• Journal of Environmental Health Sciences
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• v.50 no.2
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• pp.113-124
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• 2024

Background: The increasing need to minimize animal testing has sparked interest in alternative methods with more humane, cost-effective, and time-saving attributes. In particular, in silico-based computational toxicology is gaining prominence. Adverse outcome pathway (AOP) is a biological map depicting toxicological mechanisms, composed of molecular initiating events (MIEs), key events (KEs), and adverse outcomes (AOs). To understand toxicological mechanisms, predictive models are essential for AOP components in computational toxicology, including molecular structures. Objectives: This study reviewed the literature and investigated previous research cases related to AOP and in silico methodologies. We describe the results obtained from the analysis, including predictive techniques and approaches that can be used for future in silico-based alternative methods to animal testing using AOP. Methods: We analyzed in silico methods and databases used in the literature to identify trends in research on in silico prediction models. Results: We reviewed 26 studies related to AOP and in silico methodologies. The ToxCast/Tox21 database was commonly used for toxicity studies, and MIE was the most frequently used predictive factor among the AOP components. Machine learning was most widely used among prediction techniques, and various in silico methods, such as deep learning, molecular docking, and molecular dynamics, were also utilized. Conclusions: We analyzed the current research trends regarding in silico-based alternative methods for animal testing using AOPs. Developing predictive techniques that reflect toxicological mechanisms will be essential to replace animal testing with in silico methods. In the future, since the applicability of various predictive techniques is increasing, it will be necessary to continue monitoring the trend of predictive techniques and in silico-based approaches.

• The Korean journal of internal medicine
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• v.39 no.1
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• pp.95-109
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• 2024

Background/Aims: Sex differences in the prognosis of heart failure (HF) have yielded inconsistent results, and data from Asian populations are even rare. This study aimed to investigate sex differences in clinical characteristics and long-term prognosis among Korean patients with HF. Methods: A total of 5,625 Korean patients hospitalized for acute HF were analyzed using a prospective multi-center registry database. Baseline clinical characteristics and long-term outcomes including HF readmission and death were compared between sexes. Results: Women were older than men and had worse symptoms with higher N-terminal pro B-type natriuretic peptide levels. Women had a significantly higher proportion of HF with preserved ejection fraction (HFpEF). There were no significant differences in in-hospital mortality and rate of guideline-directed medical therapies in men and women. During median follow-up of 3.4 years, cardiovascular death (adjusted hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.07-1.78; p = 0.014), and composite outcomes of death and HF readmission (adjusted HR, 1.13; 95% CI, 1.01-1.27; p = 0.030) were significantly higher in men than women. When evaluating heart failure with reduced ejection fraction (HFrEF) and HFpEF separately, men were an independent risk factor of cardiovascular death in patients with HFrEF. Clinical outcome was not different between sexes in HFpEF. Conclusions: In the Korean multi-center registry, despite having better clinical characteristics, men exhibited a higher risk of all-cause mortality and readmission for HF. The main cause of these disparities was the higher cardiovascular mortality rate observed in men compared to women with HFrEF.

• Oncology Reports
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• v.43 no.2
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• pp.655-661
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• 2020

