Gary M.

The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeric antigen receptors.

Therapeutic T cells engineered to recognize tumour antigens are frequently short-lived and acquire unfavourable phenotypes in tumours. Here authors show that a tandem approach using autologous T cells targeted against the tumour antigen NY-ESO-1, followed by transfer of hematopoietic stem cells with the same specificity in the clinical trial NCT03240861, provides a safe and promising therapeutic option.

Zhang, Ma et al. report that ROS-activated O-GlcNAc transferase promotes FOXK2 O-GlcNAcylation and nuclear translocation to upregulate SLC7A11 expression, thereby modulating ferroptosis sensitivity, tumour development and chemoradiotherapy efficacy.

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Background/Objectives: Liver fibrosis, if left untreated, can lead to cirrhosis and cancer. The current standard liver biopsy for fibrosis staging is invasive and prone to risks of complication. The objective of this study was to develop a new noninvasive method to quantify fibrosis using diamagnetic susceptibility sources generated from multi-echo gradient echo (mGRE) data with both magnitude decay R2* modeling and phase QSM modeling. Methods: mGRE data of ex vivo liver explants was processed with fat–water separation and then susceptibility source separation. Negative susceptibility was used to measure diamagnetic fibrosis. In 20 formalin-fixed liver explant sections, negative susceptibility maps were compared with other MRI parameters against pathology for fibrosis staging. Results: The correlation between the negative susceptibility sources and the fibrosis stages was evaluated with Spearman coefficients. Negative susceptibility differentiated (i) no or mild fibrosis (stages F0 to F1) from moderate-to-advanced fibrosis (stages F2 to F3; p = 0.0025), (ii) stages F2 to F3 from cirrhosis (stage F4; p = 0.021), and (iii) no-to-moderate fibrosis (stages F0 to F2) from advanced fibrosis or cirrhosis (stages F3 to F4) with a sensitivity of 90%, a specificity of 90%, and a 0.88 Receiver Operating Characteristic Area Under the Curve (AUC) (p = 0.0017). Conclusions: For staging fibrosis, negative susceptibility was superior to other MRI parameters, including R2*, QSM, and PDFF. Negative susceptibility sources were positively correlated with the fibrosis stage (r = 0.60). Negative susceptibility could be valuable for MRI staging in liver fibrosis.

Birth defects are a leading cause of infant mortality and an important contributor to childhood and adult morbidity. Major structural birth defects are diagnosed in 2 to 4% of infants in the United States. Environmental contaminants, including air pollution, have been suggested as potential risk factors for these anomalies. This study investigates the association between wildfire smoke exposure, specifically fine particulate matter (PM2.5), and the risk of selected structural birth defects in the San Joaquin Valley of California. Data were collected from participants in the California Center of the National Birth Defects Prevention Study and the Birth Defects Study to Evaluate Pregnancy exposureS from 2000 to 2018. The study included 3005 participants, comprising livebirths, stillbirths, and pregnancy terminations. Wildfire smoke exposure was assessed using two estimates: fire density PM2.5 and fire increment PM2.5. Logistic regression was used to analyze the odds of 14 birth defects in relation to quartile-based exposure metrics during the first 8 weeks of pregnancy, adjusting for relevant covariates. Increased risk for several birth defects was observed with higher quartiles of wildfire smoke exposure. Notably, the third quartile of average fire density PM2.5 was associated with increased odds of cleft lip (OR = 2.29; 95% CI: 1.12, 4.69), and the highest quartile of maximum fire density PM2.5 was associated with increased risk of coarctation of the aorta (OR = 2.26; 95% CI: 1.02, 4.99). Spina bifida was consistently associated with higher exposure across multiple metrics, including a significant association with the highest quartile of maximum fire increment PM2.5 (OR = 2.76; 95% CI: 1.14, 6.66). Exposure to wildfire smoke during the first 8 weeks of pregnancy may contribute to the occurrence of certain structural birth defects in California’s San Joaquin Valley. These results highlight the need for further research to corroborate these findings and to understand the mechanisms underlying these associations.

Although the word finance is in the term microfinance, and the core elements of microfinance are those of the finance discipline, microfinance has yet to break into the mainstream or entrepreneurial finance literature. The purpose of this article is to introduce the finance academic community to the discipline of microfinance and microfinance institutions (MFIs). We provide a comprehensive review of over 350 articles and address the issues of MFI sustainability, products and services, management practices, clientele targeting, regulation and policy, and impact assessment.