77 research outputs found

    Polymorphic variants involved in methylation regulation: a strategy to discover risk loci for pancreatic ductal adenocarcinoma

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    INTRODUCTION: Only a small number of risk factors for pancreatic ductal adenocarcinoma (PDAC) has been established. Several studies identified a role of epigenetics and of deregulation of DNA methylation. DNA methylation is variable across a lifetime and in different tissues; nevertheless, its levels can be regulated by genetic variants like methylation quantitative trait loci (mQTLs), which can be used as a surrogate. MATERIALS AND METHODS: We scanned the whole genome for mQTLs and performed an association study in 14 705 PDAC cases and 246 921 controls. The methylation data were obtained from whole blood and pancreatic cancer tissue through online databases. We used the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium genome-wide association study (GWAS) data as discovery phase and the Pancreatic Disease Research consortium, the FinnGen project and the Japan Pancreatic Cancer Research consortium GWAS as replication phase. RESULTS: The C allele of 15q26.1-rs12905855 showed an association with a decreased risk of PDAC (OR=0.90, 95% CI 0.87 to 0.94, p=4.93×10 -8 in the overall meta-analysis), reaching genome-level statistical significance. 15q26.1-rs12905855 decreases the methylation of a 'C-phosphate-G' (CpG) site located in the promoter region of the RCCD1 antisense ( RCCD1-AS1) gene which, when expressed, decreases the expression of the RCC1 domain-containing ( RCCD1) gene (part of a histone demethylase complex). Thus, it is possible that the rs12905855 C-allele has a protective role in PDAC development through an increase of RCCD1 gene expression, made possible by the inactivity of RCCD1-AS1. CONCLUSION: We identified a novel PDAC risk locus which modulates cancer risk by controlling gene expression through DNA methylation

    Atraumatic splenic rupture in COVID-19 era: case report and systematic literature review

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    : Atraumatic splenic rupture is a rare but life-threatening condition. The Coronavirus disease 2019 (COVID-19) is still a mysterious infection, often associated with spontaneous bleeding and coagulation disorders. Among them, a rare presentation is the atraumatic splenic rupture during SARS-CoV-2 infection. We reported the case of a COVID-19 patient that underwent splenectomy for a spontaneous splenic rupture without splenomegaly or any hematological disorders. Moreover, we reviewed the literature about this matter focusing on the hypothetical etiopathogenesis of this condition in COVID-19 patients. Twelve cases of atraumatic splenic rupture without splenomegaly were reported in ten papers. Coughing, respiratory tract infections and anticoagulant treatment were postulated as the main risk factors for the spontaneous splenic rupture. COVID-19 is still a not well-known disease with multiple clinical presentations. The spontaneous splenic rupture is uncommon in general population but this event should not be neglected in this particular subset of patients

    Influenza vaccination landscape in Italy: A comprehensive study through the OBVIOUS project lens

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    Influenza annually claims an estimated 8,000 lives in Italy. Despite no-cost vaccinations for high-risk groups, hesitancy persists. This study aims to pinpoint social and behavioral vaccination determinants, forming strategies to bolster vaccine uptake. From April 11 to May 29, 2022, we surveyed a demographic-stratified sample of 10,000 Italian adults, employing the WHO's Behavioral and Social Drivers of Vaccination (BesD) framework. Of those, 4,613 (46.1%) were eligible for the influenza vaccine and included in the analysis. Roughly a third remained unvaccinated and unwilling. Central Italy showed the highest resistance, with significant percentages of seniors and professionals like teachers, law enforcement, and healthcare workers expressing noncompliance. A lack of awareness of being in a target group correlated significantly with vaccine refusal or delayed acceptance. Other refusal factors included female gender, being aged 45-54, rural residency, absence of higher education, perceived vaccine unsafety, and having vaccine-opposed acquaintances. Thus, addressing these perceptions and enhancing awareness can potentially increase vaccination rates and lessen disease impact

    Polymorphic variants involved in methylation regulation: a strategy to discover risk loci for pancreatic ductal adenocarcinoma

