Prognostic and Immunological Roles of CES2 in Breast Cancer and Potential Application of CES2-Targeted Fluorescent Probe DDAB in Breast Surgery.

Purpose: The expression and function of CES2 in breast cancer (BRCA) has not been fully elucidated. The purpose of this study was to investigate its clinical significance in BRCA. Patients and Methods: Bioinformatics analysis tools and databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, SURVIVAL packages, STRING database, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene set variation analysis (GSVA), and Tumor Immunity Estimation Resource (TIMER), were utilized to measure the expression level and clarify the clinical significance of CES2 in BRCA. In addition, we verified the expression level of CES2 in BRCA at the cellular and tissue levels by Western blot, immunohistochemistry (IHC) and real-time fluorescence quantitative PCR assays. Furthermore, DDAB is the first reported near-infrared fluorescent probe that can be used to monitor CES2 in vivo. We applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time and verified its physicochemical properties and labeling sorting ability by CCK-8, cytofluorimetric imaging, flow cytometry fluorescence detection, and isolated human tumor tissue imaging assays. Results: The expression of CES2 was higher in normal tissues than that in BRCA tissues. Patients with lower CES2 expression in the BRCA T4 stage had a poorer prognosis. Finally, we applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time, which was demonstrated to have good cellular imaging performance with low biological toxicity in BRCA cells and ex vivo human breast tumor tissue models. Conclusion: CES2 can be considered a potential biomarker to predict the prognosis of breast cancer at stage T4 and might contribute to the development of immunological treatment strategies. Meanwhile, CES2 is able to distinguish between breast normal and tumor tissues, the CES2-targeting NIR fluorescent probe DDAB may have potential for surgical applications in BRCA.

Distracted driving behavior in patients with insomnia.

Insomnia is one of the most common sleep disorders and is characterized by a subjective perception of difficulty falling asleep. Drivers with insomnia are vulnerable to distraction and exhibit higher levels of risk while driving. This study investigated the effect of two sources of in-vehicle distractions on the driving performance of drivers with insomnia and good sleepers by analyzing different driving behavior measures. Twenty-one drivers with insomnia and twenty-one healthy volunteers were recruited to complete simulated driving dual tasks. The primary task required the participants to perform: (a) a lane-keeping task, and (b) a lane-change task. The secondary task required the participants to deal with: (a) baseline (non-task), (b) internal distraction task, and (c) external distraction task. The internal distraction task required participants to complete quantitative reasoning tasks, while the external distraction task was a 0-back test. The relationship between distracted driving ability and cognitive function was also investigated. The results demonstrate that for lane-keeping tasks, drivers with insomnia had significantly higher standard deviations (SD) for speed, throttle position, acceleration, and lateral position than healthy drivers under internal distraction, but the driving performance did not differ significantly between groups under internal distraction or baseline. In the lane-change task, drivers with insomnia had higher SDs for steering wheel angle, steer angular velocity, lateral acceleration, and lateral speed than healthy drivers under external distraction. Moreover, external distraction impaired driving behavior in the healthy group, while internal distraction impaired driving ability in both groups. Healthy drivers with cognitive impairment displayed impaired lane-keeping abilities under internal distractions and impaired lane-changing abilities under external distractions. Driving performance in the insomnia group was not significantly associated with cognitive function. The results demonstrate that insomnia and distraction impair driving ability, and driver performance is affected differently by the distraction source (internal or external). The driving ability of healthy drivers with decreased cognition was impaired, but not that of insomniacs.The findings of this study provide new insights for preventing and estimating the potential influence of distracted driving behavior in individuals with insomnia.

Fatigue performance in patients with chronic insomnia.

Insomnia is associated with fatigue and poor driving performance, thus increasing the risk of traffic accidents. This study aimed to evaluate the effect of fatigue on driving in patients with chronic insomnia in a free-flow traffic scenario and car-following scenario, and to investigate the relationships between driving performance, cognitive function, and insomnia. The Trail Making Test (TMT), Stroop Color and Word Test (SCWT), Symbol Digit Modalities Test (SDMT), and Digit Span Test (DST) of 15 participants with mild-to-moderate chronic insomnia and 16 healthy participants were assessed. During the fatigue driving task, drivers completed simulated driving tasks under free-flow traffic and car-following scenarios. The mean speed (MS), mean acceleration (MA), mean lateral position (MLP), and standard deviation of lateral position (SDLP) were measured to assess driving performance. During fatigued tasks, the MA and MLP in the free-driving scenario were higher than those in the car-following scenario (P < 0.01), the SDLP was higher in the insomnia group than in the healthy group (P = 0.02), and the interaction effect was significantly different for MLP between the groups (P = 0.03). MS was negatively correlated with TMT score, SDMT score, and DST score, and positively correlated with time to complete TMT, errors in SCWT, and time to complete SCWT. SDLP was negatively correlated with DST score and positively correlated with time to complete SCWT. Furthermore, the insomnia group had poorer lateral vehicle control ability than the healthy group. The insomnia group had a more impaired driving performance in the free-driving scenario than in the car-following scenario. Drivers with impaired cognitive function exhibited impaired driving performance.

Prognostic and Immune Implications of a Novel Pyroptosis-Related Five-Gene Signature in Breast Cancer.

Background: Breast cancer (BC) is the most common cancer among women worldwide, with enormous heterogeneity. Pyroptosis has a significant impact on the development and progression of tumors. Nonetheless, the possible correlation between pyroptosis-related genes (PRGs) and the BC immune microenvironment has yet to be investigated. Materials and methods: In The Cancer Genome Atlas Breast Cancer cohort, 38 PRGs were shown to be significantly different between malignant and non-malignant breast tissues. The 38 PRGs' consensus clustering grouped 1,089 individuals into two pyroptosis-related (PR) patterns. Using univariate and LASSO-Cox analyses, a PR five-gene predictive signature was constructed based on the differentially expressed genes between two clusters. The tools estimation of stromal and immune cells in malignant tumours using expression data (ESTIMATE), cell type identification by estimating relative subsets Of RNA transcripts (CIBERSORT), and single-sample gene set enrichment analysis (ssGSEA) were used to investigate the BC tumor microenvironment (TME). Results: In TME, the two PR clusters displayed distinct clinicopathological characteristics, survival outcomes, and immunocyte infiltration features. The developed five-signature model (SEMA3B, IGKC, KLRB1, BIRC3, and PSME2) classified BC patients into two risk groups based on the estimated median risk score. Patients in the low-scoring category had a higher chance of survival and more extensive immunocyte infiltration. An external validation set can yield similar results. Conclusion: Our data suggest that PRGs have a significant impact on the BC immunological microenvironment. The PR clusters and associated predictive signature stimulate additional research into pyroptosis in order to optimize therapeutic strategies for BC patients and their responses to immune therapy.

A novel treatment strategy of HER2-targeted therapy in combination with Everolimus for HR+/HER2- advanced breast cancer patients with HER2 mutations.

The incidence of HER2 somatic mutations in breast cancer is about 2-4%, mainly occurring in the HR+/HER2- subtype. Preclinical studies suggest that HER2 mutations can lead to constitutive HER2 activation, but effective treatment options for the clinical management of patients with HER2 mutations remain obscure. Our study analyzed HER2 mutation status by performing next-generation sequencing using tumor tissues and over 300 plasma samples from 72 metastatic breast cancer patients. We observed that two patients bearing HER2 mutations (Patient #1 bearing S310F and V777L mutations, Patient #2 bearing 778insGSP mutation) achieved a durable partial response to Trastuzumab combined with Everolimus. In vitro experiments showed that T47D and MCF7 cells overexpressing these HER2 mutants (S310F, V777L, 778insGSP and L755S) were sensitive to HER2-targeted therapies combined with the mTOR inhibitor Everolimus. These findings provide a treatment option for patients with HER2 mutations by combining HER2-targeted therapies with Everolimus.