Background: This longitudinal study examined risk factors for future suicidality among North Korean defectors (NKDs) living in South Korea. Methods: The subjects were 300 NKDs registered with a regional adaptation center (the Hana Center) in South Korea. Face-to-face interviews were conducted using the North Korean version of the World Health Organization’s Composite International Diagnostic Interview to diagnose mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Subjects were also asked about sociodemographic and clinical factors at baseline. At follow-up after three years, the NKDs (n = 172 respondents) were asked to participate in an online survey, responding to self-questionnaires about suicidality. Logistic regression analyses were used to explore associations between baseline variables and future suicidality among NKDs. Results: Thirty (17.4%) of the 172 survey respondents reported suicidality at follow-up. The presence of health problems over the past year, any prior suicidality at baseline, a higher score on a trauma-related scale, and a lower score on a resilience scale at baseline were associated with greater odds of suicidality at follow-up after adjusting for age, sex, and educational level. Of all mental disorder categories, major depressive disorder, dysthymia, agoraphobia, and social phobia were also associated with significantly increased odds of suicidality at follow-up after adjusting for age, sex, educational level, and prior suicidality at baseline. Conclusion Resilience, a previous history of suicidality, and the presence of lifetime depressive disorder and anxiety disorder should be given consideration in mental health support and suicide prevention in NKDs.

Background: Remdesivir is a US Food and Drug Administration-approved drug for coronavirus disease 2019 (COVID-19). Clinical trials were conducted under strictly controlled situations for a selected population, and their reported adverse events may not fully represent conditions in real-world patients. We aimed to estimate the incidence of adverse drug events (ADEs) associated with remdesivir in hospitalized patients with COVID-19, including vulnerable subpopulations, such as those with impaired renal or hepatic function and pregnant women. Methods: This retrospective observational study included hospitalized patients with confirmed COVID-19 treated with remdesivir between January and December 2021 at ten hospitals. ADEs and severe ADEs (Common Toxicity Criteria for Adverse Events grade ≥ 3) were operationally defined and analyzed through laboratory investigations. The incidence of ADEs was compared with that of each matched control in subpopulations with renal or hepatic impairment and pregnant women. Results: Among 2,140 patients, 1,416 (66.2%) and 295 (13.8%) experienced at least one ADE and severe ADE, respectively. The most frequent ADE was 'hepatic injury' (42.9%), followed by anemia (27.6%). The most common severe ADEs were 'hypokalemia' (5.3%), 'hepatic injury' (2.9%), and 'anemia' (3.6%). There was no significant difference in the incidence of ADEs in patients relative to their respective matched-control groups, including those with renal impairment (80.0% vs. control 71.8%, P = 0.063), hepatic impairment (70.4% vs. control 75.0%, P = 0.623) and pregnant women (78.6% vs. control 63.7%, P = 0.067). However, severe ADE incidence was significantly higher in patients with renal impairment (40.8% vs. 16.0%, P < 0.001). The most common severe ADEs in those were 'anemia' (15.3%), 'hypokalemia' (10.5%), and 'thrombocytopenia' (8.9%). There was no statistically significant difference in the incidence of severe ADEs in patients with hepatic impairment or in pregnancy (P = 0.230; P = 0.085). Conclusion A significant proportion of patients with COVID-19 treated with remdesivir experienced ADEs and severe ADEs. Given the high incidence of severe ADEs, caution is required in patients with renal impairment. Further studies are needed to investigate ADEs in pregnant women and patients with hepatic impairment.

Objectives: To develop a Loneliness and Social Isolation scale (LSIS) that can measure both social isolation and loneliness in order to understand the degree of social isolation in Korea. Exploratory and confirmatory factor analysis was used to examine the factorial validity of the scale. Methods: The subjects of the study were 300 adults aged 19 or older who visited Samsung Medical Center and voluntarily expressed their willingness to participate in this research. Exploratory factor analysis (n=150) and confirmatory factor analysis (n=150) were conducted to construct the factorial structure model and to determine the model fit. Results: Exploratory factor analysis showed a three-factor structure with a total variance of 65.8%; factor 1 consisted of social support, factor 2 of social networks, and factor 3 of items representing loneliness. After conducting confirmatory factor analysis on the three-factor models, a three-factor model consisting of 8 items (LSIS-8) and a three-factor model consisting of 6 items (LSIS-6) showed significant goodness-of-fit. Internal consistency for all items was good (Cronbach’s α=0.774), and correlations with existing social isolation and loneliness measures were significant. Conclusion This study is meaningful as provides a tool that comprehensively measures social support, social networks, and loneliness. We believe that the application of such tools that are relatively easy to apply in communities will aid understanding of the current state of social isolation and loneliness in Korea.

