Annales pharmaceutiques francaises最新文献

{"title":"Unspecified degradation impurities identification and characterization in bilastine and montelukast tablet formulations by using UPLC and LCMS/MS: Robustness by design expert and green assessment.","authors":"Raj Kumar Kodishala, Kousrali Sayyad, Leela Prasad Kowtharapu, Naresh Konduru, Tanmoy Mondal, Mohan Varkolu, Sreedhar Gundekari","doi":"10.1016/j.pharma.2025.04.006","DOIUrl":"10.1016/j.pharma.2025.04.006","url":null,"abstract":"<p><strong>Objectives: </strong>This study introduces a novel ultra-performance liquid chromatography (UPLC) method for the rapid, simple, and accurate detection of contaminants in bilastine (BLS) and montelukast (MTK) tablet formulations.</p><p><strong>Material and methods: </strong>The separation of BLS impurity-A, BLS impurity-B, BLS, MTK impurity-A, MTK, and MTK impurity-B was achieved using an Acquity BEH C18 column (50×2.1mm, 1.7μm) under gradient eluent conditions. The mobile phases consisted of 0.1% triethylamine in water with the pH adjusted to 2.5 using orthophosphoric acid (mobile phase A) and acetonitrile (mobile phase B). The ratio of mobile phase A to B was 70:30 (v/v). The column flow rate was set at 0.2mL/min, and the photodiode array detector (PDA) was used to quantify the analytes. The detection wavelength was set to 224nm.</p><p><strong>Results: </strong>In a runtime of just 20minutes, 13 analytes were successfully separated. The retention times for the target compounds and impurities were as follows: BLS impurity-A: 1509min, BLS impurity-B: 3435min, BLS: 5668min, MTK impurity-A: 8137min, MTK: 9784min, MTK impurity-B: 11,853min. The unspecified impurities in the degradation samples were detected at retention times of 2174, 2657, 3368, 4143, 8239, 11,722, and 12,436minutes, and were characterized using liquid chromatography-mass spectrometry (LC-MS).</p><p><strong>Conclusion: </strong>The UPLC-based analytical method demonstrated in this study is an effective and efficient technique for the quantification of BLS, MTK, and their associated impurities in tablet formulations. This method has been validated in accordance with ICH Q2(R2) and USP <1225> guidelines.</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953248","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":"PLAROsomes as a modified liposomes delivery system for Mimosa pudica L. extract: Augmenting anticancer potential against prostate and skin cancer cell lines.","authors":"Vaishali K Gaikwad, Ravindra B Laware, Nitin Mohire, Somnath Devidas Bhinge","doi":"10.1016/j.pharma.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.pharma.2025.04.004","url":null,"abstract":"<p><strong>Objective: </strong>PLAROsomes, a modified liposomal drug carrier system, were developed to overcome the major drawback of drug leakage in conventional liposomes. This study aimed to encapsulate Mimosa pudica L. extract (MIPA) within PLAROsomes to enhance anticancer efficacy against prostate (PC-3) and skin (B16F10) cancer cell lines.</p><p><strong>Method: </strong>PLAROsomes were formulated using the thin-film hydration technique and characterized through infrared (IR) and ultraviolet (UV) spectroscopy, thermal analysis (TGA and DSC), particle size distribution, zeta potential measurement, and morphological assessment via SEM and TEM. Key formulation parameters, including encapsulation efficiency (%EE), drug loading capacity (%DLC), and drug release (%DR), were optimized for stability and efficacy. Cytotoxicity was evaluated using the MTT assay. Additionally, MIPA-loaded PLAROsomes were prepared without 2-methyl-resorcinol to assess its role in preventing drug leakage.</p><p><strong>Results: </strong>The optimized MIPA-loaded PLAROsomes had a particle size of 193.2±41.6nm, confirmed by TEM at 139±15nm. They exhibited higher encapsulation efficiency (83.45±0.45%) and drug loading (9.85%) compared to formulations without 2-methyl-resorcinol (74.56±0.65% EE and 8.80% DLC), indicating its stabilizing effect. Drug release followed the Korsmeyer-Peppas model, demonstrating a sustained profile. At 100μg/mL, MIPA-loaded PLAROsomes significantly reduced cell viability (52.22±1.54% in B16F10 and 45.57±0.80% in PC-3), outperforming the free extract.</p><p><strong>Conclusion: </strong>MIPA-loaded PLAROsomes exhibit enhanced anticancer potential and could serve as an effective targeted therapy, warranting further clinical investigation.</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974879","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":"[Pharmaceutical preparations in the management of medicine shortages at the French National Agency for Medicines and Health Products Safety].","authors":"Martine Bouley, Brigitte Rogeau, Roseline Mazet, Yvan Grange, Françoise Duperray, Guillaume Renaud, Valérie Salomon","doi":"10.1016/j.pharma.2025.04.005","DOIUrl":"10.1016/j.pharma.2025.04.005","url":null,"abstract":"<p><strong>Objectives: </strong>Among the actions implemented by the French National Agency for Medicines and Health Products Safety to manage drug shortages, the use of pharmaceutical preparations can be a solution, as a relay, when feasible, before the medicines are made available again. The aim of this work is to present the original methodology employed by the Agency to guarantee the quality and safety of these pharmaceutical preparations.