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Background Biomedical engineers in particular require fast and powerful data processing systems to process computerized tomography and magnetic resonance imaging scans and other medical imaging technologies. However, current computer data processing technologies are unable to satisfy such requirements. A promising approach to addressing these limitations is processing in memory (PIM). Unfortunately, several issues, such as the compatibility and interconnection of PIM with legacy systems, still remain. Objective This paper proposes a standard memory bus-based PIM interface for medical image processing and a PIM platform. The proposed PIM interface can overcome problems of compatibility with legacy systems. Methods We will adapt an embedded system based on a commercial application processor (AP) to a medical image system to verify the functions and the performance of the proposed PIM interface. Using the PIM platform, we apply the proposed PIM interface and the AP to execute an image processing program, measure the image processing times, and compare the results of the measurements. Results Experimental results show that while the functions of the proposed PIM interface are normal, the processing time of PIM is more than 81% faster than that of the AP. Conclusion The experimental results prove that the proposed PIM interface is able to solve problems of compatibility with legacy systems. We foresee that not only the medical image processing field but also a number of academic fields and professional sectors will use PIM in their data-intensive applications.

The separation of methanol-chloroform mixture, a minimum-boiling azeotrope, is performed using pressure- swing distillation process via process simulation. In this study, the steady-state optimization was carried out using PRO/II with PROVISION v.10. The two different column configurations (low-to-high pressure and high-to-low pressure) were compared wherein the positions of the low-pressure column and high-pressure column were operated interchangeably to attain an optimized design. Additionally, different heat-integration configurations (partial heat- and full heat-integration) were applied to lessen the overall utility consumption. It was determined that the low-to-high pressure column configuration provided a more optimized result for all heat-integrated systems as compared to high-tolow pressure column configuration. Application of heat-integration further decreases the cooling water and steam consumption by 38.86% and 35.74%, respectively, for partial heat-integrated system, and by 44.58% and 41.01%, respectively, for full heat-integrated system.

Non-small cell lung cancer (NSCLC) poses a great threat to human health. DNA methylation abnormalities play a central role in the development and outcome of most human malignancies, providing potential biomarkers for diagnosis and prognosis. Iroquois homeobox 1 (IRX1) can act as a tumor suppressor or promoter depending on the tumor microenvironment, and its role in lung cancer is still controversial. The purpose of this study was to investigate the biological role and prognostic value of IRX1 in NSCLC. We examined the methylation status of IRX1 promoter in 146 tumors from patients with NSCLC using pyrosequencing and analyzed the association between methylation status and overall patient survival. A total of 37 cases (25.3%) showed IRX1 methylation-positive tumors when compared with matched normal tissues. No association between IRX1 expression level and methylation status was found in lung cancer cell lines. IRX1 methylation significantly correlated with smoking status and TP53 mutation. Patients with IRX1 methylation showed significantly longer survival than patients without methylation (log-rank P = 0.011). In a multivariate analysis of prognostic factors, IRX1 methylation in tumor samples was an independent prognostic factor (adjusted hazard ratio = 0.35, 95% confidence interval 0.17–0.73, P = 0.005). These results suggest that IRX1 promoter methylation may be a tumor-associated event and an independent predictor of survival advantage in patients with NSCLC. Further large-scale studies are needed to confirm these findings.

