Purpose: Vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been the standard of care for advanced and metastatic clear cell renal cell carcinoma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory given the high rates of acquired resistance to TKI therapy despite favorable initial tumor response. Materials and Methods: To define the TKI-resistance mechanism and identify new therapeutic target for TKI-resistant ccRCC, an integrative differential gene expression analysis was performed using acquired resistant cohort and a public dataset. Sunitinib-resistant RCC cell lines were established and used to test their malignant behaviors of TKI resistance through in vitro and in vivo studies. Immunohistochemistry was conducted to compare expression between the tumor and normal kidney and verify expression of pathway-related proteins. Results: Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher proliferative ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 overexpression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the activation of TRAF6 and MAPK/AP-1 pathways. Conclusions These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC.

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.
Allergens ; Analgesics ; Animals ; Antipyretics ; Asian Continental Ancestry Group ; Asthma ; Bronchial Hyperreactivity ; Cats ; Child ; Classification ; Cohort Studies ; Comorbidity ; Dermatophagoides pteronyssinus ; Disease Management ; Humans ; Methacholine Chloride ; Odds Ratio ; Ownership ; Parturition ; Phenotype ; Prevalence ; Rhinitis, Allergic ; Risk Factors ; Skin

Classification ; Consensus ; Diagnosis ; Hematologic Neoplasms ; Hematology ; Lymphoid Tissue

Background/Aims: Chest pain in patients with obstructive coronary artery disease (OCAD) is affected by several social factors. The gender-based differences in chest pain among Koreans have yet to be investigated. Methods: The study consecutively enrolled 1,549 patients (male/female, 514/1,035; 61 ± 11 years old) with suspected angina. The predictive factors for OCAD based on gender were evaluated. Results: Men experienced more squeezing type pain on the left side of chest, while women demonstrated more dull quality pain in the retrosternal and epigastric area. After adjustment for risk factors, pain in the retrosternal area (odds ratio [OR], 1.491; 95% confidence interval [CI], 1.178 to 1.887) and aggravation by exercise (OR, 2.235; 95% CI, 1.745 to 2.861) were positively associated with OCAD. In men, shorter duration (OR, 1.581; 95% CI, 1.086 to 2.303) and dyspnea (OR, 1.610; 95% CI, 1.040 to 2.490) increased the probability for OCAD, while left-sided chest pain suggested a low probability for OCAD (OR, 0.590; 95% CI, 0.388 to 0.897). In women, aggravation by emotional stress (OR, 0.348; 95% CI, 0.162 to 0.746) and dizziness (OR, 0.457; 95% CI, 0.246 to 0.849) decreased the probability for OCAD. Conclusions This is the first study to focus on gender differences in chest pain among Koreans with angina. Symptoms with high probability for OCAD were different between sexes. Our findings suggest that patient’s medical history in pretest assessment for OCAD should be individualized considering gender.

Purpose: This study considers the variables related to self-leadership of Korean nursing students and verifies the results of precedent studies through meta-analysis. Methods: This study selected a total of 48 precedent studies regarding the investigation of the correlation between variables related to self-leadership of nursing students conducted between 2009 and 2019 and carried out a meta-analysis. Results: For the effect size of variables related to self-leadership of nursing students, individual characteristics had a medium effect size (ESr=.49) and the effect size was larger for meta-cognition (ESr=.65), emotional intelligence (ESr=.58), and self-efficacy (ESr=.54). The characteristics of nursing competency (ESr=.45) also had a medium effect size and the effect size was larger for professional self-concept (ESr=.60), social support (ESr=.58), and critical thinking (ESr=.56). This result shows that individual characteristics were highly correlated with self-leadership compared to the characteristics of nursing competency. Conclusion This study is significant in that it verified the effect of variables related to self-leadership and presented the direction and preliminary data for a follow-up study. It is necessary to include variables considering individual characteristics in the development of an educational program for improving self-leadership in the future.

Objectives: Previous studies have suggested that the lactic acid bacterium, Weissella cibaria CMU has beneficial effects on halitosis, but its precise effects have not been evaluated in human subjects. We evaluated the efficacy and safety of W. cibaria CMU for reducing halitosis in adults (20-70 years old) whose exhibited volatile sulfur compound (VSC) concentrations exceeded 0.015 ng/mL and who scored ≥2 points in a halitosis sensory evaluation test. Methods: A total of 60 participants were assigned to an experimental group (treated with W. cibaria CMU) and a control group (placebo). In total, 58 out of 60 participants (experimental group, 29; control group, 29) were ultimately included in gas chromatography (OralChroma) analyses of VSC concentrations and halitosis sensory evaluation tests. Results: We found that the VSC concentration decreased by 0.030±0.062 ng/ml in the experimental group after 8 weeks (P=0.0138) and increased by 0.005±0.124 ng/ml in the control group (P=0.8198). However, the difference between groups was not statistically significant (P>0.05). In a sensory evaluation test, a significantly lower score was obtained for the experimental group than for the control group. Conclusions Overall, VSC concentrations and sensory evaluation scores were lower in the experimental group than in the control group, but only the latter was statistically significant. Thus, we conclude that W. cibaria CMU is involved in the reduction of halitosis.