Translational and Clinical Pharmacology最新文献

{"title":"The use of real-world data in drug repurposing.","authors":"Kyungsoo Park","doi":"10.12793/tcp.2021.29.e18","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e18","url":null,"abstract":"<p><p>Drug repurposing, or repositioning, is to identify new uses for existing drugs. Significantly reducing the costs and time-to-market of a medication, drug repurposing has been an alternative tool to accelerate drug development process. On the other hand, 'real world data (RWD)' has been also increasingly used to support drug development process owing to its better representing actual pattern of drug treatment and outcome in real world. In the healthcare domain, RWD refers to data collected from sources other than traditional clinical trials; for example, in electronic health records or claims and billing data. With the enactment of the 21st Century Cures Act, which encourages the use of RWD in drug development and repurposing as well, such increasing trend in RWD use will be expedited. In this context, this review provides an overview of recent progresses in the area of drug repurposing where RWD was used by firstly introducing the increasing trend and regulatory change in the use of RWD in drug development, secondly reviewing published works using RWD in drug repurposing, classifying them in the repurposing strategy, and lastly addressing limitations and advantages of RWDs.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/58/tcp-29-117.PMC8492393.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498508","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 LC-MS/MS method for determination of rosuvastatin concentration in human blood collected by volumetric absorptive microsampling (VAMS).","authors":"Seol Ju Moon,&nbsp;Seon Eui Lee,&nbsp;Yong-Geun Kwak,&nbsp;Min-Gul Kim","doi":"10.12793/tcp.2021.29.e13","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e13","url":null,"abstract":"<p><p>In light of the shift toward patient-centric clinical trials, a measure of simplifying blood collection process and minimizing the volume of blood samples is on the rise. Volumetric absorptive microsampling (VAMS) is a microsampling device developed for blood sampling in non-hospital settings, which enables accurate hematocrit-independent collection of 10 or 20 µL of whole blood with a simple finger prick. In this study, liquid chromatography (LC)-tandem mass spectrometry workflow for quantification of rosuvastatin after VAMS sampling was developed and validated. The VAMS sample was stabilized by matrix drying and the optimum LC conditions and extraction methods were used to reach adequate sensitivity with lower limit of quantification verified at 1 ng/mL in 10 µL of blood. The bioanalytical method to quantify rosuvastatin from 1 to 100 ng/mL in VAMS sample was qualified by specificity, carryover, linearity, within-run and between-run reproducibility and stability. Inaccuracy was less than ± 6% and imprecision was less than 10% after analyzing the samples on 5 different days at all concentration levels. In addition, the feasibility of delivery to the analytical laboratory after home sampling during the guaranteed stability period of 10 days at room temperature was confirmed by evaluating concentration changes after VAMS sampling without adding pH buffer. Our results suggest that VAMS sampling did not have an effect on the stability of rosuvastatin, and it is a viable option for simple and accurate blood collection at home.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/24/tcp-29-125.PMC8492392.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498509","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":"Comprehensive analysis of important pharmacogenes in Koreans using the DMET™ platform.","authors":"Byungwook Kim,&nbsp;Deok Yong Yoon,&nbsp;SeungHwan Lee,&nbsp;In-Jin Jang,&nbsp;Kyung-Sang Yu,&nbsp;Joo-Youn Cho,&nbsp;Jaeseong Oh","doi":"10.12793/tcp.2021.29.e14","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e14","url":null,"abstract":"<p><p>Genetic polymorphisms of enzymes and transporters associated with the absorption, distribution, metabolism, and elimination (ADME) of drugs are one of the major factors that contribute to interindividual variations in drug response. In the present study, we aimed to elucidate the pharmacogenetic profiles of the Korean population using the Affymetrix Drug Metabolizing Enzyme and Transporters (DMET™) platform. A total of 1,012 whole blood samples collected from Korean subjects were genotyped using the DMET™ plus microarray. In total, 1,785 single nucleotide polymorphism (SNP) markers for 231 ADME genes were identified. The genotype and phenotype of 13 clinically important ADME genes implemented in the Clinical Pharmacogenetics Implementation Consortium guidelines were compared among different ethnic groups. Overall, the genotype frequencies of the Korean population were similar to those of the East Asian population. Several genes, notably <i>CYP2C19</i> and <i>VKORC1</i>, showed marked differences in Koreans compared to Europeans (EURs) or Africans (AFRs). The percentage of CYP2C19 poor metabolizers was 15% in Koreans and less than 3% in EURs or AFRs. The frequencies of causative SNPs of the <i>VKORC1</i> gene for the low warfarin dose phenotype were 90%, 60%, and 10% in Koreans, EURs and AFRs, respectively. Our findings can be utilized for optimal pharmacotherapy in Korean patients.