Purpose: Cognitive behavioral therapy (CBT) has long been recognized as an effective treatment for depression and suicidality.Virtual reality (VR) technology is widely used for cognitive training for conditions such as anxiety disorder and post-traumatic stress disorder, but little research has considered VR-based CBT for depressive symptoms and suicidality. We tested the effectiveness and safety of a VR-based CBT program for depressive disorders. Materials and Methods: We recruited 57 participants from May 2022 through February 2023 using online advertisements. This multi-center, assessor-blinded, randomized, controlled exploratory trial used two groups: VR treatment group and treat as usual (TAU) group. VR treatment group received a VR mental health training/education program. TAU group received standard pharmacotherapy. Assessments were conducted at baseline, immediately after the 6-week treatment period, and 4 weeks after the end of the treatment period in each group. Results: Depression scores decreased significantly over time in both VR treatment and TAU groups, with no differences between the two groups. The suicidality score decreased significantly only in VR group. No group differences were found in the remission or response rate for depression, perceived stress, or clinical severity. No adverse events or motion sickness occurred during the VR treatment program. Conclusion VR CBT treatment for major depressive disorder has the potential to be equivalent to the gold-standard pharmacotherapy in reducing depressive symptoms, suicidality, and related clinical symptoms, with no difference in improvement found in this study. Thus, VR-based CBT might be an effective alternative to pharmacotherapy for depressive disorders.

Purpose: Telemedicine is advantageous in providing medical care to patients with mobility difficulties. This single-center study aimed to report on the provision of video televisits to people living with amyotrophic lateral sclerosis (pALS, ALS) who were registered with a home-based medical care (HBMC) team in a tertiary hospital in South Korea. Materials and Methods: A retrospective cross-sectional study was conducted for pALS provided with video televisits by the HBMC team between July 2020 and February 2023. The patients’ demographics, disease status, mobility level, and supportive care equipment were investigated. The main issues discussed at televisits were investigated. Results: During the 32-month study period, video televisits were provided to 69 (81.2%) of the 85 pALS registered with the HBMC team. Their median (interquartile range) age was 66 (57–71) years, and 66.7% were aged 60 years or older. At the time of the televisits, 71.0% were non-ambulatory and 27.5% were at an assisted ambulatory level. Furthermore, 82.6% were receiving nutritional support with a nasogastric or gastrostomy tube, and 78.3% had received either non-invasive positive pressure ventilation (43.5%) or tracheostomy invasive ventilation (34.8%). Common issues addressed on televisits were disease-related symptoms (100%), management of supportive care equipment (92.8%), acute health issues (52.2%), and advance care planning (ACP) including goal of care discussion (14.5%). Conclusion Video telemedicine is feasible for pALS, including older adults with limited mobility due to muscle weakness or reliance on various supportive care equipment. Video televisits allow for a variety of discussions, ranging from acute health issues to ACP.

Purpose: This retrospective cohort study aimed to investigate the association between the use of pain medications with varying cyclooxygenase-2 (COX-2) selectivity and the incidence of endometriosis (EMS) in women. Materials and Methods: Medical records from January 1, 1994, to December 31, 2022, were retrospectively analyzed. The cohort included 33406 patients diagnosed with any pain-related condition who were prescribed either selective COX-2 inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs). Patients were followed for up to 5 years from the cohort entry date. The incidence of EMS was compared between the two medication groups using Cox proportional hazards models, adjusting for confounding factors such as age, past drug use, and prior diagnosis. Results: The incidence rates of EMS were 3.00 per 1000 person-years in the COX-2 inhibitor group and 3.97 per 1000 person-years in the NSAIDs group. After adjustment for confounders, the hazard ratio for EMS incidence in the COX-2 inhibitor group compared to the NSAIDs group was 0.77 [95% confidence interval (CI), 0.63 to 0.93; p<0.01], indicating a significantly lower risk in the COX-2 inhibitor group. Subgroup analysis revealed that this association was particularly significant in younger women aged 20– 44 years, with a hazard ratio of 0.71 (95% CI, 0.54 to 0.95; p<0.05) in this age group. Conclusion The findings suggest that COX-2 inhibitors may reduce the incidence of EMS compared to traditional NSAIDs, highlighting their potential as a strategic option for managing EMS, particularly among younger women. Further prospective studies are needed to confirm these findings.

