A prognostic molecular signature of hepatic steatosis is spatially heterogeneous and dynamic in human liver.

Hepatic steatosis is a central phenotype in multi-system metabolic dysfunction and is increasing in parallel with the obesity pandemic. We use a translational approach integrating clinical phenotyping and outcomes, circulating proteomics, and tissue transcriptomics to identify dynamic, functional biomarkers of hepatic steatosis. Using multi-modality imaging and broad proteomic profiling, we identify proteins implicated in the progression of hepatic steatosis that are largely encoded by genes enriched at the transcriptional level in the human liver.

Molecular and Clinical Characterization of a Founder Mutation Causing G6PC3 Deficiency.

G6PC3 deficiency is a monogenic immunometabolic disorder that causes severe congenital neutropenia type 4. Patients display heterogeneous extra-hematological manifestations, contributing to delayed diagnosis. Here, we investigated the origin and functional consequence of the G6PC3 c.

The extracellular vesicle transcriptome provides tissue-specific functional genomic annotation relevant to disease susceptibility in obesity.

We characterized circulating extracellular vesicles (EVs) in obese and lean humans, identifying transcriptional cargo differentially expressed in obesity. Since circulating EVs may have broad origin, we compared this obesity EV transcriptome to expression from human visceral adipose tissue derived EVs from freshly collected and cultured biopsies from the same obese individuals. Using a comprehensive set of adipose-specific epigenomic and chromatin conformation assays, we found that the differentially expressed transcripts from the EVs were those regulated in adipose by BMI-associated SNPs from a large-scale GWAS.

[Not Available].

In the Piedmont Region, the first mapping of the organization and research activity of the 18 Health Authorities was conducted in 2022 through the Research and Innovation Department (DAIRI), repeated in 2023. The data showed an increase in scientific production and research funding and a decrease in clinical research, although the most represented infrastructure is for the activation of clinical trials. The importance of creating a regional research system is highlighted.

Unsupervised clustering analysis-based characterization of spatial profiles of inaccuracy in apparent diffusion coefficient values with varying acquisition plan orientation and diffusion weighting gradient direction - a large multicenter phantom study.

This large multicenter study of 37 magnetic resonance imaging scanners aimed at characterizing, for the first time, spatial profiles of inaccuracy (namely, Δ-profiles) in apparent diffusion coefficient (ADC) values with varying acquisition plan orientation and diffusion weighting gradient direction, using a statistical approach exploiting unsupervised clustering analysis. A diffusion-weighted imaging (DWI) protocol (b-value: 0-200-400-600-800-1000 s mm) with different combinations of acquisition plan orientation (axial/sagittal/coronal) and diffusion weighting gradient direction (anterior-posterior/left-right/feet-head) was acquired on a standard water phantom. For each acquisition setup, Δ-profiles along the 3 main orthogonal directions were characterized by fitting data with a second order polynomial function ().

Preferences and attitudes regarding early intervention in multiple sclerosis: A systematic literature review.

Background: Multiple sclerosis (MS) is a chronic inflammatory disorder affecting the brain and spinal cord, characterized by immune-mediated myelin damage. Early intervention and detection programs have emerged as promising strategies to improve patient outcomes by identifying and treating MS in its earliest stages.

Objective: This systematic literature review aims to provide an overview of the preferences, attitudes, and opinions of both patients and healthcare professionals regarding early intervention or early detection programs for MS.

AI drives the assessment of lung cancer microenvironment composition.

Purpose: The abundance and distribution of tumor-infiltrating lymphocytes (TILs) as well as that of other components of the tumor microenvironment is of particular importance for predicting response to immunotherapy in lung cancer (LC). We describe here a pilot study employing artificial intelligence (AI) in the assessment of TILs and other cell populations, intending to reduce the inter- or intra-observer variability that commonly characterizes this evaluation.

Design: We developed a machine learning-based classifier to detect tumor, immune, and stromal cells on hematoxylin and eosin-stained sections, using the open-source framework .

