Yakhak HoejiPub Date : 2022-12-30DOI: 10.17480/psk.2022.66.6.324
Hyun Jae Lee, Choong Jae Lee
{"title":"Effect of Hyperoside on Phorbol Ester-induced Gene Expression of Mucin and NF-κB Signaling in Cultured Human Airway Epithelial Cells","authors":"Hyun Jae Lee, Choong Jae Lee","doi":"10.17480/psk.2022.66.6.324","DOIUrl":"https://doi.org/10.17480/psk.2022.66.6.324","url":null,"abstract":"We investigated whether hyperoside, an anti-inflammatory natural product, significantly affects phorbol 12- myristate 13-acetate (PMA)-induced airway expression of MUC5AC encoded mucin. Confluent NCI-H292 cells were pretreated with hyperoside for 30 min, then stimulated with PMA for 24 h or the indicated periods. MUC5AC mucin mRNA expression was measured by RT-PCR. MUC5AC mucin protein expression was quantitated by ELISA. To elucidate the mechanism of hyperoside action, we investigated the effect of hyperoside on PMA-induced NF-κB signaling by western blot analysis. The results were as follows: (1) Hyperoside significantly inhibited MUC5AC mucin protein production and down-regulated MUC5AC mucin mRNA expression; (2) Hyperoside inhibited PMA-induced activation (phosphorylation) of inhibitory kappa B kinase (IKK), thereby inhibiting phosphorylation and degradation of inhibitory kappa Bα (IκBα); (3) Hyperoside inhibited PMA-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65, thereby down-regulating MUC5AC mucin gene expression in NCI-H292 cells. These results suggest that hyperoside can regulate mucin gene expression by airway epithelial cells through regulation of the NF-κB signaling pathway.","PeriodicalId":23923,"journal":{"name":"Yakhak Hoeji","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81895365","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}
Yakhak HoejiPub Date : 2022-12-30DOI: 10.17480/psk.2022.66.6.331
Somin Lee, J. Bae, Doyoung Kwon, Young-Suk Jung
{"title":"Effect of Diet Restriction on Renal Glutathione Metabolism in Mice","authors":"Somin Lee, J. Bae, Doyoung Kwon, Young-Suk Jung","doi":"10.17480/psk.2022.66.6.331","DOIUrl":"https://doi.org/10.17480/psk.2022.66.6.331","url":null,"abstract":"Various benefits for the maintenance of metabolic homeostasis can be obtained through dietary restriction. Short-term fasting of mice may induce systemic metabolic remodeling, which may have a significant effect on the level of endogenous metabolites. This study was conducted to examine metabolic changes of sulfur-containing substances in the kidneys of fasted mice over 48 h. No change in the concentration of renal methionine was observed over 48 h; however, significant decreases in the concentrations of S-adenosylmethionine and S-adenosylhomocysteine were observed at both 24 and 48 h after fasting. A significant decrease in the concentration of renal cysteine was observed from 24 h, and this was maintained at 48 h. A significant decrease in the concentration of glutathione (GSH) was observed in the kidney at 48 h, whereas increased concentrations of taurine were observed 48 h after fasting. Although significantly increased expression levels of BHMT were observed, markedly decreased expression levels of CβS were observed at 48 h after fasting, indicating activated generation of methionine, but downregulation of cysteine synthesis. The expression level of γ-GCL was not altered by fasting for 48 h; however, a significant increase of cysteine sulfinate decarboxylase mediating the taurine synthesis was observed. Significantly decreased protein expression levels of solute carrier family 7 member 11, which imports extracellular cystine, were observed at 48 h. These results suggest that the renal methionine concentration was maintained during short-term fasting through an increase in the re-methylation of homocysteine. Moreover, a reduction in the concentration of cysteine was the result of an increase in the synthesis of taurine and a decrease in the uptake of extracellular cystine, which may result in a decreased concentration of renal GSH.","PeriodicalId":23923,"journal":{"name":"Yakhak Hoeji","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87496082","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}
Yakhak HoejiPub Date : 2022-12-30DOI: 10.17480/psk.2022.66.6.303
Min Cheol Kim, Min-Goo Kim
