Objective: This study aimed to validate the reliability and validity of the Diagnostic Interview for the Internet Addiction Scale (DIA) among Korean children and adolescents in the clinical setting. Methods: We collected the clinical data from university hospitals in South Korea and 194 children and adolescents (aged 7–18 years) completed the questionnaire. The content validity was conducted on 10 items of the DIA and an internal consistency test was performed for the verification of reliability. Results: Participants on average, aged 13.17 years (standard deviation=2.46), and 75.3% (n=146) were boys. The DIA was highly correlated with the scores of the Korean scale for Internet addiction for adolescents, Young’s Internet Addiction Test, Internet addiction proneness scale for children and adolescents. The overall sampling suitability of the 10-item scale was tested using the Kaiser–Meyer–Olkin, resulting in a high value of 0.861. The DIA revealed a two-factor structure and the Cronbach’s alpha correlation coefficient for the total scale was 0.806. Confirmatory factor analysis showed an acceptable model fit (root-mean square error of approximation=0.058, comparative fit index=0.950, and Tucker-Lewis Index=0.919). Conclusion The DIA may suggest in-depth-scale examinations of the factors that influence Internet addiction. We may expect that DIA would be used efficiently for the diagnosing of Internet addiction and further studies for the assessment.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Objective: This study aimed to validate the reliability and validity of the Diagnostic Interview for the Internet Addiction Scale (DIA) among Korean children and adolescents in the clinical setting. Methods: We collected the clinical data from university hospitals in South Korea and 194 children and adolescents (aged 7–18 years) completed the questionnaire. The content validity was conducted on 10 items of the DIA and an internal consistency test was performed for the verification of reliability. Results: Participants on average, aged 13.17 years (standard deviation=2.46), and 75.3% (n=146) were boys. The DIA was highly correlated with the scores of the Korean scale for Internet addiction for adolescents, Young’s Internet Addiction Test, Internet addiction proneness scale for children and adolescents. The overall sampling suitability of the 10-item scale was tested using the Kaiser–Meyer–Olkin, resulting in a high value of 0.861. The DIA revealed a two-factor structure and the Cronbach’s alpha correlation coefficient for the total scale was 0.806. Confirmatory factor analysis showed an acceptable model fit (root-mean square error of approximation=0.058, comparative fit index=0.950, and Tucker-Lewis Index=0.919). Conclusion The DIA may suggest in-depth-scale examinations of the factors that influence Internet addiction. We may expect that DIA would be used efficiently for the diagnosing of Internet addiction and further studies for the assessment.