A synthetic strategy for the formation of C(sp

Background Blood pressure (BP) targets in elderly patients with diabetes remain unclear. We evaluated the association between BP and cardiovascular disease in elderly patients with diabetes without cardiovascular disease or heart failure. Methods and Results We performed a retrospective cohort study of 225 563 elderly (aged ≥65 years) patients with diabetes without cardiovascular disease or heart failure from 2009 to 2017 using the National Health Information Database. We divided the participants by systolic BP (SBP) and diastolic BP. Primary composite outcomes were stroke, myocardial infarction, heart failure, and all‐cause death analyzed by Cox proportional hazards regression analysis adjusted for baseline covariates. During a median follow‐up of 7.76 years, the incidence rate of primary composite outcomes was 26.62 per 1000 person‐years. In multivariable Cox proportional hazard modeling, the risk of the primary outcome had a U‐curved association with SBP/diastolic blood pressure with a nadir between 120 and 129 mm Hg/65 and 69 mm Hg, respectively. Hypertension medication was associated with lower risk of primary composite outcomes in SBP ≥140 mm Hg ( P for interaction for SBP P for interaction for diastolic blood pressure=0.018). In participants aged ≥80 years, SBP ≥160 mm Hg was only a marginally higher risk for primary composite outcomes (hazard ratio=1.11; 95% CI, 0.98–1.24). Conclusions In this large sample of older Korean patients with diabetes, cardiovascular events were more common in people with resting SBP or diastolic BP ≥140 or 95 mm Hg, respectively, and also more common in people with resting SBP or diastolic BP

Simple Summary Gastric cancer (GC) is the fifth-leading type of cancer and the third –leading cause of death from cancer. Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is recently accountable for 10% of all the GC worldwide. Platinum drugs such as cisplatin and oxaliplatin are the first-line choice in GC chemotherapy. The widespread use of cisplatin leads to make tumor cells develop single or multiple drug resistance via various mechanisms. DNA hypermethylation on tumor suppressor genes is one of causes leading to drug resistances. 5-Azacytidine (5-AZA) is a chemical analogue of cytidine and inhibits DNA methyltransferase, resulting in DNA hypomethylation. Our main objective was to identify synergistic effect of two important GC drugs whose mechanisms may be in complementary cooperation. We found that cisplatin enhances its anticancer activity with 5-AZA through DNA demethylation in EBVaGC. Identifying this synergistic effect of two important GC drugs can be useful to treat EBVaGC which shows resistance to platinum-based chemotherapy. Abstract Epstein–Barr-virus-associated gastric carcinoma (EBVaGC), first reported in 1992, currently accounts for 10% of all gastric carcinoma worldwide. EBVaGC has unique DNA hypermethylation phenotypes that allow for higher proportions of DNA methylation than any other gastric cancer. CpG islands in the gene promoter region are one of the major regions in which DNA methylation controls gene transcription. Despite cisplatin-based chemotherapy being one of the standard treatment regimens for advanced gastric cancer, including EBVaGC, cisplatin alone or in combination with 5-fluorouracil has been limited by its less potent anticancer activity and the occurrence of cisplatin resistance. Accordingly, the current study evaluated the anticancer activities of a combination of cisplatin and 5-Azacytidine (5-AZA) against EBVaGC. Our findings showed that cisplatin upregulated the DNMT3A gene, whereas shRNA-targeted removal of DNMT3A mRNA contributed to cisplatin-mediated EBV lytic reactivation. Moreover, the removal of DNMT3A mRNA upregulated the ATM gene through DNA demethylation on the ATM promoter. Furthermore, CRISPR/Cas9-targeted removal of the ATM gene resulted in significantly reduced cell susceptibility and EBV lytic reactivation by a combination of cisplatin and DNMT3A inhibitor 5-AZA. Finally, 5-AZA exhibited a synergistic effect with cisplatin in anti-EBV and anti-EBVaGC activities by increasing drug susceptibility and EBV lytic reactivation. The aforementioned results suggest that cisplatin combined with DNA methylation inhibitors could be a novel therapeutic approach for EBVaGC.