{"title":"Study on Blood Cholesterol Improvement Functionality of Bifidobacterium breve IDCC 4401 Heat Treatment Culture Powder, a Health Functional Ingredient","authors":"Min Cheol Kim, Min-Goo Kim","doi":"10.17480/psk.2022.66.6.303","DOIUrl":"https://doi.org/10.17480/psk.2022.66.6.303","url":null,"abstract":"Blood cholesterol is an item of national health examinations in Korea, which is one of the essential health indicators that healthy and semi-healthy people, who are not in the stage of taking medicine, also need to be managed by controlling their lifestyle. HMG-CoA reductase inhibitors, which are commonly used to lower blood cholesterol, have been reported to have various adverse events, and there are several factors limiting their application. As a result, semi-healthy and healthy people who do not have critical health issues may not be able to take these drugs. Bifidobacterium breve IDCC 4401 heat treatment culture powder (BBR4401) is a functional raw material obtained by heat-treating and killing the probiotic Bifidobacterium breve which is widely used as a functional raw material for improving intestinal health in foods and health functional foods. In addition, BBR4401 is a raw material with safety and stability which has been recognized for its cholesterol-improving functionality. Therefore, healthy and semi-healthy people who wish to manage their blood cholesterol can consume BBR4401 for prevention/management purposes. Furthermore, BBR4401 has an entirely different mechanism of action from HMG-CoA reductase inhibitors in that it inhibits the reabsorption of cholesterol/bile acids in the small intestine, meaning that even those who are taking HMG-CoA reductase inhibitors can consume BBR4401 to manage their blood cholesterol; this treatment combination is expected to provide a synergic effect in improving cholesterol.","PeriodicalId":23923,"journal":{"name":"Yakhak Hoeji","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74462416","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}
Yakhak HoejiPub Date : 2022-12-30DOI: 10.17480/psk.2022.66.6.336
Su Min Lee, Jeong-Gyun Lee, Seoungjin Yun, Kyeong Soo Kim
{"title":"Solid Self-nanoemulsifying Drug Delivery System (S-SNEDDS) for Improved Solubility of Enzalutamide","authors":"Su Min Lee, Jeong-Gyun Lee, Seoungjin Yun, Kyeong Soo Kim","doi":"10.17480/psk.2022.66.6.336","DOIUrl":"https://doi.org/10.17480/psk.2022.66.6.336","url":null,"abstract":"The objective of this study was to develop a novel enzalutamide-loaded solidified self-nanoemulsifying drug delivery system formulation with enhanced solubility and dissolution rate. Various oil and surfactant were screened, then Medium Chain Triglyceride oil and Polysorbate 80 and Labrafil M2125CS were selected as oil and a surfactant. Pseudoternary phase diagram was constructed to detect the nanoemulsion zone. Among the SNEDDS formulations tested, SNEDDS consisted of MCT oil (oil), Polysorbate 80 (surfactant) and Labrafil M2125CS (co-surfactant) at a weight ratio of 20:70:10. The SNEDDS produced the emulsion droplet size 18.66±0.88 nm. Spray drying technique was used to convert the selected enzalutamide-loaded SNEDDS into solid SNEDDS with inert carrier such as silicon dioxide. Enzlautamide-loaded solid SNEDDS was characterized by scanning electron microscopy, transmission electron microscopy, powder X-ray diffractometry, dynamic light scattering, saturation solubility and in vitro dissolution study. The S-SNEDDS produced an emulsion droplet size of 15.37±0.49 nm and there was no change in particle size between with or without drug. SEM and PXRD results suggested that enzalutamide existed in amorphous form in enzalutamide-loaded solid SNEDDS. In addition, enzalutamide-loaded solid SNEDDS increased saturation solubility 42-fold and dissolution rates 23- fold compared to crystalline enzalutamide. Therefore, the solid SNEDDS could be a potential nano-sized drug delivery system for poorly water-soluble drug enzalutamide.","PeriodicalId":23923,"journal":{"name":"Yakhak Hoeji","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91153370","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}
Yakhak HoejiPub Date : 2022-10-31DOI: 10.17480/psk.2022.66.5.236
Ji Eun Park, M. Oh
{"title":"Development and Validation of LC-MS/MS Method for Determination of Astaxanthin in Dietary Supplement","authors":"Ji Eun Park, M. Oh","doi":"10.17480/psk.2022.66.5.236","DOIUrl":"https://doi.org/10.17480/psk.2022.66.5.236","url":null,"abstract":"The Ministry of Food and Drug Safety is amending its test methods for dietary supplements (functional health food) to establish regulatory standards and specifications in Korea. In this regard, we continue to research analytical method development for the items to improve their sensitivity and selectivity. In this study, we have developed liquid chromatographic-tandem mass spectrometry for astaxanthin analysis. This method can be used to characterize and quantify dietary supplement formulations containing astaxanthin. The procedure was validated at 37.5-2,400 ng/mL. Standard calibration curves presented linearity with the coefficient of determination (r²)>0.999. The limits of detection and limits of quantitation were 16 and 49 ng/mL, respectively. The recovery results ranged between 91.9-97.4% at three different concentration levels with relative standard deviations (RSDs) of less than 3.6%. The precision results (RSDs) were obtained between 1.2-3.5%, and reproducibility (1.8%) was obtained. These are in accordance with the established validation criteria (Association of Official Analytical Chemists). Our research can provide scientific evidence to amend the astaxanthin test method for Health Functional Food Codes.","PeriodicalId":23923,"journal":{"name":"Yakhak Hoeji","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78328918","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}