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/eb/tcp-29-135.PMC8492395.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The possibility of low isomerization of β-lapachone in the human body.","authors":"Kyung Min Lee,&nbsp;Mi-Ri Gwon,&nbsp;Hae Won Lee,&nbsp;Sook Jin Seong,&nbsp;Young-Ran Yoon","doi":"10.12793/tcp.2021.29.e16","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e16","url":null,"abstract":"<p><p>β-Lapachone has been reported to have anticancer and various other therapeutic effects, but is limited in clinical applications by its low bioavailability. pH-Dependent isomerization can be suggested as one plausible factor influencing its low bioavailability. Since it is known that β-lapachone is converted to its isomer, α-lapachone in hydrochloric acid (HCl) solution, isomerization in the human body may be driven by HCl in the gastric fluid. The purpose of this study was to evaluate the possibility of isomerization of β-lapachone in the human body. Chemical reactions were conducted using simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.5) at 37°C. β-Lapachone was observed in SGF at 37°C for 1 hour and SIF for 3 hours. In addition, biofluid analysis was performed on plasma samples 1 hour and 4 hours, and on urine sample 12 hours after oral administration of 100 mg MB12066, a synthetic β-lapachone, in healthy adult male. All samples were analyzed using liquid chromatography-tandem mass spectrometry. Only β-lapachone peaks existed in the spectra obtained from SGF and SIF. No isomerization of β-lapachone was observed in the analysis of any of the human samples. In the current study, the possibility of pH-dependent isomerization of β-lapachone in the human body was not confirmed.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/22/12/tcp-29-160.PMC8492396.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498512","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":"Comparison of the pharmacokinetics and pharmacodynamics of YH4808 in healthy subjects for defining an appropriate dosing regimen.","authors":"Sukyong Yoon,&nbsp;EunSil Oh,&nbsp;Min Soo Park,&nbsp;Seong Bok Jang,&nbsp;Hae Mi Byun,&nbsp;Hyeonsoo Park,&nbsp;Heeyoung Kim,&nbsp;Choon Ok Kim","doi":"10.12793/tcp.2021.29.e15","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e15","url":null,"abstract":"<p><p>YH4808 is a novel potassium-competitive acid blocker developed for gastric acid-related disorders. Previous studies indicate its potential to improve symptoms of gastric acid-related disorders. The current study was aimed to find the optimal regimen of YH4808 for night time pH control. This study was performed in two parts. Each was a randomized, open-label, active-controlled, multiple-doses, two-treatment, two-period crossover study conducted in 20 healthy Korean volunteers. Subjects were randomly assigned to one of the four groups. The three groups received different dosage regimens of YH4808 (100 mg twice a day, 200 mg once a day, or 200 mg twice a day), and the fourth group received esomeprazole 40 mg twice a day. The pharmacokinetic parameters demonstrated that the systemic exposure of YH4808 increased in a dose-proportional manner. The difference in the proportion of time above pH 4 over 24 h from the baseline was the greatest in the group receiving YH4808 200 mg twice a day. The values of the area under the effect curve at night time (12 A.M.-7 A.M.) were higher in all YH4808 groups than in the esomeprazole group. However, the differences among the YH4808 groups were not statistically significant (p > 0.05). YH4808 exhibited potential for better pH control during the night in comparison to esomeprazole. The optimal regimen for night time pH control among all the YH4808 regimens was 200 mg twice a day.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT01761513.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/80/18/tcp-29-150.PMC8492394.