Medical education has been uniquely affected by the Novel Coronavirus Disease 2019 (COVID-19). As the pandemic’s psychological impacts on medical students remain unclear, this study assessed COVID-19’s impacts on undergraduate medical students’ stress and anxiety. A nationwide, online survey was administered via email chains between June-August 2020 to first-fourth year medical students in the United States. Demographics, 4-point Perceived Stress Scale that measures stress, 7-point Generalized Anxiety Disorder Scale that measures anxiety, and the impacts of social, health, and academic stressors due to COVID-19 were collected. Of the 852 students who participated, 66.1% experienced mild, moderate, or severe anxiety. Mean PSS-4 score was 7.25/16. Stress was highest in second- through fourth-year students. Students with preexisting mental health conditions had significantly higher stress and anxiety scores, and higher percentage of stress attributed to COVID-19. Trust in government institutions during COVID-19 was the highest stressor in first- and second-year students. Delay/availability of standardized exams was the highest stressor for third-year students. Impact on rotations/residencies was the highest stressor for fourth-year students. Understanding how students’ anxiety and stress have changed due to COVID-19 will allow educators to identify students in need and guide recommendations on the implementation of psychological interventions and support strategies.

Objectives: Our previous findings demonstrate that channel-kinase transient receptor potential (TRP) ion channel subfamily M, member 7 (TRPM7) is critical in regulating human glioma cell migration and invasion. Since microRNAs (miRNAs) participate in complex regulatory networks that may affect almost every cellular and molecular process during glioma formation and progression, we explored the role of miRNAs in human glioma progression by comparing miRNA expression profiles due to differentially expressed TRPM7. Methods: First, we performed miRNA microarray analysis to determine TRPM7's miRNA targets upon TRPM7 silencing in A172 cells and validated the miRNA microarray data using A172, U87MG, U373MG, and SNB19 cell lines by stem-loop RT-qPCRs. We next determined whether TRPM7 regulates glioma cell proliferation and migration/invasion through different functional domains by overexpressing wild-type human TRPM7 (wtTRPM7), two mutants with TRPM7's α-kinase domain deleted (Δkinase-DK), or a point mutation in the ATP binding site of the α-kinase domain (K1648R-KR). In addition, we determined the roles of miR-28-5p in glioma cell proliferation and invasion by overexpressing or under expressing miR-28-5p in vitro. Lastly, we determined whether a Ras-related small GTP-binding protein (Rap1b) is a target of miR-28-5p in glioma tumorigenesis. Results: The miRNA microarray data revealed a list of 16 downregulated and 10 upregulated miRNAs whose transcripts are significantly changed by TRPM7 knock-down. Cell invasion was significantly reduced in two TRPM7 mutants with inactive kinase domain, Δkinase, and K1648R transfected glioma cells. miR-28-5p overexpression suppressed glioma cells' proliferation and invasion, and miR-28-5p under expression led to a significant increase in glioma cell proliferation and migration/invasion compared to that of the controls. miR-28-5p suppressed glioma cell proliferation and migration by targeting Rap1b. Co-transfection of siRap1b with miR28-5p inhibitor reduced the glioma cell proliferation and invasion, caused by the latter. Conclusions: These results indicate that TRPM7's channel activity is required for glioma cell growth while the kinase domain is required for cell migration/invasion. TRPM7 regulates miR-28-5p expression, which suppresses cell proliferation and invasion in glioma cells by targeting Rap1b signaling.

Dear EditorThe rapid advancement of artificial intelligence (AI) technology has been prominent and impacts all fields, including opening up new possibilities for medical education. Specifically, Ch...

