Current drug discovery technologies最新文献

{"title":"Inebilizumab-cdon: USFDA Approved for the Treatment of NMOSD (Neuromyelitis Optica Spectrum Disorder).","authors":"Faraat Ali,&nbsp;Kamna Sharma,&nbsp;Varisha Anjum,&nbsp;Asad Ali","doi":"10.2174/1570163818666210519103001","DOIUrl":"https://doi.org/10.2174/1570163818666210519103001","url":null,"abstract":"<p><p>Inebilizumab-cdon (Uplizna™) was currently approved by the United States Food and Drug Administration (USFDA) for the treatment of NMOSD (neuromyelitis optica spectrum disorder). It was developed by Viela Bio (Nasdaq: VIE) USA. Inebilizumab-cdon (formerly MEDI-551) is a humanized antibody, which induces CD19 + B cell depletion by increasing antibody-dependent cell cytotoxicity (ADCC) and cell phagocytosis (ADCP) of effector cells. Various clinical trials exhibit its safe and effective pharmacokinetic and pharmacodynamic profile. In June 2019, Viela Bio submitted Biologics License Application (BLA) to the FDA based on the findings obtained from the N-Momentum trial. This article summarizes the milestones in the development of Inebilizumab-cdon leading to this approval for the treatment of advanced NMOSD.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"19 1","pages":"e140122193419"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38997725","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":"Physical Instabilities of Therapeutic Monoclonal Antibodies: A Critical Review.","authors":"Arpit Arun K Bana,&nbsp;Priti Mehta,&nbsp;Khushboo Ashok Kumar Ramnani","doi":"10.2174/1570163819666220624092622","DOIUrl":"https://doi.org/10.2174/1570163819666220624092622","url":null,"abstract":"<p><p>The proteinaceous nature of monoclonal antibodies (mAbs) makes them highly sensitive to various physical and chemical conditions, thus leading to instabilities that are classified as physical and chemical instabilities. In this review, we are discussing in detail the physical instability of mAbs because a large number of articles previously published solely focus on the chemical aspect of the instability with little coverage on the physical side. The physical instabilities of mAbs are classified into denaturation and aggregation (precipitation, visible and subvisible particles). The mechanism involved in their formation is discussed in the article, along with the pathways correlating the denaturation of mAb or the formation of aggregates to immunogenicity. Further equations like Gibbs-Helmholtz involved in detecting and quantifying denaturation are discussed, along with various factors causing the denaturation. Moreover, questions related to aggregation like the types of aggregates and the pathway involved in their formation are answered in this article. Factors influencing the physical stability of the mAbs by causing denaturation or formation of aggregates involving the structure of the protein, concentration of mAbs, pH of the protein and the formulations, excipients involved in the formulations, salts added to the formulations, storage temperature, light and UV radiation exposure and processing factors are mentioned in this article. Finally, the analytical approaches used for detecting and quantifying the physical instability of mAbs at all levels of structural conformation like far and near UV, infrared spectroscopy, capillary electrophoresis, LC-MS, microflow imagining, circular dichroism and peptide mapping are discussed.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"19 6","pages":"e240622206367"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9184705","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":"Hydrophobically Modified <i>Abelmoschus esculentus</i> Polysaccharide Based Nanoparticles and Applications: A Review.","authors":"Prashant Upadhyay,&nbsp;Shivani Agarwal,&nbsp;Sukirti Upadhyay","doi":"10.2174/1570163819666220801121857","DOIUrl":"https://doi.org/10.2174/1570163819666220801121857","url":null,"abstract":"<p><p>Nanomaterials are indeed a nanoscale technology that deals with the creation, evaluation, fabrication, and utilization of systems at the nanometre scale by manipulating their size and shape. We consider natural polysaccharides such as promising polysaccharides, which are biodegradable, nontoxic, abundant, and inexpensive bio-polymeric precursors for preparing the materials of choice in various industries. The aim is to review different methods to produce hydrophobically modified Abelmoschus esculentus nanoparticles and study the evaluation processes of these nanoparticles as given in the literature. It proved the benefits of derivatives of gum by introducing different chemical groups. The chemical functionalization of gum mainly includes the esterification, etherification, and crosslinking reactions of the hydroxyl groups and contains a special fibre which takes sugar levels in the blood under control, providing a sugar quantity suitable for the bowels. Okra contains mucilage that helps remove poisonous chemicals and bad cholesterol, often overloads the liver. Recovering from psychological conditions, like depression, general weakness, and joint healthiness can be done with Okra. Someone additionally applied it for pulmonary inflammation, bowel irritation, and sore throat. Purgative properties okra possesses are beneficial for bowel purification. It is used to counteract the acids. Fibre okra contains a valuable nutrient for intestinal microorganisms and ensures proper intestine functionality. It also protects the mucosa of the digestive tract by covering them with an extra layer because of its alkaline nature. Nanotechnology has emerged as a critical component of pharmaceutics, with many applications in drug carriers of interest aimed at improving drug clinical outcomes such as cancer, diabetes mellitus, wound care management, atopic dermatitis, cosmeceutical, etc. Beneficial outcomes of this review are discussed briefly.