Pharmaceutical Research最新文献

{"title":"The Role of Artificial Intelligence and Machine Learning in Accelerating the Discovery and Development of Nanomedicine.","authors":"Vivek Agrahari, Yahya E Choonara, Mitra Mosharraf, Sravan Kumar Patel, Fan Zhang","doi":"10.1007/s11095-024-03798-9","DOIUrl":"10.1007/s11095-024-03798-9","url":null,"abstract":"<p><p>The unique potential of nanomedicine to address challenging health issues is rapidly advancing the field, leading to the generation of more effective products. However, these complex systems often pose several challenges with respect to their design for specific functionality, scalable manufacturing, characterization, quality control, and clinical translation. In this regard, the application of artificial intelligence (AI) and machine learning (ML) approaches can enable faster and more accurate data assessment, identifying trends and predicting outcomes, leading to efficient nanomedicine product development. This perspective paper discusses the potential of AI and ML in nanomedicine product development with a focus on their applications in discovery, assessment, manufacturing, and clinical trials. The potential limitations of AI and ML approaches in nanomedicine product development are also covered.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2289-2297"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771237","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":"Development and In-Vitro Evaluation of Doxorubicin-Loaded Methacrylate Gelatin (GelMa)-Acrylamide Hydrogels for the Treatment of Malignant Pleural Mesothelioma.","authors":"Nishant S Kulkarni, Gautam Chauhan, Mural Quadros, Dnyandev G Gadhave, Vivek Gupta","doi":"10.1007/s11095-024-03794-z","DOIUrl":"10.1007/s11095-024-03794-z","url":null,"abstract":"<p><strong>Objective: </strong>Malignant pleural mesothelioma (MPM) is the most prevalent subtype of malignant mesothelioma that affects the pleural lining of the lungs. Conventionally, chemotherapy via systemic injections has shown limited efficacy due to off-target effects, and inefficacious deposition at the disease site. In our previous study, we reported the development and optimization of UV-initiated methacrylate gelatin (GelMa)-acrylamide based hydrogel formulation for local intracavitary administration of therapies. The current study utilizes a pre-established GelMa formulation for delivering a small molecule chemotherapeutic agent, Doxorubicin (Dox), against in-vitro MPM models.</p><p><strong>Methods: </strong>Dox-loaded hydrogel (DLH) precursor solution was prepared by dissolving Dox in the precursor solution. The gels were characterized for physical properties such as gelling time, swelling index, bio adhesion, and injectability and were compared to blank hydrogels. Dox-loaded hydrogels were also tested for therapeutic efficacy in MPM cells in various 2D and 3D cell culture models.</p><p><strong>Results: </strong>It was revealed that Dox-loaded hydrogels retained similar physical properties, including gelling time (< 25 s), swelling index (~ 1,200%), bio-adhesion (> 20 g detachment force), and injectability (< 2N force for injecting precursor), compared to blank hydrogels. Moreover, the gel formulation effectively sustained the release of hydrophilic Dox HCl over a period of 12 days by increasing the degree of crosslinking between GelMa and its crosslinkers. Further, the therapeutic efficacy of Dox was retained even after loading into hydrogels, indicating that no chemical interactions took place between gel excipients and the drug. Studies in MPM cell-based models revealed that DLH showed excellent potential in inhibiting 2D and 3D cell growth, with DLH being more effective than plain Dox in suppressing tumor growth in 3D spheroid models.</p><p><strong>Conclusions: </strong>Overall, the results of the present study suggest that Dox-loaded hydrogels (DLH) may be a good candidate for efficacy study in preclinical mesothelioma models, with strong potential for clinical translation.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2331-2345"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780522","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":"An Underlying Cause and Solution to the Poor Size Exclusion Chromatography Performance of Antibody-Drug Conjugates.","authors":"Jian-Zhong Liu, Chao-Yang Du, Han Gao, Haibin Wang, Feng Hu, Wei-Jie Fang","doi":"10.1007/s11095-024-03796-x","DOIUrl":"10.1007/s11095-024-03796-x","url":null,"abstract":"<p><strong>Purposes: </strong>Antibody-drug conjugate (ADC) size variants are frequently assessed by size exclusion chromatography (SEC). However, poor chromatography performance is often observed during SEC analysis. Existing studies have primarily focused on qualitatively describing non-specific interactions between ADCs and the column matrix. The purposes of the current study are to introduce an underlying cause from a novel perspective on the protein-protein interaction (PPI) mechanism, characterized by quantifying diffusion interaction parameter (k_D) values, and to provide several strategies to reduce PPI and improve column performance during SEC analysis.