Objective: This study aims to understand the structure of meaning in life among patients with cancer through the validation of the Meaning in Life Scale among Korean patients (K-MiLS) with cancer. Methods: From August 2021 to November 2022, participants were recruited from multiple sites in South Korea. Participants completed related questionnaires, including the MiLS, on the web or mobile. Test-retest reliability was assessed between 2 and 4 weeks after the initial assessment. Exploratory and confirmatory factor analyses and Pearson’s correlations were used to evaluate the reliability and validity of the MiLS. A multiple regression analysis was conducted to examine the sociodemographic and disease-related variables correlated with the MiLS. Regarding concurrent validity, a hierarchical regression analysis was performed. Results: The results (n=345) indicated that the K-MiLS has a four-factor structure: Harmony and Peace; Life Perspective, Purpose, and Goals; Confusion and Lessened Meaning; and Benefits of Spirituality. Regarding convergent and discriminant validity, K-MiLS was negatively correlated with Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Fear of Cancer Recurrence Inventory while showing a significantly positive correlation with the Posttraumatic Growth Inventory, Self-Compassion Scale, Functional Assessment of Cancer Therapy-General, and Functional Social Support Questionnaire. Hierarchical regression analysis revealed that the demographic variable influencing MiLS was religious affiliation. Conclusion The K-MiLS had a multidimensional four-factor structure similar to that of the original version. It is also a reliable and valid measure for assessing cancer survivors’ meaning in life after a cancer diagnosis.

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: This study aimed to explore the effects of both the presence and size of posterior subependymal germinal matrix hemorrhage (PS-GMH), considered a mild form of hemorrhage, on the neurodevelopmental outcomes of extremely preterm infants. Methods: A retrospective analysis was conducted on 221 extremely preterm infants, assessing their initial and term-equivalent age (TEA) cranial ultrasound (cUS) examinations from 2016 to 2021. Infants were classified based on the presence and size (small/large) of PS-GMH. Neurodevelopmental outcomes at corrected ages of 18-24 months were analyzed in 135 infants. Results: PS-GMH was identified in 86.9% (192/221) of the infants, with 13.5% (26/192) exhibiting large PS-GMH. Among the 135 infants who were followed up, those with PS-GMH were found to have younger gestational ages (P<0.001) and a higher incidence of maternal chorioamnionitis (P=0.016) than those without PS-GMH. Significant differences were observed in the incidence of grade II intraventricular hemorrhage (IVH) on initial cUS (P=0.003) and ventriculomegaly at TEA cUS (P=0.026) across the groups with no PS-GMH, small PS-GMH, and large PS-GMH. The large PS-GMH group exhibited a higher occurrence of grade II IVH than the small PS-GMH group (P=0.006). However, ventriculomegaly incidence did not significantly vary with PS-GMH status. Neurodevelopmental outcomes were also not significantly different across PS-GMH statuses. The adjusted odds ratios for any neurodevelopmental impairment, compared to the no PS-GMH group, were 1.70 (95% confidence interval [CI], 0.40 to 7.26; P=0.471) for all PS-GMH, 1.61 (95% CI, 0.37 to 6.93; P=0.526) for small PS-GMH, and 3.84 (95% CI, 0.62 to 24.00; P=0.150) for large PS-GMH. Conclusion PS-GMH was frequently observed in extremely preterm infants; however, it did not independently predict adverse neurodevelopmental outcomes.

Purpose: This study evaluated the educational impact of an artificial intelligence (AI)–based decision support system for breast ultrasonography (US) on medical professionals not specialized in breast imaging. Methods: In this multi-case, multi-reader study, educational materials, including American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) descriptors, were provided alongside corresponding AI results during training. The AI system presented results in the form of AIheatmaps, AI scores, and AI-provided BI-RADS assessment categories. Forty-two readers evaluated the test set in three sessions: the first session (S1) occurred before the educational intervention, the second session (S2) followed education without AI assistance, and the third session (S3) took place after education with AI assistance. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and overall performance, were compared between the sessions. Results: The mean sensitivity increased from 66.5% (95% confidence interval [CI], 59.2% to 73.7%) to 88.7% (95% CI, 84.1% to 93.3%), with a statistically significant difference (P<0.001), and the AUC non-significantly increased from 0.664 (95% CI, 0.606 to 0.723) to 0.684 (95% CI, 0.620 to 0.748) (P=0.300). Both measures were higher in S2 than in S1. The AI-achieved AUC was comparable to that of the expert reader (0.747 [95% CI, 0.640 to 0.855] vs. 0.803 [95% CI, 0.706 to 0.900], P=0.217). Additionally, with AI assistance, the mean AUC for inexperienced readers was not significantly different from that of the expert reader (0.745 [95% CI, 0.660 to 0.830] vs. 0.803 [95% CI, 0.706 to 0.900], P=0.120). Conclusion The mean AUC and sensitivity improved after incorporating AI into breast US education and interpretation. AI systems with high-level performance for breast US can potentially be used as educational tools in the interpretation of breast US images.