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"19 6","pages":"e010822207168"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10616631","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":"Extracting Atomic Contributions to Binding Free Energy Using Molecular Dynamics Simulations with Mixed Solvents (MDmix).","authors":"Daniel Alvarez-Garcia,&nbsp;Peter Schmidtke,&nbsp;Elena Cubero,&nbsp;Xavier Barril","doi":"10.2174/1570163819666211223162829","DOIUrl":"https://doi.org/10.2174/1570163819666211223162829","url":null,"abstract":"<p><strong>Background: </strong>Mixed solvents MD (MDmix) simulations have proved to be a useful and increasingly accepted technique with several applications in structure-based drug discovery. One of the assumptions behind the methodology is the transferability of free energy values from the simulated cosolvent molecules to larger drug-like molecules. However, the binding free energy maps (ΔGbind) calculated for the different moieties of the cosolvent molecules (e.g. a hydroxyl map for the ethanol) are largely influenced by the rest of the solvent molecule and do not reflect the intrinsic affinity of the moiety in question. As such, they are hardly transferable to different molecules.</p><p><strong>Method: </strong>To achieve transferable energies, we present here a method for decomposing the molecular binding free energy into accurate atomic contributions.</p><p><strong>Result: </strong>We demonstrate with two qualitative visual examples how the corrected energy maps better match known binding hotspots and how they can reveal hidden hotspots with actual drug design potential.</p><p><strong>Conclusion: </strong>Atomic decomposition of binding free energies derived from MDmix simulations provides transferable and quantitative binding free energy maps.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"19 2","pages":"62-68"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/ee/CDDT-19-231221199369.PMC9906626.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9298212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In silico</i> Prediction and Pharmacokinetic Studies on Glucosinolates as a Potential Drug and Key Inhibitor Molecule for Lanosterol-14α- demethylase: A Fungal Membrane Biosynthesis Enzyme.","authors":"Gurpreet Singh","doi":"10.2174/1570163819666220615142933","DOIUrl":"https://doi.org/10.2174/1570163819666220615142933","url":null,"abstract":"<p><strong>Background: </strong>Glucosinolates (β-thioglucoside-N-hydroxysulfates) are a water-soluble organic anion with sulfur- and nitrogen-containing glycosides which are found in abundance in Cruciferous plants. Ergosterol (ERG13) lanosterol-14α-demethylase protein has been targeted for inhibition studies as a key regulator enzyme of fungal membrane biosynthesis.</p><p><strong>Objectives: </strong>To understand the molecular mechanism of inhibition of Ergosterol (ERG13) lanosterol- 14α-demethylase by various phytochemicals from brassicales, i.e., glucosinolates and their potential role as putative drug molecules.</p><p><strong>Methods: </strong>In this study, in silico analyses were performed to predict the molecular basis of various glucosinolates as a potential inhibitor of lanosterol-14α-demethylase protein, which is a key regulator of fungal membrane biosynthesis and its pharmacodynamics and toxicity profile. 3d structures of various glucosinolates were retrieved from PubChem, and the target protein, lanosterol-14α-demethylase (Pdb ID- 4lxj), was retrieved from the RCSB protein data bank. Molecular docking and interactions were carried out using the PyRx software using the AutoDOCK toolbar with default parameters. Dru- LiTo, ORISIS web servers were used to predict various drug likeliness predictions and Lipinski's Rule of 5, whereas admetSAR was used for prediction of toxicity, and PASS Program was used to study the antifungal and antimicrobial properties of these compounds.</p><p><strong>Results: </strong>This study shows that among the different compounds screened, gluconasturtiin, Glucotropaeolin, and Indolylmethyl-Glucosinolate showed the highest binding energies of -8.7 kcal/mol, -8.5 kcal/mol, and -8.3 kcal/mol with the lanosterol-14α-demethylase, respectively. Further all the compounds follow the Lipinski's rule as well as they are found to be non-carcinogenic and non-cytotoxic in nature. These compounds also show antifungal properties.</p><p><strong>Conclusion: </strong>This study thus reveals that various glucosinolates interact with the ERG13 enzyme at various amino acid positions, which behaves as a catalytic site, thus indicates the probable mechanism of inactivation, and subsequently, these can be used as potential drug molecules. In vitro studies can be taken to further examine the utility of these compounds as antifungal agents.