In this review, we describe the absorption rates (Caco-2 cell permeability) and hepatic/plasma pharmacokinetics of 53 diverse chemicals estimated by modeling virtual oral administration in rats. To ensure that a broad range of chemical structures is present among the selected substances, the properties described by 196 chemical descriptors in a chemoinformatics tool were calculated for 50,000 randomly selected molecules in the original chemical space. To allow visualization, the resulting chemical space was projected onto a two-dimensional plane using generative topographic mapping. The calculated absorbance rates of the chemicals based on cell permeability studies were found to be inversely correlated to the no-observed-effect levels for hepatoxicity after oral administration, as obtained from the Hazard Evaluation Support System Integrated Platform in Japan (r = -0.88, p < 0.01, n = 27). The maximum plasma concentrations and the areas under the concentration-time curves (AUC) of a varied selection of chemicals were estimated using two different methods: simple one-compartment models (i.e., high-throughput toxicokinetic models) and simplified physiologically based pharmacokinetic (PBPK) modeling consisting of chemical receptor (gut), metabolizing (liver), and central (main) compartments. The results obtained from the two methods were consistent. Although the maximum concentrations and AUC values of the 53 chemicals roughly correlated in the liver and plasma, inconsistencies were apparent between empirically measured concentrations and the PBPK-modeled levels. The lowest-observed-effect levels and the virtual hepatic AUC values obtained using PBPK models were inversely correlated (r = -0.78, p < 0.05, n = 7). The present simplified PBPK models could estimate the relationships between hepatic/plasma concentrations and oral doses of general chemicals using both forward and reverse dosimetry. These methods are therefore valuable for estimating hepatotoxicity.
Kim, Young Joo;Kang, Dong Hyun;Song, Geum Jong;Ahn, Tae Sung;Son, Myoung Won;Lee, Moon Soo;Baek, Moo-Jun
Korean Journal of Clinical Oncology
/
v.14
no.2
/
pp.76-82
/
2018
Purpose: Lgr5 is a well-known stem cell marker in colorectal cancer (CRC). This retrospective study evaluated the expressions of Lgr5 in CRC specimens, and examined whether these expressions were associated with survival outcomes. Methods: We used immunohistochemistry to retrospectively examine expressions of Lgr5 in paraffin-embedded specimens from 337 patients with CRC between January 2009 and December 2013. All clinicopathologic data were collected by retrospective review based on medical records. The correlation between its expression and clinicopathological data as well as clinical outcomes of patients was analyzed. Results: Low expression and high expression of Lgr5 in 337 patients were 175 (51.9%) and 162 (48.1%), respectively. There was no statistically significant difference in the association of Lgr5 expression with clinicopathologic factors (age, tumor location, lymphatic invasion, vascular invasion, perineural invasion, TNM stage, and differentiation). In the survival analysis, the high expression group of Lgr5 showed a better prognosis than the low expression group in disease-free survival (P=0.044). However, overall survival was not significantly different between the two groups (P=0.087). In multivariate analysis, we found that high expression of Lgr5 was independent prognostic factor for tumor relapse (hazard ratio, 0.601; 95% confidence interval, 0.388-0.929; P=0.022). Conclusion: In present study, high expression of Lgr5 is an independent predictor of favorable prognosis in patients with CRC. So, further well designed, prospective, large scale studies are needed to examine the value of Lgr5 as a prognostic biomarker for CRC.
The recent performance of residential mortgages demonstrated how default risk operated separately from prepayment risk. In this study, we investigated the determinants of the borrowers' decisions pertaining to early termination through default from the mortgage performance data released by Freddie Mac, involving securitized mortgage loans from January 2011 to September 2013. We estimated a Cox-type, proportional hazard model with a single risk on fundamental factors associated with default options for individual mortgages. We proposed a mortgage default model that included two specifications of delinquency: one using a delinquency binary variable, while the other using a delinquency probability. We also compared the results obtained from two specifications with respect to goodness-of-fit proposed in the spirit of Vuong (1989) in both overlapping and nested models' cases. We found that a model with our proposed delinquency probability variable showed a statistically significant advantage compared to a benchmark model with delinquency dummy variables. We performed a default prediction power test based on the method proposed in Shumway (2001), and found a much stronger performance from the proposed model.
