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Scope High sodium and low potassium (HNaLK) intake increases the risk of cardiovascular disease (CVD) and metabolic syndrome. The authors investigate if the dietary minerals interact with the gut microbiota to alter circulating lipid profiles, implicated in CVD and metabolic syndrome. Methods and results Plasma samples from Wistar rats fed a control or HNaLK diet with or without antibiotic treatment (n = 7 each, a total of 28) are subjected to lipidomics analysis. Lipidomic data are then analyzed using statistical and bioinformatics tools, which detect numerous lipid species altered by the treatments, and consistently demonstrated interactions between the gut microbiota and the HNaLK diet in altering circulating lipids, mainly triglycerides (TGs). Two distinct TG groups differentially regulated by antibiotic treatment are identified. One group (cluster 1), representing the majority of TG species detected, is downregulated, whereas the other group (cluster 2) is upregulated by antibiotic treatment. Interestingly, cluster 2 TGs are also regulated by the diet. Cluster 2 TGs exhibit greater carbon-chain length and double-bond content and include TGs composed of very-long-chain polyunsaturated fatty acids, associated with reduced diabetes risk. Conclusion The HNaLK diet interacts with gut bacteria to alter plasma lipid profiles, which may be related to its health effects.

Epoxyeicosatrienoic acids (EETs) are lipid mediators with beneficial effects on metabolic and cardiovascular (CV) health. EETs are metabolized to biologically less active diols by soluble epoxide hydrolase (sEH). Inhibition of sEH, which increases EETs, has been shown to improve glucose homeostasis, blood pressure, and CV health in insulin-resistant or diabetic animals and proposed as an effective strategy to treat diabetes and CV diseases. Despite its importance to metabolic and CV health, little is known about mechanisms by which sEH is regulated in vivo. Our recent study demonstrated that in vivo sEH activity, assessed from plasma oxylipin levels, profoundly (3-fold) decreased after a meal in rats. Interestingly, this effect was completely abolished in rats with gut bacteria depleted by antibiotic treatment, suggesting that a gut-bacteria-derived factor(s) may be responsible for the postprandial effect. Gut bacteria produce short chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, from nutrients, and plasma SCFA levels rise during feeding. In the present study, we tested the possibility that SCFAs may be involved in the postprandial inhibition of sEH activity. For this, we examined the effects of SCFAs on sEH activity in vitro by measuring EET conversion to diol in liver homogenates. Acetate showed a profound effect to inhibit sEH activity (up to 91%) with EC50 of 39 ± 3 µM (n = 4). In contrast, propionate and butyrate had no significant effects (n = 4 and 5, respectively). The acetate effect occurred at physiological concentrations, suggesting acetate may be an endogenous inhibitor of sEH, and the postprandial inhibition of sEH activity may be mediated by acetate produced by gut bacteria after a meal. Because acetate is produced in vivo predominantly by gut bacteria, these data may explain why the postprandial effect to inhibit sEH was absent in gut-bacteria-depleted rats. Taken together, our data suggest sEH activity may be regulated in vivo by gut bacteria through the production of acetate. Disclosure J. Youn: None. Y. Oh: None. Funding American Diabetes Association (1-16-IBS-332 to J.Y.)

Objective This longitudinal study aimed to analyze the prevalence of mental disorders in endometrial cancer survivors in South Korea. Methods We assessed mental disorders in a nationwide cohort of 8,155 patients who were diagnosed with endometrial cancer between January 1, 2010, and December 31, 2014. We categorized the prevalence of mental disorders based on age and time of diagnosis. Results Based on the first diagnosis, mental disorders were identified in 567 (7.0%) among patients with endometrial cancer. Of those patients, 249 (43.9%) were diagnosed with depression and 248 (43.7%) with anxiety. The overall incidence of mental disorders peaked within 2 months after hysterectomy. The rate of stress reaction/adjustment disorder increased most rapidly among the mental disorders after hysterectomy. While depression rates were relatively high among younger individuals (under 50 years), anxiety was more frequent in older people (over 50 years old). In the entire prescription (n=6,034), depression had the highest incidence (n=3,801), followed by anxiety (n=1,774). Over 89% (n=5,362) of the mental disorder treatment claims were from psychiatric medical departments. Conclusion Mental disorders showed different prevalence patterns among endometrial cancer survivors depending on patient age and the nature of the disease. Intensive and personalized management of distress is necessary for endometrial cancer survivors.

P-type semiconductors are indispensable for achieving complementary metal oxide semiconductor and integrated circuits based on two-dimensional (2D) semiconductors, and tungsten diselenide (WSe2) and molybdenum ditelluride (MoTe2) are the promising channel materials for PMOS. In this work, we report on the charge trapping effects on hysteretic behavior and field-effect mobility (μ FE) of the p-type WSe2 and MoTe2 FETs using fast pulsed current–voltage (I–V) measurements. The hysteresis is reduced by nearly 98% via ramped pulsed measurements, and μ FE is significantly enhanced via single pulse measurements by minimizing the charge trapping. Moreover, WSe2 FETs are found to be more susceptible to the charge trapping effects compared with MoTe2 FETs; WSe2 FETs exhibit more pronounced enhancement of μ FE and reduction of hysteresis. The intrinsic electrical characteristics of p-type 2D FETs under minimized charge trapping conditions can be investigated using the pulsed I–V characterizations.

Purpose Our institution has implemented two different adjuvant protocols in treating patients with non-small cell lung cancer (NSCLC): chemotherapy followed by concurrent chemoradiotherapy (CT-CCRT) and sequential postoperative radiotherapy (PORT) followed by postoperative chemotherapy (POCT). We aimed to compare the clinical outcomes between the two adjuvant protocols. Materials and methods From March 1997 to October 2012, 68 patients were treated with CT-CCRT (n = 25) and sequential PORT followed by POCT (RT-CT; n = 43). The CT-CCRT protocol consisted of 2 cycles of cisplatin-based POCT followed by PORT concurrently with 2 cycles of POCT. The RT-CT protocol consisted of PORT followed by 4 cycles of cisplatin-based POCT. PORT was administered using conventional fractionation with a dose of 50.4-60 Gy. We compared the outcomes between the two adjuvant protocols and analyzed the clinical factors affecting survivals. Results Median follow-up time was 43.9 months (range, 3.2 to 74.0 months), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were 53.9%, 68.2%, and 51.0%, respectively. There were no significant differences in OS (p = 0.074), LRFS (p = 0.094), and DMFS (p = 0.490) between the two protocols. In multivariable analyses, adjuvant protocol remained as a significant prognostic factor for LRFS, favouring CT-CCRT (hazard ratio [HR] = 3.506, p = 0.046) over RT-CT, not for OS (HR = 0.647, p = 0.229). Conclusion CT-CCRT protocol increased LRFS more than RT-CT protocol in patients with completely resected NSCLC, but not in OS. Further studies are warranted to evaluate the benefit of CCRT strategy compared with sequential strategy.