Context Some studies have suggested that patients with type 2 diabetes mellitus (T2DM) concomitant with obesity have better clinical outcomes than normal-weight patients with T2DM. Objective We evaluated associations among obesity, cardiovascular disease (CVD) events, and mortality in elderly patients with T2DM without CVD. Methods This retrospective observational study from 2009 to 2017, with a mean follow-up of 7.26 years, included 249 903 elderly (≥ 65 years) patients with T2DM and no preexisting CVD from the Korean National Health Information Database. We categorized subjects according to body mass index (BMI) and waist circumference (WC) and analyzed a composite of stroke, myocardial infarction, and all-cause death using Cox proportional hazards regression analysis, adjusting for baseline covariates. Results The incidence rate of composite primary outcomes was 30.95/1000 person-years. The primary outcome risk had an L-shaped and a U-shaped association with BMI and WC, respectively. In the multivariable Cox proportional hazard models, the risk of primary composite outcomes in the highest BMI group (≥ 30 kg/m2; hazard ratio [HR] = 0.824; 95% CI, 0.794-0.855) was lower than in the normal BMI group (≥ 18.5 and Conclusion Our study with elderly patients with diabetes results suggest that while BMI is an inadequate risk indicator for outcomes related to obesity, WC is a suitable alternative.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is characterized by different pathways of carcinogenesis and is a heterogeneous disease with diverse molecular landscapes that reflect histopathological and clinical information. Changes in the DNA methylation status of colon epithelial cells have been identified as critical components in CRC development and appear to be emerging biomarkers for the early detection and prognosis of CRC. OBJECTIVE: To explore the underlying disease mechanisms and identify more effective biomarkers of CRC. METHODS: We compared the levels and frequencies of DNA methylation in 11 genes (Alu, APC, DAPK, MGMT, MLH1, MINT1, MINT2, MINT31, p16, RGS6, and TFPI2) in colorectal cancer and its precursor adenomatous polyp with normal tissue of healthy subjects using pyrosequencing and then evaluated the clinical value of these genes. RESULTS: Aberrant methylation of Alu, MGMT, MINT2, and TFPI2 genes was progressively accumulated during the normal-adenoma-carcinoma progression. Additionally, CGI methylation occurred either as an adenoma-associated event for APC, MLH1, MINT1, MINT31, p16, and RGS6 or a tumor-associated event for DAPK. Moreover, relatively high levels and frequencies of DAPK, MGMT, and TFPI2 methylation were detected in the peritumoral nonmalignant mucosa of cancer patients in a field-cancerization manner, as compared to normal mucosa from healthy subjects. CONCLUSION: This study identified several biomarkers associated with the initiation and progression of CRC. As novel findings, they may have important clinical implications for CRC diagnostic and prognostic applications. Further large-scale studies are needed to confirm these findings.

A sound way to deliver power Implanted medical devices, such as pacemakers and neurological stimulators, require a source of power, usually in the form of a battery. If a battery is implanted with the device, replacing it would require additional surgery. On the other hand, external power packs are prone to lead to infections where their wires enter the body. Hinchet et al. describe a triboelectric generator that can convert externally applied ultrasound into an internal electricity source capable of delivering sufficient energy to recharge a battery on a daily basis. Science , this issue p. 491

BACKGROUND The blood level of alanine aminotransferase (ALT) is associated with increased coronary heart disease (CHD) risk. However, its use as an independent factor for CHD risk prediction remains unclear in Asian populations. The purpose of this study was to examine the association between serum ALT levels and CHD risk in Koreans. METHODS This was a cross-sectional study using data from the Korea National Health and Nutrition Examination Survey (V-1, 2010 and V-2, 2011). The ALT levels of 3,215 individuals were analyzed. The Framingham Risk Score (FRS) modified by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) was used to compute the 10-year CHD risk prediction. RESULTS Positive correlations were established between log-transformed ALT concentration and FRS (r=0.433, P

