• Toxicological Research
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• v.20 no.2
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• pp.89-100
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• 2004

The comet assay (also called the single-cell gel electrophoresis assay) has been widely used for detecting DNA damage and repair in individual cells. Since the conventional methods of evaluating comet assay data using frequency statistics are unsatisfactory we developed a new quantitative measure of DNA damage/repair that is based on all information residing in the dose/time-response curves of a comet experiment. Blood samples were taken from 25 breast cancer patients before undergoing radiotherapy. The comet assay was performed under alkaline conditions using isolated lymphocytes. Tail DNA, tail length, tail moment and tail inertia of the comet were measured for each patient at four doses of $\gamma$-rays (0, 2, 4 and 8 Gy) and at four time points after irradiation (0, 10, 20 and 30 min) using 100 cells each. The resulting three-dimensional dose-time response surface was modeled by multiple regression, and the second derivative, termed 2D, on dose and time was determined. A software module was programmed in SAS/AF to compute 2D values. We applied the new method successfully to data obtained from cancer patients to be assessed for their radiation sensitivity. We computed the 2D values for the four damage measures, i.e., tail moment, tail length, tail DNA and tail inertia, and examined the pairwise correlation coefficients of 2D both on the log scale and the unlogged scale. 2D values based on tail moment and tail DNA showed a high correlation and, therefore, these two damage measures can be used interchangeably as far as DNA repair is concerned. 2D values based on tail inertia have a correlation profile different from the other 2D values which may reflect different facets of DNA damage/repair. Using the dose-time response surface, other statistical models, e.g., the proportional hazards model, become applicable for data analysis. The 2D approach can be applied to all DNA repair measures, Le., tail moment, tail length, tail DNA and tail inertia, and appears to be superior to conventional evaluation methods as it integrates all data of the dose/time-response curves of a comet assay.

• Korean Journal of Biological Psychiatry
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• v.18 no.1
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• pp.36-45
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• 2011

Objectives : Though a proportion of Alzheimer's disease(AD) patients treated with donepezil have shown positive response on cognition, but the responders' characteristics are still uncertain. This study attempts to identify whether a single oral dose of donepezil(5mg) can change cognition and the relationship between single dose responder items and long-term responder are examined. Methods : Twenty-three AD patients for single donepezil challenge study group and eleven AD patients for controls were participated in the study. Seven days after baseline study for neuropsychological test and EEG, same studies were rechecked after donepezil medication in study group. In donepezil study groups, 12 weeks after donepezil medication, neuropsychological test and EEG were rechecked. Results : After single donepezil challenge, forward digit span, Rey-Osterrieth Complex Figure Test copy, SVLT delayed recall were significantly improved, and beta spectra power in anterior, theta spectra power in posterior field were significantly decreased. According to linear regression analysis, forward digit span after single donepezil challenge was significantly positive correlated with long-term responders. Conclusions : This study suggests that single donepezil medication can significantly change cognitive functions and EEG in AD patients. Among these responsive items, forward digit span was significantly correlated with long-term responder.

• Journal of Environmental Health Sciences
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• v.49 no.1
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• pp.1-10
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• 2023

Low-dose radiation exposure has received considerable attention because it reflects the general public's type and level of exposure. Still, controversy remains due to the relatively unclear results and uncertainty in risk estimation compared to high-dose radiation. However, recent epidemiological studies report direct evidence of health effects for various types of low-dose radiation exposure. In particular, international nuclear workers' studies, CT exposure studies, and children's cancer studies on natural radiation showed significantly increased cancer risk among the study populations despite their low-dose radiation exposure. These studies showed similar results even when the cumulative radiation dose was limited to an exposure group of less than 100 mGy, demonstrating that the observed excess risk was not affected by high exposure. A linear dose-response relationship between radiation exposure and cancer incidence has been observed, even at the low-dose interval. These recent epidemiological studies include relatively large populations, and findings are broadly consistent with previous studies on Japanese atomic bomb survivors. However, the health effects of low-dose radiation are assumed to be small compared to the risks that may arise from other lifestyle factors; therefore, the benefits of radiation use should be considered at the individual level through a balanced interpretation. Further low-dose radiation studies are essential to accurately determining the benefits and risks of radiation.