</p><p><strong>Methods: </strong>The various steps of this process are presented and may vary depending on the context and the severity of the shortage, in order to ensure quality and safety of pharmaceutical preparations throughout France.</p><p><strong>Results: </strong>We report on the concrete case of the amoxicillin pharmaceutical preparation set up, during the paediatric amoxicillin shortage over the winters of 2022 and 2023. Over 709,450 people were treated with pharmaceutical preparations of amoxicillin.</p><p><strong>Conclusion: </strong>The Agency's scientific supervision and the national coordination of the various stakeholders have made it possible to respond effectively to demand, thereby limiting the negative impact of drug shortage for patients. This organisation has enabled practices to be standardised and preparation activities to be made safer. Magistral and hospital preparations can be mobilised almost immediately. In the most critical cases, with the creation of a specific status for hospital or community special pharmaceutical preparations, this system can also be triggered with subcontracted manufacturers (Contract Development Manufacturing Organisations).</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965073","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":"Drug deprescribing policy and incentives in France.","authors":"Francis Megerlin, Gilles Bouvenot, Patrice Queneau","doi":"10.1016/j.pharma.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.pharma.2025.04.003","url":null,"abstract":"<p><p>Deprescribing inappropriate drug treatments is a public health issue particularly in countries with a high level of polymedication (polypharmacy). Despite the introduction of the term 'deprescribing' in France in 2002 and the clinical practice guidelines, progress in the outpatient sector has been limited. Our article describes the financial incentives adopted by national agreements between the Assurance Maladie (France's compulsory health insurer scheme) and unions of independent practitioners: pharmacists are encouraged to draw up and share medication reviews (since 2018, target population extended in 2022). As the outcomes have been modest, doctors have then been since 2024 also incentivised to offer medical consultations explicitly dedicated to deprescribing, and to prescribe medication reviews to be drawn up by pharmacists. This article describes the new legal framework for outpatient and inpatient services. It calls for the results expected from 2025 onwards to be measured and studied in national health databases, thanks to the coding associated with these new services.</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959757","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":"Ethyl cellulose-based in-situ film of itraconazole for enhanced treatment of fungal infections.","authors":"Lutfi Chabib, Yulianto, Putri Wulandari Resky Ananda, Rifka Nurul Utami, Maria Mir, Diany Elim, Andi Maqhfirah Nurul Fitri, Hilman Syamami Zaman, Anugerah Yaumil Ramadhani Aziz, Nurul Fauziah, Latifah Rahman, M Pandoman Febrian, Andi Dian Permana","doi":"10.1016/j.pharma.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.pharma.2025.04.002","url":null,"abstract":"<p><strong>Objectives: </strong>Fungal infections represent a significant global health challenge, requiring effective treatments to prevent complications and improve patient outcomes. This study aimed to develop an in-situ film-forming system (IFFS) for transcutaneous delivery of itraconazole (ITZ) as an alternative to oral administration, addressing issues such as low bioavailability, reduced efficacy, and potential side effects.</p><p><strong>Materials and methods: </strong>The IFFS was formulated using ethyl cellulose as the primary polymer, PEG 400 as a plasticizer, and a eutectic mixture of menthol and camphor as penetration enhancers. The system was characterized for viscosity, pH, drying time, water vapor permeability, bioadhesion, and physicochemical interactions (DSC and FTIR). Ex vivo skin permeation and retention studies were conducted using Franz diffusion cells, and antifungal efficacy was tested on an ex vivo Candida albicans infection model. Skin integrity and hemolysis tests were performed to evaluate safety.</p><p><strong>Results: </strong>The IFFS exhibited desirable physicochemical properties, with increased polymer concentrations enhancing skin retention and bioadhesive strength while reducing permeation rates. Ex vivo studies showed sustained ITZ release and enhanced skin retention. The antifungal activity test demonstrated complete eradication of Candida albicans within 48hours. Safety assessments confirmed no skin irritation or toxicity.