Medicine in Drug Discovery最新文献

{"title":"Nano pharmaceutical delivery in combating colorectal cancer","authors":"Sanju Kumari Singh,&nbsp;Raghu Solanki,&nbsp;Sunita Patel","doi":"10.1016/j.medidd.2023.100173","DOIUrl":"https://doi.org/10.1016/j.medidd.2023.100173","url":null,"abstract":"<div><p>Colorectal cancer (CRC), ranking as the third most common cancer globally, is associated with a high death rate. The colon, also known as the large intestine, is the site where colorectal cancer initially develops. It is a lengthy tube that facilitates the passage of digested food to the rectum and ultimately out of the body. CRC has the potential to affect other organs or regions of the body if not diagnosed or treated earlier.<!--> <!-->Delivering precise medications in a site-specific and target-oriented manner can improve chronic disease therapy in various ways. In recent years, there have been a number of innovations in nanomedicine (including chemotherapeutic medicines, biological agents, immunotherapeutic agents, and other such applications) for the treatment of various diseases, including CRC. The current review provides an up-to-date overview of the latest advancements in the field of nanomedicines and nano-based drug delivery systems for the CRC treatment. An in-depth investigation has been conducted into the study of nanomaterials such as liposomes, metal, polymeric and peptides nanomaterials, exploring their potential applications in enhancing the efficacy of both new and existing drugs. This review also focuses on the opportunities and challenges posed by nanomedicines in delivering drugs derived from natural and synthetic sources. Additionally, information on advancements and future prospects in the field of nanomedicine is provided.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"21 ","pages":"Article 100173"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098623000234/pdfft?md5=01d16a936659495397115211736305eb&pid=1-s2.0-S2590098623000234-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770058","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":"Crocin supplementation in primary open angle glaucoma: A randomized, triple-blind, placebo-controlled clinical trial","authors":"Sina Mahdiani ,&nbsp;Saeed Shokoohi-Rad ,&nbsp;Samaneh Sepahi ,&nbsp;Vahideh Sadat Motamedshariaty ,&nbsp;Seyed Ahmad Mohajeri ,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.medidd.2023.100169","DOIUrl":"https://doi.org/10.1016/j.medidd.2023.100169","url":null,"abstract":"<div><h3>Purpose</h3><p>Glaucoma is the leading cause of irreversible visual loss in the world. The present study was designed to evaluate the beneficial effects of crocin, as a supplement, in the management of primary open-angle glaucoma (POAG).</p></div><div><h3>Methods</h3><p>In total, 50 POAG patients within the age range of 30–71 years with intraocular pressure (IOP) between 12 and 21 mmHg were entered into the study, and ultimately, 40 patients (49 eyes) finished the clinical trial. The participants were randomly divided into crocin and placebo groups. Patients in the crocin group received a 15 mg crocin tablet per day for four months while others, in the placebo group, received a placebo tablet per day for four months besides the main medications during the study. After four months, all patients underwent a two-month washout period. The IOP level and optical coherence tomography of the retinal nerve fiber layer (RNFL), cup-to-disc ratio (CDR), and the best-corrected visual acuity (BCVA), as the secondary outcomes, were measured at baseline, as well as four and six months later.</p></div><div><h3>Results</h3><p>The IOP value decreased significantly in the crocin group after four (P = 0.0001) and six months (P = 0.003). The difference in CDR changes after four and six months was significant between the two groups (P = 0.00009). The crocin and placebo groups did not have a statistically significant difference regarding the changes in BCVA values and RNFL thickness (P = 0.092); however, the optical coherence tomography results showed stable conditions in the retinal nerve fiber layer.</p></div><div><h3>Conclusion</h3><p>This study indicated that administration of crocin, as a potent neuroprotective and antioxidant ingredient of saffron, could be useful as a supplement for the prevention of the POAG progression.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"21 ","pages":"Article 100169"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098623000192/pdfft?md5=e503ac9ecf552172ddef33b956f25542&pid=1-s2.0-S2590098623000192-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138435938","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":"The immunological activities and transcriptome analysis of a potent small-molecule immunomodulator","authors":"Yasser Tabana ,&nbsp;Shima Shahbaz ,&nbsp;Dinesh Babu ,&nbsp;Marawan Ahmed ,&nbsp;Tae Chul Moon ,&nbsp;Frederick G. West ,&nbsp;Richard Fahlman ,&nbsp;Arno G. Siraki ,&nbsp;Shokrollah Elahi ,&nbsp;Khaled Barakat","doi":"10.1016/j.medidd.2024.100178","DOIUrl":"https://doi.org/10.1016/j.medidd.2024.100178","url":null,"abstract":"<div><p>The use of small molecules in immunotherapy is a promising and rapidly