Purpose We compared the treatment results and toxicity in nasopharyngeal carcinoma (NPC) patients treated with concurrent chemotherapy (CCRT) alone (the CRT arm) or neoadjuvant chemotherapy followed by CCRT (the NCT arm). Materials and methods A multi-institutional retrospective study was conducted to review NPC patterns of care and treatment outcome. Data of 568 NPC patients treated by CCRT alone or by neoadjuvant chemotherapy followed by CCRT were collected from 15 institutions. Patients in both treatment arms were matched using the propensity score matching method, and the clinical outcomes were analyzed. Results After matching, 300 patients (150 patients in each group) were selected for analysis. Higher 5-year locoregional failure-free survival was observed in the CRT arm (85% vs. 72%, p=0.014). No significant differences in distant failure-free survival (DFFS), disease-free survival (DFS), and overall survival were observed between groups. In subgroup analysis, the NCT arm showed superior DFFS and DFS in stage IV patients younger than 60 years. No significant difference in compliance and toxicity was observed between groups, except the radiation therapy duration was slightly shorter in the CRT arm (50.0 days vs. 53.9 days, p=0.018). Conclusion This study did not show the superiority of NCT followed by CCRT over CCRT alone. Because NCT could increase the risk of locoregional recurrences, it can only be considered in selected young patients with advanced stage IV disease. The role of NCT remains to be defined and should not be viewed as the standard of care.

Accurate estimation of shear flows in thin-walled beam section is the key issue to evaluate shear stress distribution of ship hull transverse section under the shear forces acting on hull girder. It is regarded that the method using the warping functions obtained by finite element formulation is the state of the art of this field. Recently, however, IACS took effect the new version of CSR in which direct calculation process of shear flow was suggested. In the direct calculation process, shear flow of ship hull section can be obtained by the addition of determinate and indeterminate shear flows calculated respectively. So, in this paper, the shear flow evaluation codes based on the process proposed by IACS CSR and warping function based method were developed respectively. The calculated results of shear flows for the several examples of ship sections were compared with each other and considered in detail.

2 The most important factor in the structural design of ships and offshore structures operating in arctic region is ice load, which results from ice-structure interaction during the ice collision process. The mechanical properties of ice related to strength and failure, however, show very complicated aspect varying with temperature, volume fraction of brine, grain size, strain rate and etc. So it is nearly impossible to establish a perfect material model of ice satisfying all the mechanical characteristics completely. Therefore, in general, ice collision analysis was carried out by relatively simple material models considering only specific aspects of mechanical characteristics of ice and it would be the most significant cause of inevitable errors in the analysis. Especially, it is well-known that the most distinctive mechanical property of ice is high dependency on strain rate. Ice shows brittle attribute in higher strain rate while it becomes ductile in lower strain rate range. In this study, the simulation method of ice collision to ship hull using the nonlinear dynamic FE analysis was dealt with. To consider the strain rate effects of ice during ice-structural interaction, strain rate dependent constitutive model in which yield stress and hardening behaviors vary with strain rate was adopted. To reduce the huge amount of computing time, the modeling range of ice and ship structure were restricted to the confined region of interest. Under the various scenario of ice-ship hull collision, the structural behavior of hull panels and failure modes of ice were examined by nonlinear FE analysis technique.

Purpose The objective of this study was to explore the relationship between the circulating lymphocyte level during preoperative chemoradiotherapy (CRT) and pathologic complete response (pCR) in locally advanced rectal cancer. Materials and Methods From May 2010 to May 2013, 52 patients treated with preoperative CRT followed by surgery, were analysed. Patients received conventional fractionated radiotherapy (50-54 Gy) with fluorouracil-based chemotherapy. Surgical resection was performed at 4 to 8 weeks after the completion of preoperative CRT. Absolute blood lymphocyte counts and their relative percentage in total white blood cell counts were obtained from complete blood count tests performed prior to and after 4, 8, and 12 weeks of CRT. We analysed the association between achieving pCR and change in blood lymphocyte level during CRT, as well as clinical parameters. Results Among 52 patients, 14 (26.9%) had evidence of pCR. Sustaining the blood lymphocyte count during CRT (lymphocyte count at 4 weeks/baseline lymphocyte count > 0.35; odds ratio, 8.33; p=0.02) and initial carcinoembryonic antigen < 4.4 ng/mL (odds ratio, 6.71; p=0.03) were significantly associated with pCR in multivariate analyses. Conclusion Sustaining blood lymphocyte count during preoperative CRT was predictive for pCR in rectal cancer. Further studies are warranted to investigate the association between pathologic responses and circulating lymphocyte count with its subpopulation during preoperative CRT.

Activation of dual-specificity tyrosine-phosphorylation-regulated kinases 1A and 1B (DYRK1A and DYRK1B) requires prolyl hydroxylation by PHD1 prolyl hydroxylase. Prolyl hydroxylation of DYRK1 initiates a cascade of events leading to the release of molecular constraints on von Hippel-Lindau (VHL) ubiquitin ligase tumor suppressor function. However, the proline residue of DYRK1 targeted by hydroxylation and the role of prolyl hydroxylation in tyrosine autophosphorylation of DYRK1 are unknown. We found that a highly conserved proline in the CMGC insert of the DYRK1 kinase domain is hydroxylated by PHD1, and this event precedes tyrosine autophosphorylation. Mutation of the hydroxylation acceptor proline precludes tyrosine autophosphorylation and folding of DYRK1, resulting in a kinase unable to preserve VHL function and lacking glioma suppression activity. The consensus proline sequence is shared by most CMGC kinases, and prolyl hydroxylation is essential for catalytic activation. Thus, formation of prolyl-hydroxylated intermediates is a novel mechanism of kinase maturation and likely a general mechanism of regulation of CMGC kinases in eukaryotes.