Alterations in DNA methylation have a central role in the development and outcome of most human malignancies. Non-small cell lung cancer (NSCLC), the most common lung cancer, leads to the largest number of cancer-related deaths worldwide. FBJ murine osteosarcoma viral oncogene homolog B (FOSB) is a key component of the activator protein-1 transcription factor and regulates gene networks associated within oncogenic transformation. The role of FOSB in the development of NSCLC is still elusive. Therefore, the methylation status of the FOSB gene was investigated in NSCLC and its clinical significance in NSCLC progression was evaluated. The methylation status of the promoter and exon 4 regions of the FOSB gene were analyzed in 176 NSCLC specimens by bisulfite pyrosequencing and the association between FOSB methylation status and patient survival was investigated. Compared to adjacent non-malignant tissues, FOSB promoter exhibited exclusive unmethylation in all malignant tissues and the exon 4 region was found unmethylated in 18 (10.2% of the total) tumor samples. Exon 4 unmethylation was associated with downregulation of its mRNA and tended to occur in patients with lymph node metastasis. Univariate and multivariate analyses revealed that exon 4 unmethylation was significantly associated with unfavorable overall survival in patients with stage II-IIIA NSCLC (log-rank P=0.05, adjusted hazard ratio=2.43, 95% confidence interval=1.04-5.68, P=0.04). FOSB was identified as a novel gene with tumor-specific gene body unmethylation in NSCLC and a novel predictive biomarker for NSCLC prognosis. Moreover, the present results indicated that FOSB may have a tumor suppressor function in the progression of NSCLC.

• Journal of Advanced Navigation Technology
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• v.28 no.4
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• pp.518-523
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• 2024

The explosive increase in demand for drones poses a major threat to the safety of existing aircraft operations and important national facilities operating in low-altitude airspace. In order to determine the type and degree of safety threats for low-altitude airspace drones, the types and types of threats from drones are evaluated through analysis of AHP(analysis hierarchy process) for aviation workers in each field. The composition of the threat factor hierarchy from drones was designed using a specific operation risk assessment (SORA) technique previously studied by the European Aviation Safety Agency (EASA), an advanced aviation country. Based on this, it will be possible to secure the low-altitude safety operation of existing aircraft by identifying and removing prior hazards between each aircraft operation and mission performance.

• Clinical Nutrition Research
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• v.11 no.3
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• pp.183-193
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• 2022

We investigated the predictors of survival in patients with advanced BTC according to their baseline nutritional status estimated by the Nutritional Risk Screening (NRS)-2002. From September 2006 to July 2017, we reviewed the data of 601 inpatients with BTC. Data on demographic and clinical parameters was collected from electronic medical records, and overall survival (OS) and progression-free survival were analyzed using the Kaplan-Meier method and the stepwise Cox regression analysis. Patients with an NRS-2002 score of ≤ 2, 3, and ≥ 4 were respectively classified as "no risk," "moderate risk," "high risk." Following initial NRS-2002 score, 333 patients (55%) were classified as "no-risk," 109 patients (18%) as "moderate-risk," and 159 patients (27%) as "high-risk." Survival analysis demonstrated significant differences in the median OS: "no-risk": 12.6 months (95% confidence interval [CI], 11.5-13.7); "moderate-risk": 6.1 months (95% CI, 4.3-8.0); and "high-risk": 3.9 months (95% CI, 3.2-4.6) (p < 0.001). NRS-2002 score was an independent factor for OS (hazard ratio [HR], 1.616 for "moderate-risk", 95% CI, 1.288-2.027, p < 0.001; HR, 2.121 for "high-risk", 95% CI, 1.722-2.612, p < 0.001), along with liver metastasis, peritoneal seeding, white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, cholesterol, carcinoembryonic antigen, and carbohydrate antigen 19-9. In conclusion, baseline NRS-2002 is an appropriate method for discriminating those who are already malnourished and who have poor prognosis in advanced BTC patient. Significance of these results merit further validation to be integrated in the routine practice to improve quality of care in BTC patients.

• Clinical Endoscopy
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• v.57 no.5
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• pp.647-655
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• 2024

