• 한국환경보건학회지
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• 제39권2호
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• pp.130-137
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• 2013

Objectives: The OECD QSAR Application Toolbox was developed by the Organisation for Economic Cooperation and Development (OECD) to facilitate the practical use of QSAR approaches in regulatory contexts as well as to reduce the need for additional animal testing. In this study, human health and the ecotoxicity of chemicals were predicted by applying the OECD QSAR Application Toolbox and the results were compared with experimental data in order to evaluate the applicability of this program. Methods: Read-across, trend analysis, and QSAR of OECD QSAR Application Toolbox were used for the prediction of toxicity. Results: The toxicity prediction was conducted on 6,354 chemicals for which toxicity data have been produced on the six endpoints of skin sensitization, skin irritation, eye irritation, mutagenicity, and acute toxicities of fish and Daphnia. From the total of 6,354, we obtained prediction results for 1,621 chemicals (25.5%). Conclusions: The predicted properties of mutagenicity, skin sensitization, and acute aquatic toxicities were reasonably good when compared with experimental data, but other endpoints were not due to the limitation of applicable chemical groups.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5343-5348
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• 2014

Background: A meta-analysis was performed to examine the benefit/risk ratio for the addition of anti- HER MoAbs to chemotherapy in patients with advanced gastric and gastroesophageal cancer from six randomized phase II/III trials. Materials and Methods: We searched relative trials from Pubmed, EMBASE, Cochrane library databases, China National Knowledge Infrastructure databases, Google Scholar and the NIH ClinicalTrials. Primary outcomes were overall response rate (ORR), progression-free survival (PFS), overall survival (OS). Secondary outcomes were toxicities. All analyses were performed using STATA 12.0. Results: This meta-analysis included six randomized controlled trials (RCTs) with 2, 297 patients and we demonstrated that the anti-HER MoAbs arm did have a positive effect on ORR in the anti-HER MoAbs arm (OR 1.28, 95% CI 1.00-1.64, p=0.01). There was an increasing benefit regarding OS (HR 0.74, 95% CI 0.60-0.88, p<0.05) and PFS (HR 0.72, 95% CI 0.60-0.84, p<0.05) in the anti-HER2 subgroup, but a reduction of OS (HR 1.11, 95% CI 0.87-1.36, p<0.05) and PFS (HR 1.13, 95% CI 0.98 -1.28, P<0.05) in anti-EGFR subgroup. Some grade 3-4 toxicity had a significantly higher incidence in the anti-HER MoAbs arm. There was no significant publication bias for all endpoints. Conclusions: The addition of trstuzumab MoAb to chemotherapy for gastric and gastroesophageal cancer significantly improved outcome of OS and PFS endpoints, while other MoAbs led to no improvement in results. Some adverse events were increased in anti-HER MoAbs arm compared with the control.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4439-4445
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• 2015

Background: Because there is no clear consensus for the prognostic implication of KRAS mutations in patients with non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to draw a more accurate conclusion. Materials and Methods: A systematic computer search of articles from inception to May 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articles and extraction of data were independently performed by two authors. Results: Our analysis was based on the endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS) comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations. In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval [CI] 1.23-1.56) and PFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC. According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS and PFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However, the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treated with chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643). Conclusions: Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLC but not for those treated with chemotherapies integrating cetuximab.

• Journal of Astronomy and Space Sciences
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• 제33권3호
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• pp.221-227
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• 2016

As described in the previous paper (Park et al. 2013), the detector subsystem of optical wide-field patrol (OWL) provides many observational data points of a single artificial satellite or space debris in the form of small streaks, using a chopper system and a time tagger. The position and the corresponding time data are matched assuming that the length of a streak on the CCD frame is proportional to the time duration of the exposure during which the chopper blades do not obscure the CCD window. In the previous study, however, the length was measured using the diagonal of the rectangle of the image area containing the streak; the results were quite ambiguous and inaccurate, allowing possible matching error of positions and time data. Furthermore, because only one (position, time) data point is created from one streak, the efficiency of the observation decreases. To define the length of a streak correctly, it is important to locate the endpoints of a streak. In this paper, a method using a differential convolution mask pattern is tested. This method can be used to obtain the positions where the pixel values are changed sharply. These endpoints can be regarded as directly detected positional data, and the number of data points is doubled by this result.