Park, Ilkun;Shin, Sumin;Kim, Hong Kwan;Choi, Yong Soo;Kim, Jhingook;Zo, Jae Ill;Shim, Young Mog;Cho, Jong Ho
Journal of Chest Surgery
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v.52
no.5
/
pp.360-367
/
2019
Background: Primary chest wall sarcoma is a rare disease with limited reports of surgical resection. Methods: This retrospective review included 41 patients with primary chest wall sarcoma who underwent chest wall resection and reconstruction from 2001 to 2015. The clinical, histologic, and surgical variables were collected and analyzed by univariate and multivariate Cox regression analyses for overall survival (OS) and recurrence-free survival (RFS). Results: The OS rates at 5 and 10 years were 73% and 61%, respectively. The RFS rate at 10 years was 57.1%. Multivariate Cox regression analysis revealed old age (hazard ratio [HR], 5.16; 95% confidence interval [CI], 1.71-15.48) as a significant risk factor for death. A surgical resection margin distance of less than 1.5 cm (HR, 15.759; 95% CI, 1.78-139.46) and histologic grade III (HR, 28.36; 95% CI, 2.76-290.87) were independent risk factors for recurrence. Conclusion: Long-term OS and RFS after the surgical resection of primary chest wall sarcoma were clinically acceptable.
Journal of the Korean Society of Industry Convergence
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v.21
no.6
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pp.395-408
/
2018
Even after the Fukushima nuclear accident in 2011, the rate of production of electric energy using nuclear energy is increasing, but there is a great danger such as the radioactive waste produced when using nuclear power, the catastrophic accident of nuclear power plant, and connection with nuclear weapons. In particular, Cs present in the ionic form of alkaline elements has a long half-life (30.17 years) because it is readily absorbed by the organism and emits intense gamma rays, thus presenting a serious radiation hazard. Therefore, it must be completely removed before it can be released into the natural ecosystem, because it can adversely affect not only humans but also natural ecosystems. Many adsorbents and ion exchangers which have high Cs removal efficiency have been used in recent years to completely separate and remove by self separation in water. Many adsorbents and ion exchangers which have high Cs removal efficiency have been used in recent years to completely separate and remove by self separation in water. In addition, researches have been doing to synthesize magnetic materials with adsorbents such as HCF and PB, and it shows a great effect in the removal rate of Cs present in wastewater or the maximum Cs adsorption amount. In particular, when a magnetic material was applied, excellent results were obtained in which only Cs was selectively removed from other cations. However, new problems such as applicability in the sea where Cs is directly released, applicability in various pH ranges, and failure to preserve the magnetizing force possessed by the magnetic body have been found. However, researches using ferromagnetic field with stronger magnetic properties than those of magnetic bodies is considered to be insufficient. Therefore, it is considered that if the researches combining the ferromagnetic field with the magnetization ability and functional adsorbents more actively, the radioactive material Cs which adversely affects the natural ecosystem can be effectively removed.
Matsuo, Koji;Mandelbaum, Rachel S.;Machida, Hiroko;Purushotham, Sanjay;Grubbs, Brendan H.;Roman, Lynda D.;Wright, Jason D.
Journal of Gynecologic Oncology
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v.29
no.6
/
pp.91.1-91.12
/
2018
Objective: To examine the association between tumor grade and survival for women with squamous cervical cancer. Methods: This retrospective observational study utilized the Surveillance, Epidemiology, and End Result program data between 1983 and 2013 to examine women with squamous cervical cancer with known tumor differentiation grade. Multivariable analyses were performed to assess independent associations between tumor differentiation grade and survival. Results: A total of 31,536 women were identified including 15,175 (48.1%) with grade 3 tumors, 14,084 (44.7%) with grade 2 neoplasms and 2,277 (7.2%) with grade 1 tumors. Higher tumor grade was significantly associated with older age, higher stage disease, larger tumor size, and lymph node metastasis (all, p<0.001). In a multivariable analysis, grade 2 tumors (adjusted-hazard ratio [HR]=1.21; p<0.001) and grade 3 tumors (adjusted-HR=1.45; p<0.001) were independently associated with decreased cause-specific survival (CSS) compared to grade 1 tumors. Among the 7,429 women with stage II-III disease who received radiotherapy without surgical treatment, grade 3 tumors were independently associated with decreased CSS compared to grade 2 tumors (adjusted-HR=1.16; p<0.001). Among 4,045 women with node-negative stage I disease and tumor size ${\leq}4cm$ who underwent surgical treatment without radiotherapy, grade 2 tumors (adjusted-HR=2.54; p=0.028) and grade 3 tumors (adjusted-HR=4.48; p<0.001) were independently associated with decreased CSS compared to grade 1 tumors. Conclusion: Our study suggests that tumor differentiation grade may be a prognostic factor in women with squamous cervical cancer, particularly in early-stage disease. Higher tumor grade was associated with poorer survival.
According to the Korean Statistical Information Service, the number of fatal occupational accidents per 100,000 workers is the highest in Korea, among all the OECD countries. The safety of construction workers is managed by the construction technology promotion act (CTPA) and the occupational safety and health act (OHSA). A review of the current safety management laws is required to improve them for the construction industry, where the numbers of accidents and deaths are constantly increasing. Accordingly, the aim of this study was to identify the problems in unclear business areas through comparison and analysis of the CTPA and OHSA guidelines and establish effective site-dependent construction safety management plans. The overlapping safety and health management terms and tasks of organizations were derived along with identifying the overlapping items of the safety management and hazard and risk prevention plans. Based on these results, several improvements for the design stage, safety cost, and safety education have been suggested in this paper. In addition, an improved model based on the integration and an optimized compromise between these two laws for safety management in areas where many accidents have occurred in recent years has been reported here.
