Translational and Clinical Pharmacology最新文献

{"title":"Qualification and application of liquid chromatography-quadrupole time-of-flight mass spectrometric method for the determination of carisbamate in rat plasma and prediction of its human pharmacokinetics using physiologically based pharmacokinetic modeling.","authors":"Byeong Ill Lee,&nbsp;Jeong-Hyeon Lim,&nbsp;Min-Ho Park,&nbsp;Seok-Ho Shin,&nbsp;Jin-Ju Byeon,&nbsp;Jang-Mi Choi,&nbsp;Seo-Jin Park,&nbsp;Min-Jae Park,&nbsp;Yuri Park,&nbsp;Young G Shin","doi":"10.12793/tcp.2020.28.e15","DOIUrl":"https://doi.org/10.12793/tcp.2020.28.e15","url":null,"abstract":"<p><p>Carisbamate is an antiepileptic drug and it also has broad neuroprotective activity and anticonvulsant reaction. In this study, a liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method was developed and applied for the determination of carisbamate in rat plasma to support <i>in vitro</i> and <i>in vivo</i> studies. A quadratic regression (weighted 1/concentration²), with an equation y = ax² + bx + c, was used to fit calibration curves over the concentration range from 9.05 to 6,600 ng/mL for carisbamate in rat plasma. Preclinical <i>in vitro</i> and <i>in vivo</i> studies of carisbamate have been studied through the developed bioanalytical method. Based on these study results, human pharmacokinetic (PK) profile has been predicted using physiologically based pharmacokinetic (PBPK) modeling. The PBPK model was optimized and validated by using the <i>in vitro</i> and <i>in vivo</i> data. The human PK of carisbamate after oral dosing of 750 mg was simulated by using this validated PBPK model. The human PK parameters and profiles predicted from the validated PBPK model were similar to the clinical data. This PBPK model developed from the preclinical data for carisbamate would be useful for predicting the PK of carisbamate in various clinical settings.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"28 3","pages":"147-159"},"PeriodicalIF":0.9,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d2/29/tcp-28-147.PMC7533164.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38495214","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":"Predicting human pharmacokinetics from preclinical data: absorption.","authors":"Dong-Seok Yim,&nbsp;Suein Choi,&nbsp;Soo Hyeon Bae","doi":"10.12793/tcp.2020.28.e14","DOIUrl":"https://doi.org/10.12793/tcp.2020.28.e14","url":null,"abstract":"<p><p>Predicting the rate and extent of oral absorption of drugs in humans has been a challenging task for new drug researchers. This tutorial reviews <i>in vitro</i> and PBPK methods reported in the past decades that are widely applied to predicting oral absorption in humans. The physicochemical property and permeability (typically obtained using Caco-2 system) data is the first necessity to predict the extent of absorption from the gut lumen to the intestinal epithelium (F_a). Intrinsic clearance measured using the human microsome or hepatocytes is also needed to predict the gut (F_g) and hepatic (F_h) bioavailability. However, there are many issues with the correction of the inter-laboratory variability, hepatic cell membrane permeability, CYP3A4 dependency, etc. The bioavailability is finally calculated as F = F_a × F_g × F_h. Although the rate of absorption differs by micro-environments and locations in the intestine, it may be simply represented by k_a. The k_a, the first-order absorption rate constant, is predicted from <i>in vitro</i> and <i>in vivo</i> data. However, human PK-predicting software based on these PBPK theories should be carefully used because there are many assumptions and variances. They include differences in laboratory methods, inter-laboratory variances, and theories behind the methods. Thus, the user's knowledge and experiences in PBPK and <i>in vitro</i> methods are necessary for proper human PK prediction.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"28 3","pages":"126-135"},"PeriodicalIF":0.9,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2e/f3/tcp-28-126.PMC7533162.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38495212","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":"Pharmacodynamic evaluation of YH4808 for <i>Helicobacter pylori</i> eradication in healthy subjects.","authors":"Hyeonsoo Park,&nbsp;Choon Ok Kim,&nbsp;Mikyung Kim,&nbsp;Yeji Lim,&nbsp;Woo Yul Lee,&nbsp;Sukyong Yoon,&nbsp;Min Soo Park","doi":"10.12793/tcp.2020.28.e16","DOIUrl":"https://doi.org/10.12793/tcp.2020.28.e16","url":null,"abstract":"<p><p>YH4808 is a novel selective potassium-competitive acid blocker demonstrated to be safe and to have inhibitory effects against gastric acid secretion in previous studies. A randomized, open-label, multiple-dose, 3-treatment, 1-period, parallel design study was conducted to compare the <i>Helicobacter pylori</i> eradication rates and acid suppression capacities of three regimens in 60 healthy subjects with <i>H. pylori</i>-positive, and the potential of YH4808 to