Prognostic Value of an Inflammation-Related Index in 6,865 Chinese Patients With Postoperative Digestive Tract Cancers: The FIESTA Study

Objectives: We sought to determine the optimal cutting points for two inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), to assess their prognostic value in patients with postoperative digestive tract cancers overall and by cancer sites, and further to construct an inflammation-related index based on the two biomarkers and assess its predictive performance.Methods: Total 6,865 assessable patients with digestive tract cancers who underwent tumor resection were consecutively enrolled from Fujian Cancer Hospital between January 2000 and December 2010, including 2535/3012/1318 patients with esophageal/gastric/colorectal cancer. The latest follow-up (median: 44.9 months) ended in December 2015. Optimal cutting points were determined using survival tree analysis overall and by cancer sites.Results: Among all study patients, the optimal cutting points were 2.07 and 168.50 to define high and low NLR and PLR, respectively. High NLR (hazard ratio [HR]: 1.48, 95% confidence interval [CI]: 1.37–1.61) and high PLR (HR: 1.41, 95% CI: 1.29–1.53) were associated with a significantly increased risk for the mortality of digestive tract cancers as a whole. By cancer sites, effect-size estimates were comparable and statistically significant. Elevation over the selected optimal cutting points for both NLR and PLR was associated with 1.69-fold increased risk of cancer-specific mortality compared to patients with simultaneously low NLR and PLR among all study patients, and this association persisted by cancer sites, especially for gastric cancer.Conclusions: Our findings demonstrate that the preoperative integrated NLR and PLR, as an inflammation-related index, is a significant independent predictor for postoperative mortality in Chinese patients with digestive tract cancers both overall and by cancer sites

Quantification of ovarian lesion and fallopian tube vasculature using optical-resolution photoacoustic microscopy

The heterogeneity in the pathological and clinical manifestations of ovarian cancer is a major hurdle impeding early and accurate diagnosis. A host of imaging modalities, including Doppler ultrasound, MRI, and CT, have been investigated to improve the assessment of ovarian lesions. We hypothesized that pathologic conditions might affect the ovarian vasculature and that these changes might be detectable by optical-resolution photoacoustic microscopy (OR-PAM). In our previous work, we developed a benchtop OR-PAM and demonstrated it on a limited set of ovarian and fallopian tube specimens. In this study, we collected data from over 50 patients, supporting a more robust statistical analysis. We then developed an efficient custom analysis pipeline for characterizing the vascular features of the samples, including the mean vessel diameter, vascular density, global vascular directionality, local vascular definition, and local vascular tortuosity/branchedness. Phantom studies using carbon fibers showed that our algorithm was accurate within an acceptable error range. Between normal ovaries and normal fallopian tubes, we observed significant differences in five of six extracted vascular features. Further, we showed that distinct subsets of vascular features could distinguish normal ovaries from cystic, fibrous, and malignant ovarian lesions. In addition, a statistically significant difference was found in the mean vascular tortuosity/branchedness values of normal and abnormal tubes. The findings support the proposition that OR-PAM can help distinguish the severity of tubal and ovarian pathologies

Interaction Between Prediabetes and the ABO Blood Types in Predicting Postsurgical Esophageal Squamous Cell Carcinoma-Specific Mortality: The FIESTA Study

Background: We aimed to investigate the interaction between prediabetes and the ABO blood types in predicting esophageal squamous cell carcinoma (ESCC)-specific mortality by analysing data from the FIESTA study on normal/prediabetic patients with ESCC.Methods: Total 1,857 normal/prediabetic patients with ESCC who underwent three-field lymphadenectomy between January 2000 and December 2010 and survived hospitalization were analyzable, with follow-up beginning in 2000 and ending in 2015.Results: At the end of the follow-up, there were 1,161 survivors and 696 non-survivors. The follow-up time ranged from 0.5 to 180 months. The cumulative survival rates in normal patients were obviously better than in prediabetic patients. The cumulative survival rates were significantly higher in normal patients than in prediabetic patients for the blood types O and A (Log-rank test P < 0.05), while no significance was detected for the blood types B and AB. Adjusted risk estimates for ESCC-specific mortality for prediabetic patients relative to normal patients were statistically significant in the blood type B− group (hazard ratio [HR]: 1.71; 95% confidence interval [CI]: 1.33–2.20; P < 0.001), but not in the blood type B+ group (HR: 1.12; 95% CI: 0.77–1.64; P = 0.5544).Conclusions: Our findings indicate that prediabetes can predict the significant risk of ESCC-specific mortality in Chinese Han patients with the blood types O and A

GPX8 regulates pan-apoptosis in gliomas to promote microglial migration and mediate immunotherapy responses

IntroductionGliomas have emerged as the predominant brain tumor type in recent decades, yet the exploration of non-apoptotic cell death regulated by the pan-optosome complex, known as pan-apoptosis, remains largely unexplored in this context. This study aims to illuminate the molecular properties of pan-apoptosis-related genes in glioma patients, classifying them and developing a signature using machine learning techniques.MethodsThe prognostic significance, mutation features, immunological characteristics, and pharmaceutical prediction performance of this signature were comprehensively investigated. Furthermore, GPX8, a gene of interest, was extensively examined for its prognostic value, immunological characteristics, medication prediction performance, and immunotherapy prediction potential. ResultsExperimental techniques such as CCK-8, Transwell, and EdU investigations revealed that GPX8 acts as a tumor accelerator in gliomas. At the single-cell RNA sequencing level, GPX8 appeared to facilitate cell contact between tumor cells and macrophages, potentially enhancing microglial migration. ConclusionsThe incorporation of pan-apoptosis-related features shows promising potential for clinical applications in predicting tumor progression and advancing immunotherapeutic strategies. However, further in vitro and in vivo investigations are necessary to validate the tumorigenic and immunogenic processes associated with GPX8 in gliomas

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements