Publications by authors named "S C Koh"

1,954 Publications

  • Page 1 of 1

Letter to the Editor: Effectiveness of the Varicella Vaccine in Korea: Unresolved Issues.

J Korean Med Sci 2021 Jul 12;36(27):e200. Epub 2021 Jul 12.

Department of Preventive Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea.

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http://dx.doi.org/10.3346/jkms.2021.36.e200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275458PMC
July 2021

Purine metabolite-based machine learning models for risk prediction, prognosis, and diagnosis of coronary artery disease.

Biomed Pharmacother 2021 Jul 10;139:111621. Epub 2021 May 10.

Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, 150 Bugahyeon-ro, Seodaemun-gu, Seoul 03759, South Korea; Department of Chemistry and Nano Science, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, South Korea. Electronic address:

Alterations in xanthine oxidase activity are known to be pathologically influential on coronary artery disease (CAD), but the association between purine-related blood metabolites and CAD has only been partially elucidated. We performed global metabolomics profiling and network analysis on blood samples from the Wonju and Pyeongchang (WP) cohort study (n = 2055) to elucidate the importance of purine related metabolites associated with potential CAD risk. Then, 5 selected serum metabolites were quantified from the WP cohort, Shinchon cohort (n = 259), and Shinchon case control (n = 424) groups to develop machine learning models for 10-year risk prediction, relapse within 10 years and diagnosis of the disease via 100 repeated 5-fold cross-validations of logistic models. The combination of purine metabolite levels or only xanthine levels in blood could be applied for machine learning model development for major adverse cardiac and cerebrovascular event (MACCE, cerebrovascular death, nonfatal myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, and stroke) risk prediction, relapse of MACCEs among patients with myocardial infarction history and diagnosis of stable CAD. In particular, our research provided initial evidence that blood xanthine and uric acid levels play different roles in the development of machine learning models for primary/secondary prevention or diagnosis of CAD. In this research, we determined that purine-related metabolites in blood are applicable to machine learning model development for CAD risk prediction and diagnosis. Also, our work advances current CAD biomarker discovery strategies mainly relying on clinical features; emphasizes the differential biomarkers in first/secondary prevention or diagnosis studies.
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http://dx.doi.org/10.1016/j.biopha.2021.111621DOI Listing
July 2021

Cortical neuroanatomical changes related to specific neuropsychological deficits in subcortical vascular cognitive impairment.

Neuroimage Clin 2021 22;30:102685. Epub 2021 Apr 22.

Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea; Neuroscience Center, Samsung Medical Center, Seoul 06351, South Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea; Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, South Korea; Samsung Alzheimer Research Center and Center for Clinical Epidemiology Medical Center, Seoul, South Korea. Electronic address:

Objective: Neuropsychological test-specific neural substrates in subcortical vascular cognitive impairment (SVCI) are expected to differ from those in Alzheimer's disease-related cognitive impairment (ADCI) but the details are unclear. To determine neural substrates related to cerebral small vessel disease, we investigated the correlations between cognitive dysfunctions measured by standardized neuropsychological tests and cortical thickness in a large sample of participants with amyloid negative (Aβ (-)) SVCI.

Methods: One hundred ninety-eight participants with Aβ (-) SVCI were recruited from the memory clinic between November 2007 to August 2018. To acquire neural substrates, we performed linear regression using the scores of each neuropsychological test as a predictor, cortical thickness as an outcome, and age, sex, education years, intracranial volume and white matter hyperintensity (WMH) as confounders.

Results: Poor performances in each neuropsychological test were associated with cortical atrophy in certain brain regions regardless of WMH. Especially, not the medial temporal but the frontal and posterior cingulate regions with cortical atrophy were mainly associated with memory impairment. Poor performance in animal fluency was more likely to be associated with cortical atrophy in the left hemisphere, while poor performance in the visuospatial memory test was more likely to be associated with cortical atrophy in the right hemisphere.

Conclusions: Our findings suggested that cortical atrophy was an important factor of cognitive impairment in Aβ (-) SVCI regardless of WMH. Furthermore, our findings might give clinicians a better understanding of specific neural substrates of neuropsychological deficits in patients with SVCI.
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http://dx.doi.org/10.1016/j.nicl.2021.102685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102616PMC
April 2021

Effect of Possible Osteoporosis on Parenchymal-Type Hemorrhagic Transformation in Patients with Cardioembolic Stroke.

J Clin Med 2021 Jun 7;10(11). Epub 2021 Jun 7.

Department of Neurosurgery, Hanyang University Guri Hospital, 153 Gyeongchun-ro, Guri 471-701, Gyonggi-do, Korea.

Background: hemorrhagic transformation (HT) is a frequent complication of ischemic stroke, and parenchymal hematoma (PH)-type HT has been shown to correlate with symptomatic deterioration. Because both bone and vascular smooth muscle cells are composed of type 1 collagen, we hypothesized that the integrity of blood vessels around the infarction area might be more damaged in osteoporotic conditions after a cardioembolic stroke.

Methods: we measured frontal skull Hounsfield unit (HU) values on brain CT images from cardioembolic stroke patients. We conducted a receiver operating characteristic curve analysis in a large sample registry to identify the optimal HU threshold for predicting osteopenia and osteoporosis. Hazard ratios were estimated using a Cox regression analysis to identify whether osteoporotic conditions were an independent predictor of PH-type HT in patients with cardioembolic stroke.

Results: altogether, 600 consecutive patients (>18 years old) with cardioembolic stroke were enrolled over a 12-year period at our hospital. The infarction volume and hypothetical osteoporosis were independent predictive factors for PH-type HT development in patients with cardioembolic stroke. In the male group, hypothetical osteoporosis was an independent predictor for PH-type HT development after cardioembolic stroke (hazard ratio, 4.12; 95% confidence interval, 1.40-12.10; = 0.010).

Conclusions: our study suggests an association between possible osteoporosis and the development of PH-type HT in patients with cardioembolic stroke. Our findings could help to predict PH-type HT by providing a convenient method for measuring the HU value using brain CT images.
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http://dx.doi.org/10.3390/jcm10112526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201205PMC
June 2021

Mechanism-Based Inactivation of Cytochrome P450 3A4 and 3A5 by the Fibroblast Growth Factor Receptor Inhibitor Erdafitinib.

Chem Res Toxicol 2021 Jul 30;34(7):1800-1813. Epub 2021 Jun 30.

Department of Pharmacy, Faculty of Science, National University of Singapore, 169856 Singapore.

Erdafitinib (ERD) is a first-in-class pan inhibitor of fibroblast growth factor receptor 1-4 that has garnered global regulatory approval for the treatment of advanced or metastatic urothelial carcinoma. Although it has been previously reported that ERD elicits time-dependent inhibition (TDI) of cytochrome P450 (P450) 3A4 (CYP3A4), the exact biochemical nature underpinning this observation remains obfuscated. Moreover, it is also uninterrogated if CYP3A5-its highly homologous counterpart-could be susceptible to such interactions. Mechanism-based inactivation (MBI) of P450 is a unique subset of TDI that hinges on prior bioactivation of the drug to a reactive intermediate and possesses profound clinical and toxicological implications due to its irreversible nature. Here, we investigated and confirmed that ERD inactivated both CYP3A isoforms in a time-, concentration-, and NADPH-dependent manner with , , and partition ratio of 4.01 and 10.04 μM, 0.120 and 0.045 min, and 32 and 55 for both CYP3A4 and CYP3A5, respectively, when rivaroxaban was employed as the probe substrate. Co-incubation with an alternative substrate or direct inhibitor of CYP3A attenuated the rate of inactivation, whereas the addition of glutathione or catalase did not induce such protection. The lack of enzyme activity recovery following dialysis for 4 h and oxidation with potassium ferricyanide combined with the lack of a Soret peak in spectral scans collectively substantiated that ERD is an irreversible covalent MBI of CYP3A. Finally, glutathione trapping and high-resolution mass spectrometry experiments illuminated a plausible bioactivation mechanism of ERD by CYP3A arising from metabolic epoxidation of its quinoxaline ring.
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http://dx.doi.org/10.1021/acs.chemrestox.1c00178DOI Listing
July 2021