Cardiomyocyte-derived circulating extracellular vesicles allow a non-invasive liquid biopsy of myocardium in health and disease.

The ability to track disease without tissue biopsy in patients is a major goal in biology and medicine. Here, we identify and characterize cardiomyocyte-derived extracellular vesicles in circulation (EVs; "cardiovesicles") through comprehensive studies of induced pluripotent stem cell-derived cardiomyocytes, genetic mouse models, and state-of-the-art mass spectrometry and low-input transcriptomics. These studies identified two markers (, ) enriched on cardiovesicles for biotinylated antibody-based immunocapture.

Charge Effects and Electron Phonon Coupling in Potassium-Doped Graphene.

Herewith, we propose a comprehensive study of the vibrational response of chemical doping of free-standing graphene (Gr). Complementary insights on the increased metallicity have been demonstrated by the emerging plasmon excitation in the upper Dirac cone, observed by inelastic electron scattering and core-level photoemission. The electron migration in the π* upper Dirac band unveils an electron-phonon coupling of contaminant-free K-doped Gr, as evidenced by advanced micro-Raman spectroscopy in ultrahigh vacuum ambient.

Clinical bioinformatics desiderata for molecular tumor boards.

Clinical Bioinformatics is a knowledge framework required to interpret data of medical interest via computational methods. This area became of dramatic importance in precision oncology, fueled by cancer genomic profiling: most definitions of Molecular Tumor Boards require the presence of bioinformaticians. However, all available literature remained rather vague on what are the specific needs in terms of digital tools and expertise to tackle and interpret genomics data to assign novel targeted or biomarker-driven targeted therapies to cancer patients.

Biomolecular Classification in Endometrial Cancer: Onset, Evolution, and Further Perspectives: A Critical Review.

Since the new guidelines for endometrial cancer risk classification have been published, many reviews have proposed a critical re-evaluation. In this review, we look back to how the molecular classification system was built and its evolution in time to highlight the major flaws, particularly the biases stemming from the inherent limitations of the cohorts involved in the discoveries. A significant drawback in some cohorts is the inclusion criteria, as well as the retrospective nature and the notably sparse numbers, especially in the (nonsynonymous mutation in EDM domain of POLE) risk groups, all of which impact the reliability of outcomes.

Molecular and clinical characterization of a founder mutation causing G6PC3 deficiency.

G6PC3 deficiency is a monogenic immunometabolic disorder that causes syndromic congenital neutropenia. Patients display heterogeneous extra-hematological manifestations, contributing to delayed diagnosis. Here, we investigated the origin and functional consequence of the c.

Protecting TiS Photoanodes for Water Splitting in Alkaline Media by TiO Coatings.

Titanium trisulfide (TiS) nanoribbons, when coated with titanium dioxide (TiO), can be used for water splitting in the KOH electrolyte. TiO shells can be prepared through thermal annealing to regulate the response of TiS/TiO heterostructures by controlling the oxidation time and growth atmosphere. The thickness and structure of the TiO layers significantly influence the photoelectrocatalytic properties of the TiS/TiO photoanodes, with amorphous layers showing better performance than crystalline ones.

Towards the Fifth Pillar for the Treatment of Heart Failure with Reduced Ejection Fraction: Vericiguat in Older and Complex Patients.

Heart failure with reduced ejection fraction (HFrEF) represents an emerging epidemic, particularly affecting frail, older, and multimorbid patients. Current therapy for the management of HFrEF includes four different classes of disease-modifying drugs, commonly referred to as 'four pillars', which target the neurohormonal system that is overactivated in HF and contributes to its progression. These classes of drugs include β-blockers, inhibitors of the renin-angiotensin-aldosterone system, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors.

Potassium doping of vertically aligned multi-walled carbon nanotubes.

Alkali metal doping of multi-walled carbon nanotubes is of great interest, both fundamentally to explore the effect of dopants on quasi-one-dimensional electrical systems and for energy applications such as alkali metal storage. We present an investigation with complementary photoemission and Raman spectroscopies, fully carried out in an ultra-high vacuum, to unveil the electronic and vibrational response of a forest of highly aligned multi-walled carbon nanotubes by in situ potassium doping. The charge donation by the alkali adatoms induces a plasmon mode, and the density of states undergoes an energy shift consistent with electron donation and band filling of the multi-walled carbon nanotube band structure.