Background Epidemiological studies have suggested an association between selenium (Se) and diabetes mellitus (DM). However, different studies have reported conflicting results. Therefore, we performed a comprehensive meta-analysis to clarify the impact of Se on DM. Methods We searched the PubMed database for studies on the association between Se and DM from inception to June 2018. Results Twenty articles evaluating 47,930 participants were included in the analysis. The meta-analysis found that high levels of Se were significantly associated with the presence of DM (pooled odds ratios [ORs], 1.88; 95% confidence interval [CI], 1.44 to 2.45). However, significant heterogeneity was found (I²=82%). Subgroup analyses were performed based on the Se measurement methods used in each study. A significant association was found between high Se levels and the presence of DM in the studies that used blood (OR, 2.17; 95% CI, 1.60 to 2.93; I²=77%), diet (OR, 1.61; 95% CI, 1.10 to 2.36; I²=0%), and urine (OR, 1.49; 95% CI, 1.02 to 2.17; I²=0%) as samples to estimate Se levels, but not in studies on nails (OR, 1.24; 95% CI, 0.52 to 2.98; I²=91%). Because of significant heterogeneity in the studies with blood, we conducted a sensitivity analysis and tested the publication bias. The results were consistent after adjustment based on the sensitivity analysis as well as the trim and fill analysis for publication bias. Conclusion This meta-analysis demonstrates that high levels of Se are associated with the presence of DM. Further prospective and randomized controlled trials are warranted to elucidate the link better.

Background Because persistent fever often occurs in adrenal insufficiency, it might be confused with infectious diseases. This study aimed to identify clinical characteristics and risk factors of patients with adrenal insufficiency and fever. Methods All adult patients (n = 150) admitted to a tertiary care hospital in South Korea and diagnosed with adrenal insufficiency between 1 March 2018, and 30 June 2019, were recruited. Patients were excluded if they had: 1) proven structural problems in the adrenal or pituitary gland; 2) a history of chemotherapy within 6 months prior to the diagnosis of adrenal insufficiency; and 3) other medical conditions that may cause fever. Results Among the included patients, 45 (30.0%) had fever at the time of the diagnosis of adrenal insufficiency. The mean C-reactive protein level was higher (11.25 ± 8.54 vs. 4.36 ± 7.13 mg/dL) in patients with fever than in those without fever. A higher proportion of patients with fever changed antibiotics (33.3% vs. 1.0%). On multivariate logistic regression analysis, female sex (odds ratio [OR], 0.32) lowered the risk of adrenal insufficiency with fever, while a history of surgery within 6 months (OR, 4.35), general weakness (OR, 7.21), and cough (OR, 17.29) were significantly associated with that. Conclusion The possibility of adrenal insufficiency should be considered in patients with fever of unknown origin, especially those with risk factors., Graphical Abstract

Thyroid lobectomy is now preferred over total thyroidectomy to preserve thyroid function and reduce complications in patients with low-risk papillary thyroid carcinoma (PTC). One inevitable consequence of thyroidectomy includes hypothyroidism. This study aimed to evaluate the risk factors for hypothyroidism and thyroid hormone replacement after hemithyroidectomy in patients with PTC. We retrospectively studied 353 patients with PTC who underwent hemithyroidectomy with or without central neck dissection from January 2012 to January 2019. We excluded patients who had hypo- or hyperthyroidism preoperatively and those who underwent total or subtotal thyroidectomy. We analyzed various risk factors related to postoperative hypothyroidism and thyroid hormone supplementation. Of the patients, 54.7% showed hypothyroidism after hemithyroidectomy (n=193 with n=157, subclinical hypothyroidism; n=36, overt hypothyroidism). Ninety-one percent of postoperative hypothyroidism cases developed within 7 months postoperatively. Eventually, 43.1% (n=152) of patients received levothyroxine after hemithyroidectomy. Preoperative high thyroid-stimulating hormone (TSH) level and low free thyroxine (fT4) level were significantly associated with postoperative hypothyroidism and the need for thyroid hormone supplementation postoperatively. Preoperative TSH and fT4 levels are predictive risk factors of hypothyroidism and need for supplementation of levothyroxine after hemithyroidectomy in patients with PTC. Finally, approximately 43% of patients need levothyroxine supplementation after hemithyroidectomy, and individual preoperative counseling is necessary for these patients.

