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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer. Most patients present with advanced disease at diagnosis, which only permits palliative chemotherapeutic treatments. RNA dysregulation is a hallmark of most human cancers, including PDAC. To test the impact of RNA processing dysregulation on PDAC pathology, we performed a bioinformatics analysis to identify RNA-binding proteins (RBPs) associated with prognosis. Among the 12 RBPs associated with progression-free survival, we focused on MEX3A because it was recently shown to mark an intestinal stem cell population that is refractory to chemotherapeutic treatments, a typical feature of PDAC. Increased expression of MEX3A was correlated with higher disease stage in PDAC patients and with tumor development in a mouse model of PDAC. Depletion of MEX3A in PDAC cells enhanced sensitivity to chemotherapeutic treatment with gemcitabine, whereas its expression was increased in PDAC cells selected upon chronic exposure to the drug. RNA-sequencing analyses highlighted hundreds of genes whose expression is sensitive to MEX3A expression, with significant enrichment in cell cycle genes. MEX3A binds to its target mRNAs, like cyclin-dependent kinase 6 (CDK6), and promotes their stability. Accordingly, knockdown of MEX3A caused a significant reduction in PDAC cell proliferation and in progression to the S phase of the cell cycle. These findings uncover a novel role for MEX3A in the acquisition and maintenance of chemoresistance by PDAC cells, suggesting that it may represent a novel therapeutic target for PDAC.

The underlying mechanisms for linking Type D personality to cardiovascular stress reactivity remain unknown. The present study explored the possible mediating role of cognitive appraisals of stress and/or motivational levels involved in stress in the association between Type D personality and cardiovascular stress reactivity.

Cross-sectional.

Chinese version of Type D Scale-14 was administered to 154 undergraduate students who underwent psychosocial stress during which the physiological data were continuously monitored, and cognitive appraisals indexed by a ratio of perceived stress demands to perceived personal resources and motivational levels engaged in stress indexed by self-reported stress task engagement were immediately assessed after the stress exposure.

Results indicated that Type D personality was related to blunted HR, SBP, and DBP reactivity to stress. Self-reported stress task engagement mediated the relation between Type D personality and blunted cardiovascular stress reactivity. The mediation effect of cognitive appraisals on this link was non-significant.

These findings suggest that motivational disengagement in the psychosocial stress task might be an important pathway linking Type D personality to blunted cardiovascular stress reactivity.

These findings suggest that motivational disengagement in the psychosocial stress task might be an important pathway linking Type D personality to blunted cardiovascular stress reactivity.

Liver stiffness measurements (LSM), commonly performed by transient elastography (TE) or two-dimensional shear wave elastography (2D-SWE), are used to quantify liver fibrosis. Active hepatitis, a hallmark of autoimmune hepatitis (AIH), could bias LSM. This bias might be overcome by measurement spleen 2D-SWE. Here, we compare liver and spleen 2D-SWE to TE and liver biopsy (LB) in prospectively recruited patients with AIH.

We analysed liver and spleen 2D-SWE in relation to liver TE in 90 patients treated≥6months for AIH. Liver and spleen 2D-SWE were also compared to LB in 63 individuals with AIH. Finally, we evaluated these tools in 220 patients with AIH and during 18months follow-up.

Liver 2D-SWE correlated with surrogate markers of active hepatitis (ALT and IgG, both P<.001) but there was no link between spleen 2D-SWE and ALT. Liver 2D-SWE, but not spleen 2D-SWE, was associated with histopathological inflammatory score (P<.01). When compared to LB, the optimal cut-offs for detecting cirrhosis by liver and spleen 2D-SWE were 16.1kPa (AUROC 0.93) and 29.8kPa (AUROC 0.95), respectively. In patients with active hepatitis the combined diagnostic approach including liver and spleen 2D-SWE had significantly better AUROC for detecting cirrhosis than liver 2D-SWE alone.

Liver and spleen 2D-SWE are reliable complementary methods for the diagnosis of advanced fibrosis in AIH. Spleen 2D-SWE seems to be less biased by inflammation and could facilitate fibrosis assessment in therapy-naïve patients or in the presence of active hepatitis.

Liver and spleen 2D-SWE are reliable complementary methods for the diagnosis of advanced fibrosis in AIH. AP20187 2D-SWE seems to be less biased by inflammation and could facilitate fibrosis assessment in therapy-naïve patients or in the presence of active hepatitis.This study explored the characteristics associated with the use of self-care products and practices by people rehabilitating from stroke. A cross-sectional sub-study of the Sax Institute's 45 and Up Study in which 1300 participants who had indicated a doctor had diagnosed them as having had a stroke were mailed a sub-study survey. The survey instrument included questionnaire items on demographics, self-care products and practices, health status and stroke status. The survey was completed by 576 (44.3%) of those eligible. #link# At least one self-care product or practice was used by 39.9% of participants. Female participants were more likely than males to use self-care products (P ≤ .001) and self-care practices (P = .021). Self-care product use was higher amongst those with higher levels of fatigue (OR = 1.07) and/or those reporting slight (OR = 2.05) or moderate disability (OR = 2.28), compared with those who had no symptoms at all. As the burden of stroke survivorship increases because of improved acute stroke care in an ageing population, a stronger focus is needed by researchers, clinicians and policy makers on the self-care strategies used by stroke survivors and the ability for health professionals to appropriately support stroke survivors' in their rehabilitation and long-term management.