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Nuove tecnologie ed etica nella valutazione d'azienda
No full textL’integrazione dell’intelligenza artificiale (IA) nei processi di valutazione aziendale rappresenta una trasformazione significativa che offre notevoli opportunità ma solleva anche importanti questioni etiche. Il capitolo esamina l’impatto delle nuove tecnologie sulla valutazione d’impresa, analizzando come l’uso dell’intelligenza artificiale possa influenzare i cinque principi etici fondamentali sanciti dal Codice Etico dell’International Valuation Standards Council: integrità, obiettività, competenza, riservatezza e condotta professionale.
Lo studio identifica alcune principali problematiche etiche derivanti dall’applicazione dell’IA alla valutazione aziendale: la mancanza di trasparenza nell’uso degli algoritmi, l’opacità dei processi decisionali automatizzati (fenomeno della "black box"), i bias algoritmici che possono generare discriminazioni nei risultati, la deresponsabilizzazione del valutatore dovuta all’eccessivo affidamento agli output dell’IA, e i rischi per la sicurezza e riservatezza dei dati aziendali sensibili
Primary biliary cholangitis (PBC): evolving approaches and expert perspectives
No full textIntroduction: Primary biliary cholangitis (PBC) is a rare, chronic autoimmune cholestatic liver disease causing progressive destruction of intrahepatic bile ducts. Predominantly affecting women aged 35 to 70, PBC may remain asymptomatic for years before symptoms such as pruritus, fatigue, or sicca symptoms manifest. If untreated, PBC can progress to cirrhosis, liver failure and need for transplantation, significantly impacting life expectancy. Areas covered: Ursodeoxycholic acid (UDCA) remains the only approved first-line therapy. The recent withdrawal of obeticholic acid (OCA) from the European market, the only available second-line agent since 2016, highlighting the need for alternative options. The recent European Medicine Agency (EMA) approval of new peroxisome proliferator-activated receptor (PPAR) agonists is promising for patients with suboptimal response to UDCA. A literature review was conducted to map the patient journey and examine current treatments. Expert opinion: A panel of Italian expert hepatologists was involved to explore unmet needs along the patient journey and define clinical priorities. Focus areas included response monitoring, treatment evaluation timing, symptoms management–particularly pruritus and fatigue–and care of comorbid and high-risk patients. Many patients live with indolent disease, but some may require a more structured pathway, where emerging treatments can be an important turning point
Abiura del meno. La casa mediterranea come spazio eclettico
No full textIl saggio analizza la condizione eclettica di alcuni spazi domestici contemporanei contrapponendola alla cultura minimalista e neomoderna. L'obiettivo è sollecitare una riflessione critica sull'importanza del pluralismo nella progettazione architettonica della casa mediterranea contemporanea
Ex vivo air–liquid interface respiratory mucosa platform to study type 2–driven asthma
No full textObjective: Asthma is a heterogeneous disorder in which a subset of patients exhibits a type 2 (Th2- or T2-high) endotype driven by eosinophilic, IL-4/IL-13-mediated inflammation. Traditional animal and 2D cell-based models incompletely reproduce human airway immune responses, particularly the Th2 phenotype. To address this gap, we developed a three-dimensional (3D) ex vivo model of human nasal respiratory mucosa incorporating type-2-biased immune stimulation.
Methods: Primary nasal mucosal biopsies were expanded under air-liquid interface (ALI) conditions and either exposed to IL-4/IL-13 or co-cultured with autologous polarized CD4+ Th2 lymphocytes and dendritic cells to generate a Th2-dominated microenvironment. Tissue morphology and barrier function were monitored longitudinally by phase-contrast microscopy and transepithelial electrical resistance (TEER).
Results: Induction of a type-2 inflammatory state was confirmed by increased secretion of periostin, STAT-6, IL-4 and IL-13 in apical and basal compartments, together with modest TEER reduction and evidence of epithelial remodeling, whereas IL-8 and chitinase family proteins did not increase, thereby excluding a COPD-like or type-2-low phenotype.
