In Silico Pharmacology最新文献

{"title":"Molecular docking studies, in-silico ADMET predictions and synthesis of novel PEGA-nucleosides as antimicrobial agents targeting class B1 metallo-β-lactamases.","authors":"Jesica A Mendoza,&nbsp;Richard Y Pineda,&nbsp;Michelle Nguyen,&nbsp;Marisol Tellez,&nbsp;Ahmed M Awad","doi":"10.1007/s40203-021-00092-z","DOIUrl":"https://doi.org/10.1007/s40203-021-00092-z","url":null,"abstract":"<p><p>Class B1 metallo-β-lactamases (MBLs) are metalloenzymes found in drug resistant bacteria. The enzyme requires zinc ions, along with conserved amino acid coordination for nucleophilic attack of the lactam ring to induce hydrolysis and inactivation of β-lactam and some carbapenem antibiotics. To this date there are no clinically relevant class B1 MBL inhibitors, however L-captopril has shown significant results against NDM-1, the most difficult MBL to inhibit. Herein, we report the synthesis and evaluation of novel nucleoside analogues modified with polyethylene glycolamino (PEGA) as potential inhibitors for class B1 MBLs. Molecular dynamics simulations, using internal coordinate mechanics (ICM) algorithm, were performed on subclass B1 enzyme complex models screened with twenty-one possible PEGA-nucleosides. Analogue <b>A</b>, <i>3'-deoxy-3'-</i>(<i>2-</i>(<i>2-hydroxyethoxy</i>)<i>ethanamino</i>)<i>-β-D-xylofuranosyluracil</i> showed superior binding, with high specificity to the conserved zinc ions in the class B1 MBL active site by utilizing key β-lactam mimic points in the uridine nucleobase. The PEGA moiety showed chelating activity with zinc and disrupted the metal-binding amino acid geometry. In all subclass B1 proteins tested, analogue <b>A</b> had the most effective inhibition when compared to penicillin or L-captopril. Chemical synthesis was performed by condensation of the corresponding keto ribonucleoside with PEGA, followed by enantioselective reduction of the formed imine to produce the amino derivative with desired configuration. Pharmacokinetic and pharmacodynamic screenings revealed that PEGA-pyrimidine nucleosides are not toxic, nor violate Lipinski's rules. These results suggested that analogue <b>A</b> can be proposed as a potential metalloenzyme inhibitor against the widespread antibiotic resistant bacteria and is worth further in vitro and in vivo investigations.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"33"},"PeriodicalIF":0.0,"publicationDate":"2021-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00092-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38940715","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":"In silico analysis of the antidiabetic terpenoid acankoreagenin binding to PPARγ.","authors":"Gérard Vergoten, Christian Bailly","doi":"10.1007/s40203-021-00091-0","DOIUrl":"10.1007/s40203-021-00091-0","url":null,"abstract":"<p><p>Acankoreagenin (ACK) is a lupane triterpene found in several <i>Acanthopanax</i> and <i>Schefflera</i> plant species. ACK, also known as acankoreanogenin or HLEDA, bears a major structural analogy with other lupane triterpenoids such as impressic acid (IA) and the largely used phytochemical betulinic acid (BA). These compounds display marked anti-inflammatory, anti-diabetes, and anti-cancer properties. BA can form stable complexes with the peroxisome proliferator-activated receptor gamma (PPARγ). The tridimensional structure of the BA-PPARγ complex was used to perform a molecular docking analysis of the binding of ACK and IA to the protein. The 3-hydroxyl epimers (<i>R/S</i>) of each natural product were also modeled to examine the role of the C3-OH stereochemistry that distinguishes BA [3(<i>S</i>)] from ACK and AI [3(<i>R</i>)]. Calculations indicate that ACK can form more stable complexes with PPARγ than BA, upon insertion of the drug into the same binding pocket. The inversion of the C3-OH stereochemistry is not an obstacle for binding and the additional carboxy group of ACK at C23 position seems to reinforce the protein interaction. The 3-hydroxyl group does not play a major role in the geometry of the protein-drug complex, which is preserved between BA and ACK. Additional structure-binding relationships are provided, through the evaluation of the PPARγ binding capacity of ACK derivatives. Binding of ACK to PPARγ would account for its marked antidiabetic effect, at least partially. ACK can be used as a platform to design new antidiabetic compounds.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"32"},"PeriodicalIF":0.0,"publicationDate":"2021-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050143/pdf/40203_2021_Article_91.