replace proton-pump inhibitors (PPIs) in standard regimens for <i>H. pylori</i> eradication. Group 1 received YH4808, amoxicillin, and clarithromycin as a novel triple regimen, while Group 2 received YH4808 and amoxicillin only, and Group 3 received esomeprazole, amoxicillin, and clarithromycin, as the standard triple regimen. <i>H. pylori</i> eradication rates were 85.0% for Group 1, 25.0% for Group 2, and 83.3% for Group 3. Relative response rate between Group 1 and 3 was 1.02 (0.50-2.07; 95% CI, χ² test <i>p</i> = 0.8881). Furthermore, the novel triple regimen, YH4808, amoxicillin, and clarithromycin, stably inhibited acid secretion and maintained a gastric pH greater than 4 or 5 for 24 hours, which was comparable to the pH range in the standard triple regimen. However, the onset times of the YH4808 regimens were earlier than that for the regimens using esomeprazole. There were no differences in the incidences or severity of adverse events among the three groups. Overall, the novel triple regimen was safe and well-tolerated. YH4808 could replace PPIs in standard triple regimens used for <i>H. pylori</i> eradication.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT01921647.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"28 3","pages":"136-146"},"PeriodicalIF":0.9,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ce/0c/tcp-28-136.PMC7533165.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38495213","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":"Pharmacokinetic comparison of two bazedoxifene acetate 20 mg tablet formulations in healthy Korean male volunteers.","authors":"Ji-Sun Yeun,&nbsp;Hye-Su Kan,&nbsp;Minyu Lee,&nbsp;Namsick Kim,&nbsp;Tae-Young Oh,&nbsp;Seung-Kwan Nam,&nbsp;Yoon Seok Choi,&nbsp;In Sun Kwon,&nbsp;Jang Hee Hong","doi":"10.12793/tcp.2020.28.e7","DOIUrl":"https://doi.org/10.12793/tcp.2020.28.e7","url":null,"abstract":"<p><p>Bazedoxifene, used as bazedoxifene acetate, is a selective estrogen receptor modulator that selectively affects the uterus, breast tissue, bone metabolism, and lipid metabolism by antagonizing or enhancing estrogens in the estrogen receptor in the tissue. This study was conducted as an open, randomized, two-period, two-treatment, crossover design to compare the pharmacokinetic (PK) characteristics and tolerability of two bazedoxifene tablets when administered to 50 healthy Korean male volunteers. Enrolled subjects were randomly allocated to 2 sequences of a single oral administration of a test drug and a reference drug, or vice versa with a 14-day washout period between the two doses. Serial blood samples were collected over 96 h for PK analysis. Plasma concentration of bazedoxifene was assayed using liquid chromatography-tandem spectrometry mass. Forty-five participants completed the study with no clinically relevant safety issues. The peak concentrations (C_max, mean ± strandard deviation) of reference drug and test drug were 3.191 ± 1.080 and 3.231 ± 1.346 ng/mL, respectively, and the areas under the plasma concentration-time curve from 0 to the last measurable concentration (AUC_last) were 44.697 ± 21.168 ng∙h/mL and 45.902 ± 23.130 ng∙h/mL, respectively. The geometric mean ratios of test drug to reference drug and their 90% confidence intervals for C_max and AUC_last were 0.9913 (0.8828-1.1132) and 1.0106 (0.9345-1.0929), respectively. The incidence of adverse events between the two formulations was similar. The present study showed that PK and tolerability of two bazedoxifene tablet formulations were comparable when administered to healthy Korean male volunteers.</p><p><strong>Trial registration: </strong>Clinical Research Information Service Identifier: KCT0003978.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"28 2","pages":"102-108"},"PeriodicalIF":0.9,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/eb/tcp-28-102.PMC7327186.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38151698","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":"Development and validation of a method for the simultaneous quantification of endogenous steroids metabolized by CYP3A.","authors":"Yujin Lee,&nbsp;Woori Chae,&nbsp;Seonghae Yoon,&nbsp;Jae-Yong Chung,&nbsp;Joo-Youn Cho","doi":"10.12793/tcp.2020.28.e10","DOIUrl":"https://doi.org/10.12793/tcp.2020.28.e10","url":null,"abstract":"<p><p>Cytochrome P450 (CYP) 3A enzymes, the most important phase 1 drug-metabolizing enzymes, are responsible for 50% of the metabolism of clinically used drugs. CYP3A activity varies widely among individuals, which can affect the probability of adverse drug reactions and drug-drug interactions mediated by the induction or inhibition of the enzyme. Hence, it is important to be able to predict CYP3A activity in individuals to reduce the incidence of unexpected drug responses. To specifically and quickly measure CYP3A activity, we developed method based on gas chromatography interfaced with triple-quadrupole mass spectrometry for the quantification of cortisol, cortisone, 6β-hydroxycortisol, and 6β-hydroxycortisone simultaneously in urine and 4β-hydroxycholesterol in plasma. The results were calculated based on charcoal-stripped steroid-free urine and plasma control samples. The accuracy and precision were 93.18% to 110.0% and 1.96% to 5.34%, respectively. This method was then applied to measure endogenous steroids from urine and plasma samples of healthy Korean males and females. The calibration curves of all analytes showed good linearity with a correlation coefficient (r²) that ranged from 0.9953 to 0.9999. Therefore, this validated method can be used to measure endogenous biomarkers to predict CYP3A activity and might be applicable in the prediction of CYP3A-mediated drug interactions of new drug candidates.