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Background: The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial. Methods: We investigated the RNA gene expression profile of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), murine doble minute 4 (MDM4), and platelet derived growth factor receptor alpha (PDGFRA) in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in EGFR and PDGFRA, were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied. Results: At the RNA level, CDK4 was the most frequently overexpressed gene (90%) followed by EGFR (58%) and PDGFRA (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with EGFR gene expression levels. In turn, intragenic EGFR deletions were found in 39 patients (47%), including EGFRvIII (46%) in association with EGFRvIVa (4%), EGFRvII (2%) or other EGFR deletions (3%) and PDGFRA deletion of exons 8–9 was found in only two tumors (2%). Conclusions: Overall, none of the gene expression profiles and/or intragenic EGFR deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM.

This study examined whether methadone (hereinafter referred to as MTD) maintenance treatment (MMT) is correlated with sexual dysfunction (SD) in heroin-dependent men. This was conducted to determine the prevalence of sexual dysfunction and if there is a relationship between duration and dose among men on MMT and its impact on the quality of life. The study combined a retrospective and a cross-sectional survey based on the Kinsey Scale, TECVASP, and PRSexDQ-SALSEX clinical interviews of 85 patients who are currently engaged in MMT. Sexual dysfunction in all five PRSexDQ-SALSEX domains (lack of libido, delay in orgasm, inability to orgasm, erectile dysfunction, and tolerance or acceptance of changes in sexual function) was associated with dose and long-term use of heroin. All dimensions of SD were affected by the MTD intake. From the analysis of our sample, we may conclude that dose of MTD and overall score of SD were directly associated. However, no evidence was found to prove that treatment duration and severity of SD were linked. It is notable that only one tenth of the patients spontaneously reported their symptoms of the sexual sphere, but up to a third considered leaving the MMT for this reason.

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HJ-Biplot analysis is a multivariate graphic representation that collects data covariation structure between variables and individuals to represent them in a low-dimensional space with the highest quality in the same reference system. Consequently, it is a promising technique for evaluating dietary exposure to polyphenols and accurately characterizing female nutrition. Herein, we hypothesized that polyphenol intake defines specific clusters with dietary impacts, which can be assessed using HJ-Biplot, based on a cross-sectional study in Argentina. The study included 275 healthy postpartum women who provided information about their food frequency intake and other conditions, which were then used to evaluate polyphenolic intake using the Phenol-Explorer database. Outcomes were established using HJ-Biplot for clustering and ANOVA to compare their impact on diet quality indicators. Two HJ-Biplot models were run (for intakes >20 mg/d and 5∼20 mg/d, respectively) to identify three clusters per model with excellent statistical fitness to explain the data. Thus, specific polyphenolic clusters with potentially bioactive and safe compounds were defined despite significant interindividual variability. In fact, women with the lowest polyphenolic intake exhibited worse dietary quality, body fat, and physical activity. As a result, HJ-Biplot proved to be an effective technique for clustering women based on their dietary intake of these compounds. Furthermore, cluster membership improved the intake of antioxidants, water, fiber, and healthy fats. Additionally, women with formal jobs and a higher educational level showed a better diet. Dietary polyphenols are critical during postpartum because they exert beneficial effects on women and breastfed infants.

The molecular complexity displayed in acute myeloid leukemia (AML) hinders patient stratification and treatment decisions. Previous studies support the utility of using specific gene panels for this purpose. Focusing on two salient features of AML, the production of reactive oxygen species (ROS) by NADPH oxidases (NOX) and metabolism, we aimed to identify a gene panel that could improve patient stratification. A pairwise comparison of AML versus healthy gene expression revealed the downregulation of four members of the NOX2 complex including CYBB (coding for NOX2) in AML patients. We analyzed the expression of 941 genes related to metabolism and found 28 genes with expression correlated to CYBB. This panel of 29 genes (29G) effectively divides AML samples according to their prognostic group. The robustness of 29G was confirmed by 6 AML cohort datasets with a total of 1821 patients (overall accuracies of 85%, 78%, 80%, 75%, 59% and 83%). An expression index (EI) was developed according to the expression of the selected discriminatory genes. Overall Survival (OS) was higher for low 29G expression index patients than for the high 29G expression index group, which was confirmed in three different datasets with a total of 1069 patients. Moreover, 29G can dissect intermediate‐prognosis patients in four clusters with different OS, which could improve the current AML stratification scheme. In summary, we have found a gene signature (29G) that can be used for AML classification and for OS prediction. Our results confirm NOX and metabolism as suitable therapeutic targets in AML.

Diagnosis and classification of gliomas mostly relies on histopathology and a few genetic markers. Here we interrogated microarray gene expression profiles (GEP) of 268 diffuse astrocytic gliomas-33 diffuse astrocytomas (DA), 52 anaplastic astrocytomas (AA) and 183 primary glioblastoma (GBM)-based on multivariate analysis, to identify discriminatory GEP that might support precise histopathological tumor stratification, particularly among inconclusive cases with II-III grade diagnosed, which have different prognosis and treatment strategies. Microarrays based GEP was analyzed on 155 diffuse astrocytic gliomas (discovery cohort) and validated in another 113 tumors (validation set) via sequential univariate analysis (pairwise comparison) for discriminatory gene selection, followed by nonnegative matrix factorization and canonical biplot for identification of discriminatory GEP among the distinct histological tumor subtypes. GEP data analysis identified a set of 27 genes capable of differentiating among distinct subtypes of gliomas that might support current histological classification. DA + AA showed similar molecular profiles with only a few discriminatory genes overexpressed (FSTL5 and SFRP2) and underexpressed (XIST, TOP2A and SHOX2) in DA vs AA and GBM. Compared to DA + AA, GBM displayed underexpression of ETNPPL, SH3GL2, GABRG2, SPX, DPP10, GABRB2 and CNTN3 and overexpression of CHI3L1, IGFBP3, COL1A1 and VEGFA, among other differentially expressed genes. Diffuse gliomas comprise a variety of tumor entities of different cell lineages and histopathological features which are classified into distinct subtypes by the World Health Organization (WHO) 1,2 , from which astrocytic lineage tumors (i.e. astrocytomas and glioblastomas) are by far the most common (around 90%) 3. Relevant histological and immunohistochemical features together with the presence of codeletion of chromosome 1p/19q and isocitrate dehydrogenase 1 (IDH1) gene mutation, are currently used for the differential diagnosis between oligodendroglial tumors and diffuse astrocytomas 1,4. However, further differential diagnoses among the distinct subtypes of diffuse astrocytomas might be challenging and they might even lead to inconclusive results, particularly among grade II and III tumors. For this purpose molecular characteristics of these tumors have been recurrently investigated. However, while genetic alterations are found in the majority of tumors, they are not entirely specific, and thereby they are not considered in the current WHO-2016 classification of gliomas. Thus, astrocytic

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