Seong Kyung Kim’s research while affiliated with Ewha Womans University and other places

This study aimed to develop a model incorporating natural language processing analysis for the simplified molecular-input line-entry system (SMILES) to predict clearance (CL) and volume of distribution at steady state (Vd,ss) in humans. The construction of CL and Vd,ss prediction models involved data from 435 to 439 compounds, respectively. In machine learning, features such as animal pharmacokinetic data, in vitro experimental data, molecular descriptors, and SMILES were utilized, with XGBoost employed as the algorithm. The ChemBERTa model was used to analyze substance SMILES, and the last hidden layer embedding of ChemBERTa was examined as a feature. The model was evaluated using geometric mean fold error (GMFE), r2, root mean squared error (RMSE), and accuracy within 2- and 3-fold error. The model demonstrated optimal performance for CL prediction when incorporating animal pharmacokinetic data, in vitro experimental data, and SMILES as features, yielding a GMFE of 1.768, an r2 of 0.528, an RMSE of 0.788, with accuracies within 2-fold and 3-fold error reaching 75.8% and 81.8%, respectively. The model's performance in Vd,ss prediction was optimized by leveraging animal pharmacokinetic data and in vitro experimental data as features, yielding a GMFE of 1.401, an r2 of 0.902, an RMSE of 0.413, with accuracies within 2-fold and 3-fold error reaching 93.8% and 100%, respectively. This study has developed a highly predictive model for CL and Vd,ss. Specifically, incorporating SMILES information into the model has predictive power for CL.

This study aimed to evaluate the association between sacubitril/valsartan and dementia-related adverse events (AEs) in geographical subpopulations using subgroup disproportionality analysis. Cases from the FDA adverse event reporting system involving patients aged 60 or older with sacubitril/valsartan or angiotensin receptor blockers (ARBs) were analyzed. The adjusted reporting odds ratios (RORs) for dementia-related AEs were calculated for each continent. A total of 61,518 AEs associated with sacubitril/valsartan or ARBs were identified. Among these, 1441 were dementia-related AEs. In Asia, Europe, and Africa, the reporting risk of dementia-related AEs associated with sacubitril/valsartan was lower compared to ARBs (adjusted ROR, 0.57 [95% CI 0.31–1.01]; adjusted ROR, 0.89 [95% CI 0.69–1.14]; adjusted ROR, 0.40 [95% CI 0.27–0.61], respectively). In Latin America and Oceania, the reporting risk of dementia-related AEs associated with sacubitril/valsartan was similar to that associated with ARBs (adjusted ROR, 1.04 [95% CI 0.75–1.44]; adjusted ROR, 1.02 [95% CI 0.31–3.37], respectively). On the contrary, in North America, the reporting risk associated with sacubitril/valsartan was higher compared to ARBs (adjusted ROR, 1.29 [95% CI 1.10–1.53]). Although the ROR value did not meet the criteria for signal detection, the significantly greater than 1 ROR observed in North America suggests that caution may be warranted regarding potential dementia-related adverse events associated with sacubitril/valsartan.

Background In studies with small sample sizes, the use of nonparametric methods is generally recommended for statistical analysis. However, various studies continue to employ parametric analysis without verifying the assumption of a normal distribution. Objectives To assess the current utilization of parametric and nonparametric methods for primary outcomes, as well as the reporting of normality assumptions, in phase 3 clinical trials with small sample sizes. Methods All phase 3 trials registered on ClinicalTrials.gov until September 12, 2023, were collected. After undergoing a two-step selection process, only publications with a sample size per group of less than 30, involving two or more groups, and specifying the statistical methods used to compare the means or medians of primary outcomes between groups were selected. Statistical methods were categorized as nonparametric, parametric, and either parametric or nonparametric. The reporting of normality assumptions was also evaluated. Results A total of 317 studies were assessed in this study. Among these studies, 164 (51.7%) studies conducted parametric analysis, and 111 (35.0%) studies employed nonparametric analysis; however, 42 (13.2%) studies conducted parametric or nonparametric analysis without specifying which method was used. In addition, 63.1% of the total studies did not report normality assumptions. Specifically, within the subset of studies with parametric analysis, 70.1% of studies did not report normality assumptions. Conclusions This research demonstrated that most studies with small sample sizes employed parametric analysis without reporting normality assumptions. The findings emphasize the need for increased awareness of and compliance with statistical principles in the analysis of phase 3 clinical trials with limited sample sizes.

This study aimed to investigate geographical variation in the risk of dementia-related adverse events (AEs) associated with sacubitril/valsartan. Cases from the FDA Adverse Event Reporting System involving patients aged 60 or older with sacubitril/valsartan or angiotensin receptor blockers (ARBs) were analyzed. The reporting odds ratios (RORs) for dementia-related AEs were calculated for each continent and the correlation between MME variants and ROR was analyzed. The risk of broad dementia associated with sacubitril/valsartan usage was significantly lower in Asia and Africa (ROR = 0.53, 95% CI = 0.31–0.91; ROR = 0.34, 95% CI = 0.12–0.96, respectively). The risk was significantly higher in North America (ROR = 1.3, 95% CI = 1.16–1.60). In Europe, the risk of broad dementia was significantly lower (ROR = 0.74, 95% CI = 0.59–0.93), while that of narrow dementia was significantly higher (ROR = 8.76, 95% CI = 2.27–33.90). A strong negative correlation was found between broad dementia risk and the frequency of the rs701109 polymorphism (r = -0.9) and the rs3736187 polymorphism (r = -0.88). There are regional variations in dementia-related AEs associated with sacubitril/valsartan usage, and differences in genetic polymorphisms could be a potential cause.