Archivio Istituzionale della Ricerca- Università del Piemonte Orientale
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Rendicontazione non finanziaria e "Sustainable Procurement": un codice di condotta per i fornitori.
No full textL'importanza dei fornitori è centrale per le imprese e rappresenta un vero e proprio fattore critico di
successo (o di insuccesso) in alcuni specifici settori. Nel 2024 UN Global Compact Network Italia ha
redatto un Codice di condotta per i fornitori, che enfatizza la rilevanza della formulazione preventiva di
richieste specifiche comportamentali ai fornitori esistenti e potenziali che siano coerenti con gli obiettivi
di sostenibilità condivisi dai committenti
The integration of gene mutations and copy number variations refines the prognosis of mantle cell lymphoma: long-term results of the Fondazione Italiana Linfomi MCL0208 clinical trial
No full textCortical Excitability as a Prognostic and Phenotypic Stratification Biomarker in Amyotrophic Lateral Sclerosis
No full textObjective: Despite its clinical heterogeneity, amyotrophic lateral sclerosis is unified by early and prominent alterations in cortical excitability, increasingly recognized as contributors to disease progression. This study assessed whether the ratio between motor evoked potential (MEP) amplitude, reflecting upper motor neuron integrity, and compound muscle action potential (CMAP) amplitude, indexing lower motor neuron function, could provide an accessible marker of corticospinal excitability to stratify patients by phenotype, stage, and survival. Methods: In this multicenter retrospective study, 743 amyotrophic lateral sclerosis patients from 16 tertiary centers in Italy were analyzed. The MEP:CMAP ratio, recorded from upper limb muscles, was categorized as hyperexcitable, normal, or hypoexcitable. Phenotypes included progressive muscular atrophy (or lower motor neuron), flail arm/leg, classic, bulbar, patient with predominant upper motor neuron signs (or pyramidal), and primary lateral sclerosis. Disease stage was assessed using King's staging. Survival was analyzed using Kaplan–Meier curves and Cox regression models. Results: The MEP:CMAP ratio differed significantly across phenotypes (p < 0.0001), with hyperexcitability predominating in lower motor neuron, flail, classic, and bulbar forms, and hypoexcitability in pyramidal and primary lateral sclerosis. Hypoexcitability increased in advanced King's stages (p < 0.0001). Hyperexcitable patients had shorter survival (p = 0.004), including when tested within 1 year of onset (p = 0.006). Cox regression identified the MEP:CMAP ratio as an independent survival predictor (HR 1.84, 95% CI 1.12–3.03, p = 0.016). Interpretation: This real-world study supports the clinical value of the MEP:CMAP ratio as a scalable biomarker of cortical excitability in amyotrophic lateral sclerosis, with prognostic relevance across phenotypes and disease stages. ANN NEUROL 2025;98:801–813
A Novel HPLC-MS/MS Method for the Intracellular Quantification of the Active Triphosphate Metabolite of Remdesivir: GS-443902
No full textBackground: Remdesivir (RDV) is a broad-spectrum antiviral prodrug, which is rapidly metabolized in vivo within cells to the pharmacologically active triphosphate metabolite, GS-443902. On the other hand, the dephosphorylated metabolite GS-441524 is the main form detected in plasma. RDV acts against RNA viruses, and it was the first antiviral drug to receive EMA and FDA approval for treating COVID-19. Nevertheless, its intracellular pharmacokinetics in real life are poorly explored, particularly due to technical challenges. Methods: The aim of this study was to validate an HPLC-MS/MS method for the direct quantification of GS-443902 in peripheral blood mononuclear cells (PBMCs) with a chromatographic separation of 15 min. Results: The method was validated following EMA and FDA guidelines in terms of sensitivity, specificity, accuracy, precision, matrix effect, recovery, carryover, and stability, and then applied to PBMC isolates from a small cohort of patients with severe COVID-19 who received RDV. Conclusions: This work represents the first method for the direct quantification of GS-443902 in PBMCs, with possible future application to intracellular pharmacokinetic studies in different scenarios, such as new oral prodrugs or drug-drug interaction studies
Development of a Self-Updating System for the Prediction of Steel Mechanical Properties in a Steel Company by Machine Learning Procedures
Get PDFThis study is focused on the implementation of statistical learning methods for the prediction of the mechanical properties of steel products from the chemical profile of the raw material and the process parameters. The integration of this model into the production process allows a large-scale steel industry to predict steel properties with heightened accuracy, optimizing the manufacturing process for minimal waste and improved consistency. A workflow for process data analysis has been developed, based on the use of machine learning algorithms to build an interface for data treatment to be directly used online. The proposed approach has a comprehensive connotation, starting from data pre-treatment and cleaning, to model building and prediction. Different machine learning algorithms are compared (Polynomial Regression, LASSO, Random Forests and Gradient Boosting, ANN, SVM, and k-NN), to provide the best predictive ability, also exploiting human reinforcement. The results proved to be very promising for all the types of steel investigated, with very good RMSE and R2 values both in fitting and in prediction. The application here presented is being integrated into Total Quality Tutor (TQT) software, developed in-house in C# language, for predicting the mechanical properties of steel
Targeting the Unfolded Protein Response with Natural Products: Therapeutic Potential in ER Stress-Related Diseases
Get PDFThis review delves into the intricate relationship between ER stress, the UPR, and human disease, with a specific focus on the therapeutic potential of natural products. We classify and discuss a wide range of natural compounds based on their unique mechanisms of action, whether they act as UPR inhibitors, activators, or indirectly alleviate ER stress by reducing oxidative burden or improving protein folding. By synthesizing the current literature, this review aims to provide a valuable resource for researchers and clinicians, highlighting the most promising natural products and their potential for development into novel therapeutic agents for treating pathologies driven by ER stress