DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma

Epigenetic deregulation has emerged as a driver in human malignancies. There is no clear understanding of the epigenetic alterations in hepatocellular carcinoma (HCC) and of the potential role of DNA methylation markers as prognostic biomarkers. Analysis of tumor tissue from 304 patients with HCC treated with surgical resection allowed us to generate a methylation-based prognostic signature using a training-validation scheme. Methylome profiling was done with the Illumina HumanMethylation450 array (Illumina, Inc., San Diego, CA), which covers 96% of known cytosine-phosphate-guanine (CpG) islands and 485,000 CpG, and transcriptome profiling was performed with Affymetrix Human Genome U219 Plate (Affymetrix, Inc., Santa Clara, CA) and miRNA Chip 2.0. Random survival forests enabled us to generate a methylation signature based on 36 methylation probes. We computed a risk score of mortality for each individual that accurately discriminated patient survival both in the training (221 patients; 47% hepatitis C-related HCC) and validation sets (n = 83; 47% alcohol-related HCC). This signature correlated with known predictors of poor outcome and retained independent prognostic capacity of survival along with multinodularity and platelet count. The subset of patients identified by this signature was enriched in the molecular subclass of proliferation with progenitor cell features. The study confirmed a high prevalence of genes known to be deregulated by aberrant methylation in HCC (e.g., Ras association [RalGDS/AF-6] domain family member 1, insulin-like growth factor 2, and adenomatous polyposis coli) and other solid tumors (e.g., NOTCH3) and describes potential candidate epidrivers (e.g., septin 9 and ephrin B2). Conclusions: A validated signature of 36 DNA methylation markers accurately predicts poor survival in patients with HCC. Patients with this methylation profile harbor messenger RNA-based signatures indicating tumors with progenitor cell features

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

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

Accumulation of trace elements in feathers of the Kentish plover Charadrius alexandrinus

A non-invasive study of trace element accumulation in tail feathers of the Kentish plover (Charadrius alexandrinus) was performed along the coastline of the northern littoral strip of the Venice Lagoon, with the aim to verify whether contamination may be a factor affecting conservation status of Kentish plover populations.Body burdens in feathers of 11 trace elements including toxic metals/metalloids and essential elements (As, Cd, Co, Cr, Cu, Hg, Ni, Pb, Se, V, Zn) were quantified by ICP-MS, then concentrations were normalized to feather's age calculated using ptilochronology in order to obtain daily deposition rates.Mercury emerged as a major threat to the conservation of the species, since average feather concentration was clearly above the adverse-effect threshold associated with impairment in the reproductive success in a number of bird species. Also Cd and Se occurred at levels that may impact on the conservation status of the studied species at local scale, even if to a lesser extent than Hg.Gender-related differences in trace element accumulation emerged only for As, although for this element the risks associated to environmental exposure seem to be negligible.A non-invasive study of trace element accumulation in tail feathers of the Kentish plover (Charadrius alexandrinus) was performed along the coastline of the northern littoral strip of the Venice Lagoon, with the aim to verify whether contamination may be a factor affecting conservation status of Kentish plover populations.Body burdens in feathers of 11 trace elements including toxic metals/metalloids and essential elements (As, Cd, Co, Cr, Cu, Hg, Ni, Pb, Se, V, Zn) were quantified by ICP-MS, then concentrations were normalized to feather's age calculated using ptilochronology in order to obtain daily deposition rates.Mercury emerged as a major threat to the conservation of the species, since average feather concentration was clearly above the adverse-effect threshold associated with impairment in the reproductive success in a number of bird species. Also Cd and Se occurred at levels that may impact on the conservation status of the studied species at local scale, even if to a lesser extent than Hg.Gender-related differences in trace element accumulation emerged only for As, although for this element the risks associated to environmental exposure seem to be negligible

Complexity theory and financial regulation

Traditional economic theory could not explain, much less predict, the near collapse of the financial system and its long-lasting effects on the global economy. Since the 2008 crisis, there has been increasing interest in using ideas from complexity theory to make sense of economic and financial markets. Concepts, such as tipping points, networks, contagion, feedback, and resilience have entered the financial and regulatory lexicon, but actual use of complexity models and results remains at an early stage. Recent insights and techniques offer potential for better monitoring and management of highly interconnected economic and financial systems and, thus, may help anticipate and manage future crise