AIM This time-dependent study aimed to analyze the prevalence of psychological distress in prostate cancer survivors by using claims data in South Korea. METHODS In a nationwide cohort, 32 005 patients were identified who were diagnosed with prostate cancer between January 2010 and December 2014. We referred the diagnostic codes of mental disorders as psychological distress. We categorized the prevalence of psychological distress based on age and specific times before and after the cancer diagnosis. RESULTS The median age at diagnosis of prostate cancer was 70 years. Among 32 005 patients, 3074 (9.6%) were diagnosed at least once with a mental disorder between 1 year before the cancer diagnosis and the last follow-up. Among the first diagnoses of each patient, the common mental disorders were anxiety (39.1%) and depression (33.0%). In the total cohort, there were 54 666 claims for mental disorders and over 48.0% (26 256) were for depression. The frequency of psychological distress peaked just before cancer diagnosis. Anxiety was frequent before diagnosis of prostate cancer, whereas depression was frequent after diagnosis. Although stress reaction/adjustment disorders were relatively high in the younger group, depression was relatively high in the elderly group. CONCLUSION Psychological distress in prostate cancer survivors showed different patterns of prevalence between before and after cancer diagnosis, as well as between age groups. Timely diagnosis and intervention for mental health could promote quality of life for prostate cancer survivors.

Background This study aimed to evaluate patterns of posttransplant malignancies among renal transplant recipients (RTRs) in South Korea using nationwide data. Methods The nationwide cohort assessed in this study included RTRs from January 1, 2010, to December 31, 2014. We analyzed cancer incidence during the time course after renal transplantation. Additionally, we calculated standardized incidence ratios (SIRs) to evaluate the risk of malignancies in RTRs. Results A total of 1343 RTRs (871 males and 472 females, mean age 48.5 ± 11.6 years) were assessed. Among them, 104 (7.7%) developed malignancies after transplantation, most commonly in the thyroid cancer (23.1%). The SIR for all cancers was 3.54; particularly, the SIRs for renal cancer, myeloma, and non-Hodgkin lymphoma were 16.31, 24.02, and 28.64, respectively. Females showed a higher risk of malignancy than males (SIRs: 4.04 for women and 3.26 for men). The median interval between transplantation and malignancy diagnosis was 27.2 months (range 12.3–54.8 months). Conclusions RTRs in South Korea demonstrated a high risk of malignancy after transplantation compared with the general population. This indicates that close surveillance and routine screening for cancer in RTRs are needed.

High-sodium and low-potassium (HNaLK) content in Western diets increases the risk of hypertension and cardiovascular disease (CVD). It is investigated if the dietary minerals interact with gut bacteria to modulate circulating levels of biogenic amines, which are implicated in various pathologies, including hypertension and CVD.Using a metabolomic approach to target biogenic amines, the effects of gut bacteria depletion and HNaLK intake on circulating levels of biogenic amines in rats are examined. Forty-five metabolites whose plasma levels are significantly altered by gut bacteria depletion (p0.05) are found, indicating their regulation by gut bacteria. Many of them are not previously linked to gut bacteria; therefore, these data provide novel insights into physiological or pathological roles of gut bacteria. A number of plasma metabolites that are altered both by gut bacteria and HNaLK intake are also found, suggesting possible interactions of the diet and gut bacteria in the modulation of these metabolites. The diet effects are observed with significant changes in the gut bacterial taxa Porphyromonadaceae and Prevotellaceae (p0.05).The dietary minerals may regulate abundances of certain gut bacteria to alter circulating levels of biogenic amines, which may be linked to host physiology or pathology.

Glioblastoma (GBM) cancer stem cells (CSC) are primarily responsible for metastatic dissemination, resistance to therapy, and relapse of GBM, the most common and aggressive brain tumor. Development and maintenance of CSCs require orchestrated metabolic rewiring and metabolic adaptation to a changing microenvironment. Here, we show that cooperative interplay between the mitochondrial chaperone TRAP1 and the major mitochondria deacetylase sirtuin-3 (SIRT3) in glioma stem cells (GSC) increases mitochondrial respiratory capacity and reduces production of reactive oxygen species. This metabolic regulation endowed GSCs with metabolic plasticity, facilitated adaptation to stress (particularly reduced nutrient supply), and maintained “stemness.” Inactivation of TRAP1 or SIRT3 compromised their interdependent regulatory mechanisms, leading to metabolic alterations, loss of stemness, and suppression of tumor formation by GSC in vivo. Thus, targeting the metabolic mechanisms regulating interplay between TRAP1 and SIRT3 may provide a novel therapeutic option for intractable patients with GBM. Significance: Discovery and functional analysis of a TRAP1–SIRT3 complex in glioma stem cells identify potential target proteins for glioblastoma treatment.

A novel molecular recursive partitioning analysis classification has recently been reported integrating the MGMT promoter methylation (MGMTmeth) and IDH1 mutation (IDH1mut) status for glioblastoma (GBM-molRPA) patients treated with temozolomide-based chemoradiation. The current study was initiated to validate the model in a multi-institutional study.Four-hundred seventy-one newly diagnosed GBM patients (validation cohort) were allocated to classes I-III of the previously reported GBM-molRPA model. Of the patients, 15.7%, 56.1%, and 28.2% patients were GBM-molRPA class I, II, and III, respectively. MGMTmeth and IDH1mut were observed in 32.3 and 8.8% of patients, respectively. In the training plus validation cohort of 692 patients, 16.2%, 60.8%, and 23.0% patients were class I, II, and III, respectively.The median follow-up for survivors and the median survival (MS) of patients was 23.3 and 18.4 months, respectively. The MS for GBM-molRPA class I, II, and III was 49.7 (95% CI, 22.8-76.6), 19.2 (95% CI, 16.2-22.1), and 13.8 months (95% CI, 11.8-15.4) (P .001 for all comparisons) in the validation cohort. In the training plus validation cohort, the MS was 58.5 (95% CI, 40.7-76.3), 21. (95% CI, 18.6-23.3), and 14.3 months (95% CI, 12.5-16.1) (P .001 for all comparisons) for class I, II, and III, respectively.The GBM-molRPA is a valid model. This GBM-molRPA classification can be useful in clinics and guiding patient stratification in future clinical trials.

We investigate the electrical characteristics according to changing temperature on trap distribution in the energy gap of grain boundary (GB) and interface trap density (D(it)) between polycrystalline-silicon (poly-Si) channel and tunnel oxide in Vertical NAND (VNAND) flash cell with poly-Si channel. We confirmed that there are two factors changing GB potential barrier height such as trap distribution in GB and D(it) using technology computer-aided design (TCAD) simulation. Also, we found that the electrical characteristics according to changing temperature are significantly dependent on height and position of GB potential barrier in VNAND flash cell with poly-Si channel. We expect that it is required to develop more accurate extraction method for trap distribution in each GB and D(it) for better understanding temperature dependence of electrical characteristics in VNAND Flash cell.

