Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"Preclinical Safety.","authors":"Ronald K Wolff, James D Blanchard","doi":"10.1089/jamp.2025.52511.isam","DOIUrl":"10.1089/jamp.2025.52511.isam","url":null,"abstract":"<p><p>Several inhaled proteins and peptides have been developed to treat indications in the respiratory tract or systemically with varying degrees of success. This section will summarize the preclinical and clinical studies for inhaled Pulmozyme® (recombinant human deoxyribonuclease, rhDNase), insulin, human growth hormone (hGH), cyclosporine, alpha-1 antitrypsin, measles vaccine, and anti-immunoglobulin E (IgE). For Pulmozyme® (rhDNase), monkeys had positive serum antibody titers to rhDNase and allergic/hypersensitivity (type I) lung lesions in response to foreign protein likely due to differences in homology between monkey and human DNases. However, in patients, the levels of rhDNase antibodies were low and of no consequence. For inhaled insulin in rats, dogs and monkeys, there were no adverse effects related to insulin or excipients. In clinical trials, over 13,000 patients were safely treated with inhaled insulin for an average of 1 year. Some patients had higher antibody levels than comparators, but these antibodies did not decrease the effectiveness, safety or tolerability of inhaled insulin over time and/or affect clinical outcomes. Inhaled hGH had no adverse effects in monkeys, healthy volunteers or pediatric patients, but its absorption from the lungs was too low (<5%) in pediatric patients to be successful as a medical product. Inhaled cyclosporine had no unexpected systemic toxicity or clinically limiting findings in the respiratory tract in rat and dogs; it also had promising Phase 2 clinical data but failed in Phase 3. Inhaled alpha-1 antitrypsin also failed in a recent Phase 2/3 trial. A liquid inhaled measles vaccine was safe, well tolerated and produced an appropriate immune response in Phase 2/3 studies for children ages 10-35 months, but not younger. A dry powder inhaled vaccine in monkeys had no adverse effects and produced an immune response; Phase 1 trials are underway. Inhaled anti-IgE was well tolerated in monkeys and asthma patients, but systemic delivery had superior results in patients.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"38 3","pages":"136-144"},"PeriodicalIF":2.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"History of the International Society of Aerosols in Medicine (ISAM): Celebrating the 25th Congress.","authors":"Barbara Rothen-Rutishauser, Chantal Darquenne, David Cipolla, Omar Usmani","doi":"10.1089/jamp.2025.0007","DOIUrl":"10.1089/jamp.2025.0007","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"103-105"},"PeriodicalIF":2.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Respiratory Therapy with Digital Inhalers: Insights from Multimodal Experimental and <i>In Vitro</i> Analysis.","authors":"David Ney Gonzalez, Martijn Grinovero, Luca Ponti, Cristina Cova, Valeria Sesana, Marco Franza, Mauro Citterio, Yannick Baschung","doi":"10.1089/jamp.2024.0042","DOIUrl":"10.1089/jamp.2024.0042","url":null,"abstract":"<p><p><b><i>Background:</i></b> The RS01X is a digital dry powder inhaler (DPI) that records inhalation parameters such as technique or adherence. This offers patients and health care providers a way to have a feedback on inhalation treatments. This study used real-life data gained from 28 healthy volunteers for adherence assessment, technique evaluation, and <i>in vitro</i> testing. <b><i>Methods:</i></b> The study enrolled 28 healthy volunteers. Participants were shown how to use an inhaler and provided with empty capsules. The inhalers record several inhalation parameters such as peak inspiratory flow (PIF), volume, duration, and orientation. Half of the participants were selected to be in an \"intervention\" group with access to their inhalation data as well as feedback to improve their inhalation. The other half were a \"control\" group without access to their data nor any feedback. The data were then used for <i>in vitro</i> testing. <b><i>Results:</i></b> Overall, 28 participants were enrolled, and inhalation data were available for 13 interventions and 15 controls. Average adherence was 82.0% and 69.5% for intervention and control, respectively. The technique of inhalation was 65.58% good, 19.89% fair, and 14.53% poor for the intervention group and 36.73% good, 26.99% fair, and 36.28% poor for the control group. The variability of PIF was 9% for intervention and 30% for control. <i>In vitro</i> simulations showed the importance of proper angle orientation in inhalation, which was supported by <i>in vivo</i> data. The fine particle fraction of active pharmaceutical ingredients was similar to the inhalation profile of the intervention in comparison with a theoretical perfect inhalation. <b><i>Conclusion:</i></b> This study results showed clear improvement in inhalation technique and adherence for patients using digital DPI. In addition, <i>in vitro</i> testing provided concrete data illustrating the measurable advancements digitalization offers in enhancing patient adherence and inhalation technique.