We have reported that transient receptor potential melastatin-related 7 (TRPM7) regulates glioma stem cells (GSC) growth and proliferation through Notch, STAT3-ALDH1, and CD133 signaling pathways. In this study, we determined the major contributor(s) to TRPM7 mediated glioma stemness by further deciphering each individual Notch signaling. We first determined whether TRPM7 is an oncotarget in glioblastoma multiforme (GBM) using the Oncomine database. Next, we determined whether TRPM7 silencing by siRNA TRPM7 (siTRPM7) induces cell growth arrest or apoptosis to reduce glioma cell proliferation using cell cycle analysis and annexin V staining assay. We then examined the correlations between the expression of TRPM7 and Notch signaling activity as well as the expression of GSC markers CD133 and ALDH1 in GBM by downregulating TRPM7 through siTRPM7 or upregulating TRPM7 through overexpression of human TRPM7 (M7-wt). To distinguish the different function of channel and kinase domain of TRPM7, we further determined how the α-kinase-dead mutants of TRPM7 (α-kinase domain deleted/M7-DK and K1648R point mutation/M7-KR) affect Notch activities and CD133 and ALDH1 expression. Lastly, we determined the changes in TRPM7-mediated regulation of glioma cell growth/proliferation, cell cycle, and apoptosis by targeting Notch1. The Oncomine data revealed a significant increase in TRPM7 mRNA expression in anaplastic astrocytoma, diffuse astrocytoma, and GBM patients compared to that in normal brain tissues. TRPM7 silencing reduced glioma cell growth by inhibiting cell entry into S and G2/M phases and promoting cell apoptosis. TRPM7 expression in GBM cells was found to be positively correlated with Notch1 signaling activity and CD133 and ALDH1 expression; briefly, downregulation of TRPM7 by siTRPM7 decreased Notch1 signaling whereas upregulation of TRPM7 increased Notch1 signaling. Interestingly, kinase-inactive mutants (M7-DK and M7-KR) resulted in reduced activation of Notch1 signaling and decreased expression of CD133 and ALDH1 compared to that of wtTRPM7. Finally, targeting Notch1 effectively suppressed TRPM7-induced growth and proliferation of glioma cells through cell G1/S arrest and apoptotic induction. TRPM7 is responsible for sustained Notch1 signaling activation, enhanced expression of GSC markers CD133 and ALDH1, and regulation of glioma stemness, which contributes to malignant glioma cell growth and invasion.

Nearly half of patients with cancer are diagnosed at 70 years or older, which presents challenges in cancer care due to their high comorbidity burden and the underrepresentation of this age group in clinical trials. This retrospective study evaluated the association between comorbidity burden and immune checkpoint inhibitors (ICIs) treatment outcomes among older adults. Data were collected from patients aged 70 years or older at the time of diagnosis who were treated with ICIs from 2011 to 2022. Key clinical outcomes include changes in performance status, overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs) and were compared between low baseline Charlson Comorbidity Index (CCI) and high CCI (<4 vs. ≥4) groups. Among 1,223 patients, patients with CCI scores ≥4 (n = 300) had a significantly shorter OS (11.4 vs. 13.6 months, p = 0.0461) but similar PFS (8.0 vs. 7.7 months, p = 0.258) compared to patients with CCI scores <4. There was no significant difference in changes in performance status pre- and post-treatment (p = 0.14) or in the irAE prevalence between the two groups (39.3% vs. 38.3%, p = 0.786). Our study suggests that ICIs are safe in patients with high comorbidity burden but that the presence of pre-treatment comorbidities decreases overall survival.

Problem: Based on a specific community benefit analysis of Greenville, South Carolina, we identified the Dunean community with its increased prevalence of health inequities with respect to access to health care, poverty burden, and disease mortality on a county, state, and national level. The Dunean community’s data reflect poorer health outcomes in terms of disease and unhealthy lifestyle as well as inadequate access to medical resources compared to other communities in South Carolina. Approach: Students, residents, attendings, faculty, and staff from the University of South Carolina School of Medicine Greenville (UofSC SOMG) formed a task force to engage the community and combat the root causes of diseases. This task force built partnerships with community leaders to create Root Cause, a monthly health event designed to bring community members to a unified space, share a free community dinner, and provide a wide range of health and wellness resources to educate and inspire them to make healthy lifestyle choices. Outcomes: This report describes the formation of the community engagement task force and execution of Root Cause. In five Root Cause events, we partnered with 36 community agencies and our academic health center partners who shared their resources, served 207 Dunean neighborhood members, and facilitated 1,237 total interactions between community members and partners. Conclusion: Under the Root Cause model, medical students and neighborhood partners have initiated a trusted, bidirectional dialogue to determine their specific needs with the desire to positively transform the health and wellness of the Dunean community. Our data suggests that based on our efforts, the neighborhood of Dunean, SC increased community cohesiveness and improved perceptions of access to health care. Additionally, participating medical students advanced their understanding of social health and economic challenges which helped to facilitate their development along the active citizen continuum, as well as increase empathy for their future patients in the local community.