    No full text
    Introduction: Only a small number of risk factors for pancreatic ductal adenocarcinoma (PDAC) has been established. Several studies identified a role of epigenetics and of deregulation of DNA methylation. DNA methylation is variable across a lifetime and in different tissues; nevertheless, its levels can be regulated by genetic variants like methylation quantitative trait loci (mQTLs), which can be used as a surrogate. Materials and methods: We scanned the whole genome for mQTLs and performed an association study in 14 705 PDAC cases and 246 921 controls. The methylation data were obtained from whole blood and pancreatic cancer tissue through online databases. We used the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium genome-wide association study (GWAS) data as discovery phase and the Pancreatic Disease Research consortium, the FinnGen project and the Japan Pancreatic Cancer Research consortium GWAS as replication phase. Results: The C allele of 15q26.1-rs12905855 showed an association with a decreased risk of PDAC (OR=0.90, 95% CI 0.87 to 0.94, p=4.93Ă—10-8 in the overall meta-analysis), reaching genome-level statistical significance. 15q26.1-rs12905855 decreases the methylation of a 'C-phosphate-G' (CpG) site located in the promoter region of the RCCD1 antisense (RCCD1-AS1) gene which, when expressed, decreases the expression of the RCC1 domain-containing (RCCD1) gene (part of a histone demethylase complex). Thus, it is possible that the rs12905855 C-allele has a protective role in PDAC development through an increase of RCCD1 gene expression, made possible by the inactivity of RCCD1-AS1. Conclusion: We identified a novel PDAC risk locus which modulates cancer risk by controlling gene expression through DNA methylation

    Evaluation of Morphological, Qualitative, and Metabolomic Traits during Fruit Ripening in Pomegranate (Punica granatum L.)

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    Pomegranate is characterized by several local accessions and cultivars widespread across different countries, each with different bio-agronomic features. Physiological and biochemical processes occur during fruit ripening, leading to changes in size, color, and flavor, improving the fruit's acceptability for the consumer. The aim of this study was to evaluate the changes in physico-chemical and nutritional traits of three Italian germplasm genotypes ('Santa Lucia', 'Di Benedetto', and 'Arborea') to determine the differences for these parameters both within the same cultivar during four ripening stages, and between individual cultivars in the same ripening stage. Morphological traits and fruit pigmentation showed variation during the ripening process, with higher values at the final stage. The highest fruit weight was detected in 'Di Benedetto' (392.19 g), while 'Arborea' displayed high juice content. Qualitative traits, such as soluble solids, increased until stage III, while titratable acidity values decreased during the ripening stage in 'Di Benedetto' and 'Arborea'. In all three accessions, a reduction in the total polyphenols up to the III ripening stage was observed. Metabolomic analyses using H-1-NMR (proton nuclear magnetic resonance) showed a variation in citric acid and sugar content according to the ripening stage and accession considered. This study found high variability in nutraceutical traits among the analyzed pomegranates. The three pomegranate genotypes showed significant differences in qualitative and metabolomic characteristics. Principal component analysis revealed the main traits that contribute to the positive and negative correlations with PC1 and PC2, highlighting the great variability in the investigated pomegranate genotypes

    Radiomic and Artificial Intelligence Analysis with Textural Metrics Extracted by Contrast-Enhanced Mammography and Dynamic Contrast Magnetic Resonance Imaging to Detect Breast Malignant Lesions

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    Purpose:The purpose of this study was to discriminate between benign and malignant breast lesions through several classifiers using, as predictors, radiomic metrics extracted from CEM and DCE-MRI images. In order to optimize the analysis, balancing and feature selection procedures were performed. Methods: Fifty-four patients with 79 histo-pathologically proven breast lesions (48 malignant lesions and 31 benign lesions) underwent both CEM and DCE-MRI. The lesions were retrospectively analyzed with radiomic and artificial intelligence approaches. Forty-eight textural metrics were extracted, and univariate and multivariate analyses were performed: non-parametric statistical test, receiver operating characteristic (ROC) and machine learning classifiers. Results: Considering the single metrics extracted from CEM, the best predictors were KURTOSIS (area under ROC curve (AUC) = 0.71) and SKEWNESS (AUC = 0.71) calculated on late MLO view. Considering the features calculated from DCE-MRI, the best predictors were RANGE (AUC = 0.72), ENERGY (AUC = 0.72), ENTROPY (AUC = 0.70) and GLN (gray-level nonuniformity) of the gray-level run-length matrix (AUC = 0.72). Considering the analysis with classifiers and an unbalanced dataset, no significant results were obtained. After the balancing and feature selection procedures, higher values of accuracy, specificity and AUC were reached. The best performance was obtained considering 18 robust features among all metrics derived from CEM and DCE-MRI, using a linear discriminant analysis (accuracy of 0.84 and AUC = 0.88). Conclusions: Classifiers, adjusted with adaptive synthetic sampling and feature selection, allowed for increased diagnostic performance of CEM and DCE-MRI in the differentiation between benign and malignant lesions