</p><p><strong>Methods: </strong>Two kinds of ADCs with varying hydrophobicity properties and their corresponding monoclonal antibodies are used as models. The hydrophobicity of these products was verified using the relative calculated logarithm of the partition coefficient of a substance in n-octanol (oil) and water (rCLogP) and reversed-phase high performance liquid chromatography (RP-HPLC), and the size variants were analyzed using SEC. Finally, the PPI was characterized by k_D values of these four products.</p><p><strong>Results: </strong>The results of rCLogP and RP-HPLC indicated that ADC-1 is relatively hydrophobic, whereas ADC-2 is relatively hydrophilic. In the SEC analysis of the ADC-1, substituting sodium chloride with L-arginine hydrochloride or adding a specific concentration of acetonitrile as an organic solvent to the mobile phase resulted in reduced PPI and enhanced column performance. Conversely, the impact on ADC-2 was negligible.</p><p><strong>Conclusions: </strong>This study provides insights into improving the performance of SEC analysis for ADCs through strategies involving alterations in mobile phase composition. The changes in column performance can be quantitatively explained by the PPI mechanism.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2299-2317"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822331","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":"Which Models are USEful?","authors":"John P Prybylski","doi":"10.1007/s11095-024-03799-8","DOIUrl":"10.1007/s11095-024-03799-8","url":null,"abstract":"","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2271-2274"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771239","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":"Effect of \"In Use\" Administration on Topical Product Metamorphosis and Skin Permeation of Acyclovir Creams: Implications for Bioequivalence.","authors":"Sarika N Namjoshi, K C Telaprolu, Jeffrey E Grice, Heather A E Benson, S G Raney, Michael S Roberts, Yousuf H Mohammed","doi":"10.1007/s11095-024-03797-w","DOIUrl":"10.1007/s11095-024-03797-w","url":null,"abstract":"<p><strong>Purpose: </strong>Typical clinical \"in use\" conditions for topical semisolids involve their application as a thin film, often with rubbing that can induce metamorphic stress. Yet, product quality and performance tests often characterize the manufactured product, and may not consider product metamorphosis (e.g., shear history) during dispensing and administration. This work sought to elucidate how such metamorphosis might alter product quality and performance.</p><p><strong>Methods: </strong>We evaluated the effect of \"in use\" stresses on drug crystal metamorphosis in acyclovir creams by optical microscopy. The amount of dissolved acyclovir was determined by separation of the cream base by ultra-centrifugation and quantification by HPLC. IVPT was undertaken on Zovirax^® US and Aciclostad^® comparing static and \"in use\" application of a finite dose. A mechanistic IVPT study was also conducted to understand the influence of acyclovir particle size reduction by \"in use\" rubbing on skin permeation.</p><p><strong>Results: </strong>Reduction in acyclovir particle size was seen after \"in use\" rubbing with increases in the amount of dissolved acyclovir after rubbing (30 and 60 s) compared to static for both products. \"In use\" application resulted in significantly higher acyclovir permeation from both products. The mechanistic IVPT study proved the role of product metamorphosis.</p><p><strong>Conclusion: </strong>These results highlight the role of metamorphosis of product microstructure and its influence on performance.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2391-2401"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801980","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":"Glass Silicone Oil Free Pre-filled Syringe as Primary Container in Autoinjector.","authors":"Xi Zhao, Yueli Chen, Hassen Hamzaoui, Xiaona Wen, Jing Song, Kaitlin Wang, Guangli Hu","doi":"10.1007/s11095-024-03795-y","DOIUrl":"10.1007/s11095-024-03795-y","url":null,"abstract":"<p><strong>Objective: </strong>Pre-filled syringes (PFSs) have become popular as a convenient and cost-effective container closure system for delivering biotherapeutics. However, standard siliconized PFSs may compromise the stability of therapeutic proteins due to their exposure to the silicone oil-water interface. To address this concern, silicone oil-free (SOF) glass syringes coupled with silicone-oil free plunger stoppers have been developed. This study aims to compare the impact of silicone oil-free (SOF) and siliconized syringes as primary container on protein stability and device functionality of the combination products.