The stringent response (SR), which is activated by accumulation of (p)ppGpp under conditions of growth-inhibiting stresses, plays an important role on growth and virulence in

Background The purpose of this study was to investigate whether the minimum absolute lymphocyte count (ALC) during radiotherapy (RT) could predict clinical outcome in patients with nasopharyngeal cancer (NPC). Methods We analyzed 70 patients with NPC including 63 patients treated with chemoradiotherapy and used multivariate analysis to determine whether minimum ALC affected clinical outcome. Results Patients were grouped by minimum ALC, with a cutoff of 245 cells/μL. Five-year disease-specific survival (DSS) and progression-free survival (PFS) for patients with minimum ALC ≥245 versus minimum ALC

A Gram-stain-negative, aerobic and moderately halophilic bacterium, designated strain EMB201T, was isolated from tidal flat sediment of the South Sea in Korea. Cells were motile rods with a single polar flagellum and had catalase- and oxidase-positive activities. Growth of strain EMB201T was observed at 15–37 °C (optimum, 30 °C), at pH 5.0–9.5 (optimum, pH 7.0–7.5) and in the presence of 1–7 % (w/v) NaCl (optimum, 2–3 %). Strain EMB201T contained ubiquinone-10 as the sole isoprenoid quinone and summed feature 8 (comprising C18 : 1ω7c/ω6c), C18 : 0ω7c 11-methyl and C10 : 0 3-OH as the major fatty acids. Phosphatidylglycerol and an unidentified amino lipid were identified as the major polar lipids and an unidentified phospholipid and three unidentified lipids were detected as minor components. The G+C content of the genomic DNA was approximately 58.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain EMB201T formed a phylogenetic lineage with members of the genus Celeribacter. Strain EMB201T was related most closely to Celeribacter halophilus ZXM137T with a 16S rRNA gene sequence similarity of 98.3 %, and the level of DNA–DNA relatedness between the two strains was 17.0 ± 2.0 %. The combined chemotaxonomic and molecular properties suggest that strain EMB201T represents a novel species of the genus Celeribacter, for which the name Celeribacter naphthalenivorans sp. nov. is proposed. The type strain is EMB201T ( = KACC 18393T = JCM 30679T).

Background Clinical benefits from standard therapies against glioblastoma (GBM) are limited in part due to intrinsic radio- and chemoresistance of GBM and inefficient targeting of GBM stem-like cells (GSCs). Novel therapeutic approaches that overcome treatment resistance and diminish stem-like properties of GBM are needed. Methods We determined the expression levels of ubiquitination-specific proteases (USPs) by transcriptome analysis and found that USP1 is highly expressed in GBM. Using the patient GBM-derived primary tumor cells, we inhibited USP1 by shRNA-mediated knockdown or its specific inhibitor pimozide and evaluated the effects on stem cell marker expression, proliferation, and clonogenic growth of tumor cells. Results USP1 was highly expressed in gliomas relative to normal brain tissues and more preferentially in GSC enrichment marker (CD133 or CD15) positive cells. USP1 positively regulated the protein stability of the ID1 and CHEK1, critical regulators of DNA damage response and stem cell maintenance. Targeting USP1 by RNA interference or treatment with a chemical USP1 inhibitor attenuated clonogenic growth and survival of GSCs and enhanced radiosensitivity of GBM cells. Finally, USP1 inhibition alone or in combination with radiation significantly prolonged the survival of tumor-bearing mice. Conclusion USP1-mediated protein stabilization promotes GSC maintenance and treatment resistance, thereby providing a rationale for USP1 inhibition as a potential therapeutic approach against GBM.

When V. cholerae encounters nutritional stress, it activates (p)ppGpp-mediated stringent response. The genes relA and relV are involved in the production of (p)ppGpp, whereas the spoT gene encodes an enzyme that hydrolyzes it. Herein, we show that the bacterial capability to produce (p)ppGpp plays an essential role in glucose metabolism. The V. cholerae mutants defective in (p)ppGpp production (i.e. ΔrelAΔrelV and ΔrelAΔrelVΔspoT mutants) lost their viability because of uncontrolled production of organic acids, when grown with extra glucose. In contrast, the ΔrelAΔspoT mutant, a (p)ppGpp overproducer strain, exhibited better growth in the presence of the same glucose concentration. An RNA sequencing analysis demonstrated that transcriptions of genes consisting of an operon for acetoin biosynthesis were markedly elevated in N16961, a seventh pandemic O1 strain, but not in its (p)ppGpp(0) mutant during glucose-stimulated growth. Transposon insertion in acetoin biosynthesis gene cluster resulted in glucose-induced loss of viability of the ΔrelAΔspoT mutant, further suggesting the crucial role of acetoin production in balanced growth under glucose-rich environments. Additional deletion of the aphA gene, encoding a negative regulator for acetoin production, failed to rescue the (p)ppGpp(0) mutant from the defective glucose-mediated growth, suggesting that (p)ppGpp-mediated acetoin production occurs independent of the presence of AphA. Overall, our results reveal that (p)ppGpp, in addition to its well known role as a stringent response mediator, positively regulates acetoin production that contributes to the successful glucose metabolism and consequently the proliferation of V. cholerae cells under a glucose-rich environment, a condition that may mimic the human intestine.

Purpose To define the role of neoadjuvant and concurrent chemotherapy in stage II nasopharyngeal carcinoma, we compared the treatment outcomes of patients treated with curative radiotherapy with or without chemotherapy. Materials and Methods From 2004 to 2011, 138 patients with American Joint Committee on Cancer (AJCC) 2002 stage II nasopharyngeal carcinoma were treated with curative radiotherapy in 12 hospitals in South Korea. Treatment methods included radiotherapy alone in 34 patients, neoadjuvant chemotherapy followed by radiotherapy alone in seven, concurrent chemoradiotherapy in 80, and neoadjuvant chemotherapy followed by concurrent chemoradiotherapy in 17. Adjuvant chemotherapy was used in 42 patients. Total radiation dose ranged from 64 Gy to 74.2 Gy (median, 70 Gy). Results Median follow-up was 48 months (range, 7 to 97 months) for all patients. At the last follow-up, 13 patients had died and 32 had experienced treatment failure; locoregional failure occurred in 14, distant failure in 16, and both in two. Five-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival were 86.2%, 85.5%, 74.4%, and 88.2%, respectively. Multivariate analyses showed that the significant prognostic factors were concurrent chemotherapy and N stage for locoregional relapse-free survival, concurrent chemotherapy for progression-free survival, and age and N stage for overall survival. Neither neoadjuvant nor concurrent chemotherapy improved distant metastasis-free survival. Conclusion Concurrent chemotherapy significantly improved 5-year locoregional relapse-free survival and progression-free survival in stage II nasopharyngeal carcinoma. However, neoadjuvant chemotherapy failed to improve either.

