: </strong>Two new research-based transparent capsule-based DPI were developed-one with a fixed capsule rotational axis and another with a floating capsule configuration. High-speed imaging was used to capture capsule motion, and the effects of flow regimes (laminar, transient, and turbulent), capsule rotation, and breathing profiles on capsule RPM, wall collisions, and powder retention were analyzed.</p><p><strong>Conclusions: </strong>Fixed-axis rotation significantly outperformed free-axis rotation (~ 6 × higher RPM and lower powder retention). Higher flow rates and faster-accelerating transient profiles increased RPM and collision frequency, enhancing drug release. Fixing the rotational axis of the capsule had the greatest benefit for the slow inhalation profile. The findings offer key insights for the design of future capsule-based DPIs.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of Relative Activity Factors to Determine Fraction Glucuronidation and Clearance of Icenticaftor in Humans.","authors":"Mitesh Patel, Sahil Shaikh, Felix Huth, Sujal Deshmukh","doi":"10.1007/s11095-026-04136-x","DOIUrl":"10.1007/s11095-026-04136-x","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study is to quantify the contribution of individual UDP-glucuronosyl transferase (UGT) enzymes involved in the glucuronidation of icenticaftor, which is primarily glucuronidated in the human liver to two distinct glucuronide metabolites that are ultimately excreted in the urine.</p><p><strong>Methods: </strong>The formation of icenticaftor-glucuronide in recombinant UGT systems was scaled with relative activity factor (RAF) of involved UGT enzymes to determine the fraction glucuronidation in human liver.</p><p><strong>Results: </strong>Scaling of the glucuronidation activity of UGT enzymes in recombinant UGT systems demonstrated that hepatic UGT1A9 contributed to about two-third of the overall icenticaftor glucuronidation while the remaining was accounted by UGT2B7. Moreover, the predicted UGT-mediated clearance of icenticaftor, upon scaling the intrinsic clearance (CL_int) with RAF, correlates well with that estimated in humans.</p><p><strong>Conclusion: </strong>Collectively, current data are indicative of the utility of activity-based scalars to predict fraction glucuronidation and clearance of icenticaftor in the clinic. UGT1A9 is identified as the major UGT enzyme in the glucuronidation of icenticaftor in human liver.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2751-2759"},"PeriodicalIF":4.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-Analysis and Physiologically-Based Modeling of the Pharmacokinetics and Pharmacodynamics of Dexamethasone in Horses.","authors":"Ruihong Yu, Pierre-Louis Toutain, Carl Ekstrand, William J Jusko","doi":"10.1007/s11095-026-04120-5","DOIUrl":"10.1007/s11095-026-04120-5","url":null,"abstract":"<p><strong>Purpose: </strong>Dexamethasone (DEX) is widely used in equine practice for its potent anti-inflammatory effects and diverse studies have examined its pharmacology in horses. We integrated all available pharmacokinetic (PK) and pharmacodynamic (PD) data from 12 studies to quantify DEX disposition and endocrine effects in horses.</p><p><strong>Methods: </strong>DEX concentrations in blood, urine and synovial fluid, plus cortisol (CTS) and glucose (GLU) in plasma, following various administration routes (intravenous (IV), intramuscular (IM), intra-articular, oral) were available from original studies or digitized from literature. A minimal physiologically-based PK model and linked indirect response PD models were applied.</p><p><strong>Results: </strong>The mean clearance of DEX was 344 mL/h/kg via hepatic metabolism (98%) and renal excretion (2%). Due to nonlinear tissue binding, DEX generally exhibited a prolonged terminal phase in plasma, maintaining concentrations above a designated plasma threshold of 5 pg/mL for 67 h following 0.05 mg/kg IV dose. Dosing input parameters of DEX varied markedly across dosing routes and prodrug formulations (alcohol, isonicotinate, phosphate), with bioavailability ranging 37 ~ 100%. Oral and pro-drug doses produced rapid absorption, except for IM DEX-isonicotinate that exhibited slow (flip-flop) availability. Adrenal suppression with an IC₅₀ of 0.038 ng/mL and plasma GLU increases with an EC₅₀ of 0.79 ng/mL were observed that commonly persisted for 2 ~ 4 days after single dose.</p><p><strong>Conclusions: </strong>This meta-analysis utilized a mechanistic and physiologically-based modeling framework to provide global perspectives that may promote the rational use of DEX in equine medicine and support evidence-based regulatory decisions.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2733-2750"},"PeriodicalIF":4.1,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}