Kwak, Jung Hyun;Park, Chan Hyuk;Eun, Chang Soo;Han, Dong Soo;Kim, Yong Sung;Song, Kyu Sang;Choi, Bo Youl;Kim, Hyun Ja
Journal of Gastric Cancer
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v.21
no.4
/
pp.403-417
/
2021
Purpose: Owing to differences in the general characteristics of gastric cancer (GC) according to histological type, the association of GC risk factors, such as diet, may also differ depending on the histological type. We investigated the associations between individual and combined intake of soy products, vegetables, and dairy products and GC mortality by following up cases of death among Korean GC cases and whether these associations differ according to the histological type. Materials and Methods: A total of 508 GC cases were enrolled from two hospitals between 2002 and 2006. Their survival or death was prospectively followed up until December 31, 2016, through a review of medical records and telephonic surveys. Finally, 300 GC cases classified as intestinal- or diffuse-type GC cases were included. The median follow-up period was 7.1 years. Results: In the fully adjusted model, a high intake of soy products (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.19-0.96) and the combination of soy products and vegetables (HR, 0.34; 95% CI, 0.12-0.96) or soy products and dairy products (HR, 0.37; 95% CI, 0.14-0.98) decreased the mortality from intestinal-type GC. In particular, patients consuming various potentially protective foods (HR, 0.23; 95% CI, 0.06-0.83) showed a highly significant association with a lower mortality from intestinal-type GC. However, no significant association was found with diffuse-type GC. Conclusions: High intake of potentially protective foods, including soy products, vegetables, and dairy products, may help increase survival in intestinal-type GC.
Objective : Extremely low alanine transaminase (ALT) levels are associated with all-cause mortality in frail elderly individuals; the clinical significance of ALT as a reliable biomarker is now being considered. Predicting mortality with routine tests at the time of diagnosis is important for managing patients after intracranial hemorrhage. We aimed to investigate whether an extremely low ALT level is associated with mortality in the elderly after intracranial hemorrhage. Methods : A retrospective review was performed on 455 patients with intracranial hemorrhage admitted to a university-affiliated tertiary care hospital from February 2014 to May 2019. Multivariate Cox regression analysis was performed for all ages and for each age group to determine whether an extremely low ALT level is an independent predictor of mortality only in the elderly. Results : Overall, 294 patients were enrolled, and the mean age of the subjects was 59.1 years, with 99 (33.8%) aged ≥65 years. The variables associated with all-cause mortality in all subjects were age, C-reactive protein (CRP) levels, hemoglobin (Hb) levels (<11 g/dL), and initial Glasgow coma scale (GCS) scores. In young patients, CRP, low Hb levels, and initial GCS scores were significantly associated with all-cause mortality. However, in the elderly (≥65 years), the variables significantly associated with all-cause mortality were extremely low levels of ALT (<10 U/L) (adjusted hazard ratio, 3.313; 95% confidence interval, 1.232-8.909; p=0.018) and initial GCS scores. Conclusion : Extremely low ALT level (<10 U/L) at the time of diagnosis is a significant risk factor for all-cause mortality in the elderly after intracranial hemorrhage.
Background: No study has examined the regulatory factors associated with fatal health problems due to the use of humidified disinfectants (HD) in South Korea. Objectives: This study aimed to identify and discuss the deficiencies and limitations found in the Toxic Chemical Control Acts (TCCA) that failed to prevent the health risk of chemicals in HD products. Methods: The South Korean TCCA was reviewed focusing on acts in operation from 1994 through the end of 2011, the period when HD was allowed in manufacturing and marketing. Results: The TCCA was the act intended to regulate the toxicity of chemicals in HD products. We found the TCCA to lack three key legal clauses which would have been essential to controlling the health risk of HD. First, there was the exemption of toxic and hazard testing for existing chemicals, including chloromethylisothiazolinone (CMIT), methylisothiazolinone (MIT), and benzalkonium chloride (BKC). Secondly, there were no articles requiring industry to provide animal inhalation test result for polymers such as polyhexamethylene guanidine (PHMG) and Oligo(2-)ethoxyethoxyethyl guanidine chloride (PGH). Finally, there was a lack of articles on examining the risk of products as well as on addressing changes in the usage of products. These articles were found to be generally provided in the US Toxic Substance Chemical Act (TSCA) and the EU Registration, Evaluation and Authorization of Chemicals (REACH). Conclusions: In conclusion, the Ministry of Environment of South Korea had not updated key articles for regulating hazardous chemicals, causing large-scale health problems due to HD which had been fundamentally addressed in chemical-related acts in other countries.
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