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498511","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 properties and bioequivalence of gefitinib 250 mg in healthy Korean male subjects.","authors":"Seol Ju Moon,&nbsp;Yunjeong Kim,&nbsp;Ji-Young Jeon,&nbsp;Shin-Jung Park,&nbsp;Yong-Geun Kwak,&nbsp;Min-Gul Kim","doi":"10.12793/tcp.2021.29.e17","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e17","url":null,"abstract":"<p><p>Gefitinib is an anti-cancer drug used to treat non-small cell lung cancer. The objective of this study was to compare the pharmacokinetics and evaluate the bioequivalence of 2 orally administered gefitinib 250 mg tablets in healthy Korean subjects. A randomized, open-label, single-dose, crossover bioequivalence study was conducted. A total of 50 healthy male volunteers were randomized into 2 sequence groups. During each treatment, the subjects received the test or reference formulation of 250 mg gefitinib with a washout period of 21 days. The plasma samples were collected at pre-dose and up to 144 hours post-dose, and plasma drug concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated, and the formulations were considered as bioequivalent if the 90% confidence intervals (CIs) of the geometric mean ratios were within the bioequivalence limits of 0.8 to 1.25. Forty-one subjects completed the study and were included in the pharmacokinetic analysis. The 90% CIs of the geometric mean ratios of the test formulation to the reference formulation were 0.8115 to 0.9993 for maximum plasma concentration and 0.9119 to 1.0411 for area under the plasma concentration versus time curve from dosing to the last measurable concentration. There were no serious or unexpected adverse events during the study. In healthy Korean adult subjects, the test and reference formulations of gefitinib 250 mg had similar pharmacokinetic parameters and similar plasma concentration-time profiles. The test formulation of gefitinib met the regulatory criteria for assuming bioequivalence. Both formulations were safe and well-tolerated.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/ec/tcp-29-171.PMC8492391.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39498513","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":"Insulin sensitization causes accelerated sinus nodal dysfunction through autophagic dysregulation in hypertensive mice.","authors":"Minna Woo,&nbsp;Minsuk Kim","doi":"10.12793/tcp.2021.29.e9","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e9","url":null,"abstract":"<p><p>Insulin sensitizers, while effective in glucose-lowering for diabetes control, are linked to an increased risk of heart disease through mechanisms that are not well understood. In this study, we investigated the molecular mechanisms underlying the effects of insulin sensitization on cardiac sinus node dysfunction. We used pharmacologic or genetic approaches to enhance insulin sensitivity, by treating with pioglitazone or rosiglitazone, or through phosphatase and tensin homolog (<i>PTEN</i>) deletion in cardiomyocytes respectively. We employed an angiotensin II (Ang II)-induced hypertensive animal model which causes sinus node dysfunction and accumulation of oxidized calcium/calmodulin-dependent protein kinase II (CaMKII), which also serves as a biomarker for this defect. While neither <i>PTEN</i> deficiency nor insulin sensitizers caused sinus node dysfunction in normotensive mice, both accelerated the onset of sinus node dysfunction and CaMKII oxidation in hypertensive mice. These abnormalities were accompanied by a significant defect in autophagy as revealed by unc-51 like autophagy activating kinase 1 (ULK1) signaling. Indeed, mice deficient in <i>ulk1</i> in cardiomyocytes and the sinus node also showed early onset of slow atrial impulse conduction with frequent sinus pauses and upregulated CaMKII oxidation following Ang II infusion similar to that seen with <i>PTEN</i> deficiency, or treatment with insulin sensitizers. To further elucidate the role of autophagy in sinus node dysfunction, we treated mice with a peptide D-Tat-beclin1 that enhanced autophagy, which significantly abrogated the frequent sinus pauses and accumulation of oxidized CaMKII induced by insulin sensitizers treatment, or <i>PTEN</i> deficiency in hypertensive animals. Together, these findings provide clear evidence of the detrimental cardiac effects of insulin sensitization that occurs through failure of autophagy-mediated proteolytic clearance.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b6/13/tcp-29-92.PMC8255547.