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"127-135"},"PeriodicalIF":2.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scale-Up and Postapproval Changes in Orally Inhaled Drug Products: Scientific and Regulatory Considerations.","authors":"Gur Jai Pal Singh, S Prasad Peri","doi":"10.1089/jamp.2024.0036","DOIUrl":"10.1089/jamp.2024.0036","url":null,"abstract":"<p><p>Approved drug products may be subject to change(s) for a variety of reasons. The changes may include, but are not limited to, increase in batch size, alteration of the drug product constituent(s), improvement in the manufacturing process, and shift in manufacturing sites. The extent of pharmaceutical testing and the regulatory pathway for timely implementation of any change in the approved product and/or process depends upon the nature and extent of change. The U.S. Food and Drug Administration (FDA) has published guidelines that outline its expectations for the Scale-Up and Postapproval Changes (SUPAC) in the solid oral immediate and modified release (MR) products, and semisolid formulations. However, to date, no such guidelines have been issued to address SUPAC in the orally inhaled drug products (OIDPs), and this article represents a seminal contribution in this direction. It is hoped that it will inspire contributions from the relevant multidisciplinary experts from the pharmaceutical industry and the agency in accomplishing formal regulatory guidelines relevant to the OIDP SUPAC. The OIDPs are complex drug-device combination products. Therefore, a conceptualization of SUPAC guidelines for these products warrants consideration of contributions of effect of change(s) in individual components (drug substance, formulation, device) as well as a compound effect that a single or multiple changes may have on product performance, and its safety and efficacy. This article provides a discussion of scientific aspects and regulatory bases relevant to the development of SUPAC for OIDPs, and it attempts to outline considerations that may be applicable in addressing issues related to the OIDP SUPAC in the context of human drugs. The authors' statements should not be viewed as recommendations from any regulatory agency, as the applicable guidelines would be determined on case-by-case evaluation by the relevant authorities.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"39-63"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12127781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inspiratory Profiles Through Easyhaler Dry Powder Inhaler During Acute Bronchoconstriction.","authors":"Ville A Vartiainen, Antti Tikkakoski, L Pekka Malmberg, Liisa Vuotari, Satu Lähelmä, Ulla Sairanen, Mikko Vahteristo, Jussi Karjalainen, Lauri Lehtimäki","doi":"10.1089/jamp.2024.0045","DOIUrl":"10.1089/jamp.2024.0045","url":null,"abstract":"<p><p><b><i>Background:</i></b> Dry powder inhalers (DPIs) are passive devices, which rely on a patient's inspiratory effort for drug dispersion and delivery. The aim of this study was to assess how acute bronchoconstriction affects the ability to use Easyhaler DPI in adults. <b><i>Methods:</i></b> This study was conducted as part of a parallel-group clinical trial assessing use of Salbutamol Easyhaler, Budesonide-formoterol Easyhaler and salbutamol pMDI with spacer during a methacholine challenge (MC) test. The inhalations through both Easyhaler variants, the inhaler for the single active substance product (EH-mono) and the inhaler for the combination product (EH-combi), were recorded at baseline and during bronchoconstriction. Peak inspiratory flow (PIF), flow rate acceleration and inhalation volume after PIF were compared to the criteria for successful inhalation. <b><i>Results:</i></b> The study population consisted of 120 adult subjects indicated for MC as a diagnostic test for asthma, with 60 subjects in both Easyhaler arms. With EH-combi 98.3% and 91.4% passed the criteria (PIF ≥30 L/min, inhalation acceleration ≥0.7 L/s², and inhalation volume ≥500 mL after PIF) for successful inhalation at baseline and during bronchoconstriction, respectively. With EH-mono, success rates were 95.0% and 88.1% at baseline and during bronchoconstriction, respectively. The most common reason for not passing the criteria was slow inhalation acceleration. Aside from two subjects using EH-mono during bronchoconstriction, all subjects were able to generate PIF ≥ 30 L/min. <b><i>Conclusions:</i></b> During an acute obstructive event, the vast majority of patients have no difficulty in achieving sufficient PIF, inhalation acceleration, and volume after PIF when using an Easyhaler DPI.