A Novel PHD2/VHL-mediated Regulation of YAP1 Contributes to VEGF Expression and Angiogenesis.

The transcriptional co-activator YAP1 is the major oncogenic component of the Hippo signaling pathway and contributes to the genesis and progression of various tumors, including non-small cell lung cancer (NSCLC). YAP1 levels are regulated by the canonical Hippo kinases, MST1/2 and LATS1/2, which modulate its cytoplasmic retention and proteasomal degradation. While non-canonical regulation of YAP1 has been reported, its role in hypoxic response is not fully elucidated.

Novel HDAC11 inhibitors suppress lung adenocarcinoma stem cell self-renewal and overcome drug resistance by suppressing Sox2.

Non-small cell lung cancer (NSCLC) is known to have poor patient outcomes due to development of resistance to chemotherapy agents and the EGFR inhibitors, which results in recurrence of highly aggressive lung tumors. Even with recent success in immunotherapy using the checkpoint inhibitors, additional investigations are essential to identify novel therapeutic strategies for efficacious treatment for NSCLC. Our finding that high levels of histone deacetylase 11 (HDAC11) in human lung tumor tissues correlate with poor patient outcome and that depletion or inhibition of HDAC11 not only significantly reduces self-renewal of cancer stem cells (CSCs) from NSCLC but also decreases Sox2 expression that is essential for maintenance of CSCs, indicates that HDAC11 is a potential target to combat NSCLC.

Kinematic analysis of wrist motion during simulated colonoscopy in first-year gastroenterology fellows.

Background And Study Aims: Gastroenterology trainees acquire skill and proficiency in performing colonoscopies at different rates. The cause for heterogeneous competency among the trainees is unclear. Kinematic analysis of the wrist joint while performing colonoscopy can objectively assess the variation in wrist motion.

Characterization of right wrist posture during simulated colonoscopy: an application of kinematic analysis to the study of endoscopic maneuvers.

Background: Endoscopic maneuvers are associated with a high incidence of musculoskeletal injuries.

Objective: To quantify wrist motion patterns during simulated endoscopic procedures to identify potential causes of endoscopy-related overuse injury.

Design: Twelve endoscopists with different levels of experience were tested on 2 simulated endoscopic procedures that differed in their level of difficulty.

Age-Based Differences in Care Setting Transitions over the Last Year of Life.

Context. Little is known about the number and types of moves made in the last year of life to obtain healthcare and end-of-life support, with older adults more vulnerable to care setting transition issues. Research Objective.