Objective. To investigate structural and functional neural organization in amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS) and progressive muscular atrophy (PMA) patients. Methods. 173 ALS, 38 PLS, 28 PMA sporadic patients and 79 healthy controls were recruited from three Italian centers. Subjects underwent clinical, neuropsychological and brain MRI evaluations. Using graph analysis and connectomics, global and lobar topological network properties and regional structural and functional brain connectivity were assessed. The association between structural and...

Increasing evidences suggest that HBsAg-production varies across HBV-genotypes. HBsAg C-terminus plays a crucial role for HBsAg-secretion. Here, we evaluate HBsAg-levels in different HBV-genotypes in HBeAg-negative chronic infection, the correlation of specific mutations in HBsAg C-terminus with HBsAg-levels in-vivo, their impact on HBsAg-secretion in-vitro and on structural stability in-silico. HBsAg-levels were investigated in 323 drug-naïve HBeAg-negative patients chronically infected with HBV genotype-D(N = 228), -A(N = 65) and -E(N = 30). Genotype-D was characterized by HBsAg-levels...

Objectives. Grey matter (GM) involvement is clinically relevant in multiple sclerosis (MS). Using source-based morphometry (SBM), we characterized GM atrophy and its 1-year evolution across different MS phenotypes. Methods. Clinical and MRI data were obtained at 8 European sites from 170 healthy controls (HCs) and 398 MS patients (34 clinically isolated syndromes [CIS], 226 relapsing-remitting [RR], 95 secondary progressive [SP] and 43 primary progressive [PP] MS). Fifty-seven HC and 144 MS underwent 1-year follow-up. Baseline...

Additional file 2: Supplementary Fig. S1. Altered miR-146a expression influences BRAF/MEKi sensitivity and apoptosis in melanoma. A) Boxplots representing IC50 values of 6 matched PLX4032-resistant (R) and sensitive (S) melanoma cell lines to PLX4032 (vemurafenib), BRAFi (dabrafenib), MEKi (trametinib), to the combined treatment BRAF/MEKi, and to sTRAIL-induced apoptosis. B) Inverse correlation between miR-146a expression levels and IC50 values of PLX4032, BRAFi and MEKi in melanoma cell lines (Spearman analysis). C) Forced expression of miR-146a (+m-miR-146a)...

Additional file 1: Supplementary Table S1. List of used antibodies and molecular probes. Supplementary Table S2. Differentially expressed miR between cell lines with acquired resistance to vemurafenib and their sensitive counterparts. Supplementary Table S3. Genes directly targeted by miR-146a among the NFkB-regulated genes differentially expressed in LM16R/LM16 dataset (GSE68841). Supplementary Table S4. Characteristics of patients treated with vemurafenib and their matched pre- and post-treatment melanoma metastasis (GSE141484).

Additional file 1: Supplementary Table S1. List of used antibodies and molecular probes. Supplementary Table S2. Differentially expressed miR between cell lines with acquired resistance to vemurafenib and their sensitive counterparts. Supplementary Table S3. Genes directly targeted by miR-146a among the NFkB-regulated genes differentially expressed in LM16R/LM16 dataset (GSE68841). Supplementary Table S4. Characteristics of patients treated with vemurafenib and their matched pre- and post-treatment melanoma metastasis (GSE141484).

Increasing evidences suggest that HBsAg-production varies across HBV-genotypes. HBsAg C-terminus plays a crucial role for HBsAg-secretion. Here, we evaluate HBsAg-levels in different HBV-genotypes in HBeAg-negative chronic infection, the correlation of specific mutations in HBsAg C-terminus with HBsAg-levels in-vivo, their impact on HBsAg-secretion in-vitro and on structural stability in-silico. HBsAg-levels were investigated in 323 drug-naïve HBeAg-negative patients chronically infected with HBV genotype-D(N = 228), -A(N = 65) and -E(N = 30). Genotype-D was characterized by HBsAg-levels...

Increasing evidences suggest that HBsAg-production varies across HBV-genotypes. HBsAg C-terminus plays a crucial role for HBsAg-secretion. Here, we evaluate HBsAg-levels in different HBV-genotypes in HBeAg-negative chronic infection, the correlation of specific mutations in HBsAg C-terminus with HBsAg-levels in-vivo, their impact on HBsAg-secretion in-vitro and on structural stability in-silico. HBsAg-levels were investigated in 323 drug-naïve HBeAg-negative patients chronically infected with HBV genotype-D(N = 228), -A(N = 65) and -E(N = 30). Genotype-D was characterized by HBsAg-levels...

Objective: To determine whether hemisphere involvement and infarct location on the Alberta Stroke Program CT Score (ASPECTS) score template should serve as predictors of 90-day clinical outcome in acute ischemic stroke patients with pretreatment diffusion-weighted imaging (DWI)-ASPECTS 0-5 treated with thrombectomy. Methods: We analyzed data of all consecutive patients included in the Endovascular Treatment in Ischemic Stroke (ETIS) registry between January 1, 2012 and January 31, 2018 who presented with a pretreatment DWI-ASPECTS 0-5 score...

Abstract Background Targeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance. Methods The miR-146a-5p-regulated NFkB signaling network was identified in...

Abstract Background Targeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance. Methods The miR-146a-5p-regulated NFkB signaling network was identified in...

Additional file 2: Supplementary Fig. S1. Altered miR-146a expression influences BRAF/MEKi sensitivity and apoptosis in melanoma. A) Boxplots representing IC50 values of 6 matched PLX4032-resistant (R) and sensitive (S) melanoma cell lines to PLX4032 (vemurafenib), BRAFi (dabrafenib), MEKi (trametinib), to the combined treatment BRAF/MEKi, and to sTRAIL-induced apoptosis. B) Inverse correlation between miR-146a expression levels and IC50 values of PLX4032, BRAFi and MEKi in melanoma cell lines (Spearman analysis). C) Forced expression of miR-146a (+m-miR-146a)...