Background/Aims: Endoscopic biliary drainage using self-expandable metallic stents (SEMSs) for malignant biliary strictures occasionally induces acute cholecystitis (AC). This study evaluated the efficacy of prophylactic gallbladder stents (GBS) during SEMS placement. Methods: Among 158 patients who underwent SEMS placement for malignant biliary strictures between January 2018 and March 2023, 30 patients who attempted to undergo prophylactic GBS placement before SEMS placement were included. Results: Technical success was achieved in 21 cases (70.0%). The mean diameter of the cystic duct was more significant in the successful cases (6.5 mm vs. 3.7 mm, p<0.05). Adverse events occurred for 7 patients (23.3%: acute pancreatitis in 7; non-obstructive cholangitis in 1; perforation of the cystic duct in 1 with an overlap), all of which improved with conservative treatment. No patients developed AC when the GBS placement was successful, whereas 25 of the 128 patients (19.5%) without a prophylactic GBS developed AC during the median follow-up period of 357 days (p=0.043). In the multivariable analysis, GBS placement was a significant factor in preventing AC (hazard ratio, 0.61; 95% confidence interval, 0.37-0.99; p=0.045). Conclusions: GBS may contribute to the prevention of AC after SEMS placement for malignant biliary strictures.

• Journal of Preventive Medicine and Public Health
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• v.30 no.3 s.58
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• pp.630-642
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• 1997

The purpose of this study was to examine the mortality risk associated with cognitive impairment among the rural elderly. The subjective of study was 558 of 'A Study on the Depression and Cognitive Impairment in the Rural Elderly' of Jung Ae Rhee and Hyang Gyun Jung's study(1993). Cognitive impairment and other social and health factors were assessed in 558 elderly rural community residents. For this study, a Korean version of the Mini-Mental State Examination(MMSEK) was used as a global indicator of cognitive functioning. And mortality risk factors for each cognitive impairment subgroup were identified by univariate and multivariate Cox regression analysis. At baseline 22.6% of the sample were mildly impaired and 14.2% were severely impaired. As the age increased, the cognitive function was more impaired. Sexual difference was existed in the cognitive function level. Also the variables such as smoking habits, physical disorders had the significant relationship with cognitive function impairment. Across a 3-year observation period the mortality rate was 8.5% for the cognitively unimpaired, 11.1% for the mildly impaired, and 16.5% for the severly impaired respendents. And the survival probability was .92 for the cognitively unimpaired, .90 for the mildly impaired, and .86 for the severly impaired respondents. Compared to survival curve for the cognitively unimpaired group, each survival curve for the mildly and the severely impaired group was not significantly different. When adjustments models were not made for the effects of other health and social covariates, each hazard ratio of death of mildly and severely impaired persons was not significantly different as compared with the cognitively unimpaired. But, as MMSEK score increased, significantly hazard ratio of death decreased. Employing Cox univariate proportional hazards model, statistically other significant variables were age, monthly income, smoking habits, physical disorders. Also when adjustments were made for the effects of other health and social covariates, there was no difference in hazard ratio of death between those with severe or mild impairment and unimpaired persons. And as MMSEK score increased, significantly hazard ratio of death did not decrease. Employing Cox multivariate proportional hazards model, statistically other significant variables were age, monthly income, physical disorders. Employing Cox multivariate proportional hazards model by sex, at men and women statistically significant variable was only age. For both men and women, also cognitive impairment was not a significant risk factor. Other investigators have found that cognitive impairment is a significant predictor of mortality. But we didn't find that it is a significant predictor of mortality. Even though the conclusions of our study were not related to cognitive impairment and mortality, early detection of impaired cognition and attention to associated health problems could improve the quality of life of these older adults and perhaps extend their survival.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3607-3612
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• 2013