Purpose: Cognitive behavioral therapy (CBT) has long been recognized as an effective treatment for depression and suicidality.Virtual reality (VR) technology is widely used for cognitive training for conditions such as anxiety disorder and post-traumatic stress disorder, but little research has considered VR-based CBT for depressive symptoms and suicidality. We tested the effectiveness and safety of a VR-based CBT program for depressive disorders. Materials and Methods: We recruited 57 participants from May 2022 through February 2023 using online advertisements. This multi-center, assessor-blinded, randomized, controlled exploratory trial used two groups: VR treatment group and treat as usual (TAU) group. VR treatment group received a VR mental health training/education program. TAU group received standard pharmacotherapy. Assessments were conducted at baseline, immediately after the 6-week treatment period, and 4 weeks after the end of the treatment period in each group. Results: Depression scores decreased significantly over time in both VR treatment and TAU groups, with no differences between the two groups. The suicidality score decreased significantly only in VR group. No group differences were found in the remission or response rate for depression, perceived stress, or clinical severity. No adverse events or motion sickness occurred during the VR treatment program. Conclusion VR CBT treatment for major depressive disorder has the potential to be equivalent to the gold-standard pharmacotherapy in reducing depressive symptoms, suicidality, and related clinical symptoms, with no difference in improvement found in this study. Thus, VR-based CBT might be an effective alternative to pharmacotherapy for depressive disorders.

Purpose: Telemedicine is advantageous in providing medical care to patients with mobility difficulties. This single-center study aimed to report on the provision of video televisits to people living with amyotrophic lateral sclerosis (pALS, ALS) who were registered with a home-based medical care (HBMC) team in a tertiary hospital in South Korea. Materials and Methods: A retrospective cross-sectional study was conducted for pALS provided with video televisits by the HBMC team between July 2020 and February 2023. The patients’ demographics, disease status, mobility level, and supportive care equipment were investigated. The main issues discussed at televisits were investigated. Results: During the 32-month study period, video televisits were provided to 69 (81.2%) of the 85 pALS registered with the HBMC team. Their median (interquartile range) age was 66 (57–71) years, and 66.7% were aged 60 years or older. At the time of the televisits, 71.0% were non-ambulatory and 27.5% were at an assisted ambulatory level. Furthermore, 82.6% were receiving nutritional support with a nasogastric or gastrostomy tube, and 78.3% had received either non-invasive positive pressure ventilation (43.5%) or tracheostomy invasive ventilation (34.8%). Common issues addressed on televisits were disease-related symptoms (100%), management of supportive care equipment (92.8%), acute health issues (52.2%), and advance care planning (ACP) including goal of care discussion (14.5%). Conclusion Video telemedicine is feasible for pALS, including older adults with limited mobility due to muscle weakness or reliance on various supportive care equipment. Video televisits allow for a variety of discussions, ranging from acute health issues to ACP.

Purpose: This retrospective cohort study aimed to investigate the association between the use of pain medications with varying cyclooxygenase-2 (COX-2) selectivity and the incidence of endometriosis (EMS) in women. Materials and Methods: Medical records from January 1, 1994, to December 31, 2022, were retrospectively analyzed. The cohort included 33406 patients diagnosed with any pain-related condition who were prescribed either selective COX-2 inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs). Patients were followed for up to 5 years from the cohort entry date. The incidence of EMS was compared between the two medication groups using Cox proportional hazards models, adjusting for confounding factors such as age, past drug use, and prior diagnosis. Results: The incidence rates of EMS were 3.00 per 1000 person-years in the COX-2 inhibitor group and 3.97 per 1000 person-years in the NSAIDs group. After adjustment for confounders, the hazard ratio for EMS incidence in the COX-2 inhibitor group compared to the NSAIDs group was 0.77 [95% confidence interval (CI), 0.63 to 0.93; p<0.01], indicating a significantly lower risk in the COX-2 inhibitor group. Subgroup analysis revealed that this association was particularly significant in younger women aged 20– 44 years, with a hazard ratio of 0.71 (95% CI, 0.54 to 0.95; p<0.05) in this age group. Conclusion The findings suggest that COX-2 inhibitors may reduce the incidence of EMS compared to traditional NSAIDs, highlighting their potential as a strategic option for managing EMS, particularly among younger women. Further prospective studies are needed to confirm these findings.