Doylemcneill4264

Our study has identified a novel mechanism by which K-ras promotes PD-L1 expression, and suggests that modulation of ROS or inhibition of the FGFR1 pathway could be a novel strategy to abrogate PD-L1-mediated immunosuppression and thus potentially improve the efficacy of immunotherapy in K-ras-driven cancers.

Macrophages regulate the inflammatory response and affect re-endothelialization. Inflammation and macrophages play important roles in promoting tissue repair, but p38α mitogen-activated protein kinase's role in re-endothelialization is unknown.

Wire injuries of carotid arteries and Evans blue staining were performed in macrophage-specific p38α-knockout (p38α

LysMCre

) mice and control mice (p38α

). Re-endothelialization of the carotid arteries at 3, 5 and 7 days was significantly promoted in p38α

LysMCre

mice. In vitro experiments indicated that both the proliferation and migration of endothelial cells were enhanced in conditioned medium from peritoneal macrophages of p38α

LysMCre

mice. Interleukin-6 (IL-6) level was decreased significantly in macrophages of p38α

LysMCre

mice and an IL-6-neutralizing antibody promoted endothelial cell migration in vitro and re-endothelialization in p38α

mice in vivo. STM2457 cost Phosphoproteomics revealed that the phosphorylation level of S544/T545/S549 sites in megakaryocytic leukemia 1 (MKL1) was decreased in p38α

LysMCre

mice. The mutation of either S544/S549 or T545/S549 sites could reduce the expression of IL-6 and the inhibition of MKL1 reduced the expression of IL-6 in vitro and promoted re-endothelialization in vivo.

p38α in macrophages aggravates injury of arteries by phosphorylating MKL1, and increasing IL-6 expression after vascular injury.

p38α in macrophages aggravates injury of arteries by phosphorylating MKL1, and increasing IL-6 expression after vascular injury.

Body weight may be a modifiable risk factor predisposing to different cancers. To establish a potential impact of weight change on thyroid cancer risk, we conducted a meta-analysis to evaluate the effect of body mass index (BMI) and weight change over time as a risk of developing thyroid cancer (TC).

A systematic search was performed up to February 25, 2020. Pooled relative risk (RR) were estimated using fixed and random models. Heterogeneity between articles was examined using Q-test and I

index. Evaluation of publication bias was conducted with Egger's regression test.

A total of 31 studies including 24,489,477 cohorts were eligible. Pooled analysis revealed that normal and underweight cohorts were associated with a decreased risk of TC (RR=0.68, 95%CI=0.65-0.71, p<0.001) and (RR=0.92, 95%CI=0.91-0.93, p<0.001), respectively. In contrast, overweight and obese cohorts were more likely to develop TC (RR=1.26, 95%CI=1.24-1.28, p<0.001 and RR=1.50, 95%CI=1.45-1.55, p<0.001, respectively). Obesity was associated with higher risk of developing TC among women (RR=1.29, 95%CI=1.14-1.46, p<0.001), but not men (RR=1.25, 95%CI=0.97-1.62, p=0.08). Furthermore, weight gain increased the risk of developing TC (RR=1.18, 95%CI=1.14-1.22, p<0.001), while weight loss decreased the risk (RR=0.89, 95%CI=0.85-0.93, p<0.001). Results showed similar trends of weight change effect in both males and females.

Obesity is associated with higher risk of developing TC in women. However, maintaining a healthy weight is associated with reduced risk of TC in both women and men. Shifting our practice to include weight control strategies will help lead to cancer prevention.

Obesity is associated with higher risk of developing TC in women. However, maintaining a healthy weight is associated with reduced risk of TC in both women and men. Shifting our practice to include weight control strategies will help lead to cancer prevention.

The Asia Working Group for Sarcopenia 2019 (AWGS) recommended using the calf circumference (CC) cut-off values to facilitate the case-finding of sarcopenia. However, the validity of the proposed cut-offs has not been examined in older patients with stroke. This study investigated the validity of the AWGS-recommended CC cut-off values for identifying sarcopenia among older patients with stroke.

This cross-sectional study enrolled consecutive patients with stroke, aged 65 years and older, admitted to a convalescent rehabilitation ward. Sarcopenia was diagnosed based on the AWGS 2019 criteria. We drew a receiving operating characteristic curve to assess the ability of CC to predict sarcopenia diagnosis. Subsequently, we estimated the sensitivity, specificity, accuracy, F-value, and Matthews correlation coefficient (MCC) of the considered cut-off values.

We enrolled 256 patients (43 % women) (mean age, 76.6 ± 7.5 years). The prevalence of sarcopenia was 63.7 %. Among men who presented with CC < 34 cm (the AWGS-recommended cut-off value), sensitivity and specificity were 85 % and 66 %, respectively. Concurrently, estimates of accuracy, F-value, and MCC were the highest at cut-off value <34 cm. Among women, at <33 cm of the AWGS-recommended cut-off value, the sensitivity and specificity were 91 % and 28 %, respectively. At cut-off value <32 cm, sensitivity was maintained at 80 %, while specificity increased to 56 %; suggesting that this cut-off value might be a useful indicator for the case-finding of sarcopenia.

The AWGS-recommended CC cut-off values are valid. The predictive characteristics of sarcopenia differed among men and women with stroke.

The AWGS-recommended CC cut-off values are valid. The predictive characteristics of sarcopenia differed among men and women with stroke.

To examine whether co-existing social isolation and homebound status influence medical care utilization and expenditure in older adults.

Postal surveys on social isolation and homebound status were performed on older adults aged ≥65 years residing in a Japanese suburban city. Information on medical care utilization and expenditure was obtained from insurance claims data. These outcomes were examined over a three-year period (December 2008 to November 2011) for all participants (Analysis I, n = 1386) and during the last year of life for mortality cases (Analysis II, n = 107). A two-part model was used to analyze the influence of social isolation and homebound status on medical care utilization (first model logistic regression model) and its related expenditure (second model generalized linear model).

Almost 12 % of participants were both socially isolated and homebound. Analysis I showed that these participants were significantly less likely to use outpatient and home medical care than participants with neither characteristic (odds ratio 0.