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"83-89"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In Vitro</i> Comparison of Inspiration-Synchronized and Continuous Vibrating Mesh Nebulizer During Adult Invasive Mechanical Ventilation.","authors":"Jie Li, Caylie A Sheridan, Osama Alanazi, James B Fink","doi":"10.1089/jamp.2024.0047","DOIUrl":"10.1089/jamp.2024.0047","url":null,"abstract":"<p><p><b><i>Background:</i></b> Aerosol delivery may be enhanced by utilizing an inspiration-synchronized nebulization mode, where nebulization occurs only during inspiration. This study aimed to compare aerosol delivery of albuterol via a prototype of an inspiration-synchronized vibrating mesh nebulizer (VMN) versus continuous VMN during invasive mechanical ventilation. <b><i>Methods:</i></b> A critical care ventilator equipped with a heated-wire circuit to deliver adult parameters was attached to an endotracheal tube (ETT), a collection filter, and a test lung. The nebulizer was placed at the humidifier's inlet, inspiratory limb at the Y-piece, and between the Y-piece and ETT. Conventional VMNs producing standard size aerosol particles (Solo; Aerogen Ltd) were compared with prototype small-particle VMNs (Aerogen Pharma) in both inspiration-synchronization and continuous modes. In each run, 1 mL of albuterol (2.5 mg) was used (<i>n</i> = 5). The drug was eluted from the collection filter and assayed with UV spectrophotometry (276 nm). <b><i>Results:</i></b> The inhaled dose with inspiration-synchronization mode was 1.4 to 3.6 times that with the continuous mode, regardless of nebulizer positions (all <i>p</i> < 0.001). The small-particle VMN delivered an 8%-69% greater inhaled dose than the conventional VMN (Solo), regardless of the nebulizer placement or aerosol generation mode (all <i>p</i> < 0.001). The highest inhaled dose (50%-60%) with the inspiration-synchronized VMN was observed when it was placed at the ETT (all <i>p</i> < 0.001), whereas the continuous VMN performed better when positioned near the humidifier, with an inhaled dose of 21%-37% (<i>p</i> < 0.001). <b><i>Conclusion:</i></b> The inspiration-synchronized VMN delivered a greater inhaled dose than continuous VMN, irrespective of nebulizer placement. The prototype VMN producing smaller aerosol particles resulted in a greater inhaled dose than the conventional VMN (Solo), regardless of placement or aerosol generation modes. The inspiration-synchronized VMN achieved the highest delivery when placed close to the airway, whereas the continuous VMN delivered the most when positioned near the ventilator.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"64-70"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhaled Chemotherapy.","authors":"Janakiraman Subramanian, Rajiv Dhand","doi":"10.1089/jamp.2025.19211.js","DOIUrl":"10.1089/jamp.2025.19211.js","url":null,"abstract":"<p><p>Cytotoxic chemotherapy remains the cornerstone of treatment for patients diagnosed with advanced stage cancers and is an important component in the multi-disciplinary treatment of several early stage cancers. In the majority of patients with cancer, cytotoxic chemotherapy is administered intravenously and in some instances by oral administration. Systemic administration of cytotoxic chemotherapy is well known to cause adverse effects, which can be severe and debilitating. Regional therapy with cytotoxic agents has the potential to reduce the extent of systemic exposure to the drug and reduce the risk of systemic adverse effects. Regional chemotherapy has been successfully employed in the treatment of certain solid tumors such as hepatocellular carcinoma. However, regional chemotherapy has not been commonly utilized for treatment of lung tumors. Inhaled cytotoxic chemotherapy has the potential to become an effective regional therapy for both primary lung cancer and metastases to the lung from other primary tumors. Aerosol administration of chemotherapy could potentially avoid some of the adverse effects seen with systemic therapy. In addition, some chemotherapeutic agents when administered as an aerosol are absorbed directly into the arterial circulation and have therapeutic effects at extrapulmonary sites. Aerosol administration of several different chemotherapeutic agents is currently under evaluation either in the preclinical setting or in early phase human trials. Some of these studies have shown that inhaled chemotherapy is feasible and effective in treating lung tumors. In this chapter, we review the published studies and ongoing trials on inhaled chemotherapy to better understand the current status of this field of cancer treatment.