Epoxides of free fatty acids (FFAs), especially epoxyeicosatrienoic acids (EETs), are lipid mediators with beneficial effects in metabolic and cardiovascular (CV) health. FFA epoxides are quickly metabolized to biologically less active diols by soluble epoxide hydrolase (sEH). Inhibition of sEH, which increases EET levels, improves glucose homeostasis and CV health and is proposed as an effective strategy for the treatment of diabetes and CV diseases. Here, we show evidence that sEH activity is profoundly reduced in postprandial states in rats; plasma levels of 17 sEH products (i.e., FFA diols), detected by targeted oxylipin analysis, all decreased after a meal. In addition, the ratios of sEH product to substrate (sEH P/S ratios), which may reflect sEH activity, decreased ~70% on average 2.5 h after a meal in rats (P < 0.01). To examine whether this effect was mediated by insulin action, a hyperinsulinemic euglycemic clamp was performed for 2.5 h, and sEH P/S ratios were assessed before and after the clamp. The clamp resulted in small increases rather than decreases in sEH P/S ratios (P < 0.05), indicating that insulin cannot account for the postprandial decrease in sEH P/S ratios. Interestingly, in rats treated with antibiotics to deplete gut bacteria, the postprandial effect to decrease sEH P/S ratios was completely abolished, suggesting that a gut bacteria-derived factor(s) may be responsible for the effect. Further studies are warranted to identify such a factor(s) and elucidate the mechanism by which sEH activity (or sEH P/S ratio) is reduced in postprandial states.

The pathogen Vibrio cholerae is the causative agent of cholera. Emergence of antibiotic-resistant V. cholerae strains is increasing, but the underlying mechanisms remain unclear. Herein, we report that the stringent response regulator and stress alarmone guanosine tetra- and pentaphosphate ((p)ppGpp) significantly contributes to antibiotic tolerance in V. cholerae. We found that N16961, a pandemic V. cholerae strain, and its isogenic (p)ppGpp-overexpressing mutant ΔrelAΔspoT are both more antibiotic-resistant than (p)ppGpp(0) (ΔrelAΔrelVΔspoT) and ΔdksA mutants, which cannot produce or utilize (p)ppGpp, respectively. We also found that additional disruption of the aconitase B–encoding and tricarboxylic acid (TCA) cycle gene acnB in the (p)ppGpp(0) mutant increases its antibiotic tolerance. Moreover, expression of TCA cycle genes, including acnB, was increased in (p)ppGpp(0), but not in the antibiotic-resistant ΔrelAΔspoT mutant, suggesting that (p)ppGpp suppresses TCA cycle activity, thereby entailing antibiotic resistance. Importantly, when grown anaerobically or incubated with an iron chelator, the (p)ppGpp(0) mutant became antibiotic-tolerant, suggesting that reactive oxygen species (ROS) are involved in antibiotic-mediated bacterial killing. Consistent with that hypothesis, tetracycline treatment markedly increased ROS production in the antibiotic-susceptible mutants. Interestingly, expression of the Fe(III) ABC transporter substrate–binding protein FbpA was increased 10-fold in (p)ppGpp(0), and fbpA gene deletion restored viability of tetracycline-exposed (p)ppGpp(0) cells. Of note, FbpA expression was repressed in the (p)ppGpp-accumulating mutant, resulting in a reduction of intracellular free iron, required for the ROS-generating Fenton reaction. Our results indicate that (p)ppGpp-mediated suppression of central metabolism and iron uptake reduces antibiotic-induced oxidative stress in V. cholerae.

Purpose Postoperative radiation therapy may have a detrimental effect on survival in patients with non-small cell lung cancer. We investigated the association of the lung radiation dose with the risk of death in patients treated with postoperative radiation therapy. Methods We analyzed 178 patients with non-small cell lung cancer who received postoperative radiation therapy. The mean lung dose was calculated from dose–volume data, and we categorized patients into the high and low lung dose groups using 2 different methods; (1) simple grouping using the median lung dose of all patients, and (2) stratified grouping using the median lung dose of each subgroup sharing the same confounders. We compared clinical variables, and survival between the high and low lung dose groups. Results In the simple grouping, there were no significant differences in survivals between the high and low lung dose groups. After stratification, the overall survival of low lung dose group was significantly longer than that of high lung dose group (5-year survival, 60.1% vs. 35.3%, p = 0.039). On multivariable analyses, the lung dose remained a significant prognostic factor for overall survival (hazard ratio, HR = 2.08, p = 0.019). Conclusions The lung dose was associated with the risk of death in patients with non-small cell lung cancer having the same confounders. Further studies evaluating the risk of death according to the lung dose will be helpful to administer more precise and individualized postoperative radiation therapy.

Background Treatment of tonsil cancer, a subset of oropahryngeal cancer, varies between surgery and radiotherapy. Well-designed studies in tonsil cancer have been rare and it is still controversial which treatment is optimal. This study aimed to assess the outcome and failure patterns in tonsil cancer patients treated with either approaches. Methods We retrospectively reviewed medical records of 586 patients with tonsil cancer, treated between 1998 and 2010 at 16 hospitals in Korea. Two hundred and one patients received radiotherapy and chemotherapy (CRT), while 385 patients received surgery followed by radiotherapy and/or chemotherapy (SRT). Compared with the SRT group, patients receiving CRT were older, with more advanced T stage and received higher radiotherapy dose given by intensity modulation techniques. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and clinicopathologic factors were analyzed. Results At follow-up, the 5-year OS, DFS, LRRFS and DMFS rates in the CRT group were 82, 78, 89, and 94%, respectively, and in the SRT group were 81, 73, 87, and 89%, respectively. Old age, current smoking, poor performance status, advanced T stage, nodal involvement, and induction chemotherapy were associated with poor OS. Induction chemotherapy had a negative prognostic impact on OS in both treatment groups (p = 0.001 and p = 0.033 in the CRT and SRT groups, respectively). Conclusions In our multicenter, retrospective study of tonsil cancer patients, the combined use of radiotherapy and chemotherapy resulted in comparable oncologic outcome to surgery followed by postoperative radiotherapy, despite higher-risk patients having been treated with the definitive radiotherapy. Induction chemotherapy approaches combined with either surgery or definitive radiotherapy were associated with unfavorable outcomes. Electronic supplementary material The online version of this article (10.1186/s12885-017-3571-3) contains supplementary material, which is available to authorized users.

