Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution.

Somatic L1 retrotransposition events have been shown to occur in epithelial cancers. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), we studied different stages of four colorectal cancers arising from colonic polyps, seven pancreatic carcinomas, as well as seven gastric cancers. Surprisingly, we found somatic L1 insertions not only in all cancer types and metastases but also in colonic adenomas, well-known cancer precursors. Some insertions were also present in low quantities in normal GI tissues, occasionally caught in the act of being clonally fixed in the adjacent tumors. Insertions in adenomas and cancers numbered in the hundreds, and many were present in multiple tumor sections, implying clonal distribution. Our results demonstrate that extensive somatic insertional mutagenesis occurs very early during the development of GI tumors, probably before dysplastic growth.

LINE-1 expression and retrotransposition in Barrett's esophagus and esophageal carcinoma.

Barrett's esophagus (BE) is a common disease in which the lining of the esophagus transitions from stratified squamous epithelium to metaplastic columnar epithelium that predisposes individuals to developing esophageal adenocarcinoma (EAC). We hypothesized that BE provides a unique environment for increased long-interspersed element 1 (LINE-1 or L1) retrotransposition. To this end, we evaluated 5 patients with benign BE, 5 patients with BE and concomitant EAC, and 10 additional patients with EAC to determine L1 activity in this progressive disease. After L1-seq, we confirmed 118 somatic insertions by PCR in 10 of 20 individuals. We observed clonal amplification of several insertions which appeared to originate in normal esophagus (NE) or BE and were later clonally expanded in BE or in EAC. Additionally, we observed evidence of clonality within the EAC cases; specifically, 22 of 25 EAC-only insertions were present identically in distinct regions available from the same tumor, suggesting that these insertions occurred in the founding tumor cell of these lesions. L1 proteins must be expressed for retrotransposition to occur; therefore, we evaluated the expression of open reading frame 1 protein (ORF1p), a protein encoded by L1, in eight of the EAC cases for which formalin-fixed paraffin embedded tissue was available. With immunohistochemistry, we detected ORF1p in all tumors evaluated. Interestingly, we also observed dim ORF1p immunoreactivity in histologically NE of all patients. In summary, our data show that somatic retrotransposition occurs early in many patients with BE and EAC and indicate that early events occurring even in histologically NE cells may be clonally expanded in esophageal adenocarcinogenesis.

Environmental, meteorological and pandemic restriction-related variables affecting SARS-CoV-2 cases.

Three years have passed since the outbreak of Coronavirus Disease 2019 (COVID-19) brought the world to standstill. In most countries, the restrictions have ended, and the immunity of the population has increased; however, the possibility of new dangerous variants emerging remains. Therefore, it is crucial to develop tools to study and forecast the dynamics of future pandemics. In this study, a generalized additive model (GAM) was developed to evaluate the impact of meteorological and environmental variables, along with pandemic-related restrictions, on the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Córdoba, Argentina. The results revealed that mean temperature and vegetation cover were the most significant predictors affecting SARS-CoV-2 cases, followed by government restriction phases, days of the week, and hours of sunlight. Although fine particulate matter (PM2.5) and NO2 were less related, they improved the model's predictive power, and a 1-day lag enhanced accuracy metrics. The models exhibited strong adjusted coefficients of determination (R2adj) but did not perform as well in terms of root-mean-square error (RMSE). This suggests that the number of cases may not be the primary variable for controlling the spread of the disease. Furthermore, the increase in positive cases related to policy interventions may indicate the presence of lockdown fatigue. This study highlights the potential of data science as a management tool for identifying crucial variables that influence epidemiological patterns and can be monitored to prevent an overload in the healthcare system.

Fracture Resistance Analysis of CAD/CAM Interim Fixed Prosthodontic Materials: PMMA, Graphene, Acetal Resin and Polysulfone.

The aim of this study was to evaluate and compare the fracture resistance of temporary restorations made of polymethylmethacrylate (PMMA), graphene-modified PMMA (GRA), acetal resin (AR) and polysulfone (PS) obtained by a subtractive technique (milling) using a computer-aided design and manufacturing (CAD/CAM) system of a three-unit fixed dental prosthesis (FDP). METHODS: Four groups of ten samples were fabricated for each material. Each specimen was characterized by a compression test on a universal testing machine, all specimens were loaded to fracture and the value in Newtons (N) was recorded by software connected to the testing machine. The fracture mode was evaluated on all samples using a stereomicroscope. RESULTS: There were statistically significant differences (p value < 0.005) between PMMA and the other three materials (PMMA: 1302.71 N; GRA: 1990.02 N; RA: 1796.20 N; PS: 2234.97). PMMA presented a significantly lower value than the other materials, and PS showed the highest value. GRA and RA presented a similar range of values but they were still higher than those of PMMA. CONCLUSIONS: GRA, RA and PS are presented as valid options within the range of interim milled restorative materials and as alternatives to PMMA.