Introduction: Reported prognostic roles of hypoxic inducible factor (HIF) expression in non-small cell lung cancer (NSCLC) have varied. This meta-analysis aimed to examine the relationship between HIF expression and clinical outcome in NSCLC patients. Methods: PubMed were used to identify relevant literature with the last report up to December $20^{th}$, 2012. After careful review, survival data were collected from eligible studies. We completed the meta-analysis using Stata statistical software (Version 11) and combined hazard ratio (HR) for overall survival (OS). Subgroup specificity, heterogeneity and publication bias were also assessed. All of the results were verified by two persons to ensure accuracy. Results: Eight studies were finally stepped into this meta-analysis in which seven had available data for HIF-$1{\alpha}$ and three for HIF-$2{\alpha}$. Combined HRs suggested that higher expression of $HIF1{\alpha}$ had a negative impact on NSCLC patient survival (HR=1.50; 95%CI=1.07-2.10; p=0.019). The expression of HIF-$2{\alpha}$ was also relative to a poorer survival (HR=2.02; 95%CI=1.47-2.77; p=0.000). No bias existed in either of the two groups. Conclusion: This study suggests that elevations of HIF-$1{\alpha}$ and HIF-$2{\alpha}$ expression are both associated with poor outcome for patients with NSCLC. The data support further and high quality investigation of HIF expression for predicting poor outcome in patients with NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6761-6766
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• 2014

Background: CD44v6 (CD44 variant exon 6) is the chief CD44 variant isoform regulating tumor invasion, progression, and metastasis. The prognostic value of CD44v6 expression in non small cell lung cancer (NSCLC) has been evaluated in many studies, but the results have remained controversial. Thus, we performed a meta-analysis of currently available studies to investigate the prognostic value of CD44v6 expression in NSCLC patients and the relationship between the expression of CD44v6 and clinicopathological features. Materials and Methods: Two independent reviewers searched the relevant literature in Pubmed, Medline and Embase from 1946 to January 2014. Overall survival (OS) and various clinicopathological features were collected from included studies. This meta-analysis was accomplished using STATA 12.0 and Revman 5.2 software. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated to estimate the effects. Results: A total of 921 NSCLC patients from ten studies met the inclusion criteria. The results showed that CD44v6 high expression was a prognostic factor for poor survival (HR=1.91, 95%CI=1.12-3.26, p<0.05). With respect to clinicopathological features, CD44v6 high expression was related to histopathologic type (squamous cell carcinoma versus adenocarcinoma: OR=2.72, 95%CI=1.38-5.38, p=0.004), and lymph node metastasis (OR=3.02, 95%CI=1.93-4.72, p<0.00001). Conclusions: Our results suggested CD44v6 high expression as a poor prognostic factor for NSCLC, and CD44v6 expression is associated with lymph node metastasis and histopathologic type. Therefore, CD44v6 expression can be used as a novel prognostic marker in NSCLC cases.

• Radiation Oncology Journal
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• v.37 no.2
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• pp.110-116
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• 2019

Purpose: This study aimed to identify prognostic factors for locoregional recurrence (LRR) in pT3N0 rectal cancer patients who were treated with surgery alone and had negative resection margin including circumferential resection margin (CRM) for optimal indication of adjuvant radiotherapy. Materials and Methods: We reviewed patients with pT3N0 rectal cancer who were treated via upfront surgery and had no other adjuvant treatment from January 2003 to December 2012. In total, 122 patients who had negative resection margin including negative CRM were included in the analysis. Results: The median follow-up period after surgery was 60 months (range, 3 to 161 months). During this time, 6 patients (4.9%) experienced LRR at the anastomotic site (4 patients), and regional lymphatic area (2 patients). The estimated 5-year rates of overall survival, recurrence-free survival, and LRR-free survival were 96.7%, 84.6%, and 94.0%, respectively. Multivariate analysis showed that level of tumor ≤5 cm was a significant prognostic factor for LRR-free survival (LRRFS) (p = 0.04; hazard ratio = 7.08; 95% confidence interval, 1.06-47.30). Patients with level of tumor ≤5 cm had an estimated 5-year LRRFS of 66.8%, which was much higher than 2.3% in patients with level of tumor >5 cm. There was no significant factor for recurrence-free survival or overall survival. Conclusion: In T3N0 rectal cancer, adjuvant chemoradiotherapy should be recommended in patients with level of tumor ≤5 cm for better local control. However, in patients with pT3N0 disease, negative resection margin, and level of tumor >5 cm, adjuvant chemoradiotherapy should be carefully suggested.