Background: Chronic pain significantly affects daily activities, mental health, and the interpersonal relationships of patients. Consequently, physicians use various treatments to manage pain. This study investigated the perceptions of treatment, accompanying symptoms, and other problems in patients with chronic pain. Methods: The authors enrolled patients with chronic pain from 19 university hospitals in South Korea. Data was collected on age, gender, diagnosis, disease duration, severity of pain, perception of pain treatment, and accompanying symptoms or problems using an anonymous survey comprising 19 questions. Results: In total, 833 patients with chronic pain completed the survey, and 257 (31.0%) and 537 (64.5%) patientsexpressed concerns about the potential adverse effects of medication and opioid addiction, respectively. Personalitychanges such as irritability or anger were the most frequent accompanying symptoms in 507 (63.8%) patients, followed by depression and sleep disturbance in 462 (58.1%) and 450 (54.5%) patients, respectively. Depression (P = 0.001) and anxiety (P = 0.029) were more common among women, whereas divorce (P = 0.016), family conflict (P < 0.001), unemployment (P < 0.001), suicide attempts (P < 0.001), and restrictions on economic activity (P < 0.001) were more common among men. The frequency of accompanying symptoms, except for suicidal ideation,was higher in the younger patients aged ≤ 40 years than in the older patients aged > 40 years. Conclusions Many patients with chronic pain had concerns about adverse effects or medication tolerance and experienced anxiety, depression, or sleep disturbances. The prevalence of accompanying problems varies according to age and gender.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Purpose: Methacholine bronchial provocation tests (MBPTs) are commonly used to assess airway hyperresponsiveness, but some patients show no significant response. This study aimed to compare the clinical characteristics of asthmatic patients based on their sensitivity to MBPTs. Methods: We conducted a retrospective cross-sectional study involving adult asthmatic patients from 6 university hospitals in South Korea. Patients were categorized into 2 groups: those with MBPT sensitivity (the provocative concentration of methacholine that leads to a 20% reduction in forced expiratory volume in 1 second [PC20]≤ 16 mg/mL) and those with lower sensitivity (PC 20 > 16 mg/mL). Clinical characteristics were compared between the 2 groups. Results: Among 346 patients, 213 had PC 20 ≤ 16 mg/mL and 133 had PC 20 > 16 mg/mL. The PC20> 16 mg/mL group had a higher prevalence of late-onset asthma (P= 0.024) and obesity (P= 0.045). While no significant differences in immunoglobulin E (≥ 200 IU/mL) were found, the PC 20 ≤ 16 mg/mL group had greater T2-high inflammation, such as elevated eosinophil counts and fractional exhaled nitric oxide (P< 0.001 and P= 0.004, respectively). Asthma exacerbations requiring emergency visits or hospitalizations were more frequent in the PC 20 > 16 mg/mL group, despite a lower proportion of patients on higher-step treatments according to Global Initiative for Asthma guidelines. Conclusion Asthmatic patients with PC 20 > 16 mg/mL tend to present with late-onset asthma, less T2-high inflammation, and higher rates of asthma exacerbations. Further studies are needed to clarify the clinical features of asthma patients with PC 20 > 16 mg/mL and assess the long-term significance of these findings.

Purpose: Methacholine bronchial provocation tests (MBPTs) are commonly used to assess airway hyperresponsiveness, but some patients show no significant response. This study aimed to compare the clinical characteristics of asthmatic patients based on their sensitivity to MBPTs. Methods: We conducted a retrospective cross-sectional study involving adult asthmatic patients from 6 university hospitals in South Korea. Patients were categorized into 2 groups: those with MBPT sensitivity (the provocative concentration of methacholine that leads to a 20% reduction in forced expiratory volume in 1 second [PC20]≤ 16 mg/mL) and those with lower sensitivity (PC 20 > 16 mg/mL). Clinical characteristics were compared between the 2 groups. Results: Among 346 patients, 213 had PC 20 ≤ 16 mg/mL and 133 had PC 20 > 16 mg/mL. The PC20> 16 mg/mL group had a higher prevalence of late-onset asthma (P= 0.024) and obesity (P= 0.045). While no significant differences in immunoglobulin E (≥ 200 IU/mL) were found, the PC 20 ≤ 16 mg/mL group had greater T2-high inflammation, such as elevated eosinophil counts and fractional exhaled nitric oxide (P< 0.001 and P= 0.004, respectively). Asthma exacerbations requiring emergency visits or hospitalizations were more frequent in the PC 20 > 16 mg/mL group, despite a lower proportion of patients on higher-step treatments according to Global Initiative for Asthma guidelines. Conclusion Asthmatic patients with PC 20 > 16 mg/mL tend to present with late-onset asthma, less T2-high inflammation, and higher rates of asthma exacerbations. Further studies are needed to clarify the clinical features of asthma patients with PC 20 > 16 mg/mL and assess the long-term significance of these findings.

Fournier gangrene (FG) is a rare life-threatening infection j that can occasionally extend beyond the perineum into the retroperitoneal space. Preperitoneal involvement in female patients is extremely rare. We report a unique case of a 59-year-old female with FG, characterized by atypical preperitoneal extension. Despite initial treatment failure, the patient recovered following emergency debridement, and targeted antibiotic therapy. This case underscores the importance of early diagnosis, timely surgical intervention, and multidisciplinary care in managing atypical FG presentations in female patients. It emphasizes the need for prompt and aggressive management to improve survival in these rare instances.