</p><p><strong>Conclusion: </strong>The developed IFFS provides a safe and effective transcutaneous delivery system for ITZ. This innovative approach enhances antifungal efficacy, improves skin retention, and offers a promising alternative to oral administration, minimizing systemic side effects.</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968500","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":"Cheminformatic profiling of Azardirachta indica phytochemicals as dual SHP2/HSP90 oncogenic inhibitors: Identification of nimbocinol, nimbidinin, and margolone.","authors":"Oluwaseun E Agboola, Zainab A Ayinla, Oladayo E Apalowo, Samuel S Agboola, Omotola M Fajana, Bidemi E Ekundayo, Babamotemi O Itakorode, Babatunji E Oyinloye","doi":"10.1016/j.pharma.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.pharma.2025.04.001","url":null,"abstract":"<p><p>Cancer therapy faces challenges due to drug resistance and signaling pathway redundancy, allowing cancer cells to evade treatment. Dual inhibition of Src homology region 2 domain-containing phosphatase-2 (SHP2) and heat shock protein 90 (HSP90) offers a promising strategy to overcome these limitations. We evaluated neem-derived compounds against SHP2 (PDB ID: 5EHR) and HSP90 (PDB ID: 1YET) using molecular docking, hierarchical clustering, and structural similarity analyses. Drug-likeness was assessed using Lipinski's rule of five, and Tanimoto similarity coefficients were calculated. Nimbocinol, nimbidin, and margolone showed promising binding affinities to both targets. Nimbocinol demonstrated superior binding to SHP2 (-10.463kcal/mol) compared to SHP099 (-10.009kcal/mol). Margolone formed specific interactions, including a salt bridge between its carboxylate group and His100 in HSP90. All compounds complied with Lipinski's rule, with margolone showing structural similarities to geldanamycin and SHP099. This study identifies neem-derived compounds as potential dual inhibitors of SHP2 and HSP90, presenting a paradigm shift in cancer therapeutic strategy. These findings provide a foundation for developing novel multi-targeted anticancer therapeutics.</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957758","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":"The paradigm shift from Stringent Regulatory Authorities to WHO-Listed Authorities.","authors":"Valérie Faillat","doi":"10.1016/j.pharma.2025.03.006","DOIUrl":"10.1016/j.pharma.2025.03.006","url":null,"abstract":"<p><p>Regulatory systems play a key role in assuring the quality, safety, and efficacy of health products. After more than 20 years of efforts on regulatory capacity improvement of the less-equipped National Regulatory Authorities, the transition from the concept of Stringent Regulatory Authorities (SRAs) to WHO-Listed Authorities (WLAs) represents a significant paradigm shift in global health ecosystem. This review aims to provide a better understanding of this evolution and to clarify the WLA concept, as a component for the long-term success of this framework.</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778728","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 and validation of a novel reverse-phase high-performance liquid chromatography (RP-HPLC) method for the quantification of related substances of vasopressin injection: A characterization and comparative analysis of vasopressin formulation samples against vasostrict (RLD) in various diluents.","authors":"Sivaji Maganti, Suryakala Duvvuri, Prudhvi Raju Pericharla, Ravi Kumar Bellam, Ameer Khan Shaik","doi":"10.1016/j.pharma.2025.03.007","DOIUrl":"10.1016/j.pharma.2025.03.007","url":null,"abstract":"<p><p>In the present study, we developed and validated a sensitive, accurate, robust and simple RP-HPLC method for quantification of related substances of vasopressin (VPS) injection. The development phase prioritized the optimization of wavelength, mobile phase composition and column selection to enhance separation and sensitivity for the analytical evaluation of VPS injection. By considering peak symmetry, resolution and retention time, chromatographic conditions of VPS injection were established. The YMC PACK ODS AM (100×4.6) mm, 3μm was employed in the study. Mobile phase A was prepared with 0.113M NaH₂PO₄.H₂O (pH 3.0) while mobile phase B was a 50:50 (v/v) ratio of acetonitrile and water, pumped through a flow rate of 1.0mL/min. VPS injection was exposed to thermal, photolytic, acid, base and peroxide degradation conditions and these were analysed by the current method. The method was validated following the guidelines set by the International Council for Harmonization guideline (ICH). The linearity studies demonstrating that a correlation coefficient value is more than 0.999 for VPS and its related substances. The detection and quantification limits for all related substances were found to be 0.01% and 0.05%, respectively. All the impurities exhibited consistent recoveries ranging from 85 to 105%. The unknown impurities were eluting at RRT 1.23 and RRT 1.25 in the RS methodology (HPLC-UV) of VPS injection are identified and assessed the impurity levels. Furthermore, aggregate profiles and secondary structure analysis studies were carried out using FTIR and LC-HRMS, comparing the VPS formulation samples with the reference listed drug (RLD) (Vasostrict) samples across various diluents.