Conclusions: Rather than fully recapitulating clinical asthma, this methodological model reproduces key immunopathologic features of T2-high airway inflammation in a patient-derived 3D context. It provides a stable, human-relevant platform for mechanistic studies and for future preclinical screening of targeted anti-inflammatory therapies
Moving from the South of Italy: The parental role on student mobility for tertiary education
No full textThis article examines how differently the family background affects the choice of sons and daughters to move to another region for tertiary education and how the mother's role on student mobility differs from that of the father. We apply multinomial logistic regression models to longitudinal data on high school-university transition regarding southern students enrolled at university in Italy. We treat missing data for parental educational and occupational variables using multiple imputation combined with inverse probability weighting. In light of a re-examination of the concept of dominance, the results are an interplay amongst parental education and occupation, parental and descendant gender, and geographical mobility trajectories. The findings highlight that a linear order of dominance exists on student mobility from the South to the northern regions, which is associated to the parents with high education level and in the highest positions in the occupational hierarchy. Nonlinear dominance in some cases may emerge, because disadvantaged parents invest in student mobility to allow to the descendants to better their social position with respect to their parents. Mothers are more dominant on daughters' mobility for the universities in the South or Centre of Italy. Self-employed parents matter for the sons, if they are South to Centre movers
Per l’inammissibilità del rinvio pregiudiziale di cui all’art. 363-bis c.p.c. da parte del giudice amministrativo (a margine di Tar Liguria, sez. II, ord. 28 febbraio 2025 n. 230 e di Cass., Primo Presidente, assegnazione del 6 maggio 2025)
No full textThe paper concerns the possibility for the administrative judge to preliminarily refer the question of jurisdiction to the Court of Cassatio
Nutritional, Functional, and Technological Outcomes of Fortification Strategies in Unleavened Bakery Products: A Systematic Review
No full textUnleavened bakery products—breadsticks, crackers, taralli, and flatbreads—are widely consumed and represent promising carriers for nutritional fortification. Studies have explored adding dietary fibers, plant proteins, phytochemicals, vitamins, minerals, and agro- industrial by- products, but findings remain scattered. We systematically reviewed studies on fortification strategies for
unleavened bakery products, searching PubMed, MEDLINE, Embase, Ovid, and Web of Science without time restrictions (last
search 20 August 2025). Two reviewers independently conducted screening, data extraction, and quality appraisal. Risk of bias
was assessed with validated and adapted tools according to design, and certainty of evidence with GRADE. Ninety- seven studies
met inclusion criteria: 88 experimental laboratory studies, 7 randomized controlled trials, 1 cross- sectional survey, and 1 ani
mal feeding trial. The most frequently investigated ingredient macrocategories were Cereals & Bran by- products (24.7%), Wine
& Olive by- products (18.6%), and Plant skins & Extracts (18.6%). Marked heterogeneity precluded meta- analysis; evidence was
synthesized narratively. Fortification—typically involving substitution levels between 5% and 30% of wheat flour with legume
flours, pseudo- cereals, or plant by- products—increased fiber, phenolics, micronutrients, and antioxidant capacity, while improving or maintaining physical and textural properties and overall acceptability. Human trials were few and brief, showing mixed effects on glycemia, satiety, and cardiometabolic markers; bioavailability and dose–response were seldom tested. Gaps included
poor reporting of processing parameters, small samples, inconsistent sensory and shelf- life evaluation, and scarcity of clinically
meaningful endpoints. This review provides the first comprehensive synthesis of fortification approaches for unleavened bakery products, consolidates the evidence base, and identifies priorities: standardized analytical and sensory protocols, assessment of
shelf- life and consumer acceptance, nutrient bioavailability, and powered clinical studies aligned with public- health nutrition and product innovation
From Single Neuron Models to Network Simulations: Computational Insights into Physiological and Pathological Brain Function
No full textLe neuroscienze computazionali offrono un potente framework per collegare i meccanismi molecolari, cellulari e di rete del cervello. Con il continuo avanzamento delle tecniche sperimentali, che producono quantità sempre maggiori di dati ad alta risoluzione e multiscala, la modellazione computazionale è diventata uno strumento essenziale per integrare tali risultati e generare interpretazioni meccanicistiche della funzione neuronale, sia in condizioni fisiologiche sia patologiche. In questo contesto, la presente tesi contribuisce combinando modelli di singola cellula biofisicamente dettagliati, metodi di ottimizzazione basati sui dati e simulazioni di rete su larga scala, al fine di studiare come la dinamica dei canali ionici influenzi l’eccitabilità intrinseca e il comportamento emergente dei circuiti neuronali corticali e ippocampali.La prima parte del lavoro si concentra su modelli neuronali multicompartimentali costruiti a partire da morfologie realistiche e registrazioni elettrofisiologiche, seguendo il formalismo di Hodgkin–Huxley. Questo approccio viene applicato a diverse regioni cerebrali, consentendo l’integrazione sistematica di osservazioni sperimentali e la formulazione di previsioni testabili. Nei neuroni stellati dello strato II della corteccia entorinale mediale (mEC), mostriamo che i canali del Ca2+ di tipo T agiscono in sinergia con le correnti persistenti del Na+ nel regolare l’eccitabilità intrinseca. Nei neuroni piramidali dello strato V della neocorteccia murina, le simulazioni rivelano che i canali del Ca2+ di tipo N e i canali BK formano un microdominio funzionalmente e spazialmente accoppiato, che determina sia la temporizzazione sia l’ampiezza dei segnali dendritici di Ca2+ associati ai potenziali d’azione retropropaganti.Viene inoltre esplorata l’eccitabilità patologica associata alle canalopatie del sodio legate al gene SCN2A, incorporando nel