SummaryThe trillions of cells that constitute the human body are developed from a fertilized egg through embryogenesis. However, cellular dynamics and developmental outcomes of embryonic cells in humans remain to be largely unknown due to the technical and ethical challenges. Here, we explored whole-genomes of 334 single-cell expanded clones and targeted deep-sequences of 379 bulk tissues obtained from various anatomical locations from seven individuals. Using the discovered 1,688,652 somatic mutations as an intrinsic barcode, we reconstructed cellular phylogenetic trees that provide novel insights into early human embryogenesis. Our findings suggest (1) endogenous mutational rate that is higher in the first cell division of life but decreases to ~1 per cell per cell division later in life, (2) universal unequal contribution of early cells into embryo proper resulting from early cellular bottlenecks that stochastically separate epiblasts from embryonic cells (3) uneven differential outcomes of early cells into three germ layers, left-right and cranio-caudal tissues, (4) emergence of a few ancestral cells that will contribute to the substantial fraction of adult blood cells, and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach additionally provides insights into the age-related mutational processes including UV-mediated mutagenesis and loss of chromosome X or Y in normal somatic cells. Taken together, this study scrutinized somatic mosaicism, clonal architecture, and cellular dynamics in human embryogenesis at an unprecedented level and provides a foundation for future studies to complete cellular phylogenies in human embryogenesis.

Background The study aimed to evaluate the sensory changes on the chin and neck in transoral thyroidectomy. Methods We prospectively assessed the cutaneous sensation of 10 zones of the chin, face, and neck in 43 patients who underwent transoral robotic or endoscopic thyroidectomy using the Semmes-Weinstein monofilaments test, preoperatively and postoperatively at 1 week, 1 month, and 3 months. Results The sensation of the chin and lower lip did not differ before and after surgery. However, the pressure threshold of the submental and level VI area increased significantly after surgery, and returned to the preoperative level 1 month and 3 months postoperatively, respectively. Conclusion In terms of mental nerve injury, transoral thyroidectomy is safe when performed successfully. However, proper placement of oral vestibular incisions and minimal dissection of the chin is essential to avoid mental nerve injury.

AIM To evaluate the efficacy and safety of ipragliflozin vs placebo as add-on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM). METHODS This double-blind, placebo-controlled, multi-centre, phase III study was conducted in Korea in 2015 to 2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT). RESULTS In total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90 (0.69)% for ipragliflozin add-on and 7.92 (0.79)% for placebo. The corresponding mean (SD) changes from baseline to EOT were -0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference -0.83% [95% CI -1.07 to -0.59]; P < .0001). More ipragliflozin-treated patients than placebo-treated patients achieved HbA1c target levels of

BACKGROUND Metabolic syndrome (MS) is a well-known risk factor of cardiovascular diseases that is focused on central obesity. Recent studies have reported the association between pericardial adipose tissue (PAT) volume and MS. However, no studies have demonstrated the cutoff PAT volume that represents the best association with MS. METHODS The data of 374 subjects were analyzed cross-sectionally to compare PAT, measured on coronary multidetector computed tomography, and various metabolic parameters according to MS. After PAT volumes were divided into tertiles, various metabolic parameters were compared among tertiles; furthermore, the odds ratio for developing MS was calculated. Finally, we demonstrated the cutoff PAT volume that represented the best association with MS by using the receiver-operating characteristic curve. RESULTS We found that 27.5% of the subjects had MS, and the mean PAT volume was 123.9 cm3 . PAT showed a significant positive correlation with body mass index, waist circumference, and levels of glucose, triglyceride, high-sensitivity C-reactive protein, uric acid, and homocysteine, but a negative correlation with high-density lipoprotein cholesterol. Furthermore, after dividing into tertiles, PAT volume was also significantly associated with various metabolic parameters. The odds ratio for having MS was 4.19 (95% confidence interval, 2.27-7.74) in the top tertile of PAT volumes after adjusting for age, sex, and smoking. The cutoff PAT volume that represented the best association with MS was 142.2 cm3 . CONCLUSION PAT was significantly associated with MS and various metabolic parameters. The cutoff PAT volume of 142.2 cm3 showed the best association with MS.