</p><p><strong>Methods: </strong>The stability of proteins with different modalities was assessed in SOF and siliconized 1 mL glass syringes for up to 6 months at 5℃, 25℃, and 40℃ with levels of subvisible particles and soluble aggregate determined by micro-flow imaging (MFI) and ultra performance size-exclusion chromatography (UP-SEC). The functionality of SOF glass syringes, including break loose force, extrusion force and delivery time in autoinjectors, was evaluated at different time points during the stability study. Additionally, SOF glass syringes were filled with viscosity surrogate ranging from 1 to 90 cP to understand the impact of solution viscosity on break loose force, extrusion force, and autoinjector delivery time.</p><p><strong>Results: </strong>SOF demonstrates compatibility with proteins and exhibited significantly low particle counts compared to siliconized PFS. SOF syringes show significantly higher break-loose and extrusion forces. However, unlike siliconized syringes where silicone oil migration increases extrusion force, no significant change in functionality was observed in SOF glass syringe during stability testing. Overall, SOF glass syringes showed great potential as an alternative package for biologics with comparable performance on functionality as siliconized PFS.</p><p><strong>Conclusions: </strong>The combination of SOF glass and its PTFE coated stopper presents a new primary container closure system with both adequate protein stability and desired functionality features.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2319-2329"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786445","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":"Photodegradation of Dacarbazine Catalyzed by Vitamin B₂ and Flavin Adenine Dinucleotide Under Visible-Light Irradiation.","authors":"Yuka Kimura, Mayuko Suga, Kayo Nakamura, Hidetsugu Tabata, Tetsuta Oshitari, Hideaki Natsugari, Hideyo Takahashi","doi":"10.1007/s11095-024-03802-2","DOIUrl":"10.1007/s11095-024-03802-2","url":null,"abstract":"<p><strong>Purpose: </strong>Drug photodegradation is a matter of great concern because it can result in potency loss and adverse side effects. This study examines the light-induced degradation of dacarbazine catalyzed by vitamin B₂ and flavin adenine dinucleotide (FAD) under light-emitting diode (LED) or fluorescent light irradiation.</p><p><strong>Methods: </strong>Dacarbazine was irradiated with LED (405 nm) or fluorescent light in the presence of various equivalents of vitamin B₂ or FAD. The photodegradation of the drug in D₂O was monitored by ¹H nuclear magnetic resonance spectroscopy.</p><p><strong>Results: </strong>Dacarbazine dissolved in D₂O decomposed in the presence of vitamin B₂ or FAD under irradiation with LED or fluorescent light. The decomposition products were 2-azahypoxanthine 2, which has previously been observed after light irradiation in the absence of vitamin B₂, and 1H-imidazole-5-carboxamide 6, a new product formed in the presence of vitamin B₂. Irradiation with LED light was more effective than irradiation with fluorescent light in degrading dacarbazine.</p><p><strong>Conclusion: </strong>Vitamin B₂ and FAD induced dacarbazine photodegradation. Thus, the interfusion of vitamin B₂ or FAD under excessive light exposure should be avoided during the intravenous administration of dacarbazine.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2363-2375"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11682012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854932","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":"Exploring Multivalency in the Development of Anti-PD-L1 Peptides for Cancer Immunotherapy.","authors":"Umar-Farouk Mamani, Mohammed Nurudeen Ibrahim, Yanli Liu, John Fetse, Chien-Yu Lin, Sashi Kandel, Maryam Nakhjiri, Sushil Koirala, Yuhan Guo, Mohammed Alahmari, Kun Cheng","doi":"10.1007/s11095-024-03803-1","DOIUrl":"10.1007/s11095-024-03803-1","url":null,"abstract":"<p><strong>Purpose: </strong>The PD-1/PD-L1 pathway is one of the most effective immune checkpoint pathways utilized for cancer immunotherapy. Despite the success of anti-PD-1/PD-L1 mAbs, there is growing interest in developing low molecular weight anti-PD-1/PD-1 agents, such as peptides, because of their improved tumor penetration. We recently developed a small anti-PD-L1 peptide and demonstrated its promising anti-tumor activity. In this study, we investigate multivalency as a strategy to increase the binding avidity and blocking efficiency of the anti-PD-L1 peptide.</p><p><strong>Methods: </strong>Multivalent peptide inhibitors are designed with multiple copies of a peptide inhibitor in a single molecule. We synthesized peptides with different valences and examined their activity. We also investigated how spacer length affects the activity of these multivalent peptides.</p><p><strong>Results: </strong>Using this strategy, we developed a multivalent peptide that demonstrated approximately 40 times higher blocking efficiency and improved stability compared to the original peptide. Increasing the valency enhanced the peptide's specificity, which is essential for minimizing side effects.</p><p><strong>Conclusions: </strong>Multivalency approach represents a promising platform for improving the efficacy of peptide-based checkpoint inhibitors.