Pan-cancer genomic analysis shows hemizygous PTEN loss tumors are associated with immune evasion and poor outcome.

In tumors, somatic mutations of the PTEN suppressor gene are associated with advanced disease, chemotherapy resistance, and poor survival. PTEN loss of function may occur by inactivating mutation, by deletion, either affecting one copy (hemizygous loss) leading to reduced gene expression or loss of both copies (homozygous) with expression absent. Various murine models have shown that minor reductions in PTEN protein levels strongly influence tumorigenesis. Most PTEN biomarker assays dichotomize PTEN (i.e. presence vs. absence) ignoring the role of one copy loss. We performed a PTEN copy number analysis of 9793 TCGA cases from 30 different tumor types. There were 419 (4.28%) homozygous and 2484 (25.37%) hemizygous PTEN losses. Hemizygous deletions led to reduced PTEN gene expression, accompanied by increased levels of instability and aneuploidy across tumor genomes. Outcome analysis of the pan-cancer cohort showed that losing one copy of PTEN reduced survival to comparable levels as complete loss, and was associated with transcriptomic changes controlling immune response and the tumor microenvironment. Immune cell abundances were significantly altered for PTEN loss, with changes in head and neck, cervix, stomach, prostate, brain, and colon more evident in hemizygous loss tumors. These data suggest that reduced expression of PTEN in tumors with hemizygous loss leads to tumor progression and influences anticancer immune response pathways.

Sexual dimorphism in Kinosternon scorpioides (Linnaeus, 1766) from the Brazilian Amazon.

The sexual dimorphism of the Kinosternon scorpioides was evaluated using two different techniques (linear and geometric morphometry) from images and linear measurements of the carapace and plastron of adults (male and female). Linear morphometry indicated that the height and width of carapace and plastron are statistically different between sexes, with females being wider and taller. In the evaluation of geometric morphometry, ANOVA demonstrated variation in the size of the plastron and the shape of the carapace and plastron, expressing a tendency in shape for each sex. Sexual dimorphism, therefore, is verified for this species, notably by the plastron. This study indicates an additional tool for the phenotypic knowledge of animals, contributing to the study of threatened populations.

Role of Proteolytic Enzyme Inhibitors on Carious and Eroded Dentin Associated With a Universal Bonding System.

OBJECTIVES: The aim of this study was to evaluate the effect of proteolytic inhibitors on the bond strength of a universal adhesive system (etch-and-rinse mode) applied to artificial carious and eroded dentin. METHODS: Ninety molars were prepared and randomly divided into three groups according to the substrate: N, no challenges; ACD, artificial carious dentin simulation and ERO, artificial erosion simulation with orange juice. All groups were redivided into three subgroups according to the dentin pretreatment: W, water; CHX, 2% digluconate chlorhexidine; and E-64 (trans-epoxysuccinyl-L-leucylamido-[4-guanidino] butane), 5 µM E-64 inhibitor. They constituted a total of nine groups (n=10): N-W, N-CHX, N-E64, ACD-W, ACD-CHX, ACD-E64, ERO-W, ERO-CHX, and ERO-E64. All specimens were restored with Adper Single Bond Universal/Filtek Z250. Beams (0.64 mm2) were obtained and subjected to the microtensile test (µTBS) in a universal testing machine at 0.5 mm/min. The failure mode of the interfaces was determined by optical microscopy (40× magnification). Data were statistically analyzed by three-way analysis of variance and Tukey tests (p<0.05). RESULTS: All individual factors (p<0.0001) and the interaction between substrate and treatment (p=0.0011) and between substrate and time (p=0.0003) were statistically significant. The caries substrate contributed negatively to bond strength. Chlorhexidine reduced bond strength for normal and eroded conditions. Only the normal substrate was negatively affected by time despite the pretreatment. CONCLUSIONS: The universal bonding system appears to be a promising bonding strategy for the maintenance of bond strength to affected dentin. E-64 did not affect bonding to the dentin in contrast to the use of chlorhexidine, which, when associated with the universal system, did affect the microtensile bond strength for artificial carious dentin.

Childhood separation experiences and psycho-social status in primiparous women: preliminary findings.

In a group of British-born primiparous women, admission of a separation experience from parents in childhood was found to be associated with unmarried status, teenage pregnancy, having had psychiatric treatment, housing problems and a high score on a 'Malaise' inventory. Within the separated group the unmarried and teenage status were associated only with separations occurring in the context of a disrupted childhood, but were not related to the age of the separations. The Malaise score, however, was raised both for disrupted separations and for those occurring below the age of 5. It is noted that the factors associated with the separation in the mothers are those which have been found to be more common in the mothers of children with behaviour disorders.