Genome-wide analysis of gene expression and alternative splicing in human medulloblastoma

Medulloblastoma is a malignant embryonal tumour of the cerebellum which most commonly affects children. A subset of tumours is thought to arise from cerebellar granule cell precursors (GCPs) that fail to undergo normal neuronal development, following the hyper-activation of the Sonic hedgehog (Shh) signalling pathway. To identify candidate genes that might be important for medulloblastoma pathogenesis, I investigated patterns of gene expression and alternative splicing in 14 paediatric medulloblastoma and five normal cerebellar samples using Affymetrix Human Exon arrays. Statistical analysis of the gene expression data identified a group of medulloblastomas with a molecular signature of Shh pathway activation. These tumours showed higher expression levels of genes involved in spindle formation, cytokines, and cell cycle regulation. Further studies using an in vitro mouse GCP cell culture model, in which Shh is necessary for the maintenance of the progenitor state, showed that a selection of candidate genes was also over-expressed when GCPs were cultured in the presence of Shh, as compared to control cells, as well as in human medulloblastoma cell lines. Ongoing and future in vitro experiments will investigate the potential role of candidate genes in sustaining the growth of precursor and tumour cells. Exon-level analysis of gene expression showed that abnormal expression of different transcript variants is likely to occur in medulloblastoma. I selected several examples of differential exon usage and validated these using an independent set of normal and tumour specimens. Tumour-associated splicing alterations were highly consistent, enabling clear separation of normal and cancer samples and in some cases of different medulloblastoma molecular subgroups. Interestingly, Shh-treated GCPs recapitulated the splicing patterns observed in the tumour samples for six out of the eight genes analysed, suggesting that the preferential expression of specific transcript forms is regulated during normal cerebellar development. The possible relationship between inappropriate splicing and medulloblastoma pathogenesis will be the subject of future investigation

Does the ‘Mountain Pasture Product’ claim affect local cheese acceptability?

This paper aims to explore the impact of “mountain pasture product” information on the acceptability of local protected designation of origin (PDO) cheese produced from the raw milk of cows grazing in mountain pastures (P) or reared in valley floor stalls (S). A total of 156 consumers (55% males, mean age 41 years) were asked to evaluate their overall liking on a 9-point hedonic scale of four samples: Cheeses P and S were presented twice with different information about the origin of the milk (cows grazing on mountain pasture or reared in a valley floor stall). Demographics, consumer habits, and opinions on mountain pasture practice (MPP), attitudes towards sustainability, and food-related behaviours (i.e., diet, food waste production, organic food, and zero food miles products purchase) were recorded and used to segment consumers. The cheeses were all considered more than acceptable, even though they were found to be significantly different in colour and texture by instrumental analyses. In the whole consumer panel, the cheese P was preferred, while in consumer segments less attentive to product characteristics, this effect was not significant. External information had a strong effect: Overall liking was significantly higher in cheeses presented as “mountain pasture product”, both in the whole panel and in consumer segments with different attitudes (except for those with a low opinion of MPP

Radiomics in the characterization of lipid-poor adrenal adenomas at unenhanced CT: time to look beyond usual density metrics

Objectives: In this study, we developed a radiomic signature for the classification of benign lipid-poor adenomas, which may potentially help clinicians limit the number of unnecessary investigations in clinical practice. Indeterminate adrenal lesions of benign and malignant nature may exhibit different values of key radiomics features. Methods: Patients who had available histopathology reports and a non-contrast-enhanced CT scan were included in the study. Radiomics feature extraction was done after the adrenal lesions were contoured. The primary feature selection and prediction performance scores were calculated using the least absolute shrinkage and selection operator (LASSO). To eliminate redundancy, the best-performing features were further examined using the Pearson correlation coefficient, and new predictive models were created. Results: This investigation covered 50 lesions in 48 patients. After LASSO-based radiomics feature selection, the test dataset’s 30 iterations of logistic regression models produced an average performance of 0.72. The model with the best performance, made up of 13 radiomics features, had an AUC of 0.99 in the training phase and 1.00 in the test phase. The number of features was lowered to 5 after performing Pearson’s correlation to prevent overfitting. The final radiomic signature trained a number of machine learning classifiers, with an average AUC of 0.93. Conclusions: Including more radiomics features in the identification of adenomas may improve the accuracy of NECT and reduce the need for additional imaging procedures and clinical workup, according to this and other recent radiomics studies that have clear points of contact with current clinical practice. Clinical relevance statement: The study developed a radiomic signature using unenhanced CT scans for classifying lipid-poor adenomas, potentially reducing unnecessary investigations that scored a final accuracy of 93%. Key Points: • Radiomics has potential for differentiating lipid-poor adenomas and avoiding unnecessary further investigations. • Quadratic mean, strength, maximum 3D diameter, volume density, and area density are promising predictors for adenomas. • Radiomics models reach high performance with average AUC of 0.95 in the training phase and 0.72 in the test phase

Epilepsy With Auditory Features: From Etiology to Treatment

Epilepsy with auditory features (EAF) is a focal epilepsy belonging to the focal epileptic syndromes with onset at variable age according to the new ILAE Classification. It is characterized by seizures with auditory aura or receptive aphasia suggesting a lateral temporal lobe involvement of the epileptic discharge. Etiological factors underlying EAF are largely unknown. In the familial cases with an autosomal dominant pattern of inheritance several genes have been involved, among which the first discovered, LGI1, was thought to be predominant. However, increasing evidence now points to a multifactorial etiology, as familial and sporadic EAF share a virtually identical electro-clinical characterization and only a few have a documented genetic etiology. Patients with EAF usually have an unremarkable neurological examination and a good response to antiseizure medications. However, it must be underscored that total remission might be lower than expected and that treatment withdrawal might lead to relapses. Thus, a proper understanding of this condition is in order for better patient treatment and counseling. Further studies are still required to further characterize the many facets of EAF