Progression independent of relapse activity in relapsing multiple sclerosis: impact and relationship with secondary progression.

Objectives: We investigated the occurrence and relative contribution of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) to confirmed disability accrual (CDA) and transition to secondary progression (SP) in relapsing multiple sclerosis (MS).

Methods: Relapsing-onset MS patients with follow-up > / = 5 years (16,130) were extracted from the Italian MS Registry. CDA was a 6-month confirmed increase in Expanded Disability Status Scale (EDSS) score.

Molecular and clinical characterization of a founder mutation causing G6PC3 deficiency.

Background: G6PC3 deficiency is a rare genetic disorder that causes syndromic congenital neutropenia. It is driven by the intracellular accumulation of a metabolite named 1,5-anhydroglucitol-6-phosphate (1,5-AG6P) that inhibits glycolysis. Patients display heterogeneous extra-hematological manifestations, contributing to delayed diagnosis.

Anti-rubella seroprevalence assessment in an adult sample population in Italy.

Introduction: Despite global immunization efforts, rubella remains a public health concern, particularly in high- and middle-income countries. This study focused on rubella seroprevalence in the province of Florence, Italy, aiming to identify susceptibility clusters, especially among women in their childbearing age.

Methods: A cross-sectional study was conducted between April 2018 and December 2019, enrolling 430 adult subjects (age over 18 years).

The clinical trial activation process: a case study of an Italian public hospital.

Background/aims: In order to make the centers more attractive to trial sponsors, in recent years, some research institutions around the world have pursued projects to reorganize the pathway of trial activation, developing new organizational models to improve the activation process and reduce its times. This study aims at analyzing and reorganizing the start-up phase of trials conducted at the Research and Innovation Department (DAIRI) of the Public Hospital of Alessandria (Italy).

Methods: A project was carried out to reorganize the trial authorization process at DAIRI by involving the three facilities responsible for this pathway: clinical trial center (CTC), ethics committee secretariat (ESC), and administrative coordination (AC).

Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis.

Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRS) and UC (PRS) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients.

Intermixing of Unoccupied States of Metal Phthalocyanine Chains Assembled on Au(110).

A detailed inverse photoemission study unveils the unoccupied electronic structure induced by the adsorption of CuPc and CoPc phthalocyanines on Au(110) reconstructed channels. The different behavior in the two systems is related to the different intermixing of orbitals with the underlying gold states. Broadening of the density of states at the Fermi level is detected after CoPc adsorption, absent in the case CuPc.

Spectromicroscopy Study of Induced Defects in Ion-Bombarded Highly Aligned Carbon Nanotubes.

Highly aligned multi-wall carbon nanotubes were investigated with scanning electron microscopy (SEM), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) before and after bombardment performed using noble gas ions of different masses (argon, neon and helium), in an ultra-high-vacuum (UHV) environment. Ion irradiation leads to change in morphology, deformation of the carbon (C) honeycomb lattice and different structural defects in multi-wall carbon nanotubes. One of the major effects is the production of bond distortions, as determined by micro-Raman and micro-X-ray photoelectron spectroscopy.

Comprehensive genomic profiling on metastatic Melanoma: results from a network screening from 7 Italian Cancer Centres.

Background: The current therapeutic algorithm for Advanced Stage Melanoma comprises of alternating lines of Targeted and Immuno-therapy, mostly via Immune-Checkpoint blockade. While Comprehensive Genomic Profiling of solid tumours has been approved as a companion diagnostic, still no approved predictive biomarkers are available for Melanoma aside from BRAF mutations and the controversial Tumor Mutational Burden. This study presents the results of a Multi-Centre Observational Clinical Trial of Comprehensive Genomic Profiling on Target and Immuno-therapy treated advanced Melanoma.