Point-of-care AI-enhanced novice echocardiography for screening heart failure (PANES-HF).

The increasing prevalence of heart failure (HF) in ageing populations drives demand for echocardiography (echo). There is a worldwide shortage of trained sonographers and long waiting times for expert echo. We hypothesised that artificial intelligence (AI)-enhanced point-of-care echo can enable HF screening by novices. The primary endpoint was the accuracy of AI-enhanced novice pathway in detecting reduced LV ejection fraction (LVEF) < 50%. Symptomatic patients with suspected HF (N = 100, mean age 61 ± 15 years, 56% men) were prospectively recruited. Novices with no prior echo experience underwent 2-weeks' training to acquire echo images with AI guidance using the EchoNous Kosmos handheld echo, with AI-automated reporting by Us2.ai (AI-enhanced novice pathway). All patients also had standard echo by trained sonographers interpreted by cardiologists (reference standard). LVEF < 50% by reference standard was present in 27 patients. AI-enhanced novice pathway yielded interpretable results in 96 patients and took a mean of 12 min 51 s per study. The area under the curve (AUC) of the AI novice pathway was 0.880 (95% CI 0.802, 0.958). The sensitivity, specificity, positive predictive and negative predictive values of the AI-enhanced novice pathway in detecting LVEF < 50% were 84.6%, 91.4%, 78.5% and 94.1% respectively. The median absolute deviation of the AI-novice pathway LVEF from the reference standard LVEF was 6.03%. AI-enhanced novice pathway holds potential to task shift echo beyond tertiary centres and improve the HF diagnostic workflow.

Increased double strand breaks in diabetic ß-cells with a p21 response that limits apoptosis.

DNA damage and DNA damage response (DDR) pathways in ß-cells have received little attention especially in the context of type-2 diabetes. We postulate that p21 plays a key role in DDR by preventing apoptosis, associated through its overexpression triggered by DNA stand breaks (DSBs). Our results show that ß-cells from chronic diabetic mice had a greater extent of DSBs as compared to their non-diabetic counterparts. Comet assays and nuclear presence of γH2AX and 53bp1 revealed increased DNA DSBs in 16 weeks old (wo) db/db ß-cells as compared to age matched non-diabetic ß-cells. Our study of gene expression changes in MIN6 cell line with doxorubicin (Dox) induced DNA damage, showed that the DDR was similar to primary ß-cells from diabetic mice. There was significant overexpression of DDR genes, gadd45a and p21 after a 24-hr treatment. Western blot analysis revealed increased cleaved caspase3 over time, suggesting higher frequency of apoptosis due to Dox-induced DNA strand breaks. Inhibition of p21 by pharmacological inhibitor UC2288 under DNA damage conditions (both in Dox-induced MIN6 cells and older db/db islets) significantly increased the incidence of ß-cell apoptosis. Our studies confirmed that while DNA damage, specifically DSBs, induced p21 overexpression in ß-cells and triggered the p53/p21 cellular response, p21 inhibition exacerbated the frequency of apoptosis.