Purpose The aim of this time-dependent study was to analyze the prevalence of mental disorders in ovarian cancer survivors using claims data in South Korea. Materials and methods We confirmed mental disorders in a nationwide cohort of 9763 patients who were diagnosed with ovarian cancer between January 1, 2010 and December 31, 2014. We categorized the prevalence of mental disorders based on the age and the time of diagnosis. Results A total of 821 ovarian cancer patients were diagnosed with a mental disorder, 1 year prior to the cancer diagnosis. Of those patients, 311 were diagnosed with depression (37.9%) and 245 with anxiety (29.8%) during their first visit. The overall frequency of mental disorders peaked within 2 months after the cancer diagnosis. The highest rate of increase after diagnosis was noted in stress reaction/adjustment disorders. While depression was relatively high (40.4%) in the younger age group under 60 years, anxiety was higher (39.4%) in the elderly group over 60 years old. Age was a significant predictive factor for mental disorders (P = 0.002), and patients over 50 years were at a higher risk for mental disorders (hazard ratio: 1.29, P = 0.002). Conclusion Mental disorders in ovarian cancer survivors showed different patterns of prevalence depending on age at the time of diagnosis and the nature of disease. Timely diagnosis and intervention for psychological distress could increase the quality of life for ovarian cancer survivors.

We investigated the role of adjuvant concurrent chemoradiation therapy (CCRT) in patients with a microscopically positive resection margin (R1) after curative resection for extrahepatic cholangiocarcinoma (EHCC). A total of 84 patients treated with curative resection for EHCC were included. Fifty-two patients with negative resection margins did not receive any adjuvant treatments (R0 + S group). The remaining 32 patients with microscopically positive resection margins received either adjuvant CCRT (R1 + CCRT group, n = 19) or adjuvant radiation therapy (RT) alone (R1 + RT group, n = 13). During the median follow-up period of 26 months, the 2-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival rates (OS) were: 81.8, 62.6, and 61.5% for R0 + S group; 71.8, 57.8, and 57.9% for R1 + CCRT group; and 16.8, 9.6, and 15.4% for R1 + RT group, respectively. Multivariate analysis revealed that the R1 + CCRT group did not show any significant difference in survival rates compared with the R0 + S group. The R1 + RT group had lower LRRFS [hazard ratio (HR) 3.008; p = 0.044], DFS (HR 2.364; p = 0.022), and OS (HR 2.417; p = 0.011) when compared with the R0 + S and R1 + CCRT group. A lack of significant survival difference between R0 + S group and R1 + CCRT group suggests that adjuvant CCRT ameliorates the negative effect of microscopic positive resection margin. In contrast, adjuvant RT alone is appeared to be inadequate for controlling microscopically residual tumor.

The purpose of this study is to review simulation CT scans and evaluate their diagnostic value in patients treated with adjuvant radiotherapy for pancreatic adenocarcinoma.73 patients who had undergone simulation CT scans for adjuvant radiotherapy in pancreatic adenocarcinoma were reviewed. All simulation CT scans were reviewed by professional abdominal radiologists, who compared the images with corresponding prior CT scans to identify new lesions. Newly detected cancer-related lesions were classified into one of three categories: distant metastasis, locoregional recurrence and indeterminate lesions. Indeterminate lesions were reviewed for malignancy during follow-up imaging work-ups.Of 73 patients, distant metastasis, locoregional recurrence and indeterminate lesions were found in 4 (5.5%), 5 (6.8%) and 32 patients (43.8%), respectively. Among 32 indeterminate lesions, 24 (75.0%) were soft tissue lesions neighbouring the superior mesenteric vessels. Follow-up PET-CT and diagnostic CT scans revealed that 43.7% of indeterminate lesions were malignant presenting local failures. The 3-year overall survival was significantly higher among patients who had no cancer-related lesions than among who did have such findings (44.8% vs 10.8%, p = 0.002).Professional review of simulation CT scans have ample diagnostic value as they help detect early progressions or potential failures in patients treated with adjuvant radiotherapy for pancreatic adenocarcinoma. Simulation CT scans should be carefully reviewed before the delivery of adjuvant radiotherapy. Advances in knowledge: Generally, simulation CT scan has been known to provide limited diagnostic values and clinical impact. However, the results of this study showed a high detection rate of cancer-related lesions, which could potentially affect subsequent treatment strategies in patients with pancreatic adenocarcinoma.

Background/aim In this study, we analyzed the prevalence of influenza disease in breast cancer survivors using claims data from the Health Insurance Review and Assessment Service (HIRA) in South Korea. Patients and methods We defined influenza among a nationwide cohort of 87,843 patients who were diagnosed with breast cancer and underwent surgery from January 1, 2010 to December 31, 2014, based on HIRA claim data. Descriptive statistics were calculated to estimate the frequency of influenza disease using diagnostic code and utilization pattern at medical institutions. Results Two thousand four hundred breast cancer survivors (2.7%) were diagnosed with influenza. The overall frequency of influenza increased from November (n=98) and peaked in February (n=1,745). Over 60% (2,693) of claims for influenza disease treatment were in the clinic, whereas general hospitals accounted for 22.0% (873). Among 3,967 claims, admission rate was 7.6% (n=301) and the average length of hospitalization was 4.7 days. Elderly breast cancer survivors over 70 years old had the longest length of hospitalization at 5.9 days. Conclusion Breast cancer survivors are more susceptible to influenza than non-cancer survivors. It is important not only to raise the vaccination rate among young cancer survivors, but also to quickly identify symptoms and begin treatment for flu in elderly cancer survivors.

Salvage therapy for recurrent high grade gliomas (HGG) includes surgery, radiotherapy and chemotherapy, however, standard treatment does not exist. We evaluated the tolerability and efficacy of re-irradiation (re-RT) with hyperthermia (HT) for patients with recurrent HGG. From September 2010 to July 2015, 20 patients with recurrent HGG were treated with re-RT and HT. The radiotherapy dose of 30 Gray (Gy) was delivered with 2 Gy per fraction daily, and HT was performed twice weekly. Primary endpoints were treatment compliance and toxicity. Second endpoints were overall survival (OS) and progression free survival (PFS). The median interval between initial RT and re-RT was 11 months. During re-RT with HT, there were no significant acute morbidities over grade 3. Median overall survival (OS) from re-irradiation was 8.4 months and the 6 and 12 months survival rate were 67% and 30%, respectively. The median progression free survival (PFS) from re-irradiation was 4.1 month. Our findings suggested that concurrent re-RT with HT was a safe and well-tolerated. In addition, the combination re-RT and HT could be a valuable salvage treatment option for selected recurrent HGG patients with poor performance status.