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38940714","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":"Comparative performance of extreme learning machine and Hammerstein-Weiner models for modelling the intestinal hyper-motility and secretory inhibitory effects of methanolic leaf extract of <i>Combretumhypopilinum</i> Diels (Combretaceae).","authors":"Mubarak Hussaini Ahmad,&nbsp;A G Usman,&nbsp;S I Abba","doi":"10.1007/s40203-021-00090-1","DOIUrl":"https://doi.org/10.1007/s40203-021-00090-1","url":null,"abstract":"<p><p>In this article, three data-driven approaches were explored, including two artificial intelligence (AI) based models namely; Extreme Learning Machine (ELM) and Hammerstein-Weiner (HW) models and a trivial linear model namely; multilinear regression (MLR). In this context, the models were developed using the onset of diarrhoea, the total number of wet faeces, total number of faeces, weight of intestinal content (g) and length of the small intestine (cm) as the independent variables. In contrast, distance travelled by charcoal meal (C) and volume of intestinal content (I) were considered as the dependent variables for the prediction of the intestinal hypermotility and secretory inhibitory effects of the methanol leaf extract of <i>Combretum hypopilinum</i> (MECH). Three different performance indicators including; mean absolute percentage error (MAPE), Nash-Sutcliffe efficiency (NSE) and Root mean square error (RMSE) were employed in this research to calculate and determine the performance skills of the models. The obtained results indicated the reliable capability of ELM and HW over MLR model having NSE-values higher than 0.90 in both the calibration and verification stages. The results further demonstrated that, in terms of MAPE and RMSE, ELM and HW models showed higher performance efficiency than the MLR model. Even though HW outperformed the ELM and MLR models in the prediction of I. Whereas, ELM outperformed HW and MLR models in the prediction of C. Overall; the results proved the satisfactory ability of the AI-based models (HW and ELM) for modelling the Intestinal hypermotility and secretory inhibitory effects of MECH.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"31"},"PeriodicalIF":0.0,"publicationDate":"2021-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00090-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38932258","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":"Identification of PTP1B regulators from <i>Cymbopogon citratus</i> and its enrichment analysis for diabetes mellitus.","authors":"Prarambh S R Dwivedi, Pukar Khanal, Vishakha Parab Gaonkar, V P Rasal, B M Patil","doi":"10.1007/s40203-021-00088-9","DOIUrl":"10.1007/s40203-021-00088-9","url":null,"abstract":"<p><p>PTP1B is identified as the insulin signaling pathway downregulator; involved in pancreatic β-cell apoptosis. Further, it associates in regulating multiple pathways in diabetes mellitus; kindled us to identify the binding affinity of bioactives from <i>Cymbopogon citratus</i> by targeting PTP1B and identify the probably associated with it; further identifying the probable pathways involved in diabetes mellitus. In this regard, ChEBI database was used to retrieve bio-actives from <i>C. citrates</i> and 3D structures for the same were obtained from the PubChem database. The energy of bioactives was minimized and converted into ligand and the docking was carried using autodock 4.0 against PTP1B. Further, multiple characters of bio-actives like drug-likeness score, ADMET profile, probable adverse effects, and boiled egg model for bioavailability were also studied. Swertiajaponin was predicted for the highest drug-likeness score i.e. 0.26. However, swertiajaponin was predicted with the highest probable side effect of nephrotoxicity with pharmacological activity of 0.478. Similarly, swertiajaponin was predicted for the highest binding affinity with PTP1B with the binding energy of - 8.3 kcal/mol. Likewise, KEGG identified 80 pathways associated with PTP1B modulation in which 7 pathways were involved in diabetes mellitus in which FoxO signaling pathway was predicted to have the least false discovery rate by modulating 7 genes. Swertiajaponin could act as the potent inhibitor of PTP1B; scored highest druglikeness score but possessed minimum GIT absorptivity; further, PTP1B was identified to be linked with multiple pathways that are concerned with diabetes mellitus.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"30"},"PeriodicalIF":0.0,"publicationDate":"2021-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039068/pdf/40203_2021_Article_88.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38932257","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":"Clinical pharmacokinetic study of latrepirdine via in silico sublingual administration.","authors":"Joana Santos,&nbsp;Luísa Lobato,&nbsp;Nuno Vale","doi":"10.1007/s40203-021-00083-0","DOIUrl":"https://doi.org/10.1007/s40203-021-00083-0","url":null,"abstract":"<p><p>In recent decades, numerous in silico methodologies have been developed focused on the study of pharmacodynamic, pharmacokinetics and toxicological properties of drugs. The study of the pharmacokinetic behavior of new chemical entities is an essential part of the successful development of a new drug and Gastroplus™ is a simulation software used to predict the pharmacokinetic behavior of chemical entities. Latrepirdine is a drug that has been studied for Alzheimer's disease and Huntington's disease and later abandoned by the pharmaceutical industry already in the clinical trials because it has not demonstrated therapeutic efficacy. During this project, through Gastroplus™ simulations, it was possible to achieve predicted values of C_max coincident with those found in clinical trials, showing its utility in the prediction of pharmacokinetic parameters. Besides, sublingual delivery has the potential to offer improved bioavailability by circumventing first-pass metabolism. This study used GastroPlus™ to simulate sublingual administration of latrepirdine and the results showed improvements in bioavailability and plasma concentrations achieved though this route of administration.