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"38 2","pages":"90-101"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Systemic Exposure Between Epinephrine Delivered via Metered-Dose Inhalation and Intramuscular Injection.","authors":"Jack Yongfeng Zhang, Mary Ziping Luo, Tony Marrs, Edward M Kerwin, Don A Bukstein","doi":"10.1089/jamp.2024.0025","DOIUrl":"10.1089/jamp.2024.0025","url":null,"abstract":"<p><p><b><i>Background:</i></b> Primatene^® MIST, an epinephrine metered-dose inhaler (MDI), has long been questioned by some medical professionals for asthma treatment despite having been approved by the Food and Drug Administration. One of the primary reasons for their concerns stemmed from potential cardiovascular complications following epinephrine administration. However, the majority of documented cardiovascular complications seemed to occur following the injection route of the epinephrine. The aim of this study was to evaluate the systemic exposure of epinephrine delivered through different administration routes and to understand its relationship with cardiovascular effects. Since albuterol inhalers are commonly recommended for asthma, albuterol was also studied as a comparator drug. <b><i>Method:</i></b> A randomized, evaluator-blinded, three-arm crossover study was conducted in 28 healthy adult subjects to compare the profiles of systemic exposure for epinephrine delivered by MDI versus epinephrine intramuscular (IM) injection and albuterol MDI. Serially sampled plasma epinephrine and albuterol levels were measured and compared between treatment groups. Safety was assessed by adverse events, serial vital signs, electrocardiograms (ECGs), and clinical laboratory tests obtained at each crossover dosing visit. <b><i>Results:</i></b> Systemic exogenous drug exposure for inhaled epinephrine MDI (39 pg/mL × hour) was ∼9 times lower than that of epinephrine IM (435 pg/mL × hour) and 122 times lower than that of albuterol MDI (3453 pg/mL × hour) after dose normalization. The C_max in epinephrine MDI (345 pg/mL) was approximately half of that of epinephrine IM (816 pg/mL) and that of albuterol MDI (681 pg/mL). Plasma drug concentrations for epinephrine MDI dropped rapidly to baseline (∼0.6 hour), while epinephrine IM took ∼8 hours, and albuterol MDI required more than 24 hours. Epinephrine MDI and albuterol MDI resulted in minimal, clinically insignificant changes in vital signs and ECGs, whereas epinephrine IM led to mild transient increases in systolic blood pressure, heart rate, and corrected QT interval. <b><i>Conclusion:</i></b> Epinephrine MDI (Primatene MIST) had ∼9 times lower systemic drug exposure (SDE) than that of epinephrine IM and ∼122 times lower than that of albuterol MDI. The lower SDE of inhaled epinephrine also correlated with reassuring safety findings, with no significant cardiovascular adverse effects found, compared with transient effects seen after IM epinephrine. <b>Clinical trial registration number:</b> NCT04207840.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"71-82"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgment of Reviewers 2024.","authors":"","doi":"10.1089/jamp.2024.11568.revack","DOIUrl":"https://doi.org/10.1089/jamp.2024.11568.revack","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"38 1","pages":"37"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmaceutical, Clinical, and Regulatory Challenges of Reformulating Pressurized Metered-Dose Inhalers to Reduce Their Environmental Impact.","authors":"Nicolas Roche, Omar Usmani, Laura Franzini, Lorenza Labadini, Kusum S Mathews, Sara Panigone, Job F M van Boven","doi":"10.1089/jamp.2024.0023","DOIUrl":"10.1089/jamp.2024.0023","url":null,"abstract":"<p><p>The chlorofluorocarbons (CFCs) that were used as propellants in early pressurized metered-dose inhalers (pMDIs) had substantial ozone-depleting potential. Following the Montreal Protocol in 1987, the manufacture of a range of ozone-depleting substances, including CFCs, was gradually phased out, which required the propellants used in pMDIs to be replaced. Current pMDIs use hydrofluoroalkanes (HFAs) as propellants, such as 1,1,1,2-tetrafluoroethane (HFA-134a). Although these HFAs have no ozone-depleting potential, they have a high global warming potential (GWP), and consequently, their use is being phased down. One option for the discontinuation of HFA use in inhalers would be to discontinue all pMDIs, switching patients to dry powder inhalers (DPIs). However, a switch from pMDIs to DPIs may not be a clinically appropriate option for some patients; furthermore, the full lifecycle carbon footprint and the overall environmental impact of different inhalers should be considered. An alternative is therefore to reformulate the current HFA pMDIs to use low-GWP propellants, such as 1,1-difluoroethane (HFA-152a). This article summarizes the various steps and challenges associated with this change, illustrated using data from the inhaled triple combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide, a complex formulation of three molecules in a solution that contains liquid-phase propellant.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":"26-36"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}