Lung cancer is the leading cause of cancer-associated mortality due to high incidence and poor survival rates, irrespective of global variations in its biology and treatment. Changes in DNA methylation are frequent in cancer and constitute an important mechanism in tumorigenesis. Normal mucosa of esophagus-specific 1 (NMES1) is expressed in epithelial tissue and is believed to be a tumor suppressor gene. The present study investigated the methylation status of the NMES1 promoter in 178 cases of primary non-small cell lung cancer (NSCLC) by pyrosequencing and evaluated the prognostic value of this methylation. NMES1 methylation-positive tumors above the background threshold for non-malignant tissue were found in 15 cases (8.4%) and were detected exclusively in malignant tissues. In addition, univariate and multivariate analyses showed that methylation-positive patients experienced worse overall survival rate (OSR) compared with methylation-negative patients (adjusted hazard ratio, 2.62; 95% confidence interval, 1.20-5.69; P=0.02). Notably, within the methylation-positive group, patients with strong methylation tended to experience worse OSR compared with those with weak methylation (adjusted hazard ratio, 2.45 vs. 3.05; Ptrend=0.02). These findings suggest that NMES1 may serve an important role in lung cancer pathogenesis, and its methylation could be considered a prognostic marker for NSCLC. Further studies with large numbers of samples are required to confirm this conclusion.

Nakashita, S.; Woo, H.; Kim, K.; Kim, K.; Lee, I.-C.; Kim, D.-S., and Hibino, T., 2018. Influence of Kuroshio path on Salinity distribution in Seto Inland Sea. In: Shim, J.-S.; Chun, I., and Lim, H.S. (eds.), Proceedings from the International Coastal Symposium (ICS) 2018 (Busan, Republic of Korea). Journal of Coastal Research, Special Issue No. 85, pp. 21–25. Coconut Creek (Florida), ISSN 0749-0208.This study analyzes residual current and salinity distribution in Seto Inland Sea induced by Kuroshio Path variation. The salinity ranged 30 - 34 PSU and it decreased by approximately 1 - 2 PSU at near center of Bisanseto during non-meandering period. Sea level height variations at both boundary of Seto Inland Sea which induces residual current mainly depends on distance between boundaries and Kuroshio Path because of higher sea level hight at Kuroshio path than than that at northern part of Kuroshio path approximately 1 m. Westward residual flow during the non-meandering period (year 1997) was estimated to be faster than that during the meandering period with maximum relative velocity of 4.5 cm/sec. Decrease of salinity at near center of Bisanseto is due to the westward movement of the river water plume from the eastern Bisanseto. From the results obtained above, it is concluded that location of low salinity water at Bisanseto is mainly depends on the residual current due to variation of Kuroshio Path.

The role of Class-F fly ash in the removal of phosphate from aqueous solutions and the removal mechanism were quantitatively investigated. The relative contributions of precipitation and adsorption...

Numerical modeling was conducted to understand characteristics of nutrient distributions caused by wind currents which occur upwelling in the East sea of Korea. Averaged northeastward wind speed of 9.1m per second which occurred upwelling strongly in 2013 was applied in numerical modeling and wind-driven currents was calculated. Water moved northeastward from coastal area to open sea in surface layer, which develop clockwise or counterclockwise eddies. In bottom layer, However, water moved westward to compensate the surface water. Spatio-temporal distributions of nutrient affected by wind-dirven currents were investigated using the numerical model. As time passes, nutrient concentrations increased gradually, spreading to open sea in coastal area from Pohang to Yeongdeok. Highly accumulated nutrients in bottom layer was risen to the surface by upwelling currents. Risen nutrients spread open sea gradually.