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"29"},"PeriodicalIF":0.0,"publicationDate":"2021-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00083-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38828298","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":"Computational screening of FDA approved drugs of fungal origin that may interfere with SARS-CoV-2 spike protein activation, viral RNA replication, and post-translational modification: a multiple target approach.","authors":"Rajveer Singh,&nbsp;Anupam Gautam,&nbsp;Shivani Chandel,&nbsp;Vipul Sharma,&nbsp;Arijit Ghosh,&nbsp;Dhritiman Dey,&nbsp;Syamal Roy,&nbsp;V Ravichandiran,&nbsp;Dipanjan Ghosh","doi":"10.1007/s40203-021-00089-8","DOIUrl":"https://doi.org/10.1007/s40203-021-00089-8","url":null,"abstract":"<p><p>Coronavirus spread is an emergency reported globally, and a specific treatment strategy for this significant health issue is not yet identified. COVID-19 is a highly contagious disease and needs to be controlled promptly as millions of deaths have been reported. Due to the absence of proficient restorative alternatives and preliminary clinical restrictions, FDA-approved medications can be a decent alternative to deal with the coronavirus malady (COVID-19). The present study aims to meet the imperative necessity of effective COVID-19 drug treatment with a computational multi-target drug repurposing approach. This study focused on screening the FDA-approved drugs derived from the fungal source and its derivatives against the SARS-CoV-2 targets. All the selected drugs showed good binding affinity towards these targets, and out of them, bromocriptine was found to be the best candidate after the screening on the COVID-19 targets. Further, bromocriptine is analyzed by molecular simulation and MM-PBSA study. These studies suggested that bromocriptine can be the best candidate for TMPRSS2, Main protease, and RdRp protein.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-021-00089-8.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"27"},"PeriodicalIF":0.0,"publicationDate":"2021-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00089-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25591200","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":"In silico local QSAR modeling of bioconcentration factor of organophosphate pesticides.","authors":"Purusottam Banjare, Balaji Matore, Jagadish Singh, Partha Pratim Roy","doi":"10.1007/s40203-021-00087-w","DOIUrl":"10.1007/s40203-021-00087-w","url":null,"abstract":"<p><p>The persistent and accumulative nature of the pesticide of indiscriminate use emerged as ecotoxicological hazards. The bioconcentration factor (BCF) is one of the key elements for environmental assessments of the aquatic compartment. Limitations of prediction accuracy of global model facilitate the use of local predictive models in toxicity modeling of emerging compounds. The BCF data of diverse organophosphate (n = 55) was collected from the Pesticide Properties Database and used as a model data set in the present study to explore physicochemical properties and structural alert concerning BCF. The structures were downloaded from Pubchem, ChemSpider database. Two splitting techniques (biological sorting and structure-based) were used to divide the whole dataset into training and test set compounds. The QSAR study was carried out with two-dimensional descriptors (2D) calculated from PaDEL by applying genetic algorithm (GA) as chemometric tools using QSARINS software. The models were statistically robust enough both internally as well as externally (Q²: 0.709-0.722, Q² _Ext: 0.717-0.903, CCC: 0.857-0.880). Overall molecular mass, presence of fused, and heterocyclic ring with electron-withdrawing groups affect the BCF value. The developed models reflected extended applicability domain (AD) and reliable predictions than the reported models for the studied chemical class. Finally, predictions of unknown organophosphate pesticides and the toxic nature of unknown organophosphate pesticides were commented on. These findings may be useful for the scientific community in prioritizing high potential pesticides of organophosphate class.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"28"},"PeriodicalIF":0.0,"publicationDate":"2021-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019672/pdf/40203_2021_Article_87.