• Proceedings of the Korean Nuclear Society Conference
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• 2002.05a
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• pp.427.1-427
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• 2002

• Asian Journal of Atmospheric Environment
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• v.12 no.1
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• pp.1-16
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• 2018

Ground-level ozone ($O_3$) can be a menace for vegetation, especially in Asia where $O_3$ levels have been dramatically increased over the past decades. To ensure food security and maintain forest ecosystem services, such as nutrient cycling, carbon sequestration and functional diversity of soil biota, in the over-populated Asia, environmental standards are needed. To set proper standards, dose-response relationships should be established from which critical levels are derived. The predictor of the response in the dose-response relationship is an $O_3$ metric that indicates the dose level to which the plant has been exposed. This study aimed to review the relevant scientific literature and summarize the $O_3$ metrics used worldwide to provide insights for Asia. A variety of $O_3$ metrics have been used, for which we discuss their strengths and weaknesses. The most widely used metrics are based only on $O_3$ levels. Such metrics have been adopted by several regulatory agencies in the global. However, they are biologically irrelevant because they ignore the plant physiological capacity. Adopting AOT40 ($O_3$ mixing ratios Accumulated Over the Threshold of $40nmol\;mol^{-1}$) as the default index for setting critical levels in Asia would be a poor policy with severe consequences at national and Pan-Asian level. Asian studies should focus on flux-based $O_3$ metrics to provide relevant bases for developing proper standards. However, given the technical requirements in calculating flux-based $O_3$ metrics, which can be an important limitation in developing countries, no-threshold cumulative exposure indices like AOT0 should always accompany flux-based indices.

• Safety and Health at Work
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• v.9 no.3
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• pp.290-295
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• 2018

Background: There is little information on the dose-response relationship between exposure to occupational carcinogenic agents and mesothelioma. This study aimed to investigate this association as well as the existence of agents other than asbestos that might cause mesothelioma. Methods: The Swedish component of the Nordic Occupational Cancer (NOCCA) study consists of 6.78 million individuals with detailed information on occupation. Mesothelioma diagnoses recorded in 1961-2009 were identified through linkage to the Swedish Cancer Registry. We determined cumulative exposure, time of first exposure, and maximum exposure intensity by linking data on occupation to the Swedish NOCCA job-exposure matrix, which includes 29 carcinogenic agents and corresponding exposure for 283 occupations. To assess the risk of mesothelioma, we used conditional logistic regression models to estimate hazard ratios and 95% confidence intervals. Results: 2,757 mesothelioma cases were identified in males, including 1,416 who were exposed to asbestos. Univariate analyses showed not only a significant excess risk for maximum exposure intensity, with a hazard ratio of 4.81 at exposure levels 1.25-2.0 fb/ml but also a clear dose-response effect for cumulative exposure with a 30-, 40-, and 50-year latency time. No convincing excess risk was revealed for any of the other carcinogenic agents included in the Swedish NOCCA job-exposure matrix. Conclusion: When considering asbestos exposure, past exposure, even for short periods, might be enough to cause mesothelioma of the pleura later in life.

• Radiation Oncology Journal
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• v.29 no.2
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• pp.63-70
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• 2011

Purpose: To evaluate the extent of pain response and objective response to palliative radiotherapy (RT) for bone metastases from hepatocellular carcinoma according to RT dose. Materials and Methods: From January 2007 to June 2010, palliative RT was conducted for 103 patients (223 sites) with bone metastases from hepatocellular carcinoma. Treatment sites were divided into the high RT dose and low RT dose groups by biologically effective dose (BED) of 39 $Gy_{10}$. Pain responses were evaluated using the numeric rating scale. Pain scores before and after RT were compared and categorized into 'Decreased', 'No change' and 'Increased'. Radiological objective responses were categorized into complete response, partial response, stable disease and progression using modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria; the factors predicting patients' survival were analyzed. Results: The median follow-up period was 6 months (range, 0 to 46 months), and the radiologic responses existed in 67 RT sites (66.3%) and 44 sites (89.8%) in the high and low RT dose group, respectively. A dose-response relationship was found in relation to RT dose (p=0.02). Pain responses were 75% and 65% in the high and low RT dose groups, respectively. However, no statistical difference in pain response was found between the two groups (p=0.24). There were no differences in the toxicity profiles between the high and low RT dose groups. Median survival from the time of bone metastases diagnosis was 11 months (range, 0 to 46 months). The Child-Pugh classification at the time of palliative RT was the only significant predictive factor for patient survival after RT. Median survival time was 14 months under Child-Pugh A and 2 months under Child-Pugh B and C. Conclusion: The rate of radiologic objective response was higher in the high RT dose group. Palliative AT with a high dose would provide an improvement in patient quality of life through enhanced tumor response, especially in patients with proper liver function.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.2
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• pp.163-173
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• 2021