Flat panel displays are often exposed to the electrostatic damage during various panel manufacturing processes. In this paper, we report the electrostatic discharge failure in a unique process condition of OLED display process during which the substrate of OLED display is turned over while in the vacuum chucking condition. In order to solve this failure, we adopted newly developed technology of VUV (Vacuum Ultraviolet) radiation to neutralize the electrostatic electricity. This technology generates ions and electrons by ionizing residual molecules in vacuum chamber such that it enables the charged substrates to be neutralized in the chamber. While this new neutralization method is certainly effective in high vacuum process, the lifetime and performance of the VUV ionizer are not validated. To understand the lifetime and performance of VUV ionizer, we conducted the experiments in the vacuum chamber of an 8th generation display facility with various operating time of UV lamp. We analyzed the characteristic of VUV lamp and suggested the neutralization mechanism of VUV ionizer in a low pressure. Based on the experiments, this new neutralization method performs well under the high vacuum environment and is able to completely reduce the electrostatic potential down to 0 V within a short time.

Epstein–Barr-virus-associated gastric carcinoma (EBVaGC), first reported in 1992, currently accounts for 10% of all gastric carcinoma worldwide. EBVaGC has unique DNA hypermethylation phenotypes that allow for higher proportions of DNA methylation than any other gastric cancer. CpG islands in the gene promoter region are one of the major regions in which DNA methylation controls gene transcription. Despite cisplatin-based chemotherapy being one of the standard treatment regimens for advanced gastric cancer, including EBVaGC, cisplatin alone or in combination with 5-fluorouracil has been limited by its less potent anticancer activity and the occurrence of cisplatin resistance. Accordingly, the current study evaluated the anticancer activities of a combination of cisplatin and 5-Azacytidine (5-AZA) against EBVaGC. Our findings showed that cisplatin upregulated the DNMT3A gene, whereas shRNA-targeted removal of DNMT3A mRNA contributed to cisplatin-mediated EBV lytic reactivation. Moreover, the removal of DNMT3A mRNA upregulated the ATM gene through DNA demethylation on the ATM promoter. Furthermore, CRISPR/Cas9-targeted removal of the ATM gene resulted in significantly reduced cell susceptibility and EBV lytic reactivation by a combination of cisplatin and DNMT3A inhibitor 5-AZA. Finally, 5-AZA exhibited a synergistic effect with cisplatin in anti-EBV and anti-EBVaGC activities by increasing drug susceptibility and EBV lytic reactivation. The aforementioned results suggest that cisplatin combined with DNA methylation inhibitors could be a novel therapeutic approach for EBVaGC.

Concentrations of heavy metals (As, Cd, Cr, Cu, Hg, Pb, and Zn) were determined in edible parts (muscle) of 34 marine wild fish caught from the southern sea of Korea in 2007 and 2008 in order to understand the accumulation pattern of heavy metals in wild fish and to assess the potential health risk posed by fish consumption. The highest concentrations in the muscle of 17 pelagic and 17 demersal fishes were Zn and As, respectively, while the lowest concentration in both fishes was Cd. The mean concentrations of all metals except As in wild fish were much lower than the regulatory limits for fish and fishery products applied in a number of countries. Unlike other metals, As concentration in wild fish of this study region was relatively higher than that found in other country. Estimated daily intake (EDI) of the metals was in the range of 0.05% to 22.5% of the provisional maximum tolerable daily intakes (PMTDI). Similarly, the target hazard quotient (THQ) was below 1.0 for each metal. These results imply that the consumption of the investigated wild fish do not cause significant adverse health effects.

Mutations in the promoter region of telomerase reverse transcriptase (TERT) and alterations in telomere length (TL) have been the focus of research in various types of cancer. In the present study, the frequency and clinical characteristics of TERT promoter mutations and TL were studied in non-small cell lung cancers (NSCLC). TERT promoter mutations and TL were analyzed in 188 patients using DNA sequencing and the reverse transcription-quantitative polymerase chain reaction, respectively. The TERT promoter mutation rate was observed to be 2.2% (4/188 NSCLC cases), and it was significantly associated with regional lymph node invasion (P