Yakhak HoejiPub Date : 2022-10-31DOI: 10.17480/psk.2022.66.5.283
Jeong-Gyun Lee, Su Min Lee, Seoungjin Yun, Kyeong Soo Kim
{"title":"Development of Enzalutamide Solid Dispersion Loaded Tablet with Enhanced Solubility","authors":"Jeong-Gyun Lee, Su Min Lee, Seoungjin Yun, Kyeong Soo Kim","doi":"10.17480/psk.2022.66.5.283","DOIUrl":"https://doi.org/10.17480/psk.2022.66.5.283","url":null,"abstract":"The objective of this study was to develop a novel enzalutamide tablet formulation with enhanced solubility and bioavailability, and inhibited recrystallization. Kollidon VA64 was selected as a soluble polymer for preparing enzalutamide solid dispersions. Solid dispersions with different enzalutamide to Kollidon VA64 weight ratios were prepared via solvent evaporation method. The enzalutamide solid dispersion consisting of enzalutamide and Kollidon VA64 at a weight ratio of 1:1, exhibited an excellent dissolution rate and potent inhibition of recrystallization. Enzalutamide solid dispersions were characterized by scanning electron microscopy, powder X-ray diffractometry, differential scanning calorimetry, and in vitro dissolution studies. The 1:1 solid dispersion exhibited excellent productivity, an elevated dissolution rate, and recrystallization inhibition. Therefore, enzalutamide solid dispersion loaded tablets were prepared and their dissolution was evaluated compared to a commercial product (Xtandi® soft capsule). The selected tablet formulation containing enzalutamide solid dispersion exhibited a higher dissolution rate in pH 1.0 solution than did the Xtandi® soft capsule, and prevented recrystallization of the enzalutamide. This research suggests that enzalutamide-containing solid dispersion tablets could be the most effective method to date for improving the dosing compliance of Xtandi® soft capsules, improving the dissolution rate of enzalutamide, and preventing recrystallization.","PeriodicalId":23923,"journal":{"name":"Yakhak Hoeji","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79643487","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}
Yakhak HoejiPub Date : 2022-10-31DOI: 10.17480/psk.2022.66.5.292
YeongAe Lee, Sun-Hong Kwon, Na-Hyun Kim, Eui-Kyung Lee
{"title":"Cost-effectiveness of Combination Therapy of Anticoagulants/antiplatelets with Proton Pump Inhibitors: A Systematic Review","authors":"YeongAe Lee, Sun-Hong Kwon, Na-Hyun Kim, Eui-Kyung Lee","doi":"10.17480/psk.2022.66.5.292","DOIUrl":"https://doi.org/10.17480/psk.2022.66.5.292","url":null,"abstract":"Anticoagulants/antiplatelets are effective in preventing cardiovascular diseases (CVDs). However, as an adverse effect, the risk of upper gastrointestinal bleeding (UGIB) leads to additional costs due to increased treatment and decreased quality of life. Accordingly, the administration of proton pump inhibitors (PPI) is recommended to prevent UGIB. We conducted a systematic review of economic evaluations of PPI co-therapy for patients taking long-term anticoagulants/ antiplatelets to prevent CVDs to examine the cost effectiveness of PPI co-therapy. We searched literature from PubMed and EMBASE with keywords including types of economic evaluations and active ingredients of anticoagulants and antiplatelets on 13/07/2022. Two independent reviewers conducted a systematic review. As a result, six economic evaluation studies were identified. All studies compared PPI co-therapy with low-dose aspirin to prevent CVDs. We confirmed the cost-effectiveness of PPI co-therapy with the respective incremental cost-effectiveness ratio (ICER) in each base case. In the sensitivity analyses, the PPI cost and adherence influenced the ICER the most. The quality of reporting, which was assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist, was 87-96%. In the present study, we found that PPI co-therapy was cost-effective and tended to improve the patient’s life years and quality-adjusted life years. These results can be used as evidence for further economic evaluation studies to verify the costeffectiveness of anticoagulants/antiplatelets and PPI co-therapy.","PeriodicalId":23923,"journal":{"name":"Yakhak Hoeji","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84968483","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}
Yakhak HoejiPub Date : 2022-10-31DOI: 10.17480/psk.2022.66.5.249
Suhyun Lee, Young-Mi Ah, Kyu-Nam Heo, A. Lee, Sang il Min, A. Kim, Sung Hwan Kim, Y. H. Jo, Y. Cho, Ji Min Han, Ju-Yeun Lee
