Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness.

Genes limiting T cell antitumor activity may serve as therapeutic targets. It has not been systematically studied whether there are regulators that uniquely or broadly contribute to T cell fitness. We perform genome-scale CRISPR-Cas9 knockout screens in primary CD8 T cells to uncover genes negatively impacting fitness upon three modes of stimulation: (1) intense, triggering activation-induced cell death (AICD); (2) acute, triggering expansion; (3) chronic, causing dysfunction. Besides established regulators, we uncover genes controlling T cell fitness either specifically or commonly upon differential stimulation. Dap5 ablation, ranking highly in all three screens, increases translation while enhancing tumor killing. Loss of Icam1-mediated homotypic T cell clustering amplifies cell expansion and effector functions after both acute and intense stimulation. Lastly, Ctbp1 inactivation induces functional T cell persistence exclusively upon chronic stimulation. Our results functionally annotate fitness regulators based on their unique or shared contribution to traits limiting T cell antitumor activity.

Do medical student's surgical examination scores correlate with performance markers?

BACKGROUND: Some medical school training consists of oral examinations. METHODS: We conducted a 9-year review of third-year medical student examinations including oral examinations, National Board of Medical Examiners Surgery Subject Examination (SSE, ie, shelf), and United States Medical Licensing Examinations Step 1 and Step 2. RESULTS: Step 1 showed a moderate to strong association with Period 1 orals (Somers' D = .297, P < .001), but not Period 2 orals (Somers' D = .048, P = .053). Period 1 orals (percentage) had a strong association with SSE (Somers' D = .356, P < .001) and Step 2 (Somers' D = .368, P < .001). Period 2 orals (pass/fail) suggested a positive, but not statistically significant, association with SSE (Somers' D = .334, P = .085) and Step 2 (Somers' D = .370, P = .055). Step 1 shows a strong association with SSE (Somers' D = .490, P < .001). SSE showed a strong association with Step 2 (Somers' D = .506, P < .001). CONCLUSIONS: Orals can be used to identify students who may have difficulty passing the SSE. Step 1 can be used to identify students at risk of poor performance on the SSE, and SSE can be used to identify students at risk for poor performance on Step 2.