</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778725","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":"Formulation of repurposed celecoxib-loaded nanostructured lipid carriers using Box-Behnken design, its characterization, and anticancer evaluation.","authors":"Ashwini Bhavar, Kaustubh Ajit Kolekar, Tejashree Yadav, Kapil Kole, Durgacharan Bhagwat, Sachin Kumar Singh, Popat S Kumbhar, John Disouza","doi":"10.1016/j.pharma.2025.03.005","DOIUrl":"10.1016/j.pharma.2025.03.005","url":null,"abstract":"<p><strong>Objectives: </strong>The key objective of present research is to effectively treat lung cancer with repurposed celecoxib while overcoming challenges such as solubility, bioavailability, non-selectivity, and negative effects by delivering celecoxib through nanostructured lipid carriers via the parenteral route.</p><p><strong>Methods: </strong>Celecoxib-laden nanostructured lipid carriers were manufactured by melt-emulsification ultrasonication approach and optimized through Box-Behnken design. The celecoxib nanostructured lipid carriers were examined for particle size, % entrapment efficiency, zeta potential, in vitro release, cytotoxicity, stability, etc. RESULTS: The optimized celecoxib nanostructured lipid carriers displayed a % entrapment efficiency of 91.69±4.9% and particle size of 132.1±6.8nm with a polydispersity index of 0.41±0.06, and a zeta potential of -39.1±3.0mV. Notably, celecoxib nanostructured lipid carriers exhibited better and controlled celecoxib release at phosphate buffer solution pH 6.8 than pH 7.4, revealing the tumor-targeting potential of nanostructured lipid carriers. Also, the release of celecoxib from nanostructured lipid carriers was controlled for 48h, indicating reduced chances of systemic toxicity. The in vitro cytotoxicity against A549 cells of celecoxib nanostructured lipid carriers was 1.5-fold greater than that of pure celecoxib, confirming significant anti-lung cancer effectiveness. Further, the celecoxib-loaded nanostructured lipid carriers remained stable for twelve weeks at cold and ambient temperatures.</p><p><strong>Conclusion: </strong>Thus, the given research concludes that parenteral administration of nanostructured lipid carriers could be a harmless, efficient, and novel choice to treat lung cancer using repurposed celecoxib.</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741904","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":"Formulation and evaluation of a smart mucoadhesive nasal gel containing oregano, chamomile, and lavender for seizure control in PTZ-induced seizure model in rats.","authors":"Samin Sheikholeslami, Amir Baghaei, Marziyeh Amiri-Andebili, Faranak Salmannejad, Mohammad Mahdi Ahmadian-Attari","doi":"10.1016/j.pharma.2025.03.004","DOIUrl":"10.1016/j.pharma.2025.03.004","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is a prevalent neurological disorder characterized by recurrent seizures, affecting approximately 1% of the global population. Despite the availability of antiepileptic drugs, a significant proportion of patients experience uncontrolled seizures, which necessitates the development of alternative therapeutic strategies. Herbal medicine has gained attention due to its potential anticonvulsant properties.</p><p><strong>Objectives: </strong>This study aimed to assess the anticonvulsant effects of hydroalcoholic extracts of oregano, chamomile, and lavender in rats' pentylenetetrazol (PTZ)- induced seizure model. Furthermore, it sought to formulate and evaluate a mucoadhesive nasal hydrogel containing these extracts.</p><p><strong>Methods: </strong>The herbal extracts were prepared using ethanol (70%) through maceration and analyzed based on the Iranian Herbal Pharmacopeia standards. Total phenolic content (TPC) was quantified using the spectrophotometric method to standardize the extracts. Using various gelling agents, the nasal hydrogel formulation was optimized for mucoadhesion and gelation properties. The anticonvulsant activity was evaluated in vivo using seizure models induced by pentylenetetrazol (PTZ).</p><p><strong>Results: </strong>The herbal extracts met the pharmacopeial standards, and the nasal hydrogel formulation demonstrated favorable physicochemical properties, including optimal pH and mucoadhesive strength. In vivo studies showed that intranasal administration of the herbal extracts significantly delayed seizure onset and reduced seizure intensity at a dose of 34mg/kg, compared to the negative control group (P<0.001).</p><p><strong>Conclusion: </strong>The smart mucoadhesive nasal hydrogel containing oregano, chamomile, and lavender extracts exhibited promising anticonvulsant activity, suggesting its potential as a novel, non-invasive alternative for epilepsy management.</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673408","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}