BRAF and ErbB inhibitors directly activate GCN2 in an off-target manner to limit cancer cell proliferation.

Targeted kinase inhibitors are well known for their promiscuity and off-target effects. Herein, we define an off-target effect in which several clinical BRAF inhibitors, including the widely used dabrafenib and encorafenib, interact directly with GCN2 to activate the Integrated Stress Response and ATF4. Blocking this off-target effect by co-drugging with a GCN2 inhibitor in A375 melanoma cells causes enhancement rather than suppression of cancer cell outgrowth, suggesting that the off-target activation of GCN2 is detrimental to these cells.

Strategically aligning a mandala of competencies to advance a transformative vision.

Objective: This paper offers insight into the processes that have shaped the Eskind Biomedical Library's (EBL's) strategic direction and its alignment to the institution's transformative vision.

Setting: The academic biomedical library has a notable track record for developing and pioneering roles for information professionals focused on a sophisticated level of information provision that draws from and fuels practice evolutions.

Strategy: The medical center's overall transformative vision informs the creation of a fully aligned library strategic plan designed to effectively contribute to the execution of key organizational goals.

Outcome after partial-hospital treatment of severely disturbed adolescents.

Results of a follow-up study of 50 adolescents treated in a day-hospital program are reported. The program admits seriously disturbed adolescents, over two-thirds with a personality diagnosis. Patients are treated in the day hospital for an average of 3 to 9 months.