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"19 6","pages":"e150622206033"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668713","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":"Synthesis, Cytotoxicity Evaluation and Molecular Docking of Fluorine Containing Hexahydroquinoline-3-Carbonitrile Derivatives.","authors":"Nishith Teraiya,&nbsp;Subhas S Karki,&nbsp;Ashlesha Chauhan","doi":"10.2174/1570163817666201229154848","DOIUrl":"https://doi.org/10.2174/1570163817666201229154848","url":null,"abstract":"<p><strong>Background: </strong>Fluorine containing hexahydroquinoline-3-carbonitrile derivatives were found to have potent cytotoxicity. Furthermore, fluorine can modulate pharmacokinetic and pharmacodynamic profile of drugs. Hence, new derivatives containing fluorine were explored as potential cytotoxic agents.</p><p><strong>Objective: </strong>Difluoro substituted compounds containing aromatic/heteroaromatic rings were designed, synthesized and screened for in vitro cytotoxicity on cancer cell lines. The active compounds were subjected to docking on Mcl-1 and ADME/T prediction.</p><p><strong>Methods: </strong>The synthesized compounds were characterized using various spectral techniques like FT-IR, ¹H NMR, ¹³C NMR and Mass spectra. Compounds were screened for cytotoxicity on NCI-60 cell lines at the National Cancer Institute. The active compounds were evaluated additionally by MTT and SRB assay.</p><p><strong>Results: </strong>Compounds (6l and 6o) showed maximum cytotoxicity with (% GI) of 69 and 63.7 at 10 μM drug concentration, respectively. Compound 6i showed potent cytotoxicity with GI₅₀ of 7.2 μM against Ishikawa cell line. Compound 6o was nearly as active as a reference with IC₅₀ of 9.39 μM and 13.54 μM against HT-29 and HCT-116, respectively, and compound 6l also showed equal potency to that of reference with IC₅₀ of 9.66 μM against Caco-2. Compounds 6i, 6o and 6l showed high docking scores, suggesting their cytotoxicity. Furthermore, ADME/T prediction revealed that all the compounds had drug-likeness properties.</p><p><strong>Conclusion: </strong>Enhanced lipophilic interaction of compounds due to the presence of fluorine in compounds 6i and 6l was revealed during the docking study. Compound 6i can be explored as a lead molecule against other endometrial cancer in futuristic drug development.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"19 1","pages":"e140122189603"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39107562","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":"Effect of Anti-Retroviral Drug Impurity/Related Substances on the CCR5 and/or CXCR4 Receptors Binding Sites to Revise Resistance Mechanisms in the Clinical Implications Using Molecular Docking Studies.","authors":"Rinchi Bora,&nbsp;M R Jeyaprakash,&nbsp;S Jubie","doi":"10.2174/1570163818666210329102901","DOIUrl":"https://doi.org/10.2174/1570163818666210329102901","url":null,"abstract":"<p><strong>Background: </strong>CCR5 and/or CXCR4 receptors on CD4+ T cell membranes are the active sites for HIV to bind. The different classes of drugs have a unique mechanism of action to cease the virus, but we are concentrating in the first-class i.e. NNRTI that destroys the virus while it binds to the cell surface gp120 protein. The drugs are having several impurities that can be genotoxic and few are reported in the monographs.</p><p><strong>Objective: </strong>This study proposes the affinity of the impurities to the active site through molecular docking to a receptor (PDB ID 4MBS) from the library of analogs available for antiretroviral drugs. As these drugs are taken for the long term, this study will give a prominent idea for testing the impurities and their genotoxicity.</p><p><strong>Methods: </strong>We have done molecular docking of 37 impurities and drugs with the GLIDE module of schrodinger software for their binding affinities. In this study, receptor CCR5 and/or CXCR4 is selected containing glycoprotein that mediates virus binding to CD4+ T cell.</p><p><strong>Results: </strong>Didanosine E and Zidovudine D shows maximum and minimum score respectively. The selected impurities were interfering with the active binding site that may lead to any ADR or reduce the effect of API.</p><p><strong>Conclusion: </strong>Conclusively, a significant role is played by Protein-Ligand interaction in structuralbased designing. Summarizing that there might be a genotoxicity effect due to competition between API and the impurities. The molecular docking was used to study the binding mechanism and to establish the docking score along with the activity. The outcome of the study can be used to design and development of novel compounds having genotoxicity.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"19 1","pages":"e140122192497"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25539397","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":"In-silico Screening of Phytoconstituents on Wound Healing Targets - Approaches and Current Status.","authors":"Vijaya Mandale,&nbsp;Asha Thomas,&nbsp;Ravindra Wavhale,&nbsp;Sohan Chitlange","doi":"10.2174/1570163819666211130141442","DOIUrl":"https://doi.org/10.2174/1570163819666211130141442","url":null,"abstract":"<p><p>Over recent years, there has been tremendous research focused on the effective utilization of natural products in wound management. Natural or herbal products contain several phytoconstituents that may act on various stages in wound healing and thereby provide a multi-targeted approach especially in the treatment of chronic wounds. Currently, attempts