Depression fully mediates the effects of problematic internet use on nonsuicidal self-injury among adolescents during the COVID-19 outbreak.

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic threatened adolescents' mental health and livelihoods, which can worsen their non-suicidal self-injury (NSSI) behaviors. With the significant increase of total online time use, adolescents become more prone to problematic internet use (PIU). This study examined whether depression mediated the relationship between PIU and NSSI among adolescence during the COVID-19 outbreak. Constructed with a cross-sectional design during the COVID-19 outbreak in Taiwan, 1060 participants were drawn from junior high schools through stratified and cluster sampling, and completed a set of comprehensive surveys. The mediation model demonstrated a good fit to the data, GFI = .96, CFI = .97, NFI = .97, NNFI = .95, IFI = .97, and SRMR = .02. The overall fit of the mediational model was adequate. The path from PIU to depression, ß = .41, p < .001, and the path from depression to NSSI, ß = .40, p < .001, were both significant. Moreover, the effect of PIU to NSSI decreased from .23 (p < .001) to .05 (p = .099) when depression was incorporated into the analysis. Moreover, results in bootstrapping analysis displayed that the indirect effect (PIU on NSSI via depression) was statistically significant (p < .001) and the direct effect (PIU on NSSI) was statistically non-significant (p = .134). The full mediation model was confirmed. The findings of the structure equation modeling and bootstrap analysis showed that PIU significantly and positively predicted NSSI, and that depression fully mediated this relationship.

The INMSG Survey on the Loss of Signal Management on the First Side During Planned Bilateral Thyroid Surgery.

BACKGROUND: The aim of this study is to describe the management and associated follow-up strategies adopted by thyroid surgeons with different surgical volumes when loss of signal (LOS) occurred on the first side of planned bilateral thyroid surgery, and to further define the consensus on intraoperative neuromonitoring (IONM) applications. METHODS: The International Neural Monitoring Study Group (INMSG) web-based survey was sent to 950 thyroid surgeons worldwide. The survey included information on the participants, IONM team/equipment/procedure, intraoperative/postoperative management of LOS, and management of LOS on the first side of thyroidectomy for benign and malignant disease. RESULTS: Out of 950, 318 (33.5%) respondents completed the survey. Subgroup analyses were performed based on thyroid surgery volume: <50 cases/year (n = 108, 34%); 50 to 100 cases/year (n = 69, 22%); and >100 cases/year (n = 141, 44.3%). High-volume surgeons were significantly (P < .05) more likely to perform the standard procedures (L1-V1-R1-S1-S2-R2-V2-L2), to differentiate true/false LOS, and to verify the LOS lesion/injury type. When LOS occurs, most surgeons arrange otolaryngologists or speech consultation. When first-side LOS occurs, not all respondents decided to perform stage contralateral surgery, especially for malignant patients with severe disease (eg, extrathyroid invasion and poorly differentiated thyroid cancer). CONCLUSIONS: Respondents felt that IONM was optimized when conducted under a collaborative team-based approach, and completed IONM standard procedures and management algorithm for LOS, especially those with high volume. In cases of first-site LOS, surgeons can determine the optimal management of disease-related, patient-related, and surgical factors. Surgeons need additional education on LOS management standards and guidelines to master their decision-making process involving the application of IONM.

BET inhibition sensitizes innate checkpoint inhibitor resistant melanoma to anti-CTLA-4 treatment.

Approximately 50% of melanoma patients fail to respond to immune checkpoint blockade (ICB), and acquired resistance hampers long-term survival in about half of initially responding patients. Whether targeting BET reader proteins, implicated in epigenetic dysregulation, can enhance ICB response rates and durability, remains to be determined. Here we show elevated BET proteins correlate with poor survival and ICB responses in melanoma patients. The BET inhibitor IBET151, combined with anti-CTLA-4, overcame innate ICB resistance however, sequential BET inhibition failed against acquired resistance in mouse models. Combination treatment response in the innate resistance model induced changes in tumor-infiltrating immune cells, reducing myeloid-derived suppressor cells (MDSCs). CD4+ and CD8+ T cells showed decreased expression of inhibitory receptors, with reduced TIM3, LAG3, and BTLA checkpoint expression. In human PBMCs in vitro, BET inhibition reduced expression of immune checkpoints in CD4+ and CD8+ T cells, restoring effector cytokines and downregulating the transcriptional driver TOX. BET proteins in melanoma may play an oncogenic role by inducing immune suppression and driving T cell dysfunction. The study demonstrates an effective combination for innately unresponsive melanoma patients to checkpoint inhibitor immunotherapy, yet highlights BET inhibitors' limitations in an acquired resistance context.