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Dopamine is reduced in the brain of rats treated with fipronil, a broad-spectrum insecticide. VGF (no acronym) is a neurotrophin-inducible protein expressed as the 75 kDa form (precursor or pro-VGF) or its truncated peptides. VGF immunostaining has been revealed using an antibody against the C-terminal nonapeptide of the rat pro-VGF in the nerve terminals of the rat substantia nigra, where it was reduced after 6-hydroxydopamine treatment. It is unknown whether pro-VGF and/or its shortened peptides are present in these neurons. Therefore, the aim of this study was first to determine which types of VGF are expressed in the normal substantia nigra (and striatum) and then to determine VGF modulations and whether they occur in parallel with locomotor changes after fipronil injection. Rats were divided into two groups that received a unilateral intranigral infusion of either fipronil (25 µg) diluted in dimethyl sulfoxide (DMSO) or DMSO alone, and then were tested for locomotor activity. An untreated group of rats (n=4) was used for identification of the VGF fragments using high performance liquid chromatography-mass spectrometry and western blot, while changes in treated groups (fipronil vs DMSO, each n=6) were investigated by immunohistochemistry using an antibody against the rat pro-VGF C-terminal nonapeptide in parallel with the anti-tyrosine hydroxylase antibody. In untreated rats, the VGF C-terminal antibody identified mostly a 75 kDa band in the substantia nigra and striatum, supporting the finding of high-resolution mass spectrometry, which revealed fragments covering the majority of the pro-VGF sequence. Furthermore, several shortened VGF C-terminal forms (varying from 10 to 55 kDa) were also found by western blot, while high-resolution mass spectrometry revealed a C-terminal peptide overlapping the immunogen used to create the VGF antibody in both substantia nigra and striatum. In the substantia nigra of fipronil-treated rats, immunostaining for tyrosine hydroxylase and VGF was reduced compared to DMSO-treated rat group, and this was related with significant changes in locomotor activity. Fipronil has the ability to modulate the production of pro-VGF and/or its C-terminal truncated peptides in the nigrostriatal system indicating its intimate interaction with the dopaminergic neurotransmission and implying a potential function in modulating locomotor activity. [ABSTRACT FROM AUTHOR]

• The behavior of radiomic features on unenhanced and contrast-enhanced chest CT imaging is evaluated. • Several radiomic features were affected by high variability when moving from unenhanced to contrast-enhanced CT imaging. • A subset of four stable features was isolated that produces the same tumor lesion partition on both types of images. • The Gini's coefficient proved effective to outline the discrimination power of radiomic features on both types of images. The aim of this methods work is to explore the different behavior of radiomic features resulting by using or not the contrast medium in chest CT imaging of non-small cell lung cancer. Chest CT scans, unenhanced and contrast-enhanced, of 17 patients were selected from images collected as part of the staging process. The major T1-T3 lesion was contoured through a semi-automatic approach. These lesions formed the lesion phantoms to study features behavior. The stability of 94 features of the 3D-Slicer package Radiomics was analyzed. Feature discrimination power was quantified by means of Gini's coefficient. Correlation between distance matrices was evaluated through Mantel statistic. Heatmap, cluster and silhouette plots were applied to find well-structured partitions of lesions. The Gini's coefficient evidenced a low discrimination power, <0.05, for four features and a large discrimination power, around 0.8, for five features. About 90% of features was affected by the contrast medium, masking tumor lesions variability; thirteen features only were found stable. On 8178 combinations of stable features, only one group of four features produced the same partition of lesions with the silhouette width greater than 0.51, both on unenhanced and contrast-enhanced images. Gini's coefficient highlighted the features discrimination power in both CT series. Many features were sensitive to the use of the contrast medium, masking the lesions intrinsic variability. Four stable features produced, on both series, the same partition of cancer lesions with reasonable structure; this may merit being objects of further validation studies and interpretative investigations. [ABSTRACT FROM AUTHOR]