have been made to screen the phytoconstituents present in herbs on various targets involved in wound healing. This review includes a systematic evaluation of scientific reports by various groups of researchers on the herbals evaluated for wound management, their phytochemical profiling, pre-clinical studies, and molecular modeling studies. Various wound targets discussed include Interleukin-1, Interleukin-6, Tumor necrosis factor-α (TNF-α), Thymosin beta-4 (Tβ-4) that regulate the early inflammatory stage and the novel T cell immune response cDNA 7(TIRC7) that regulates angiogenesis. Also, neuropeptides P and Y act on the inflammatory, migratory, and proliferation phases, and growth factors like vascular endothelial growth factor family (VEGF) and placental growth factor family (PGF) are involved in angiogenesis, while the role of Fibroblast growth factor in tissue remodeling is discussed. As many of the natural products include polyherbal systems, this approach can help in the judicious selection of a combination of herbs that will act on multiple targets in the wound healing process and provide a multi-factorial approach in wound management.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"19 3","pages":"e301121198426"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39932312","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":"Predicting the Anticancer Activity of 2-alkoxycarbonylallyl Esters against MDA-MB-231 Breast Cancer - QSAR, Machine Learning and Molecular Docking.","authors":"Babatunde Samuel Obadawo,&nbsp;Oluwatoba Emmanuel Oyeneyin,&nbsp;Adesoji Alani Olanrewaju,&nbsp;Damilohun Samuel Metibemu,&nbsp;Sunday Adeola Emaleku,&nbsp;Taoreed Olakunle Owolabi,&nbsp;Nureni Ipinloju","doi":"10.2174/1570163819666220811094019","DOIUrl":"https://doi.org/10.2174/1570163819666220811094019","url":null,"abstract":"<p><strong>Background: </strong>The continuous increase in mortality of breast cancer and other forms of cancer due to the failure of current drugs, resistance, and associated side effects calls for the development of novel and potent drug candidates.</p><p><strong>Methods: </strong>In this study, we used the QSAR and extreme learning machine models in predicting the bioactivities of some 2-alkoxycarbonylallyl esters as potential drug candidates against MDA-MB-231 breast cancer. The lead candidates were docked at the active site of a carbonic anhydrase target.</p><p><strong>Results: </strong>The QSAR model of choice satisfied the recommended values and was statistically significant. The R²_pred (0.6572) was credence to the predictability of the model. The extreme learning machine ELM-Sig model showed excellent performance superiority over other models against MDAMB- 231 breast cancer. Compound 22 with a docking score of 4.67 kcal mol^-1 displayed better inhibition of the carbonic anhydrase protein, interacting through its carbonyl bonds.</p><p><strong>Conclusion: </strong>The extreme learning machine's ELM-Sig model showed excellent performance superiority over other models and should be exploited in the search for novel anticancer drugs.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"19 6","pages":"e110822207398"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10616637","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 Repositioning: A Unique Approach to Refurbish Drug Discovery.","authors":"Mayura A Kale,&nbsp;Prashant B Shamkuwar,&nbsp;Vishnukant K Mourya,&nbsp;Aishwarya B Deshpande,&nbsp;Priyanka A Shelke","doi":"10.2174/1570163818666210316114331","DOIUrl":"https://doi.org/10.2174/1570163818666210316114331","url":null,"abstract":"<p><p>For a decade, it has been observed that there is a remarkable decrease in the quantum of novel clinically approved drugs, in spite of modernization in the research and development process. We have highlighted repositioning of drugs as a methodology that has found new therapeutic implications for clinically approved drugs but with different indications. This can be considered as an upbringing strategy to deliver timely and cost-effective solutions, which still need exploration for getting over the shortage of novel drugs reaching the market. This review focuses on an activity-based drug repositioning approach, which is used to explore new uses of known drugs that are already approved for specific indications and are now being used for other indications on the basis that a single drug interacts with multiple targets. It also includes current research trends related to drug repositioning, which depends on strong knowledge of medicinal chemistry and involves elucidation of mechanisms of action and validation of novel targets. The review highlights the importance of computational tools and databases of various forms for drug repositioning purposes, which have enhanced the ability to pose reasonable and testable hypotheses. The critical nature of this aspect is obvious in cases where data gathered from in vitro, or animal models do not confirm in subsequent clinical trials. Hence, considering the positive outcomes of drug repositioning, it can be surmised that this approach can serve as a promising one that can develop into a robust drug discovery strategy.</p>","PeriodicalId":10858,"journal":{"name":"Current drug discovery technologies","volume":"19 1","pages":"e140122192307"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25494657","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}