growing field with the potential to revolutionize the way we treat a wide range of immunological diseases. The success stories of using small molecules in immunotherapy have been highlighted with many drugs, such as checkpoint inhibitors, which have achieved significant success in treating several types of tumors. However, despite this success, the development of small molecules for immunotherapy is still in its infancy, and there are many challenges that remain to be addressed. In a recent study, our laboratory reported the immunostimulatory effect of a small molecule (Compound A) (A). In this paper, we studied a derivative of this molecule (Compound B) (<span>Fig. 1</span>B). and analysed its physiochemical properties, immunological activities, and transcriptome profiling. Compound B exhibited acceptable metabolic stability and no toxicity against PBMCs. We also demonstrated that Compound B was capable of modulating the immune system by inducing pro-inflammatory cytokines and promoting T-cell proliferation. RNAseq results showed that Compound B was able to significantly upregulate genes involved in stimulating the immune response pathways. Our findings suggest that Compound B may serve as a promising therapeutic agent to modulate the immune system. The identification and validation of the molecular targets responsible for its immunological activities are underway.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"21 ","pages":"Article 100178"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000034/pdfft?md5=eeea728aad91880605a126d378551ea8&pid=1-s2.0-S2590098624000034-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139675288","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":"Therapeutic potential of snake venom: Toxin distribution and opportunities in deep learning for novel drug discovery","authors":"Anas Bedraoui ,&nbsp;Montamas Suntravat ,&nbsp;Salim El Mejjad ,&nbsp;Salwa Enezari ,&nbsp;Naoual Oukkache ,&nbsp;Elda E. Sanchez ,&nbsp;Jacob A. Galan ,&nbsp;Rachid El Fatimy ,&nbsp;Tariq Daouda","doi":"10.1016/j.medidd.2023.100175","DOIUrl":"https://doi.org/10.1016/j.medidd.2023.100175","url":null,"abstract":"<div><p>Snake venom is a rich source of bioactive molecules that hold great promise for therapeutic applications. These molecules can be broadly classified into enzymes and non-enzymes, each showcasing unique medicinal properties. Noteworthy compounds such as Bradykinin Potentiating Peptides (BPP) and Three-Finger Toxins (3FTx) are showing therapeutic potential in areas like cardiovascular diseases (CVDs) and pain-relief. Meanwhile, components like snake venom metalloproteinases (SVMP), L-amino acid oxidases (LAAO), and Phospholipase A₂s (PLA₂) are paving new ways in oncology treatments. The full medicinal scope of these toxins is still emerging. In this review, we discuss drugs derived from snake venoms that address CVDs, cancer, diabetes, strokes, and pain. Further, we outline the toxin distribution across 130 snake species, categorized by their genus within the Crotalidae, Viperidae, and Elapidae families. Conclusively, we spotlight the potential of Deep Learning (DL) in discovering groundbreaking drug prospects from these toxins.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"21 ","pages":"Article 100175"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098623000258/pdfft?md5=0181aadcf2ae497d00ce69590c6e8d11&pid=1-s2.0-S2590098623000258-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139100924","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":"Biomarkers navigate drug development: Pharmacology, effectiveness and safety","authors":"Daohong Chen","doi":"10.1016/j.medidd.2023.100174","DOIUrl":"10.1016/j.medidd.2023.100174","url":null,"abstract":"<div><p>Recent decades have witnessed a paradigm shift from traditional therapy to precision medicine, which was substantially facilitated by implementing biomarker strategy. Taking the advantages of contemporary biological sciences and advanced technology, novel biomarkers are increasingly identified and validated in numerous aspects of pharmaceutical development, thus leading to the success of emerging medications for unmet clinical needs. Herein, this article presents a comprehensive update on evolving trends of biomarkers in the field, covering the applied pharmacology, therapeutic guidance/monitoring, patient stratification, toxicity detection, among others. In this light, it tends not only to improve the efficiency of drug development and the outcome of medical care, but also to optimize the entire life cycle assessment of pharmaceutical products.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"21 ","pages":"Article 100174"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098623000246/pdfft?md5=a9ba2092529170ebd6ce2ff2e4137966&pid=1-s2.0-S2590098623000246-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139020207","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":"The use of furosemide during Intravenous Immunoglobulin therapy should not always be considered contraindicated","authors":"Serdar EFE ,&nbsp;Fatih Demircan ,&nbsp;Anıl UÇAN ,&nbsp;Volkan İNAL","doi":"10.1016/j.medidd.2023.100171","DOIUrl":"https://doi.org/10.1016/j.medidd.2023.100171","url":null,"abstract":"<div><h3>Aims</h3><p>Endothelial damage in acute respiratory distress syndrome (ARDS) increases capillary permeability, resulting in an increase in free lung fluid, interstitial pulmonary edema, and ventilation-perfusion imbalance. Due to their high osmolarity, Intravenous Immunoglobulin (IVIG) treatment may deepen hypoxemia by increasing lung fluid leakage. Adding furosemide to IVIG treatment in ARDS secondary to COVID-19 (CARDS) cases may increase treatment tolerance and success.