modello del neurone piramidale dello strato V gli effetti di mutazioni con perdita di funzione. Le simulazioni mostrano come alterazioni nella distribuzione dei canali nel segmento iniziale dell’assone compromettano l’inizio del potenziale d’azione, fornendo una spiegazione meccanicistica dei fenotipi elettrofisiologici divergenti osservati nell’epilessia e nei disturbi dello spettro autistico associati a SCN2A. Parallelamente, modelli biofisici recentemente ottimizzati dei neuroni CA1 dell’ippocampo murino riproducono la diversità elettrofisiologica delle cellule piramidali e dei principali sottotipi di interneuroni, costituendo una base solida per simulazioni realistiche a livello di circuito.La parte finale della tesi estende l’analisi dal livello del singolo neurone a quello delle reti, esaminando come i meccanismi cellulari intrinseci si propaghino e contribuiscano a modellare l’attività di popolazione. Viene presentata la ricostruzione e la simulazione di reti CA1 dell’ippocampo su larga scala, realizzate utilizzando sia neuroni multicompartimentali con dettagli biofisici completi sia modelli di neuroni puntiformi computazionalmente efficienti. Nonostante le significative differenze nel livello di dettaglio biologico, entrambi gli approcci sono in grado di riprodurre le principali dinamiche di rete osservate sperimentalmente. In particolare, il modello point-neuron emerge come uno strumento robusto e scalabile per l’esplorazione del comportamento dei circuiti ippocampali, grazie al suo ridotto costo computazionale e alla capacità di preservare le caratteristiche dinamiche essenziali.Nel complesso, i risultati di questa tesi dimostrano come la modellazione computazionale multiscala possa rivelare i principi biofisici alla base dell’eccitabilità neuronale e del comportamento delle reti. Integrando dati sperimentali, biofisica dettagliata dei canali ionici e simulazioni su larga scala, questo lavoro fornisce nuove intuizioni meccanicistiche sull’interazione tra funzione dei canali, integrazione dendritica e dinamica dei circuiti, in condizioni sia fisiologiche sia patologiche. Tali risultati sottolineano il valore delle neuroscienze computazionali non solo come strumento interpretativo, ma anche come mezzo per generare previsioni verificabili e orientare future ricerche sui meccanismi che governano la funzione cerebrale sana e alterata.Computational neuroscience offers a powerful framework for linking molecular, cellular, and network-level mechanisms in the brain. As experimental techniques increasingly provide high-resolution, multi-scale data, computational modelling has become essential for integrating these findings and generating mechanistic insights into both physiological and pathological neuronal function. This thesis contributes to this effort by combining biophysically detailed single-cell models, data-driven optimisation methods, and large-scale network simulations to investigate how ion-channel dynamics shape intrinsic excitability and emergent circuit behaviour in cortical and hippocampal neurons. The first part focuses on multicompartmental neuron models constructed from realistic morphologies and electrophysiological recordings, following the Hodgkin–Huxley formalism. This framework is applied to distinct brain regions, enabling the integration of experimental observations and the formulation of testable predictions. In medial entorhinal cortex (mEC) layer II stellate neurons, we show that T-type Ca2+ channels operate synergistically with persistent Na+ currents to regulate intrinsic excitability. In mouse neocortical layer-5 pyramidal neurons, simulations reveal that N-type Ca2+ channels and BK channels form a tightly coupled microdomain that shapes both the timing and amplitude of dendritic Ca2+ signals during back-propagating action potentials. We further explore pathological excitability associated with SCN2A-related sodium channelopathies by incorporating loss-of-function mutation effects into the L5 pyramidal neuron model. Our simulations demonstrate how altered channel distributions in the axon initial segment disrupt action potential initiation, offering a mechanistic explanation for the divergent electrophysiological phenotypes observed in SCN2A-linked epilepsy and autism spectrum disorders. In parallel, newly optimised biophysical models of mouse hippocampal CA1 neurons reproduce the electrophysiological diversity of pyramidal cells and interneuron subtypes, providing a foundation for realistic circuit-level simulations. The final part of the thesis transitions from single neurons to networks, analysing how intrinsic cellular mechanisms propagate to shape population activity. We present the reconstruction and simulation of large-scale hippocampal CA1 networks built using both biophysically detailed multicompartmental neurons and computationally efficient point-neuron models. Despite the substantial differences in biological detail, both modelling approaches reproduce key experimentally observed network dynamics. The point-neuron model, in particular, emerges as a robust and scalable tool for exploring hippocampal circuit behaviour thanks to its low computational cost and its ability to preserve essential dynamical features. Taken together, the results of this thesis demonstrate how multiscale computational modelling can reveal the biophysical principles underlying neuronal excitability and network behaviour. By bridging experimental data, detailed ion-channel biophysics, and large-scale simulations, this work provides new mechanistic insights into the interplay between channel function, dendritic integration, and circuit dynamics under both physiological and pathological conditions. These findings underscore the value of computational neuroscience not only as a tool for interpreting experimental observations, but also as a means of generating testable predictions and guiding future investigations into the mechanisms governing healthy and disordered brain function
A new class of Caffarelli-Kohn-Nirenberg type differential inclusion problems with singular terms and multivalued convection
No full textThe present article focuses on the research of a new kind of Caffarelli-Kohn-Nirenberg type differential inclusion problems (CKNDI, for short) involving a singular perturbation and a multivalued convection term. We develop a new framework by combining the super-sub solutions method, truncation techniques and the theory of multivalued pseudomonotone operators, to prove the existence of a positive solution to our class of problems