• Journal of Chest Surgery
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• 제50권1호
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• pp.14-21
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• 2017

Background: Off-pump coronary artery bypass (OPCAB) is performed worldwide, but significant risks are associated with conversion to on-pump surgery. Therefore, we evaluated the composite outcomes between an OPCAB group and a conversion group. Methods: From January 2008 to December 2012, 100 consecutive patients underwent OPCAB at Hallym University Sacred Heart Hospital, of whom 84 underwent OPCAB without adverse events (OPCAB group), and 16 were converted to on-pump surgery (conversion group). Early morbidity, early and long-term mortality, and major adverse cardiac and cerebrovascular events (MACCEs) were the primary and long-term composite endpoints. Results: The mean follow-up period was $55{\pm}26months$, with 93% of the patients completing follow-up. The composite outcomes in the OPCAB and conversion groups were as follows: early morbidity, 2.3% versus 12.5%; early mortality, 4.7% versus 0%; long-term mortality, 14.3% versus 25.0%; and MACCEs, 14.3% versus 18.8%, respectively. No composite endpoints showed statistically significant differences. Preoperative acute myocardial infarction (AMI) was identified as an independent risk factor for conversion (p=0.025). Conclusion: The conversion group showed no statistically significant differences in early mortality and morbidity, MACCEs, or long-term mortality compared with the OPCAB group. The preoperative diagnosis of AMI was associated with an increased number of conversions to on-pump surgery.

• Toxicological Research
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• 제6권2호
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• pp.167-182
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• 1990

Dietary restriction (caloric restriction) is the only intervention which has been reliably shown to extend the maximum life span of warm-blooded animals and delay the many phenomena associated with aging. It is also one of the most effective modulators of toxicity, especially cancer endpoints. In spite of the known modulator effects of caloric restriction, the biological mechanisms responsible for these effects had not been in vestigated until recently. The National Center for Toxicological Research (NCTR), in a collaborative effort with the National Institute of Aging (NIA), initiated a project whereby nine (9) combinations of rodent species/strains and diets were fed both restricted and ad libitum. The NIA's initiative was to identify biomarkers of aging whereas NCTR's initiative was to identify the biological effects associated with the profound effects caloric restriction has in protecting against both spontaneous (age-related) and chemically-induced toxic endpoints. Independent of sex or species, caloric restriction has similar effects on body temperature, oxygen consumption and $CO_2$production. Caloric restriction also decreased lipid glycolysis and metabolism in rats and mice, which suggest decreased production of metabolites which could lead to fatty acid epoxide formation. The age-associated loss of ciradian regulation of intermediate enzymes is also significantly reduced. Moreover, caloric restriction reduced the age-associated feminization of sexually dimorphic liver isozymes, increased several glucocorticoid responsive isozymes, elevated glucagon/insulin ratios, produced less microsomal superoxide and enhanced the capacity for utilzing detoxicating metabolic pathways. Calorically restricted rats have less than half the number of aflatoxin ($AFB_1$)-DNA adducts than ad libitum animals and urinary excretion of $AFB_1$ was increased significantly. Finally, DNA repair mechanisms are enhanced and oncogene expression is decreased in calorically restricted animals.

• 약학회지
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• 제54권2호
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• pp.75-90
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• 2010

Biomarkers are likely to be important in the study of various pulmonary diseases for many reasons. Research efforts in developing biomarkers and surrogate endpoints of lung diseases have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in new drug development and advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. Identification of suitable end points not only would help investigators design appropriate clinical trials but would assist clinicians in caring for this patient population. Though the area of pulmonology has received much attention in the past decades, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility. This review critically summarized several biomarker researches such as Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study with objectives of identifying the parameters that predict disease progression of COPD, as well as biomarkers that may serve as surrogate end-points.