Objective: This study aimed to characterize a validated model for predicting oocyte retrieval in controlled ovarian stimulation (COS) and to construct model-based nomograms for assistance in clinical decision-making regarding the gonadotropin protocol and dose. Methods: This observational, retrospective, cohort study included 636 women with primary unexplained infertility and a normal menstrual cycle who were attempting assisted reproductive therapy for the first time. The enrolled women were split into an index group (n=497) for model building and a validation group (n=139). The primary outcome was absolute oocyte count. The dose-response relationship was tested using modified Poisson, negative binomial, hybrid Poisson-E_max, and linear models. The validation group was similarly analyzed, and its results were compared to that of the index group. Results: The Poisson model with the log-link function demonstrated superior predictive performance and precision (Akaike information criterion, 2,704; λ=8.27; relative standard error (λ)=2.02%). The covariate analysis included women's age (p<0.001), antral follicle count (p<0.001), basal follicle-stimulating hormone level (p<0.001), gonadotropin dose (p=0.042), and protocol type (p=0.002 and p<0.001 for short and antagonist protocols, respectively). The estimates from 500 bootstrap samples were close to those of the original model. The validation group showed model assessment metrics comparable to the index model. Based on the fitted model, a static nomogram was built to improve visualization. In addition, a dynamic electronic tool was created for convenience of use. Conclusion: Based on our validated model, nomograms were constructed to help clinicians individualize the stimulation protocol and gonadotropin doses in COS cycles.

• Progress in Medical Physics
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• v.32 no.4
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• pp.179-184
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• 2021

This study aimed to determine the optimal thickness of the active layer and scan mode for a flexible radiochromic film (F-RCF) based on the active lithium salt of pentacosa-10,12-diynoic acid (LiPCDA). F-RCFs of 90, 120, 140, and 170-㎛ thickness were fabricated using LiPCDA. Several pieces of the F-RCFs were exposed to doses ranging from 0 to 3 Gy. Transmission and reflection modes were used to scan the irradiated F-RCFs. Their dose-response curves were obtained using a second-order polynomial equation. Their sensitivity was evaluated for both scanning modes, and the uniformity of the batch was also examined. For both the transmission and reflection modes, the sensitivity increased as the film thickness increased. For the reflection mode, the dose response increased dramatically under 1 Gy. The value of the net optical density varied rapidly as the thickness of the film increased. However, the dose-response curves showed a supralinear-curve relationship at doses greater than 2 Gy. The sensitivity of the reflection scan at doses greater than 2 Gy was higher than that of the reflection scan within 0-2 Gy. The sensitivity steadily decreased with increasing doses, and the sensitivity of the two modes was within 0.1 to 0.2 at 2 Gy and was saturated beyond that. For the transmission scan, the sensitivity was approximately 0.2 at 3 Gy. For the intra-batch test result, the maximum net optical density difference of the intra-batch was 5.5% at 2 Gy and 7.4% at 0.2 Gy in the transmission and reflection scans, respectively. In the low-dose range, film thickness of more than 120-㎛ was proper in the transmission mode. In contrast, the transmission mode showed a better result compared to the reflection mode. Therefore, the proper scan mode should be selected according to the dose range.

• Biomolecules & Therapeutics
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• v.15 no.4
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• pp.224-229
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• 2007

Depurination, the release of purine bases from nucleosides by hydrolysis of the N-glycosidic bond, gives rise to alterations of the cell genome. Although, cells have evolved mechanisms to repair these lesions, unrepaired apurinic sites have been shown to have two biological consequences: lethality and base substitution errors. 2-Bromopropane (2-BP) is used as an intermediate in the synthesis of pharmaceuticals, dyes, and other organics. In addition, 2-BP has been used as a cleaning solvent in electronics industry. But, 2-BP was found to cause reproductive and hematopoietic disorders in local workers exposed to it. We observed massive depurination after incubation of 2'-deoxyadenosine (dA) and 2'-deoxyguanosine (dG) with the excess amount 2-BP at the physiological condition (pH 7.4, $37^{\circ}C$), which were analyzed by HPLC and LC-MS/MS. In addition, time and dose response relationship of depurination in dA and dG induced by 2-BP at the physiological condition were investigated.