</p></div><div><h3>Materials and methods</h3><p>In our study, we aimed to measure the effectiveness of this treatment combination in CARDS cases and to report the observed complications. Patients who were followed up in the 34-bed adult COVID intensive care unit between March 2020/2021 and who received IVIG, high-dose corticosteroid, and furosemide combination therapy were included in the study. Patients' age, gender, comorbidities, Acute Physiology, and Chronic Health Assessment II (APACHE-II), and Sequential Organ Failure Assessment (SOFA) scores were recorded. The day IVIG duration of treatment, additional medical treatments, respiratory support treatments, laboratory examinations, the percentage of involvement of lung lesions (Covid Visual Assessment Scale), clinical outcomes, and treatment complications were recorded.</p></div><div><h3>Results</h3><p>Combination therapy with found to improve respiratory failure in 50 % of patients. Troponin elevation was found in two patients, femoral artery embolism in one patient, and thrombosis in the femoral vein in one patient. In addition to IVIG treatment, the administration of two doses of immune plasma increased the chance of discharge (P = 0.037)</p></div><div><h3>Conclusion</h3><p>In severe viral ARDS refractory to standard therapy, using furosemide in addition to IVIG therapy has an acceptable side-effect profile and may increase treatment success. Furosemide given during IVIG therapy should not be considered a contraindication in every patient.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"21 ","pages":"Article 100171"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098623000210/pdfft?md5=139e029bcef93e7f95d84e13b1e3e7c5&pid=1-s2.0-S2590098623000210-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138474242","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":"Revealing key structural features for developing new agonists targeting δ opioid receptor: Combined machine learning and molecular modeling perspective","authors":"Zeynab Fakhar ,&nbsp;Ali Hosseinpouran ,&nbsp;Orde Q. Munro ,&nbsp;Sorena Sarmadi ,&nbsp;Sajjad Gharaghani","doi":"10.1016/j.medidd.2024.100176","DOIUrl":"10.1016/j.medidd.2024.100176","url":null,"abstract":"<div><p>Despite being the most widely prescribed and misused type of medication, opioids continue to function as robust pain relief agents; however, overdosing is a significant cause of fatalities among opioid users. The δ-opioid receptor (DOR) has immense promise in treating long-term pain by producing anxiolytic and antidepressant-like outcomes. Although DOR agonists play a crucial role, their clinical implementation is restricted because of the probable manifestation of severe, life-threatening complications. A Python-based machine learning approach was employed to develop a quantitative structure–activity relationship (QSAR) model in this study. To address this, 4217 compounds and their associated biological inhibition activities were retrieved from the gpcrdb database. The K-best features selection method revealed three key structural features such as SLOGPVSA2, Chi6ch, and S17 contributed significantly to the best model performance. Statistical analysis, K-fold cross-validation, applicability domain analysis, and external validation using 38 unseen FDA-approved drug data confirmed the robustness of the predictive model. A molecular docking study in along with Ligand–Receptor Contact Fingerprints (LRCFs) using the essential chemical interactions described for analog ligands releaved the key contact interactions of Asp 128, Tyr 129, Met 132, Trp 274, Ile 277, and Tyr 308 residues in the total binding affinities upon complexation. Our combinatorial study using regression QSAR and ligand–receptor Contact, analysis could serve in the design of more rational compounds for drug discovery targeting DOR.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"21 ","pages":"Article 100176"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098624000010/pdfft?md5=dcc745d04bc41e8a714b7b19587b9f57&pid=1-s2.0-S2590098624000010-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139538669","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":"Microemulsions for enhancing drug delivery of hydrophilic drugs: Exploring various routes of administration","authors":"Khushwant S. Yadav ,&nbsp;Govind Soni ,&nbsp;Deepak Choudhary ,&nbsp;Arushee Khanduri ,&nbsp;Ayush Bhandari ,&nbsp;Garima Joshi","doi":"10.1016/j.medidd.2023.100162","DOIUrl":"https://doi.org/10.1016/j.medidd.2023.100162","url":null,"abstract":"<div><p>Microemulsions are a promising drug delivery system that can be used to enhance the bioavailability, solubility, and therapeutic efficacy of hydrophilic drugs. The downside of hydrophilic drugs is the poor solubility in lipid-based media; therefore, they require frequent dosing or high doses to achieve the therapeutic level. This may lead to unintended adverse effects and<!