Current Research in Pharmacology and Drug Discovery最新文献

{"title":"Present status with impacts and roles of miRNA on Soil Transmitted Helminthiosis control: A review","authors":"Imon Mitra ,&nbsp;Arijit Bhattacharya ,&nbsp;Joydeep Paul ,&nbsp;Anisuzzaman","doi":"10.1016/j.crphar.2023.100162","DOIUrl":"10.1016/j.crphar.2023.100162","url":null,"abstract":"<div><p>Soil-Transmitted Helminthiasis (STH) is one of the most widespread Neglected Tropical Diseases (NTDs), and almost 1.5 billion of the global population is affected, mostly in the indigent, countryside sectors of tropics/subtropics. STH, commonly caused by various nematodes, adversely affects the hosts’ growth, cognatic development, and immunity. Albendazole is most commonly used against STH (Soil-Transmitted Helminths) but resistance has already been reported in different countries. To date, no effective vaccine is present against STH. miRNAs are a unique class of small non-coding RNA, regulating various biological activities indulging host immune responses in host-pathogen interaction of STH. Dysregulation of miRNAs are being considered as one of the most important aspect of host-parasite interactions. Thus, it is the prime importance to identify and characterize parasite-specific as well as host-derived miRNAs to understand the STH infection at the molecular level. Systematic bibliometric analysis reveals a huge knowledge gap in understanding the disease by using both host and parasitic miRNAs as a potential biomarker. In this study, we addressed the present status of the STH prevalence, and therapy under the light of miRNAs. This would further help in designing new inhibitors and therapeutic strategies to control STH.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"5 ","pages":"Article 100162"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c9/5b/main.PMC10371793.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9963935","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":"Characterization of a novel positive allosteric modulator of the α1A-Adrenergic receptor","authors":"Robert S. Papay ,&nbsp;Jonathan D. Macdonald ,&nbsp;Shaun R. Stauffer ,&nbsp;Dianne M. Perez","doi":"10.1016/j.crphar.2022.100142","DOIUrl":"https://doi.org/10.1016/j.crphar.2022.100142","url":null,"abstract":"<div><p>α₁-Adrenergic Receptors (ARs) are G-protein Coupled Receptors (GPCRs) that regulate the sympathetic nervous system via the binding and activation of norepinephrine (NE) and epinephrine (Epi). α₁-ARs control various aspects of neurotransmission, cognition, cardiovascular functions as well as other organ systems. However, therapeutic drug development for these receptors, particularly agonists, has been stagnant due to unwanted effects on blood pressure regulation. We report the synthesis and characterization of the first positive allosteric modulator (PAM) for the α₁-AR based upon the derivation of the α_1A-AR selective imidazoline agonist, cirazoline. Compound 3 (Cmpd-3) binds the α_1A-AR with high and low affinity sites (0.13pM; 54 ​nM) typical of GPCR agonists, and reverts to a single low affinity site of 100 ​nM upon the addition of GTP. Comparison of Cmpd-3 versus other orthosteric α_1A-AR-selective imidazoline ligands reveal unique properties that are consistent with a type I PAM. Cmpd-3 is both conformationally and ligand-selective for the α_1A-AR subtype. In competition binding studies, Cmpd-3 potentiates NE-binding at the α_1A-AR only on the high affinity state of NE with no effect on the Epi-bound α_1A-AR. Moreover, Cmpd-3 demonstrates signaling-bias and potentiates the NE-mediated cAMP response of the α_1A-AR at nM concentrations with no effects on the NE-mediated inositol phosphate response. There are no effects of Cmpd-3 on the signaling at the α_1B- or α_1D-AR subtypes. Cmpd-3 displays characteristics of a pure PAM with no intrinsic agonist properties. Specific derivation of Cmpd-3 at the R1 <em>ortho</em>-position recapitulated PAM characteristics. Our results characterize the first PAM for the α₁-AR and holds promise for a first-in-class therapeutic to treat various diseases without the side effect of increasing blood pressure intrinsic to classical orthosteric agonists.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100142"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49771910","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":"A novel drug-like water-soluble small molecule Focal Adhesion Kinase (FAK) activator promotes intestinal mucosal healing","authors":"Qinggang Wang ,&nbsp;Ricardo Gallardo-Macias ,&nbsp;Emilie E. Vomhof-DeKrey ,&nbsp;Rashmi Gupta ,&nbsp;Svetlana A. Golovko ,&nbsp;Mikhail Y. Golovko ,&nbsp;Sema Oncel ,&nbsp;Vadim J. Gurvich ,&nbsp;Marc D. Basson","doi":"10.1016/j.crphar.2022.100147","DOIUrl":"10.1016/j.crphar.2022.100147","url":null,"abstract":"<div><p>Non-steroidal anti-inflammatory drugs (NSAIDs) injure the proximal and distal gut by different mechanisms. While many drugs reduce gastrointestinal injury, no drug directly stimulates mucosal wound healing. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, induces epithelial sheet migration.</p><p>We synthesized and evaluated a water-soluble FAK-activating small molecule, M64HCl, with drug-like properties. Monolayer wound closure and Western blots measured migration and FAK phosphorylation in Caco-2 ​cells, in vitro kinase assays established FAK activation, and pharmacologic tests assessed drug-like properties. 30 ​mg/kg/day M64HCl was administered in two murine small intestine injury models for 4 days.</p><p>M64HCl (0.1–1000 ​nM) dose-dependently increased Caco-2 FAK-Tyr 397 phosphorylation, without activating Pyk2 and accelerated Caco-2 monolayer wound closure. M64HCl dose-responsively activates the FAK kinase domain vs. the non-salt M64, increasing the V_max of ATP-binding. Pharmacologic tests suggested M64HCl has drug-like properties and is enterally absorbed. M64HCl 25 ​mg/kg/day continuous infusion promoted healing of ischemic jejunal ulcers and indomethacin-induced small intestinal injury in C57Bl/6 mice. M64HCl-treated mice exhibited smaller ulcers 4 days after ischemic ulcer induction or indomethacin injury. Renal histology and plasma creatinine were normal. Mild hepatic inflammatory changes and ALT elevation were similar among M64HCl-treated mice and controls. M64HCl was concentrated in kidney and gastrointestinal mucosa and functional nephrectomy studies suggested predominantly urinary excretion. Little toxicity was observed in vitro or in single-dose mouse toxicity studies until &gt;1000x higher than effective concentrations. M64HCl, a water-soluble FAK activator, promotes epithelial restitution and intestinal mucosal healing and may be useful to treat gut mucosal injury.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100147"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/2b/main.PMC9827036.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9954430","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":"WITHDRAWN: Myoinositol supplementation for the prevention of gestational diabetes in at-risk patients. Systematic review and meta-analysis","authors":"Anthéa Bertrand ,&nbsp;Denis Gallot ,&nbsp;Bruno Pereira ,&nbsp;Amélie Delabaere","doi":"10.1016/j.crphar.2022.100140","DOIUrl":"https://doi.org/10.1016/j.crphar.2022.100140","url":null,"abstract":"<div><p>This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (<span>http://www.elsevier.com/locate/withdrawalpolicy)</span><svg><path></path></svg>.</p><p>This article has been withdrawn at the request of Author.</p><p>The publisher apologizes to the readers for this unfortunate error.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100140"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49769293","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":"Sex differences in drug effects and/or toxicity in oncology","authors":"H.T. Rakshith ,&nbsp;S. Lohita ,&nbsp;Anvil Preem Rebello ,&nbsp;Prakash S. Goudanavar ,&nbsp;N. Raghavendra Naveen","doi":"10.1016/j.crphar.2022.100152","DOIUrl":"10.1016/j.crphar.2022.100152","url":null,"abstract":"<div><p>The prevalence, incidence, and severity of a wide variety of diseases and ailments are significantly influenced by the significant disparities that occur between the sexes. The way that men and women react to pharmacological treatment also varies. Therefore, it is crucial to comprehend these reactions in order to conduct risk assessment correctly and to develop safe and efficient therapies. Even from that limited vantage point, the manner and timing of our drug usage might have unintended and unanticipated consequences. There are sex-specific differences in the incidence and mortality of certain malignancies. One of the most important discoveries in cancer epidemiology is the gender inequalities. Cancer incidence differences between the sexes are thought to be regulated at the genetic and molecular levels and by sex hormones like oestrogen. Differences based on sex and gender are among the least investigated factors impacting cancer susceptibility, progression, survival, and therapy response despite their established importance in clinical care. The molecular mechanisms underlying sex differences in particular are poorly known, hence the majority of precision medicine approaches employ mutational or other genetic data to assign therapy without taking into account how the patient's sex may affect therapeutic efficacy. In patients receiving chemotherapy, there are definite gender-dependent disparities in response rates and the likelihood of side effects. This review explores the influence of sex as a biological variable in drug effects or toxicity in oncology.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100152"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/72/main.PMC9881040.