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2275-2288"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838472","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":"Identification of Patients Who Require Two-Point Blood Sampling for the Peak and Trough Values Rather Than One-Point Blood Sampling for the Trough Value for the Evaluation of AUC of Vancomycin Using Bayesian Estimation.","authors":"Ayako Suzuki, Masaru Samura, Tomoyuki Ishigo, Satoshi Fujii, Yuta Ibe, Hiroaki Yoshida, Hiroaki Tanaka, Fumiya Ebihara, Takumi Maruyama, Yukihiro Hamada, Hisato Fujihara, Fumihiro Yamaguchi, Fumio Nagumo, Toshiaki Komatsu, Atsushi Tomizawa, Akitoshi Takuma, Hiroaki Chiba, Yoshifumi Nishi, Yuki Enoki, Kazuaki Taguchi, Kazuaki Matsumoto","doi":"10.1007/s11095-024-03781-4","DOIUrl":"10.1007/s11095-024-03781-4","url":null,"abstract":"<p><strong>Objectives: </strong>It is recommended to adjust the dose of vancomycin (VCM) with a target area under the concentration-time curve (AUC) of 400-600 μg·h/mL. Factors that affect the deviation between AUCs are estimated from the trough value alone and the trough and peak values using practical AUC-guided therapeutic drug monitoring (PAT) for vancomycin. In this study, factors that affect AUC were evaluated.</p><p><strong>Methods: </strong>AUCs were estimated from a single trough value and trough and peak values, and the patients were classified into those who showed a 10% or greater deviation (deviation group) and those in whom the deviation was less than 10% (no-deviation group). Risk factors related to ≥ 10% deviation of AUC were identified by univariate and multivariate analysis.</p><p><strong>Results: </strong>As a result of univariate and multivariate analysis of 30 patients in the deviation group and 344 patients in the no-deviation group, a creatinine clearance (CLcr) of ≥ 110 mL/min (odds ratio (OR) = 3.697, 95% confidence interval (CI) = 1.616-8.457, p = 0.002), heart failure with a brain natriuretic peptide (BNP) of ≥ 300 pg/mL (OR = 4.854, 95%CI = 1.199-19.656, p = 0.027), and the concomitant use of angiotensin converting enzyme inhibitor or angiotensin II receptor blocker (ACE-I/ARB) (OR = 2.544, 95%CI = 1.074-6.024, p = 0.034) were identified as risk factors of ≥ 10% deviation of AUC.</p><p><strong>Conclusions: </strong>Estimation of AUC by two-point blood sampling for the trough and peak values rather than one-point blood sampling for the trough value is suggested to improve the prediction accuracy in patients with enhanced renal function, severe heart failure, and patients using ACE-I/ARB.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2161-2171"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472346","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":"Development of Mathematical Function Control-Based 3D Printed Tablets and Effect on Drug Release.","authors":"Honghe Wang, Indrajeet Karnik, Prateek Uttreja, Peilun Zhang, Sateesh Kumar Vemula, Michael A Repka","doi":"10.1007/s11095-024-03780-5","DOIUrl":"10.1007/s11095-024-03780-5","url":null,"abstract":"<p><strong>Purpose: </strong>The application of 3D printing technology in drug delivery is often limited by the challenges of achieving precise control over drug release profiles. The goal of this study was to apply surface equations to construct 3D printed tablet models, adjust the functional parameters to obtain multiple tablet models and to correlate the model parameters with the in vitro drug release behavior.</p><p><strong>Methods: </strong>This study reports the development of 3D-printed tablets using surface geometries controlled by mathematical functions to modulate drug release. Utilizing fused deposition modeling (FDM) coupled with hot-melt extrusion (HME) technology, personalized drug delivery systems were produced using thermoplastic polymers. Different tablet shapes (T1-T5) were produced by varying the depth of the parabolic surface (b = 4, 2, 0, -2, -4 mm) to assess the impact of surface curvature on drug dissolution.</p><p><strong>Results: </strong>The T5 formulation, with the greatest surface curvature, demonstrated the fastest drug release, achieving complete release within 4 h. In contrast, T1 and T2 tablets exhibited a slower release over approximately 6 h. The correlation between surface area and drug release rate was confirmed, supporting the predictions of the Noyes-Whitney equation. Differential Scanning Calorimetry (DSC) and Scanning Electron Microscope (SEM) analyses verified the uniform dispersion of acetaminophen and the consistency of the internal structures, respectively.</p><p><strong>Conclusions: </strong>The precise control of tablet surface geometry effectively tailored drug release profiles, enhancing patient compliance and treatment efficacy. This novel approach offers significant advancements in personalized medicine by providing a highly reproducible and adaptable platform for optimizing drug delivery.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":"2235-2246"},"PeriodicalIF":3.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472344","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}