    Protein Binding of Benzofuran Derivatives: A CD Spectroscopic and In Silico Comparative Study of the Effects of 4-Nitrophenyl Functionalized Benzofurans and Benzodifurans on BSA Protein Structure

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    Benzofuran derivatives are synthetic compounds that are finding an increasing interest in the scientific community not only as building blocks for the realization of new materials, but also as potential drugs thanks to their ability to interact with nucleic acids, interfere with the amyloid peptide aggregation and cancer cell cycle. However, their ability to interact with proteins is a theme still in need of investigation for the therapeutic importance that benzofurans could have in the modulation of protein-driven processes and for the possibility of making use of serum albumins as benzofurans delivery systems. To this scope, we investigated the protein binding ability of two 4-nitrophenyl-functionalized benzofurans previously synthesized in our laboratory and herein indicated as BF1 and BDF1, which differed for the number of furan rings (a single moiety in BF1, two in BDF1), using bovine serum albumin (BSA) as a model protein. By circular dichroism (CD) spectroscopy we demonstrated the ability of the two heteroaromatic compounds to alter the secondary structure of the serum albumin leading to different consequences in terms of BSA thermal stability with respect to the unbound protein (ΔTm > 3 °C for BF1, −0.8 °C for BDF1 with respect to unbound BSA, in PBS buffer, pH 7.5) as revealed in our CD melting studies. Moreover, a molecular docking study allowed us to compare the possible ligand binding modes of the mono and difuranic derivatives showing that while BF1 is preferentially housed in the interior of protein structure, BDF1 is predicted to bind the albumin surface with a lower affinity than BF1. Interestingly, the different affinity for the protein target predicted computationally was confirmed also experimentally by fluorescence spectroscopy (kD = 142.4 ± 64.6 nM for BDF1 vs. 28.4 ± 10.1 nM for BF1). Overall, the above findings suggest the ability of benzofurans to bind serum albumins that could act as their carriers in drug delivery applications

    Acute Delta Hepatitis in Italy spanning three decades (1991-2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

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    Soft drinks and sweeteners intake: Possible contribution to the development of metabolic syndrome and cardiovascular diseases. Beneficial or detrimental action of alternative sweeteners?

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    Abstract The rapid increase in obesity, metabolic syndrome, and cardiovascular diseases (CVDs) has been related to the rise in sugar-added foods and sweetened beverages consumption. An interesting approach has been to replace sugar with alternative sweeteners (AS), due to their impact on public health. Preclinical and clinical studies, which analyze the safety of AS intake, are still limited. Major pathogenic mechanisms of these substances include ROS and AGEs formation. Indeed, endothelial dysfunction involving in the pathogenesis of micro- and macro-vascular diseases is mitochondrial dysfunction dependent. Hyperglycemia and endoplasmic reticulum stress together produce ROS, contributing to the development and progression of cardiovascular complications during type 2 diabetes (T2D), thus causing oxidative changes and direct damage of lipids, proteins, and DNA. Epidemiological studies in healthy subjects have suggested that the consumption of artificial AS can promote CV complications, such as glucose intolerance and predisposition to the onset of T2D, whereas natural AS could reduce hyperglycemia, improve lipid metabolism and have antioxidant effects. Long-term prospective clinical randomized studies are needed to evaluate precisely whether exposure to alternative sugars can have clinical implications on natural history and clinical outcomes, especially in children or during the gestational period through breast milk

    Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

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    Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come
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