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39162865","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":"Associations between HLA-A, -B, and -C alleles and iodinated contrast media-induced hypersensitivity in Koreans.","authors":"Eun-Young Kim,&nbsp;Seok Jin Choi,&nbsp;Jong-Lyul Ghim,&nbsp;Mi-Yeong Kim,&nbsp;Jung Eun Seol,&nbsp;Minkyung Oh,&nbsp;Chan Sun Park,&nbsp;Jae-Gook Shin","doi":"10.12793/tcp.2021.29.e10","DOIUrl":"10.12793/tcp.2021.29.e10","url":null,"abstract":"<p><p>A common cause of drug hypersensitivity reactions is iodinated contrast media (ICM). ICM-induced hypersensitivity had been considered to be a non-immunological reaction, but evidence for an immunological mechanism has increased recently. Thus, we evaluated whether HLA-A, -B, and -C alleles were associated with ICM-induced hypersensitivity. In total, 126 patients who underwent contrast-enhanced computed tomography studies through outpatient clinics at a tertiary referral hospital between 2008 and 2012 were assessed. Sixty-one patients experienced ICM-induced hypersensitivity and the remainder, 65, were ICM-tolerant patients (control). ICM-induced hypersensitivity patients showed 51 with immediate, 7 with non-immediate, 3 with both or mixed type. HLA-A, -B, and -C genotyping was performed using a PCR sequence-based typing method. Four kinds of ICM were used: iopromide, iohexol, iobitridol, and iodixanol. The most used ICM among the hypersensitivity patients was iopromide. Significant difference in the frequency of <i>HLA-B*58:01</i> (odds ratios [OR], 3.90; <i>p</i> = 0.0200, 95% confidence interval [CI], 1.16-13.07) was observed between ICM-induced immediate hypersensitivity and control. There were statistically significant differences in the frequencies of the <i>HLA-B*38:02</i> (OR, 10.24; <i>p</i> = 0.0145; 95% CI, 1.09-96.14) and <i>HLA-B*58:01</i> (OR, 3.98; <i>p</i> = 0.0348; 95% CI, 1.03-15.39) between iopromide-induced immediate hypersensitivity and control. The mechanism of ICM-induced hypersensitivity remains unknown, but this study showed associations, although weak, with <i>HLA-B*58:01</i> alleles for ICM-induced immediate hypersensitivity and <i>HLA-B*38:02 and HLA-B*58:01</i> for iopromide-induced immediate hypersensitivity as risk predictors. Further studies are needed to validate the associations in larger samples and to identify the functional mechanism behind these results.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8b/18/tcp-29-107.PMC8255545.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39162866","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: clearance.","authors":"Dong-Seok Yim,&nbsp;Soo Hyeon Bae,&nbsp;Suein Choi","doi":"10.12793/tcp.2021.29.e12","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e12","url":null,"abstract":"<p><p>We have streamlined known <i>in vitro</i> methods used to predict the clearance (CL) of small molecules in humans in this tutorial. There have been many publications on <i>in vitro</i> methods that are used at different steps of human CL prediction. The steps from initial intrinsic CL measurement <i>in vitro</i> to the final application of the well-stirred model to obtain predicted hepatic CL (CL_H) are somewhat complicated. Except for the experts on drug metabolism and PBPK, many drug development scientists found it hard to figure out the entire picture of human CL prediction. To help readers overcome this barrier, we introduce each method briefly and demonstrate its usage in the chain of related equations destined to the CL_H. Despite efforts in the laboratory steps, huge <i>in vitro</i> (predicted CL_H)-<i>in vivo</i> (observed CL_H) discrepancy is not rare. A simple remedy to this discrepancy is to correct human predicted CL_H using the ratio of <i>in vitro-in vivo</i> CL_H obtained from animal species.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/31/26/tcp-29-78.PMC8255549.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39163329","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":"Acetaminophen-induced anaphylaxis: a case report.","authors":"Jung Sunwoo,&nbsp;Hyungsub Kim,&nbsp;Kyun-Seop Bae","doi":"10.12793/tcp.2021.29.e8","DOIUrl":"https://doi.org/10.12793/tcp.2021.29.e8","url":null,"abstract":"<p><p>Acetaminophen is known to be generally safe, and the occurrence of anaphylaxis due to acetaminophen has been rarely reported. We report a case of acetaminophen-induced anaphylaxis in a healthy male subject who participated in a clinical trial on the pharmacokinetics of ibandronate. The subject had not experienced an allergic reaction to acetaminophen prior to this incident. The patient received 1300 mg oral acetaminophen at about 12 hours after receiving 150 mg ibandronate. After about 10 minutes, the subject developed whole-body urticaria and hypotension. The temporal association suggested that the anaphylaxis was due to acetaminophen and not ibandronate. Anaphylaxis could occur due to acetaminophen even in the absence of allergic reactions in the first dosing.</p>","PeriodicalId":23288,"journal":{"name":"Translational and Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/21/tcp-29-88.PMC8255548.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39163330","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}