Exposure to suicide in social relationships may be associated with suicidal ideation among survivors. In South Korea, which is known for having the highest suicide rate among OECD countries, exposure to suicide in social relationships can have serious consequences as social relationships are greatly emphasized in the society. The purpose of this study was to examine the association between survivors' suicidal ideation and their exposure to suicide in close relationships. Data collected through a telephone survey of a total of 1,000 men and women selected from across the nation using a stratified sampling method were analyzed. The results show that individuals who lost a family member, friend, or acquaintance in their lifetime are 4.5 times, 3.7 times, 2.2 times, respectively, more likely to have suicidal ideation in the past year compared to those without such experience. These findings suggest that special intervention for suicide survivors should be considered for those who experience suicide in close relationships.

Although affective disorders have been known to have sex differences in the associated clinical characteristics and quality of life (QOL), sex differences among patients with panic disorder (PD) have remained relatively unexplored in Korea. We examined the sex differences in different types of stressful life events (SLEs), coping styles, symptom severity, and health-related QOL (HRQOL) in patients with PD. Data from 291 female and 254 male participants diagnosed with PD were analyzed using a structured clinical interview following the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Females with PD reported more SLEs including separation issues, physical illness or disability, and pregnancy-related problems than males. They also reported lower levels of confrontation and help-seeking coping strategies and higher levels of agoraphobia in symptom severity than males. The HRQOL of females with PD was significantly lower than male in physical functioning of HRQOL. This study suggests that the patient's sex is relevant to the assessment and treatment of PD.

Several emerging therapies kill cancer cells primarily by inducing necrosis. As necrosis activates immune cells, potentially, uncovering the molecular drivers of anticancer therapy–induced necrosis could reveal approaches for enhancing immunotherapy efficacy. To identify necrosis-associated genes, we performed a genome-wide CRISPR-Cas9 screen with negative selection against necrosis-inducing preclinical agents BHPI and conducted follow-on experiments with ErSO. The screen identified transient receptor potential melastatin member 4 (TRPM4), a calcium-activated, ATP-inhibited, sodium-selective plasma membrane channel. Cancer cells selected for resistance to BHPI and ErSO exhibited robust TRPM4 downregulation, and TRPM4 reexpression restored sensitivity to ErSO. Notably, TRPM4 knockout (TKO) abolished ErSO-induced regression of breast tumors in mice. Supporting a broad role for TRPM4 in necrosis, knockout of TRPM4 reversed cell death induced by four additional diverse necrosis-inducing cancer therapies. ErSO induced anticipatory unfolded protein response (a-UPR) hyperactivation, long-term necrotic cell death, and release of damage-associated molecular patterns that activated macrophages and increased monocyte migration, all of which was abolished by TKO. Furthermore, loss of TRPM4 suppressed the ErSO-induced increase in cell volume and depletion of ATP. These data suggest that ErSO triggers initial activation of the a-UPR but that it is TRPM4-mediated sodium influx and cell swelling, resulting in osmotic stress, which sustains and propagates lethal a-UPR hyperactivation. Thus, TRPM4 plays a pivotal role in sustaining lethal a-UPR hyperactivation that mediates the anticancer activity of diverse necrosis-inducing therapies. Significance: A genome-wide CRISPR screen reveals a pivotal role for TRPM4 in cell death and immune activation following treatment with diverse necrosis-inducing anticancer therapies, which could facilitate development of necrosis-based cancer immunotherapies.

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