• Journal of Chest Surgery
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• 제55권3호
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• pp.189-196
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• 2022

Background: This study investigated the predictive value of the frailty index calculated using laboratory data and vital signs (FI-L) in patients who underwent coronary artery bypass grafting (CABG). Methods: This study included 508 patients (age 67.3±9.7 years, male 78.0%) who underwent CABG between 2018 and 2021. The FI-L, which estimates patients' frailty based on laboratory data and vital signs, was calculated as the ratio of variables outside the normal range for 32 preoperative parameters. The primary endpoints were operative and medium-term all-cause mortality. The secondary endpoints were early postoperative complications and major adverse cardiac and cerebrovascular events (MACCEs). Results: The mean FI-L was 20.9%±10.9%. The early mortality rate was 1.6% (n=8). Postoperative complications were atrial fibrillation (n=148, 29.1%), respiratory complications (n=38, 7.5%), and acute kidney injury (n=15, 3.0%). The 1- and 3-year survival rates were 96.0% and 88.7%, and the 1- and 3-year cumulative incidence rates of MACCEs were 4.87% and 8.98%. In multivariable analyses, the FI-L showed statistically significant associations with medium-term all-cause mortality (hazard ratio [HR], 1.042; 95% confidence interval [CI], 1.010-1.076), MACCEs (subdistribution HR, 1.054; 95% CI, 1.030-1.078), atrial fibrillation (odds ratio [OR], 1.02; 95% CI, 1.002-1.039), acute kidney injury (OR, 1.06; 95% CI, 1.014-1.108), and re-operation for bleeding (OR, 1.09; 95% CI, 1.032-1.152). The minimal p-value approach showed that 32% was the best cutoff for the FI-L as a predictor of all-cause mortality post-CABG. Conclusion: The FI-L was a significant prognostic factor related to all-cause mortality and postoperative complications in patients who underwent CABG.

• Clinical Endoscopy
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• 제55권6호
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• pp.793-800
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• 2022

Background/Aims: Fully covered self-expanding metal stents (FCSEMSs) are a relatively novel option for treating painful main pancreatic duct refractory strictures in patients with chronic pancreatitis. Herein, we aimed to assess the efficacy, feasibility, and safety of FCSEMSs in this patient group. Methods: This prospective single-center study included patients who underwent endoscopic retrograde pancreatography with FCSEMS placement. The primary endpoints were the technical and clinical success rates. A reduction in visual analog scale pain score of >50% compared with that before stent placement was defined as clinical success. Secondary endpoints were resolution of pancreatic strictures on fluoroscopy during endoscopic retrograde pancreatography and the development of stent-related adverse events. Results: Thirty-six patients were included in the analysis. The technical success rate was 100% (n=36) and the clinical success rate was 86.1% (n=31). There was a significant increase in stricture diameter from 1.7 mm to 3.5 mm (p<0.001) after stent removal. The mean visual analog scale pain score showed statistically significant improvement. At 19 months of follow-up, 55.6% of the patients were asymptomatic. Stent migration (16.7%), intolerable abdominal pain (8.3%), development of de novo strictures (8.3%), and mild pancreatitis (2.8%) were the most common adverse events. Conclusions: FCSEMS placement showed good technical and clinical success rates for achieving pain relief in patients with refractory main pancreatic duct strictures.

• 대한수학회보
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• 제50권1호
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• pp.263-273
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• 2013

A mean-value result, saying that the difference quotient of a differentiable function in a real interval is a mean value of its derivatives at the endpoints of the interval, leads to the functional equation $$\frac{f(x)-F(y)}{x-y}=M(g(x),\;G(y)),\;x{\neq}y$$, where M is a given mean and $f$, F, $g$, G are the unknown functions. Solving this equation for the arithmetic, geometric and harmonic means, we obtain, respectively, characterizations of square polynomials, homographic and square-root functions. A new criterion of the monotonicity of a real function is presented.