NUAK2 Inhibitors, KHKI-01128 and KHKI-01215, Exhibit Potent Anticancer Activity Against SW480 Colorectal Cancer Cells.

BACKGROUND/AIM: NUAK family kinase 2 (NUAK2) is a promising target for cancer therapeutics due to its reported role in protein phosphorylation, a critical process in cancer cell survival, proliferation, invasion, and senescence. This study aimed to identify novel inhibitors that disrupt NUAK2 activity. We have already identified two KRICT Hippo kinase inhibitor (KHKI) compounds, such as KHKI-01128 and KHKI-01215. Our aim was to evaluate the impact of KHKI-01128 and KHKI-01215 on NUAK2 activity and elucidate its mechanism in colorectal cancer cells. MATERIALS AND METHODS: To evaluate anticancer properties of these inhibitors, four in vitro assays in the SW480 cell line (time-resolved fluorescence resonance energy transfer assay, KINOMEscan kinase profiling, viability, and apoptosis assays) and two pharmacological mechanism analyses (Gene Set Enrichment Analysis and western blotting) were performed. RESULTS: KHKI-01128 and KHKI-01215 exhibited potent inhibitory activity against NUAK2 (half-maximal inhibitory concentration=0.024±0.015 µM and 0.052±0.011 µM, respectively). These inhibitors suppressed cell proliferation, with half-maximal inhibitory concentrations of 1.26±0.17 µM and 3.16±0.30 µM, respectively, and induced apoptosis of SW480 cells. Gene Set Enrichment Analysis revealed negative enrichment scores of -0.84 for KHKI-01128 (false-discovery rate=0.70) and 1.37 for KHKI-01215 (false-discovery rate=0.18), indicating that both effectively suppressed the expression of YES1-associated transcriptional regulator (YAP) target genes. CONCLUSION: These results suggest that KHKI-01128 and KHKI-01215 are potent NUAK2 inhibitors with promising potential for pharmaceutical applications.

A Randomized Trial of Behavioral Nudges Delivered Through Text Messages to Increase Influenza Vaccination Among Patients With an Upcoming Primary Care Visit.

PURPOSE: To evaluate if nudges delivered by text message prior to an upcoming primary care visit can increase influenza vaccination rates. DESIGN: Randomized, controlled trial. SETTING: Two health systems in the Northeastern US between September 2020 and March 2021. SUBJECTS: 74,811 adults. INTERVENTIONS: Patients in the 19 intervention arms received 1-2 text messages in the 3 days preceding their appointment that varied in their format, interactivity, and content. MEASURES: Influenza vaccination. ANALYSIS: Intention-to-treat. RESULTS: Participants had a mean (SD) age of 50.7 (16.2) years; 55.8% (41,771) were female, 70.6% (52,826) were White, and 19.0% (14,222) were Black. Among the interventions, 5 of 19 (26.3%) had a significantly greater vaccination rate than control. On average, the 19 interventions increased vaccination relative to control by 1.8 percentage points or 6.1% (P = .005). The top performing text message described the vaccine to the patient as "reserved for you" and led to a 3.1 percentage point increase (95% CI, 1.3 to 4.9; P < .001) in vaccination relative to control. Three of the top five performing messages described the vaccine as "reserved for you." None of the interventions performed worse than control. CONCLUSIONS: Text messages encouraging vaccination and delivered prior to an upcoming appointment significantly increased influenza vaccination rates and could be a scalable approach to increase vaccination more broadly.

Preoperative risk factors in recurrent endometrioma after primary conservative surgery.

OBJECTIVE: Endometriosis is a common gynecological disorder caused by ectopic implantation of endometrial glandular and stromal cells outside the uterine cavity. Among several types of endometriosis, endometrioma is the only subtype that could be determined preoperatively using pelvic ultrasonography, and guidelines recommend pathologic confirmation of endometrioma greater than 3 cm in diameter. However, although surgery is performed in cases of endometrioma, endometrioma has a high cumulative rate of recurrence. Therefore, because determining the possibility of recurrence before performance of initial surgery is important, we examined preoperative factors associated with recurrent endometrioma. METHODS: This was a retrospective, comparative study including 236 patients who visited the outpatient clinic between January 2009 and December 2011. Patients who were pathologically diagnosed with endometrioma were included in this study. They were followed up postoperatively and were divided into two groups according to presence of recurrent endometrioma. RESULTS: We examined associations between baseline factors and recurrent endometrioma. In multivariate analysis, dysmenorrhea and cyst septation were statistically significant after adjusting with age, parity, surgical staging and postoperative management. We examined cumulative recurrence free survival within cases of recurrent endometriosis, based on the presence of inner cyst septation. The cumulative recurrence free survival was lower in cases with septation. CONCLUSION: Our study found that recurrent endometrioma is more likely in patients with inner cyst septation and the recurrence occurred within a shorter duration of time than in patients without inner cyst septation on preoperative ultrasonography. Therefore intensive caution and postoperative long term medical therapy would be appropriate in patients with inner cyst septation on preoperative ultrasonography before undergoing primary surgery for endometrioma.