{"title":"Developing National Level High-alert Medication Lists for Community/primary Care Patients","authors":"Suhyun Lee, Young-Mi Ah, Kyu-Nam Heo, A. Lee, Sang il Min, A. Kim, Sung Hwan Kim, Y. H. Jo, Y. Cho, Ji Min Han, Ju-Yeun Lee","doi":"10.17480/psk.2022.66.5.249","DOIUrl":"https://doi.org/10.17480/psk.2022.66.5.249","url":null,"abstract":"Despite the fact that a considerable number of preventable adverse events are managed in primary care settings, medication-related risks have been evaluated mainly through hospital admissions. While interest in high-alert medication management in the community and primary care settings is increasing internationally, Korea does not have accreditation for the same and lacks established standards for high-alert medications. Therefore, this study aimed to develop a nationallevel list of high-alert medications for community and primary care. The candidates for the high-alert medication list included medications recommended by Institute for Safe Medication Practices and those suggested by each guideline of the World Health Organization, Japan and Korea. We analyzed the adverse events related to medication errors reported by the patients' safety reporting system. Seven experts working in the community and primary care settings evaluated the adequacy and priority of the candidate medications. The final list included 20 high-alert medications, including nine essential and eleven optional medications. The national-level list of high-alert medications which we developed may be useful in formulating accreditation guidelines or treatment standards for community and primary care patients.","PeriodicalId":23923,"journal":{"name":"Yakhak Hoeji","volume":"83 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86641356","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}
Yakhak HoejiPub Date : 2022-10-31DOI: 10.17480/psk.2022.66.5.242
Yong Soo Lee
{"title":"Involvement of Intracellular Ca²⁺ and Nitric Oxide in the Hydroxyurea-Induced Melanogenesis","authors":"Yong Soo Lee","doi":"10.17480/psk.2022.66.5.242","DOIUrl":"https://doi.org/10.17480/psk.2022.66.5.242","url":null,"abstract":"The molecular mechanism underlying hyperpigmentation as an adverse side effect of the anticancer drug, hydroxyurea (HU), was investigated in B16 melanoma cells. HU increased the melanin content and intracellular Ca²⁺ concentration in a dose-dependent manner. These effects were significantly reduced by treatment with the intracellular Ca²⁺ release blockers, dantrolene and 2-aminoethoxidiphenylborate (2-APB). Additionally, HU induced the production of nitric oxide (NO) in a time- and dose-dependent manner, and this was significantly blocked by inhibitors of the increase in intracellular Ca²⁺ levels(bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl ester, dantrolene, and 2- APB). Furthermore, the HU-induced increases in NO and melanin production were significantly suppressed by NG-nitro- L-arginine methyl ester and 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide, an NO synthase inhibitor and an NO scavenger, respectively. These results suggest that HU-induced melanogenesis through NO and an increase in intracellular Ca²⁺ levels may be involved in the mechanism of its hyperpigmentation effect.","PeriodicalId":23923,"journal":{"name":"Yakhak Hoeji","volume":"2013 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82681478","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}
Yakhak HoejiPub Date : 2022-10-31DOI: 10.17480/psk.2022.66.5.278
Y. Son, C. Lee, In Tag Yu, Mijin Lee, Hangun Kim
{"title":"Evaluation of Anti-cancer Efficacy of Potassium Usnate using NIR Imaging of Orthotopic Breast Cancer Mouse Model","authors":"Y. Son, C. Lee, In Tag Yu, Mijin Lee, Hangun Kim","doi":"10.17480/psk.2022.66.5.278","DOIUrl":"https://doi.org/10.17480/psk.2022.66.5.278","url":null,"abstract":"Mouse cancer models are useful tools for evaluating in vivo tumor growth and metastasis, providing valuable information for preclinical testing. In this process, optical imaging enables the mouse models to easily identify the progress of disease in a non-invasive way. Here, we established an experimental bioimaging animal model of near-infrared (NIR) fluorescence by using a fluorescence-labeled organism bioimaging instrument (FOBI) and evaluated the anti-cancer effect of potassium usnate (KU) in an orthotopic breast cancer model. The cell viability assay revealed that KU had cytotoxicity with half maximal inhibitory concentration of approximately 138.57, 167.69, and 144.17 μM in 4T1-Fluc-Neo/iRFP-Puro (4T1-iRFP), MDA-MB-231, and MCF-7 cells, respectively. The measurement of NIR fluorescence from the 4T1-iRFP cells in a microtube via FOBI exhibited a strong correlation between cell number and fluorescence intensity, and the minimal detection limit was 10⁵ cells. Accordingly, NIR imaging was performed on the orthotopic breast cancer mouse model by using FOBI, and regression of tumor progression through intraperitoneal KU administration was successfully monitored. Our results demonstrated the establishment of NIR imaging in the orthotopic breast cancer animal model for evaluating the anti-cancer effect of KU.","PeriodicalId":23923,"journal":{"name":"Yakhak Hoeji","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79527967","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}