--> <!-->poor patient compliance Microemulsions can improve drug delivery by incorporating hydrophilic drugs within a thermodynamically stable and transparent oil-in-water emulsion. This can optimize the drug's solubility and permeability, leading to enhanced bioavailability and therapeutic efficacy. This review provides an insight to various routes of administration for delivering hydrophilic drugs using microemulsion. It will explore the use of microemulsion for oral, nasal, transdermal, and ocular delivery. The review also discusses the advantages, disadvantages and the physicochemical properties associated with each one of it. Overall, the article aims to provide a comprehensive overview of the use of microemulsions as a drug delivery system for hydrophilic drugs administered via different routes.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"20 ","pages":"Article 100162"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50185703","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":"Bac-EPIC: A web interface for developing novel efflux pump inhibitor compounds targeting Escherichia coli","authors":"Shweta Singh Chauhan ,&nbsp;Priyam Pandey ,&nbsp;Sabrina Manickam ,&nbsp;Ramakrishnan Parthasarathi","doi":"10.1016/j.medidd.2023.100164","DOIUrl":"https://doi.org/10.1016/j.medidd.2023.100164","url":null,"abstract":"<div><p>Multidrug resistance (MDR) poses a severe threat to human health. The existence of efflux pumps primarily contributes to resistance in Gram-negative bacterial infections. Efflux pump inhibitors (EPIs) can potentially improve the efficacy of antibiotics and reduce bacterial pathogenicity by inhibiting the mechanism of these pumps. Here we report Bac-EPIC, a web interface consisting of AcrA_Ipred, and AcrB_Ipred tools, can aid in the identification of potential EPIs that might bind to AcrAB-TolC pump subunits, alter its structure <em>in vivo</em>, prevent efflux, and enhance antibiotic efficacy in <em>Escherichia coli (E. coli)</em> and other Gram-negative bacteria. The web server is developed by collecting and archiving structural moieties from literature-reported EPIs. The web interface can be utilized in decision-making upon structural similarity-based screening on whether a compound should be examined experimentally or disregarded. It takes the SMILES<!--> <!-->format of chemical structure as an input. Users can also draw the 2D structure and get the output report of the possible structural similarity profile, similarity percentage, and the active moieties in the compound. The designed web interface is publicly accessible for <em>in silico</em> efflux pump inhibition prediction, at <span>http://14.139.62.46/AcrAB_Ipred/</span><svg><path></path></svg>. Overall, the webserver increases the diversity of EPIs, and proposes mechanistic insights to understand and regulate the efflux pump assembly &amp; its function, ultimately aiding in fight against antibiotic resistance.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"20 ","pages":"Article 100164"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590098623000143/pdfft?md5=8dfb28f7021c5ffa0d1e8f0c741f1fb7&pid=1-s2.0-S2590098623000143-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92046167","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":"Exploring potential of exosomes drug delivery system in the treatment of cancer: Advances and prospective","authors":"Deepika Yadav,&nbsp;Rishabha Malviya","doi":"10.1016/j.medidd.2023.100163","DOIUrl":"https://doi.org/10.1016/j.medidd.2023.100163","url":null,"abstract":"<div><p>Exosomes are vital for cellular communication and the transfer of materials between cells. Recently, it has been shown that nanoparticles may be used as diagnostic indicators and as a potential medicine delivery strategy due to their nanoscale size and capacity to carry biological components to target cells. Exosomes have the potential to be an appealing and practical approach for drug administration in cancer treatment due to their biocompatibility, high stability, favoured tumour homing, and adjustable targeting efficacy. While exosomes have properties that make them useful for transporting bioactive compounds, the gap between our present understanding of exosome biology and the most optimal condition for their use remains. The rationale for using exosomes as a drug delivery strategy, their production and purification, bioengineering and targeting, uptake and distribution, efficacy, immune response, and other factors will all be discussed in this study. Modern methods are required for observing, categorising, and sorting exosome diversity. Improvements in nanotechnology and our knowledge of exosome biology will undoubtedly speed up the field's medical uses.</p></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"20 ","pages":"Article 100163"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50185702","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}