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38818771","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 the antidiabetic potential of compounds isolated from <i>Anacardium occidentale</i> using computational aproach: ligand-based virtual screening.","authors":"Victor Okoliko Ukwenya,&nbsp;Sunday Aderemi Adelakun,&nbsp;Olusola Olalekan Elekofehinti","doi":"10.1007/s40203-021-00084-z","DOIUrl":"https://doi.org/10.1007/s40203-021-00084-z","url":null,"abstract":"<p><p>Diabetes mellitus is becoming an important public health challenge worldwide and especially in developing nations. About 8.8 percent of the world adult population has been reported to have diabetes. Glutamine-fructose-6-phosphate amidotransferase 1 (GFAT1) catalyses the first committed step in the pathway for biosynthesis of hexosamines in mammals, and its inhibition has been thought to prevent hyperglycaemia. Dipeptidyl peptidase-4 (DPP-4), on the other hand, degrades hormone glucagon-like peptide-1 (GLP-1), an enzyme that plays a major role in the enhancement of glucose-dependent insulin secretion, making these two proteins candidate targets for diabetes. To find potential inhibitors of DPP-4 and GFAT1 from Anacardium occidentale using a computational approach, glide XP (extra precision) docking, Induced Fit Docking (IFD), Binding free energy of the compounds were determined against prepared crystal structure of DPP-4 and GFAT1 using the Maestro molecular interface of Schrödinger suites. The Lipinski's rule of five (RO5) and ADME properties of the compounds were assessed. Predictive models for both protein targets were built using AutoQSAR. This study identified 8 hit compounds. Most of these compounds passed the RO5 and were within the recommended range for defined ADME parameters. In addition, the predicted pIC50 for the hit compounds were promising. The results obtained from the present study can be used to design an antidiabetic drug.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-021-00084-z.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"25"},"PeriodicalIF":0.0,"publicationDate":"2021-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00084-z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38805984","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":"Topoisomerase II as a target for repurposed antibiotics in <i>Candida albicans</i>: an in silico study.","authors":"Ashwini Khanderao Jadhav,&nbsp;Sankunny Mohan Karuppayil","doi":"10.1007/s40203-021-00082-1","DOIUrl":"https://doi.org/10.1007/s40203-021-00082-1","url":null,"abstract":"<p><p>Fluoroquinolines, the widely used antibacterial antibiotics, have been shown to interact with human DNA topoisomerases supporting their use as repurposed cancer drugs in humans. In this communication molecular docking of eleven Fluoroquinolines against predicted structure of <i>Candida albicans DNA</i> Topoisomerase II is reported for the first time. <i>C. albicans</i> topoisomerase II structure prediction was done by using homology modeling tool. Ligand preparation and molecular docking with <i>C. albicans</i> topoisomerase II were done by using Autodock tool. These antibiotics formed hydrogen bond with good binding affinity at ARG 841, GLN803, ALA840 amino acid residues in the active site of <i>C. albicans</i> Topoisomerase II. We hypothesize that DNA toposiomerases may be the targets of Fluroquinoline group of antibiotics in <i>C. albicans</i> causing inhibition of growth.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2021-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00082-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38805983","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":"Optimizing Bedaquiline for cardiotoxicity by structure based virtual screening, DFT analysis and molecular dynamic simulation studies to identify selective MDR-TB inhibitors.","authors":"Iqrar Ahmad,&nbsp;Harsha Jadhav,&nbsp;Yashodeep Shinde,&nbsp;Vilas Jagtap,&nbsp;Rukaiyya Girase,&nbsp;Harun Patel","doi":"10.1007/s40203-021-00086-x","DOIUrl":"https://doi.org/10.1007/s40203-021-00086-x","url":null,"abstract":"<p><p>Since the last 4 decades, Bedaquiline has been the first drug discovered as a new kind of anti-tubercular agent and received FDA approval in December 2012 to treat pulmonary multi-drug resistance tuberculosis (MDR-TB). It demonstrates excellent efficacy against MDR-TB by effectively inhibiting mycobacterial ATP synthase. In addition to these apparent assets of Bedaquiline, potential disadvantages of Bedaquiline include inhibition of the hERG (human Ether-à-go-related gene; KCNH2), potassium channel (concurrent risk of cardiac toxicity), and risk of phospholipidosis due to its more lipophilic nature. To assist the effective treatment of MDR-TB, highly active Bedaquiline analogs that display a better safety profile are urgently needed. A structure-based virtual screening approach was used to address the toxicity problems associated with Bedaquiline. Among the virtually screened compound, CID 15947587 had significant docking affinity (- 5.636 kcal/mol) and highest binding free energy (ΔG bind - 85.2703 kcal/mol) towards the <i>Mycobacterial</i> ATP synthase enzyme with insignificant cardiotoxicity and lipophilicity. During MD simulation studies (50 ns), the molecule optimizes its conformation to fit better the active receptor site justifying the binding affinity. The obtained results showed that CID15947587 could be a useful template for further optimizing the MDR-TB inhibitor.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-021-00086-x.</p>","PeriodicalId":13380,"journal":{"name":"In Silico Pharmacology","volume":" ","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2021-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40203-021-00086-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25592046","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}