Machine learning developed a CD8+ exhausted T cells signature for predicting prognosis, immune infiltration and drug sensitivity in ovarian cancer.

CD8+ exhausted T cells (CD8+ Tex) played a vital role in the progression and therapeutic response of cancer. However, few studies have fully clarified the characters of CD8+ Tex related genes in ovarian cancer (OC). The CD8+ Tex related prognostic signature (TRPS) was constructed with integrative machine learning procedure including 10 methods using TCGA, GSE14764, GSE26193, GSE26712, GSE63885 and GSE140082 dataset. Several immunotherapy benefits indicators, including Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore (IPS), TMB score and tumor escape score, were used to explore performance of TRPS in predicting immunotherapy benefits of OC. The TRPS constructed by Enet (alpha = 0.3) method acted as an independent risk factor for OC and showed stable and powerful performance in predicting clinical outcome of patients. The C-index of the TRPS was higher than that of tumor grade, clinical stage, and many developed signatures. Low TRPS score indicated a higher level of CD8+ T cell, B cell, macrophage M1, and NK cells, representing a relative immunoactivated ecosystem in OC. OC patients with low risk score had a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score, suggesting a better immunotherapy response. Moreover, higher TRPS score indicated a higher score of cancer-related hallmarks, including angiogenesis, EMT, hypoxia, glycolysis, and notch signaling. Vitro experiment showed that ARL6IP5 was downregulated in OC tissues and inhibited tumor cell proliferation. The current study constructed a novel TRPS for OC, which could serve as an indicator for predicting the prognosis, immune infiltration and immunotherapy benefits for OC patients.

Finite Element Analysis of Stress Distributions for Mandibular Dental Implant-Supported Overdentures with Magnetic Attachments in Osteoporotic and Normal Bone.

PURPOSE: To compare the biomechanical responses of a normal mandible to an osteoporotic mandible with two-implant-supported magnetic attachments. MATERIALS AND METHODS: A 3D finite-element model of a two-implant-supported mandibular overdenture with magnetic attachments was developed, and normal and osteoporotic bone samples were prepared. Four types of load were applied to the overdenture in each model: 100 N vertical and oblique loads on the right first molar, and a 100 N vertical load on the right canine and incisors. Biomechanical behaviors of the peri-implant bone, implant, and mucosa were recorded. Maximum equivalent stresses and elastic strains were analyzed. RESULTS: Equivalent elastic strain in osteoporotic cortical and cancellous bone was 9% to 71% and was 142% and 207% greater than in normal cortical bone, respectively. Equivalent elastic strain in the first molar oblique loading condition was 101% to 190% greater than in the first molar vertical loading condition. CONCLUSIONS: Osteoporotic cancellous bone was weaker and less resistant to deformation than normal bone, and oblique loading was more harmful than vertical loading.

High Expression of E2F4 Is an Adverse Prognostic Factor and Related to Immune Infiltration in Oral Squamous Cell Carcinoma.

Background: We aimed to evaluate the prognostic value of E2F4 expression in oral squamous cell carcinoma (OSCC) and clarify its influence on immune cell infiltration and biological functions. Methods: The Cancer Genome Atlas (TCGA) database, the STRING database, and related online tools as well as single-sample gene set enrichment analysis (ssGSEA) were used for the analyses in our study. Results: The E2F4 expression was elevated in OSCC tumor tissue compared with paracancerous tissues. The high expression of E2F4 was closely related to the poorer overall survival, disease-free survival, and progression-free interval of OSCC. In addition, pathway enrichment analyses revealed that the top 49 genes most closely related to E2F4 were strongly associated with the cell cycle. E2F4-related proteins were closely related to the following KEGG pathways: cell cycle, cellular senescence, PI3K-Akt signaling pathway, Wnt signaling pathway, and notch signaling pathway. It was also demonstrated that the E2F4 expression was negatively correlated with immune purity and strongly related to immune cell infiltration in OSCC. Conclusions: E2F4 can be used as a novel biomarker for the diagnosis and prognosis of OSCC.

Finite element analysis of stress distributions in osteoporotic and normal mandibular dental implant-supported overdentures with magnetic attachments.

PURPOSE: To compare the biomechanical responses of a normal mandible to an osteoporotic mandible with two implant-supported magnetic attachments. MATERIALS AND METHODS: A 3D finite element model of a two-implant-supported mandibular overdenture with magnetic attachments was developed, and normal and osteoporotic bone samples were prepared. Four types of load were applied to the overdenture in each model: 100-N vertical and oblique loads on the right first molar, and 100-N vertical load on the right canine and the incisors. Biomechanical behaviors of the peri-implant bone, implant, and mucosa were recorded. Maximum equivalent stresses and elastic strains were analyzed. RESULTS: Equivalent elastic strain in osteoporotic cortical and cancellous bone was 9% to 71% and, respectively, 142% and 207% greater than in normal cortical bone. Equivalent elastic strain in the first molar oblique loading condition was 101% to 190% greater than in the first molar vertical loading condition. CONCLUSION: Osteoporotic cancellous bone was weaker and less resistant to deformation than normal bone, and oblique loading was more harmful than vertical loading.