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10586700","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":"Mechanistic update of Trisenox in blood cancer","authors":"Ananta ,&nbsp;Swati Benerjee ,&nbsp;Paul B. Tchounwou ,&nbsp;Sanjay Kumar","doi":"10.1016/j.crphar.2023.100166","DOIUrl":"https://doi.org/10.1016/j.crphar.2023.100166","url":null,"abstract":"<div><p>Acute promyelocytic leukemia (APL)/blood cancer is M3 type of acute myeloid leukemia (AML) formed inside bone marrow through chromosomal translocation mutation usually between chromosome 15 &amp; 17. It accounts around 10% cases of AML worldwide. Trisenox (TX/ATO) is used in chemotherapy for treatment of all age group of APL patients with highest efficacy and survival rate for longer period. High concentration of TX inhibits growth of APL cells by diverse mechanism however, it cures only PML-RARα fusion gene/oncogene containing APL patients. TX resistant APL patients (different oncogenic make up) have been reported from worldwide. This review summarizes updated mechanism of TX action via PML nuclear bodies formation, proteasomal degradation, autophagy, p53 activation, telomerase activity, heteromerization of pRb &amp; E2F, and regulation of signaling mechanism in APL cells. We have also provided important information of combination therapy of TX with other molecules mechanism of action in acute leukemia cells. It provides updated information of TX action for researcher which may help finding new target for further research in APL pathophysiology or new TX resistant APL patients drug designing.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"5 ","pages":"Article 100166"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257123000147/pdfft?md5=e35d9be6096f3a275318fe96a9be2041&pid=1-s2.0-S2590257123000147-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138430849","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":"OCE-205 in rats and non-human primates: Pharmacokinetic and pharmacodynamic analysis","authors":"Stan Bukofzer ,&nbsp;Geoff Harris ,&nbsp;Edward E. Cable","doi":"10.1016/j.crphar.2023.100163","DOIUrl":"10.1016/j.crphar.2023.100163","url":null,"abstract":"<div><p>Treatment for complications associated with the hemodynamic consequences of decompensated cirrhosis remains suboptimal. Terlipressin, the latest pharmacological management of hepatorenal syndrome–acute kidney injury (HRS-AKI), targets the vasopressin system but has serious side effects. OCE-205 is a novel peptide designed to target the vasopressin receptor system as a mixed V1a agonist/antagonist, resulting in effective partial agonism without V2 agonism. We examined the <em>in vivo</em> pharmacokinetic/pharmacodynamic properties of OCE-205 in healthy rats and cynomolgus monkeys. OCE-205 was administered by IV or SC bolus injection; arginine vasopressin (AVP) or terlipressin were comparators. After IV OCE-205 administration in rats, mean plasma concentration decreased in a mostly linear manner to 2 mg/mL after 120 min, and for SC administration, slowly decreased to ∼50 ng/mL after 300 min. Compared with pre-test values, arterial blood pressure values significantly increased after all OCE-205 doses tested. For monkeys, the concentration after IV OCE-205 administration was mostly linear to 5 ng/mL after 180 min, and for SC administration, ∼3 ng/mL after 480 min. Subcutaneous OCE-205 administration increased mean arterial pressure (MAP) versus baseline, with ΔMAP in OCE-205–treated animals marked and long-lasting while terlipressin induced an increase from baseline in MAP, with negligible ΔMAP, on average, by 150 min after administration in all groups. AVP, but not OCE-205, significantly increased blood lactate concentrations. OCE-205 was well tolerated in adult male rats and cynomolgus monkeys following single-dose bolus administration. The preclinical results of OCE-205, with its demonstrated V1a selective partial agonist activity and potentially tolerable safety profile, suggest its potential utility for treatment of the cardiovascular complications of cirrhosis.</p></div><div><h3>Institutional protocol number</h3><p>Procedures were approved by the Ferring Research Institute (FRI) Institutional Animal Care and Use Committee (IACUC) on November 27, 2006 under protocol FRI 06-011, and by the Sinclair Research Center IACUC under protocol S11177.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"5 ","pages":"Article 100163"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ca/d8/main.PMC10440361.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10055261","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 genetic and immune underpinnings of the sexual dimorphism in tumor response to immune checkpoints inhibitors: A narrative review","authors":"Giulia Mazzaschi ,&nbsp;Federico Quaini ,&nbsp;Sebastiano Buti","doi":"10.1016/j.crphar.2022.100146","DOIUrl":"10.1016/j.crphar.2022.100146","url":null,"abstract":"<div><h3>Introduction</h3><p>In spite of the undisputed relevance of sex as critical biologic variable of the immune landscape, still limited is our understanding of the basic mechanisms implicated in sex-biased immune response thereby conditioning the therapeutic outcome in cancer patients. This hindrance delays the actual attempts to decipher the heterogeneity of cancer and its immune surveillance, further digressing the achievement of predictive biomarkers in the current immunotherapy-driven scenario. <em>Body</em>: The present review concisely reports on genetic, chromosomal, hormonal, and immune features underlying sex-differences in the response to immune checkpoint inhibitors (ICIs). In addition to outline the need of robust data on ICI pharmaco-kinetics/dynamics, our survey might provide new insights on sex determinants of ICI efficacy and suggests uncovered pathways that warrant prospective investigations.</p></div><div><h3>Conclusion</h3><p>According to a sharable view, we propose to widely include sex among the co-variates when assessing the clinical response to ICI in cancer patients.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100146"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/32/c7/main.PMC9772791.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10438228","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":"Recent advancements of miRNAs in the treatment of bone diseases and their delivery potential","authors":"Ashish Ranjan Sharma,&nbsp;Yeon-Hee Lee,&nbsp;Sang-Soo Lee","doi":"10.1016/j.crphar.2022.100150","DOIUrl":"10.1016/j.crphar.2022.100150","url":null,"abstract":"<div><p>Advances in understanding miRNAs as endogenous posttranscriptional regulatory units have projected them as novel therapeutics for several untreatable diseases. miRNAs are endogenous non-coding small single-stranded RNA molecules (20–24 nucleotides) with specific gene regulatory functions like repression of mRNA translation by degrading mRNAs. Emerging evidence suggests the role of miRNAs in various stages of bone growth and development. Undoubtedly, due to their critical role in bone remodeling, miRNAs might be projected as a novel approach to treating bone-related diseases. However, the instability associated with miRNAs in their complex environment, such as degradation by nucleases, is a concern. Thus, recent attention is being paid to maintaining the miRNAs' safety and efficacy in the cells. Various efficient delivery systems and chemical modifications of miRNAs are being developed to make them a potential therapeutic option for bone diseases. Here, we have tried to recapitulate the recent advances in the role of miRNAs in bone disease, along with the potential delivery systems for their efficient delivery to the cells.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100150"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c0/79/main.PMC9860349.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9183230","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":"Kinetic conversion of BIOGF1K enriched in compound K from in vitro 3-D human tissue model","authors":"Woo-Hyun Kim ,&nbsp;Won-Jo Choi ,&nbsp;Jeong-Eun Kim ,&nbsp;Joonho Choi ,&nbsp;Yong-Deok Hong ,&nbsp;Jin Nam ,&nbsp;Won-Seok Park ,&nbsp;Soon-Mi Shim","doi":"10.1016/j.crphar.2023.100165","DOIUrl":"https://doi.org/10.1016/j.crphar.2023.100165","url":null,"abstract":"<div><p>The purposes of current study were to investigate the effect of ginsenosides from BIOGF1K enriched in compound K (CK) and compound Y (CY) on the skin barrier function, the deposition in <em>in vitro</em> 3-D human tissue model (EpiDermFT™ Full Thickness 400), and to identify and quantify kinetic bioconversion of the ginsenosides in artificial skin by utilizing the Fourier transform infrared spectroscopy (FT-IR) and liquid chromatography mass spectrometry (LC-MS), respectively. Epidermal barrier integrity evaluated using transepithelial electrical resistance (TEER) was significantly higher in the BIOGF1K treatment than the CY or CK individual treatment throughout incubation (p &lt; 0.05). Skin deposition (%) of CY and CK from BIOGF1K treatment was approximately 4 and 2 times higher than the CY and CK single component treatment, respectively. Total amount of CK found in human skin by deposition and bioconversion was approximately 1087.3, 528.82, and 867.76 μM after topical treatment of BIOGF1K, CK, and CY. Results from the current study reveal that topical treatment of BIOGF1K more effectively induced CK deposition as well as bioconversion of CY to CK than that of a single treatment of CY or CK, suggesting that BIOGF1K could be a useful cosmetic preparation for enhancing skin function.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"5 ","pages":"Article 100165"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49854422","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}