Objectives: This study examined the stigma against social withdrawal syndrome (hikikomori) among mental health practitioners, and compared levels of stigma against social withdrawal syndrome versus mental illness. Methods: The participants were 133 mental health practitioners (28 males, 105 females) with experience of social withdrawal syndrome that self-reported levels of stigma against social withdrawal syndrome and mental illness. Results: Stigma against social withdrawal syndrome was generally significantly lower than stigma against mental illness. However, mental health practitioners tended to agree they would be reluctant to become personally involved with a person that had experienced social withdrawal syndrome (e.g., dating, hiring). Levels of stigma also differed across mental health occupations. Conclusion This study suggests although mental health practitioners may generally have less negative attitudes toward social withdrawal syndrome in the context of mental illness, that they may also have some reservations about personal interactions with individuals with social withdrawal syndrome.

OBJECTIVE: The aim of this study was to investigate the level of awareness and knowledge regarding elective oocyte cryopreservation (OC) among unmarried women of reproductive age in Korea. METHODS: A survey was conducted among 86 women who visited a fertility preservation clinic for counseling about elective OC between December 2016 and May 2018. Participants were asked to fill out a questionnaire regarding their awareness and knowledge of fertility and OC. RESULTS: The questionnaire was completed by 71 women. Among them, 73% decided to undergo OC after counseling. The main reason for making this decision was that they wished to maintain their fertility in the future (70.6%). Conversely, the high cost for the procedure was the main reason given by those who chose to forego this procedure. Regarding fertility and OC, the participants' knowledge was poor. Most women expected greater financial support from the government or from their place of employment. CONCLUSION: This study demonstrated that the awareness and knowledge about elective OC were relatively poor among the female Korean population. These findings may help clinicians in better counselling of their patients.
Counseling ; Cryopreservation ; Employment ; Female ; Fertility Preservation ; Fertility ; Financial Support ; Humans ; Korea ; Oocytes ; Single Person ; Surveys and Questionnaires

BACKGROUND: JAK2 V617F is the most common mutation in myeloproliferative neoplasms (MPNs) and is a major diagnostic criterion. Mutation quantification is useful for classifying patients with MPN into subgroups and for prognostic prediction. Droplet digital PCR (ddPCR) can provide accurate and reproducible quantitative analysis of DNA. This study was designed to verify the correlation of ddPCR with pyrosequencing results in the diagnosis of MPN and to investigate clinical implications of the mutational burden. METHODS: Peripheral blood or bone marrow samples were obtained from 56 patients newly diagnosed with MPN or previously diagnosed with MPN but not yet indicated for JAK2 inhibitor treatment between 2012 and 2016. The JAK2 V617F mutation was detected by pyrosequencing as a diagnostic work-up. The same samples were used for ddPCR to determine the correlation between assays and establish a detection sensitivity cut-off. Clinical and hematologic aspects were reviewed. RESULTS: Forty-two (75%) and 46 (82.1%) patients were positive for JAK2 V617F by pyrosequencing and ddPCR, respectively. The mean mutated allele frequency at diagnosis was 37.5±30.1% and was 40.7±31.2% with ddPCR, representing a strong correlation (r=0.9712, P < 0.001). Follow-up samples were available for 12 patients, including eight that were JAK2 V617F-positive. Of these, mutational burden reduction after treatment was observed in six patients (75%), consistent with trends of hematologic improvement. CONCLUSIONS: Quantitative analysis of the JAK2 V617F mutation using ddPCR was highly correlated with pyrosequencing data and may reflect the clinical response to treatment.
Bone Marrow ; Diagnosis ; DNA ; Follow-Up Studies ; Gene Frequency ; Humans ; Polymerase Chain Reaction*

Objective: This study aimed to investigate the association between gaming time and problematic game use (PGU) within a large sample of Korean male gamers and to examine the potential moderating effects of loneliness, living alone, and household size. Methods: This study employed data from 743 male gamers from the National Mental Health Survey 2021, a nationally representative survey of mental illness conducted in South Korea. Self-reported data on the average gaming time per day, severity of PGU, loneliness, living alone, and household size were used. Results: Gaming time was positively associated with PGU and this relationship was significantly moderated by loneliness such that the positive effect of gaming time on PGU was greater when the levels of loneliness were high. The three-way interaction effect of gaming time, loneliness, and living alone was also significant, in that the moderating effect of loneliness on the relationship between gaming time and PGU was significant only in the living alone group. However, household size (i.e., number of housemates) did not moderate the interaction between gaming time and loneliness among gamers living with housemates. Conclusion These results suggest the importance of considering loneliness and living arrangements of male gamers, in addition to gaming time, in identifying and intervening with individuals at heightened risk of PGU.

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: 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: 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.