PURPOSE The purpose of this study was to investigate the effect of hospital case volume on clinical outcomes in patients with nasopharyngeal carcinoma (NPC). Materials and Methods Data on 1,073 patients with cT1-4N0-3M0 NPC were collected from a multi-institutional retrospective database (KROG 11-06). All patients received definitive radiotherapy (RT) either with three-dimensional-conformal RT (3D-CRT) (n=576) or intensity-modulated RT (IMRT) (n=497). The patients were divided into two groups treated at high volume institution (HVI) (n=750) and low volume institution (LVI) (n=323), defined as patient volume ≥ 10 (median, 13; range, 10 to 18) and < 10 patients per year (median, 3; range, 2 to 6), respectively. Endpoints were overall survival (OS) and loco-regional progression-free survival (LRPFS). RESULTS At a median follow-up of 56.7 months, the outcomes were significantly better in those treated at HVI than at LVI. For the 614 patients of propensity score-matched cohort, 5-year OS and LRPFS were consistently higher in the HVI group than in the LVI group (OS: 78.4% vs. 62.7%, p < 0.001; LRPFS: 86.2% vs. 65.8%, p < 0.001, respectively). According to RT modality, significant difference in 5-year OS was observed in patients receiving 3D-CRT (78.7% for HVI vs. 58.9% for LVI, p < 0.001) and not in those receiving IMRT (77.3% for HVI vs. 75.5% for LVI, p=0.170). CONCLUSION A significant relationship was observed between HVI and LVI for the clinical outcomes of patients with NPC. However, the difference in outcome becomes insignificant in the IMRT era, probably due to the standardization of practice by education.

Background The aim of the present study was to investigate the long-term survival outcomes and toxicities associated with our experienced early administration of adjuvant concurrent chemoradiotherapy (CCRT). Methods Ninety-eight patients with pelvic lymph node metastasis, positive resection margin, and/or parametrial invasion who received adjuvant CCRT between 1995 and 2011 were analyzed retrospectively. The first cycle of platinum-based adjuvant chemotherapy was initiated within 2–3 weeks after surgery (median, 12 days) and continued every 4 weeks for a total of 4 cycles. Adjuvant radiotherapy was performed during the second and third cycles of chemotherapy. Results After a median follow-up period of 119 months for survivors, 13 patients (13.3%) experienced recurrence and 11 patients died of cancer during the follow-up period. The 5-year recurrence-free survival and cancer specific survival rates were 87.6% and 90.6%, respectively. Ninety-four patients (95.9%) received ≥3 cycles of chemotherapy. Total radiation dose of ≥45 Gy was delivered in 91 patients (92.9%). Grade 3–4 hematologic and gastrointestinal toxicities developed in 37 (37.8%) and 14 (14.3%) patients during CCRT, respectively. Conclusion The present study confirmed the long-term safety and encouraging survival outcomes of early administration of adjuvant CCRT, suggesting the benefits of early time to initiation of adjuvant treatments.

Background A major drawback of conventional manual image fusion is that the process may be complex, especially for less-experienced operators. Recently, two automatic image fusion techniques called Positioning and Sweeping auto-registration have been developed. Purpose To compare the accuracy and required time for image fusion of real-time ultrasonography (US) and computed tomography (CT) images between Positioning and Sweeping auto-registration. Material and Methods Eighteen consecutive patients referred for planning US for radiofrequency ablation or biopsy for focal hepatic lesions were enrolled. Image fusion using both auto-registration methods was performed for each patient. Registration error, time required for image fusion, and number of point locks used were compared using the Wilcoxon signed rank test. Results Image fusion was successful in all patients. Positioning auto-registration was significantly faster than Sweeping auto-registration for both initial (median, 11 s [range, 3–16 s] vs. 32 s [range, 21–38 s]; P Conclusion Positioning auto-registration offers faster image fusion between real-time US and pre-procedural CT images than Sweeping auto-registration. The final registration error is similar between the two methods.

Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPβ, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-κB activation and further degraded DNA damage–inducible transcript 3 (GADD153) to induce C/EBPβ expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM. Cancer Res; 77(18); 4973–84. ©2017 AACR.

We aimed to present the clinical outcomes of adjuvant concurrent chemoradiotherapy (CCRT) with low-dose daily cisplatin regimen compared to the conventional 5-fluorouracil (5-FU)-based regimen for extrahepatic bile duct cancer (EHBDC). From October 1994 to April 2013, 41 patients received adjuvant CCRT with low-dose daily regimen or 5-FU-based regimens. Nineteen patients received low-dose of cisplatin just before every delivery of radiation therapy, and 21 patients received two cycles of 5-FU-based regimen during radiotherapy. We compared the clinical outcomes between two adjuvant CCRT regimens. Adjuvant CCRT with low-dose daily cisplatin showed comparable toxicity profiles compared with that of a 5-FU-based regimen. The median follow-up time was 33 months (range, 5–205), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 34.2, 50.8, and 49.7%, respectively. Univariable analyses showed no significant differences in OS, LRRFS, and DMFS between the groups with two regimens. In multivariable analyses, chemotherapeutic regimen was a significant prognostic factor for OS, favoring the low-dose daily cisplatin regimen (HR = 2.491, p = 0.036) over 5-FU-based regimen, though not for LRRFS (p = 0.642) and DMFS (p = 0.756). Adjuvant CCRT with low-dose daily cisplatin regimen showed acceptable toxicities and survivals compared to those of the 5-FU-based regimen. Low-dose daily cisplatin can be one of the feasible regimens for adjuvant CCRT for EHBDC.

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PurposeThe purpose of this study was to investigate the prognostic effect of pulmonary function at the beginning of postoperative radiotherapy (PORT) in non-small cell lung cancer (NSCLC).Materials and methodsFrom January 2002 to December 2012, 115 patients with NSCLC who underwent PORT and took the forced expiratory volume in 1 second (FEV1) at the beginning of PORT were analysed. PORT began within 4–6weeks following surgery, and the 3-dimensional conformal technique was used with conventional fractionation. The high and low FEV1 groups were divided by the median absolute value of FEV1 at the beginning of PORT, and we compared the clinical factors and survival between two groups.ResultsThe median absolute value of FEV1 at the beginning of PORT was 1.68L (range, 0.83–3.89), and patients were divided into low and high FEV1 groups (

Alginate-overproducing mucoid Pseudomonas aeruginosa, responsible for chronic airway infections in cystic fibrosis (CF) patients, is resistant to antibiotic treatments and host immune clearance. In this study, we performed a phenotype microarray screen and identified sulfate ion as a molecule that can suppress alginate production. When a mucoid P. aeruginosa strain CM21 and additional mucoid isolates were grown with 5% sodium sulfate, significantly decreased levels of alginate were produced. Suppression of alginate production was also induced by other sulfate salts. Expression of a reporter gene fused to the algD promoter was considerably decreased when grown with sulfate. Furthermore, bacterial cell shape was abnormally altered in CM21, but not in PAO1, a prototype nonmucoid strain, suggesting that sulfate-stimulated cell shape change is associated with transcriptional suppression of the alginate operon. Finally, a CM21 lpxC mutant defective in lipid A biosynthesis continued to produce alginate and maintained the correct cell shape when grown with sulfate. These results suggest a potential involvement of lipoploysaccharide biosynthesis in the sulfate-induced reversion to nonmucoid phenotype. This study proposes a novel strategy that can be potentially applied to treat persistent infection by recalcitrant mucoid P. aeruginosa.

