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High-risk human papillomaviruses (HR-HPVs) cause almost all cervical cancers and a significant number of vaginal, vulvar, penile, anal, and oropharyngeal cancers. HPV16 and 18 are the most prevalent types among HR-HPVs and together cause more than 70% of all cervical cancers. Low vaccination rate and lack of molecularly-targeted therapeutics for primary therapy have led to a slow reduction in cervical cancer incidence and high mortality rate. Hence, creating new models of HPV-induced cancer that can facilitate understanding of the disease mechanism and identification of key cellular targets of HPV oncogenes are important for development of new interventions. Here in this study, we used the tissue-specific expression technique, Gal4-UAS, to establish the first Drosophila model of HPV16-induced cancer. Using this technique, we expressed HPV16 oncogenes E5, E6, E7 and the human E3 ligase (hUBE3A) specifically in the epithelia of Drosophila eye, which allows simple phenotype scoring without affecting the viability of the organism. We found that, as in human cells, hUBE3A is essential for cellular abnormalities caused by HPV16 oncogenes in flies. Several proteins targeted for degradation by HPV16 oncoproteins in human cells were also reduced in the Drosophila epithelial cells. Cell polarity and adhesion were compromised, resulting in impaired epithelial integrity. Cells did not differentiate to the specific cell types of ommatidia, but instead were transformed into neuron-like cells. These cells extended axon-like structures to connect to each other and exhibited malignant behavior, migrating away to distant sites. Our findings suggest that given the high conservation of genes and signaling pathways between humans and flies, the Drosophila model of HPV16- induced cancer could serve as an excellent model for understanding the disease mechanism and discovery of novel molecularly-targeted therapeutics.

Decision-making is a fundamental aspect of human behavior, especially in uncertain situations where social interactions play a significant role. Social dominance, which involves power dynamics within groups, holds the potential to shape decision-making. Individuals’ expectations and certainty about outcomes are crucial for monitoring their performance in social dominance situations. However, the impact of expected and unexpected uncertainty on decision-making in social dominance contexts remains unclear. This study aimed to unravel the neural and behavioral patterns associated with decision-making across varying social dominance levels under conditions of uncertainty. Researchers investigated this by analyzing brain activity in 51 students. Participants were presented with both positive and negative feedback under conditions of both expectation and uncertainty, while their brain activity was recorded using electroencephalography (EEG). Specifically, we investigated the properties of key neural correlates of feedback processing, including feedback-related negativity (FRN), and P3 components of event-related potential (ERP), and reward prediction error (RPE) signals. The results revealed that the low-dominance group exhibited a larger FRN amplitude than the high-dominance group. Also, unexpected-uncertain negative feedback elicits a stronger FRN amplitude than other conditions. P3 amplitude was larger for high-dominance compared to low-dominance individuals. Additionally, P3 amplitude varied by feedback valence and condition, with larger amplitudes for positive feedback and unexpected-uncertain conditions. In FRN wave difference, the high-dominance individuals exhibited more negative amplitude in unexpected-uncertain conditions. This reveals distinct neural responses to uncertainty and feedback between individuals with high and low dominance, suggesting that social hierarchy modulates brain mechanisms underlying decision-making and reward processing.

Introduction The aim of this study was to evaluate the efficacy of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) scanning in the staging of oesophageal adenocarcinoma. Methods One hundred four patients with biopsy-proven adenocarcinoma underwent 18 F-FDG-PET scan. FDG avid lesions were further investigated to their diagnostic conclusion. Results Nineteen patients (18.26%) were found to have non-loco-regional FDG uptake. Of the patients, 3.84% were found to have M1 disease and 7.69% were found to have a second primary tumour. The sensitivity and specificity of FDG-PET scanning to detect metastatic disease in our series was 57.14% and 84.53%, respectively. The overall diagnostic accuracy was 82.69%. Conclusions PET scanning improves staging and prevents unnecessary surgery in patients with M1 disease. It represents a good adjunct to computed tomography scanning and endoscopic ultrasound in the staging of oesophageal adenocarcinoma. The detection of asymptomatic coexisting synchronous cancers is an added benefit provided by PET scanning over similar diagnostic modalities.