Chromatin remodelling and DNA repair genes are frequently mutated in endometrioid endometrial carcinoma

In developed countries, endometrial carcinoma is the most common cancer that affects the female genital tract. Endometrial carcinoma is divided into two main histological types, type I or endometrioid and type II or non‐endometrioid, each of which have characteristic, although not exclusive, molecular alterations and mutational profiles. Nevertheless, information about the implication and relevance of some of these genes in this disease is lacking. We sought here to identify new recurrently mutated genes in endometrioid cancers that play a role in tumourigenesis and that influence the clinical outcome. We focused on low‐grade, non‐ultramutated tumours as these tumours have a worse prognosis than the ultramutated POLE‐positive endometrioid endometrial carcinomas (EECs). We performed exome‐sequencing of 11 EECs with matched normal tissue and subsequently validated 15 candidate genes in 76 samples. For the first time, we show that mutations in chromatin remodelling‐related genes (KMT2D, KMT2C, SETD1B and BCOR) and in DNA‐repair‐related genes (BRCA1, BRCA2, RAD50 and CHD4) are frequent in this subtype of endometrial cancer. The alterations to these genes occurred with frequencies ranging from 35.5% for KMT2D to 10.5% for BRCA1 and BCOR, with some showing a tendency toward co‐occurrence (RAD50‐KMT2D and RAD50‐SETD1B). All these genes harboured specific mutational hotspots. In addition, the mutational status of KMT2C, KMT2D and SETD1B helps to predict the degree of myometrial invasion, a critical prognostic feature. These results highlight the possible implication of these genes in this disease, creating opportunities for new therapeutic approaches.     

Bone‐induced c‐kit expression in prostate cancer: A driver of intraosseous tumor growth

Loss of BRCA2 function stimulates prostate cancer (PCa) cell invasion and is associated with more aggressive and metastatic tumors in PCa patients. Concurrently, the receptor tyrosine kinase c‐kit is highly expressed in skeletal metastases of PCa patients and induced in PCa cells placed into the bone microenvironment in experimental models. However, the precise requirement of c‐kit for intraosseous growth of PCa and its relation to BRCA2 expression remain unexplored. Here, we show that c‐kit expression promotes migration and invasion of PCa cells. Alongside, we found that c‐kit expression in PCa cells parallels BRCA2 downregulation. Gene rescue experiments with human BRCA2 transgene in c‐kit‐transfected PCa cells resulted in reduction of c‐kit protein expression and migration and invasion, suggesting a functional significance of BRCA2 downregulation by c‐kit. The inverse association between c‐kit and BRCA2 gene expressions in PCa cells was confirmed using laser capture microdissection in experimental intraosseous tumors and bone metastases of PCa patients. Inhibition of bone‐induced c‐kit expression in PCa cells transduced with lentiviral short hairpin RNA reduced intraosseous tumor incidence and growth. Overall, our results provide evidence of a novel pathway that links bone‐induced c‐kit expression in PCa cells to BRCA2 downregulation and supports bone metastasis.     

Advanced Biofuels from ABE (Acetone/Butanol/Ethanol) and Vegetable Oils (Castor or Sunflower Oil) for Using in Triple Blends with Diesel: Evaluation on a Diesel Engine

From a technical and economic point of view, our aim is to provide viable solutions for the replacement of fossil fuels which are currently used in internal combustion diesel engines. In this research, two new biofuels composed of second-generation vegetable oils (SVO),used oil sunflower (SO) or castor oil (CO), and the ABE blend (acetone/butanol/ethanol) were evaluated. ABE is an intermediate product from the fermentation of carbohydrates to obtain bio-butanol. Besides, the ABE blend exhibits suitable properties as biofuel, such asvery low kinematic viscosity, reasonable energy density, low autoignition temperature, and broad flammability limits. Diesel/ABE/SVO triple blends were prepared, characterized and then, tested on a diesel engine, evaluating power output, consumption, and exhaust emissions. The power output was slightly reduced due to the low heating values of ABE blend. Also, engine consumed more fuel with the triple blends than with diesel under low engine loads whereas, at medium and high loads, the fuel consumption was very similar to that of diesel. Regarding exhaust gas emissions, soot wasnotably reduced, and nitrogen oxides (NO_x) and carbon monoxide (CO₂) emissions were lower or comparable to that of diesel, while the CO emissions increased. The use of these biofuels allows the replacement of high percentagesof diesel without compromising engine power and achievinga significant reduction in pollution emissions. Furthermore, a notable improvement in cold flow properties of the fuel blends is obtained, in comparison with diesel.     

Excessive Dental Bleaching with 22% Carbamide Peroxide Combined with Erosive and Abrasive Challenges: New Insights into the Morphology and Surface Properties of Enamel

This study aimed to evaluate the effects of 22% carbamide peroxide combined with an erosive challenge and simulated brushing on enamel. Bovine incisor teeth were divided into G1, tooth bleaching; G2, tooth bleaching + erosive challenge; and G3, tooth bleaching + erosive challenge + simulated brushing, and evaluated at T0, before any intervention; T1, 14 days after the proposed treatments; and T2, 28 days after the proposed treatments. Tooth bleaching was performed daily for 1 h for 28 days. The microhardness, surface roughness, mass variation, and ultrastructure were analyzed at T0, T1, and T2. Two-way analysis of variance for repeated measures was performed and Tukey’s post hoc test (α = 5%) was used. The surface roughness increased in groups G2 and G3 as a function of time, whereas microhardness and mass measurements demonstrated a significant reduction for groups associated with challenges. Ultrastructural evaluation indicated a loss of the aprismatic layer and exposure of the enamel prisms in all groups after 14 days of bleaching, with more pronounced results in G2 and G3 after 28 days. In conclusion, abrasive and erosive challenges potentiated the deleterious effects of tooth whitening on microhardness, ultramorphology, and mass, without affecting the roughness of dental enamel.     

Vaccination Decreases the Infectious Viral Load of Delta Variant SARS-CoV-2 in Asymptomatic Patients

The Delta variant of SARS-CoV-2 has caused many breakthrough infections in fully vaccinated individuals. While vaccine status did not generally impact the number of viral RNA genome copies in nasopharyngeal swabs of breakthrough patients, as measured by Ct values, it has been previously found to decrease the infectious viral load in symptomatic patients. We quantified the viral RNA, infectious virus, and anti-spike IgA in nasopharyngeal swabs collected from individuals asymptomatically infected with the Delta variant of SARS-CoV-2. Vaccination decreased the infectious viral load, but not the amount of viral RNA. Furthermore, vaccinees with asymptomatic infections had significantly higher levels of anti-spike IgA in their nasal secretions compared to unvaccinated individuals with asymptomatic infections. Thus, vaccination may decrease the transmission risk of Delta, and perhaps other variants, despite not affecting the amount of viral RNA measured in nasopharyngeal swabs.     

COVID-19 mRNA vaccine effectiveness (second and first booster dose) against hospitalisation and death during Omicron BA.5 circulation: cohort study based on electronic health records,Portugal, May to July 2022

We measured vaccine effectiveness (VE) against COVID-19-related severe outcomes in elderly people in Portugal between May and July 2022. In ≥ 80 year-olds, the second booster dose VE was 81% (95% CI: 75–85) and 82% (95% CI: 77–85), respectively, against COVID-19-related hospitalisation and death. The first booster dose VE was 63% (95% CI: 55–70) in ≥ 80 year-olds and 74% (95% CI: 66–80) in 60–79 year-olds against hospitalisation, and 63% (95% CI: 57–69) and 65% (95% CI: 54–74) against death.