The impact of variance in carnitine palmitoyltransferase-1 expression on breast cancer prognosis is stratified by clinical and anthropometric factors.

CPT1A is a rate-limiting enzyme in fatty acid oxidation and is upregulated in high-risk breast cancer. Obesity and menopausal status' relationship with breast cancer prognosis is well established, but its connection with fatty acid metabolism is not. We utilized RNA sequencing data in the Xena Functional Genomics Explorer, to explore CPT1A's effect on breast cancer patients' survival probability. Using [18F]-fluorothymidine positron emission tomography-computed tomography images from The Cancer Imaging Archive, we segmented these analyses by obesity and menopausal status. In 1214 patients, higher CPT1A expression is associated with lower breast cancer survivability. We confirmed a previously observed protective relationship between obesity and breast cancer in pre-menopausal patients and supported this data using two-sided Pearson correlations. Taken together, these analyses using open-access databases bolster the potential role of CPT1A-dependent fatty acid metabolism as a pathogenic factor in breast cancer.

Multimodal analysis suggests differential immuno-metabolic crosstalk in lung squamous cell carcinoma and adenocarcinoma.

Immunometabolism within the tumor microenvironment is an appealing target for precision therapy approaches in lung cancer. Interestingly, obesity confers an improved response to immune checkpoint inhibition in non-small cell lung cancer (NSCLC), suggesting intriguing relationships between systemic metabolism and the immunometabolic environment in lung tumors. We hypothesized that visceral fat and 18F-Fluorodeoxyglucose uptake influenced the tumor immunometabolic environment and that these bidirectional relationships differ in NSCLC subtypes, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). By integrating 18F-FDG PET/CT imaging, bulk and single-cell RNA-sequencing, and histology, we observed that LUSC had a greater dependence on glucose than LUAD. In LUAD tumors with high glucose uptake, glutaminase was downregulated, suggesting a tradeoff between glucose and glutamine metabolism, while in LUSC tumors with high glucose uptake, genes related to fatty acid and amino acid metabolism were also increased. We found that tumor-infiltrating T cells had the highest expression of glutaminase, ribosomal protein 37, and cystathionine gamma-lyase in NSCLC, highlighting the metabolic flexibility of this cell type. Further, we demonstrate that visceral adiposity, but not body mass index (BMI), was positively associated with tumor glucose uptake in LUAD and that patients with high BMI had favorable prognostic transcriptional profiles, while tumors of patients with high visceral fat had poor prognostic gene expression. We posit that metabolic adjunct therapy may be more successful in LUSC rather than LUAD due to LUAD's metabolic flexibility and that visceral adiposity, not BMI alone, should be considered when developing precision medicine approaches for the treatment of NSCLC.

A Vaccination Simulator for COVID-19: Effective and Sterilizing Immunization Cases.

In this work, we present a particle-based SEIR epidemic simulator as a tool to assess the impact of different vaccination strategies on viral propagation and to model sterilizing and effective immunization outcomes. The simulator includes modules to support contact tracing of the interactions amongst individuals and epidemiological testing of the general population. The particles are distinguished by age to represent more accurately the infection and mortality rates. The tool can be calibrated by region of interest and for different vaccination strategies to enable locality-sensitive virus mitigation policy measures and resource allocation. Moreover, the vaccination policy can be simulated based on the prioritization of certain age groups or randomly vaccinating individuals across all age groups. The results based on the experience of the province of Lecco, Italy, indicate that the simulator can evaluate vaccination strategies in a way that incorporates local circumstances of viral propagation and demographic susceptibilities. Further, the simulator accounts for modeling the distinction between sterilizing immunization, where immunized people are no longer contagious, and effective immunization, where the individuals can transmit the virus even after getting immunized. The parametric simulation results showed that the sterilizing-age-based vaccination scenario results in the least number of deaths. Furthermore, it revealed that older people should be vaccinated first to decrease the overall mortality rate. Also, the results showed that as the vaccination rate increases, the mortality rate between the scenarios shrinks.