Dietary potassium loading results in rapid kaliuresis, natriuresis, and diuresis associated with reduced phosphorylation (p) of the distal tubule Na+-Cl− cotransporter (NCC). Decreased NCC-p inhibits NCC-mediated Na+ reabsorption and shifts Na+ downstream for reabsorption by epithelial Na+ channels (ENaC), which can drive K+ secretion. Whether the signal is initiated by ingesting potassium or a rise in plasma K+ concentration ([K+]) is not understood. We tested the hypothesis, in male rats, that an increase in plasma [K+] is sufficient to reduce NCC-p and drive kaliuresis. After an overnight fast, a single 3-h 2% potassium (2%K) containing meal increased plasma [K+] from 4.0 ± 0.1 to 5.2 ± 0.2 mM; increased urinary K+, Na+, and volume excretion; decreased NCC-p by 60%; and marginally reduced cortical Na+-K+-2Cl− cotransporter (NKCC) phosphorylation 25% ( P = 0.055). When plasma [K+] was increased by tail vein infusion of KCl to 5.5 ± 0.1 mM over 3 h, significant kaliuresis and natriuresis ensued, NCC-p decreased by 60%, and STE20/SPS1-related proline alanine-rich kinase (SPAK) phosphorylation was marginally reduced 35% ( P = 0.052). The following were unchanged at 3 h by either the potassium-rich meal or KCl infusion: Na+/H+ exchanger 3 (NHE3), NHE3-p, NKCC, ENaC subunits, and renal outer medullary K+ channel. In summary, raising plasma [K+] by intravenous infusion to a level equivalent to that observed after a single potassium-rich meal triggers renal kaliuretic and natriuretic responses, independent of K+ ingestion, likely driven by decreased NCC-p and activity sufficient to shift sodium reabsorption downstream to where Na+ reabsorption and flow drive K+ secretion.

Objectives: We propose a method to model and represent formulas in Korean medicine information systems. Methods: All the formulas were codified in the form of graphs representing the relationship between a formula and its constituents. To identify a unique formula in a graph, the formula’s name, the book in which the formula was written, the book where the formula was extracted, and the page number in the extracted book are used. All the formulas and the relationship between formulas are modelled as an ontology based on graphs. Results: A formula search system was constructed using our ontology, which can represent formula information efficiently by grouping and filtering of formulas. Our formula model was also constructed as a mobile application. Conclusions: The information in our formula search system depends on our ontology. However, our model or our search scenarios could be extended according to formula information.

Numerous studies' attempts to improve radiation-induced oral mucositis have not produced a qualified treatment yet. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in an in vivo rat model. After 20 Gy of irradiation, rats were divided randomly into the following 4 groups: control, KRG only, radiotherapy (RT) only, and RT + KRG group. The rats were monitored in terms of survival rate, activity, mucositis grade, oral intake, and body weight. The tongue, buccal mucosa, and submandibular gland (SMG) were harvested, and the weight of the SMG was analyzed. The samples then underwent hematoxylin and eosin, TUNEL, and immunohistochemical staining. Radiation-induced severe oral mucositis and SMG injury led to poor oral intake and delayed healing, resulting in the death of some rats. We found that survival rate, oral intake, and body weight increased. Moreover, rats treated with KRG showed less severe mucositis and decreased histologic changes of the oral mucosa and SMG. Furthermore, we showed that the protective effects of KRG were caused by inhibition of the apoptotic signal transduction pathway linked to caspase-3. In conclusion, KRG protects the oral mucosa and SMG from radiation-induced damage by inhibiting caspase-mediated apoptosis in rats.

We previously showed that a fall in the plasma free fatty acid (FFA) level increases plasma corticosterone levels in rats by activating the hypothalamic-pituitary-adrenal axis. In the present study, we tested whether this regulation is mediated by specific or all species of FFAs. Nicotinic acid (NA) (30 μmol/h) was infused in rats to decrease plasma FFAs and increase plasma ACTH and corticosterone. The NA infusion was combined with an infusion of lipids with different FFA compositions to selectively prevent falls in individual FFA levels; coconut, olive, and safflower oils (n = 7 for each), which are predominantly (>70%) composed of saturated, monounsaturated (oleic acid), and polyunsaturated (linoleic acid) FFAs, respectively, were used. At an infusion rate (0.1 g/h) that only partially prevented a fall in the total FFA level, coconut oil, but not olive or safflower oil, completely prevented NA-induced increases in plasma ACTH or corticosterone, suggesting that these responses are mainly mediated by saturated FFAs. In addition, quantification of individual FFA species in the blood using FFA-specific fluorescent probes revealed that plasma corticosterone and ACTH correlated significantly with plasma palmitate but not with other FFAs, such as oleate, linoleate, or arachidonate. Taken together, our data suggest that the regulation of the hypothalamic-pituitary-adrenal axis by FFAs is mainly mediated by the saturated fatty acid palmitate, but not by unsaturated fatty acids, such as oleate and linoleate.

Radiation is a widely used treatment for head and neck cancers, and one of its most severe side effects is ototoxicity. Radiation-induced ototoxicity has been demonstrated to be linked to the increased production of ROS and MAPK. We intended to investigate the effect of p38 inhibition on radiation-induced ototoxicity in cochlea-derived HEI-OC1 cells and in a zebrafish model. The otoprotective effect of p38 inhibition against radiation was tested in vitro in the organ of Corti-derived cell line, HEI-OC1, and in vivo in a zebrafish model. Radiation-induced apoptosis, mitochondrial dysfunction, and an increase of intracellular NO generation were demonstrated in HEI-OC1 cells. The p38-specific inhibitor, SB203580, ameliorated radiation-induced apoptosis and mitochondrial injury in HEI-OC1 cells. p38 inhibition reduced radiation-induced activation of JNK, p38, cytochrome c, and cleavage of caspase-3 and PARP in HEI-OC1 cells. Scanning electron micrography showed that SB203580 prevented radiation-induced destruction of kinocilium and stereocilia in zebrafish neuromasts. The results of this study suggest that p38 plays an important role in mediating radiation-induced ototoxicity and inhibition of p38 could be a plausible option for preventing radiation ototoxicity.