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"28 2","pages":"73-82"},"PeriodicalIF":0.9,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/28/84/tcp-28-73.PMC7327190.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38151694","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":"Validation of \"sasLM,\" an R package for linear models with type III sum of squares.","authors":"Jung Sunwoo,&nbsp;Hyungsub Kim,&nbsp;Dohyun Choi,&nbsp;Kyun-Seop Bae","doi":"10.12793/tcp.2020.28.e9","DOIUrl":"https://doi.org/10.12793/tcp.2020.28.e9","url":null,"abstract":"<p><p>The general linear model (GLM) describes the dependent variable as a linear combination of independent variables and an error term. The GLM procedure of SAS^® and the \"car\" package in R calculate the type I, II, or III ANOVA (analysis of variance) tables. In this study, we validated the newly-developed R package, \"sasLM,\" which is compatible with the GLM procedure of SAS^®. The \"sasLM\" package was validated by comparing the output with SAS^®, which is the current gold standard for statistical programming. Data from ten books and articles were used for validation. The results of the \"sasLM\" and \"car\" packages were compared with those in SAS^® using 194 models. All of the results in \"sasLM\" were identical to those of SAS^®, whereas more than 20 models in \"car\" showed different results from those of SAS^®. As the results of the \"sasLM\" package were similar to those in SAS^® PROC GLM, the \"sasLM\" package could be a viable alternative method for calculating the type II and III sum of squares. The newly-developed \"sasLM\" package is free and open-source, therefore it can be used to develop other useful packages as well. We hope that the \"sasLM\" package will enable researchers to conveniently analyze linear models.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"28 2","pages":"83-91"},"PeriodicalIF":0.9,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/99/tcp-28-83.PMC7327187.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38151696","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":"Common data model-based real-world data for practical clinical practice guidelines: clinical pharmacology perspectives.","authors":"Yoomin Jeon,&nbsp;Yoona Choi,&nbsp;Esther Hehsun Kim,&nbsp;SeonYeong Oh,&nbsp;Howard Lee","doi":"10.12793/tcp.2020.28.e11","DOIUrl":"https://doi.org/10.12793/tcp.2020.28.e11","url":null,"abstract":"Clinical practice guidelines (CPGs) are a set of statements systematically developed to assist healthcare professionals and decision makers to practice evidence-based medicine by promoting cost-effective interventions while discouraging ineffective, wasteful, or potentially harmful treatments [1]. CPGs can improve the consistency and quality of care by providing the gold standard, which also helps reduce variation in clinical practice [1]. To ensure the validity of CPGs, clinically important recommendations in CPGs need to be updated periodically as scientific evidence constantly expands and evolves [1].","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"28 2","pages":"67-72"},"PeriodicalIF":0.9,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/53/tcp-28-67.PMC7327188.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38145878","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":"Pharmacokinetics and bioequivalence of fixed-dose combination of candesartan cilexetil/amlodipine besylate (16/10 mg) versus coadministration of individual formulations in healthy subjects.","authors":"Hae Won Lee,&nbsp;Woo Youl Kang,&nbsp;Wookjae Jung,&nbsp;Mi-Ri Gwon,&nbsp;Dong Heon Yang,&nbsp;Eun Hee Kim,&nbsp;Kyunghee Cho,&nbsp;Young-Ran Yoon,&nbsp;Sook Jin Seong","doi":"10.12793/tcp.2020.28.e8","DOIUrl":"https://doi.org/10.12793/tcp.2020.28.e8","url":null,"abstract":"<p><p>This study compared the pharmacokinetics of a fixed-dose combination (FDC) of candesartan (16 mg) and amlodipine (10 mg) versus coadministration of individual formulations to clarify the bioequivalence of the FDC. In this randomized, open-label, single-dose, 2-treatment, 2-way crossover study, healthy Korean volunteers received a single dose of candesartan (16 mg) with amlodipine (10 mg) as either an FDC or single agents concomitantly administered, with a 2-week washout period. Serial blood samples were collected up to 72 hours after dosing for each treatment period, and plasma concentrations of candesartan and amlodipine were measured using a validated liquid chromatography-tandem mass spectrometry method. A total of 39 subjects completed the study. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the area under the plasma concentration-time curve from time 0 to the last measurement (AUC_0-t) and the peak plasma concentration (C_max) for candesartan were 1.0182 (0.9562-1.0841) and 0.9492 (0.8726-1.0324), respectively. The GMR and 90% CI for the AUC_0-t and C_max for amlodipine were 1.0552 (1.0255-1.0857) and 1.0668 (1.0259-1.1094), respectively. In conclusion, the new FDC formulation of candesartan (16 mg) and amlodipine (10 mg) was bioequivalent to the concomitant administration of single agents. A single dose of candesartan/amlodipine as the FDC or as single agents was well tolerated.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT02988362.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"28 2","pages":"92-101"},"PeriodicalIF":0.9,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/a0/tcp-28-92.PMC7327189.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38151697","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":"Survey of physicians' views on the clinical implementation of pharmacogenomics-based personalized therapy.","authors":"Woo-Young Kim,&nbsp;Ho-Sook Kim,&nbsp;Minkyung Oh,&nbsp;Jae-Gook Shin","doi":"10.12793/tcp.2020.28.e6","DOIUrl":"https://doi.org/10.12793/tcp.2020.28.e6","url":null,"abstract":"<p><p>Despite quantitative increases and qualitative advances in pharmacogenomics (PGx) research, the clinical implementation of PGx-based personalized therapy has still been limited. The objective of this study was to assess physicians' self-reported knowledge of PGx-based personalized therapy, and to explore the most problematic and highest priority barriers preventing physicians from applying PGx into clinical practice under the Korean healthcare system. A 36-question survey was distributed to 53 physicians with various specialties in Korea. In the physicians' self-perceived knowledge, twenty-eight physicians (53%) reported a lack sufficient knowledge about PGx. The perceived largest barrier to clinical implementation of PGx was the high cost of PGx testing, followed by a lack of PGx education for healthcare providers or lack of clinical PGx experts. Physicians without clinical PGx experience or with indirect experience reported that the largest barrier to clinical implementation of PGx was the high cost of PGx testing, while physicians with clinical PGx experience pointed out that a lack of patients' education was the major concern, followed by a lack of PGx education for healthcare providers or lack of clinical PGx experts. The highest priority problem was reported to be a lack of actionable guidelines for drug selection and dosing using PGx. In conclusion, we should increase and expand extensive educational programs for healthcare providers and patients, and to develop and establish a clinical decision support systems for PGx-based personalized therapy in Korea.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"28 1","pages":"34-42"},"PeriodicalIF":0.9,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f4/d9/tcp-28-34.PMC7136078.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37819958","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":"What is the optimal fit-for-purpose design in an oncology first-in-human trial?: 3+3 vs. Bayesian logistic regression model.","authors":"Sun Young Yum","doi":"10.12793/tcp.2020.28.e1","DOIUrl":"https://doi.org/10.12793/tcp.2020.28.e1","url":null,"abstract":"Primary goals When designing a clinical trial, the goals must be clearly and specifically defined, and this should guide decision making on the details of the study. The goals of phase 1 oncology studies may include: 1) determine maximal tolerated dose (MTD), 2) provide recommended phase 2 dose (RP2D), 3) describe/characterize dose-limiting toxicity (DLT), 4) expand understanding of the investigational product, e.g. pharmacokinetics, efficacy. These goals may be coupled with business/development timeline (e.g., as quickly as possible) and/or cost goals (with fewest possible subjects). For novel targets or mode of action, these many goals are further complicated by limited information about clinical efficacy and toxicity. The ethical dilemma regarding dose selection has evolved from being centered on limiting the number of patients who experience toxicity to also minimize underdosing of patients in need of treatment.","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":"28 1","pages":"1-6"},"PeriodicalIF":0.9,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/74/61/tcp-28-1.PMC7136082.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37820051","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}