Search Results (162,283)

Tyrosine kinases (TKs) are drug targets in diffuse intrinsic pontine glioma (DIPG). Ion channels are emerging targets in cancer. TKIs targeting different kinases such as everolimus, crizotinib, dasatinib, erlotinib, lapatinib, perifosine and midostaurin (0.001–100 μM) were investigated on cell proliferation and ion channel currents. Methods: Cell viability assays in parallel with a patch-clamp study and Western blot of target proteins are performed in SU-DIPG-36 and SU-DIPG-50 cells. Results: Midostaurin is the most effective drug in different assays. Patch-clamp investigations show that the application of midostaurin reduced the inward and outward whole-cell cation channel currents vs. controls in the presence of low internal ATP. These currents were sensitive to the KATP channel inhibitors glibenclamide and repaglinide and were fully reduced by the unselective blocker TEA-BaCl₂. Midostaurin also reduced currents that are sensitive to TRPV1 channel blockers capsazepine and ruthenium-red. The IC₅₀ values of midostaurin as an antiproliferative drug and ion channel inhibitor in either cell line are in the sub-micromolar range. In SU-DIPG-36 cells midostaurin causes a concentration-dependent upregulation of autophagy markers. Conclusions: The inhibition of cation channel currents by midostaurin in SU-DIPG-36 and SU-DIPG-50 cells and the autophagy potentiation in SU-DIPG-36 cells can be novel mechanisms in DIPG. Full article

Purpose: Hearing loss (HL) is a prevalent condition significantly impairing quality of life, with genetic mutations accounting for a substantial proportion of congenital cases, notably those involving the GJB2 gene encoding connexin 26. This study aims to analyze the current knowledge, feasibility, and challenges of gene therapy targeting GJB2-related HL, emphasizing both embryonic and postnatal interventions. Methods: A comprehensive scoping review was conducted across electronic databases up to October 2025, including studies focusing on GJB2-associated HL, gene therapy approaches, and the timing of interventions. Data extraction encompassed mutation types, animal models, delivery strategies, outcomes, and ethical considerations. Results: The results indicated over 467 GJB2 variants which could impair cochlear ion homeostasis and development. Animal models, mainly murine, demonstrated early-onset degeneration with limited recovery following delayed gene therapy, while early postnatal intervention showed greater efficacy. Viral vectors like AAV have been employed for targeted gene delivery via cochlear injections, achieving partial restoration of connexin expression and cochlear function, yet they have faced limitations including transduction efficiency, immune responses, and long-term stability. Challenges in translating these findings to humans have been compounded by anatomical, immunological, ethical, and safety issues, particularly regarding embryonic gene therapy and germline modifications. Ethical frameworks can vary internationally, highlighting the necessity for careful regulation. Conclusions: While promising advances in gene therapy for GJB2-related HL have been achieved in preclinical studies, significant scientific, technical, and ethical barriers must be addressed before clinical application, especially during embryogenesis. A multidisciplinary, cautious approach is essential to realize the potential of gene therapy in restoring natural hearing while safeguarding individual and societal interests. Full article

Thermodynamics is commonly presented as a theory of macroscopic systems in stable equilibrium, built upon assumptions of extensivity and scaling with system size. In this paper, we present a universal formulation of the elementary foundations of thermodynamics, in which entropy and energy are defined and employed beyond equilibrium and without assuming extensivity. The formulation applies to all systems—large and small, with many or few particles—and to all states, whether equilibrium or nonequilibrium, by relying on carefully stated operational definitions and existence principles rather than macroscopic idealizations. Key thermodynamic concepts, including adiabatic availability and available energy, are developed and illustrated using the energy–entropy diagram representation of nonequilibrium states, which provides geometric insight into irreversibility and the limits of work extraction for systems of any size. A substantial part of the paper is devoted to the analysis of entropy transfer in non-work interactions, leading to precise definitions of heat interactions and heat-and-diffusion interactions of central importance in mesoscopic continuum theories of nonequilibrium behavior in simple and complex solids and fluids. As a direct consequence of this analysis, Clausius inequalities and the Clausius statement of the second law are derived in forms explicitly extended to nonequilibrium processes. The resulting framework presents thermodynamics as a universal theory whose concepts apply uniformly to all systems, large and small, and provides a coherent foundation for both teaching and modern applications. Full article

Background: Brucella canis is an emerging zoonotic pathogen responsible for canine reproductive disorders and public health concerns. This study assessed the seroprevalence of B. canis in dogs from Campania, Southern Italy (2022–2025). Methods: Serum samples (n = 400) were retrospectively screened using an indirect immunofluorescence assay (IFAT), performed according to the manufacturer’s instructions. Screening was conducted at a 1:40 cut-off, followed by serial dilutions to determine endpoint titres. Statistical analysis included chi-square tests for univariable screening, followed by nominal logistic regression models to evaluate the association between IFAT positivity and predictive factors (year, province, and sex of dogs). Additionally, a general linear model (GLM) was applied to the seropositive subset (n = 69) to analyse the magnitude of the antibody response, expressed as geometric mean titres (GMTs). Results: The overall seroprevalence was 17.3% (95% CI: 13.6–21.0%). Dog’s sex, year of sampling, and province were not significant independent predictors of infection (p > 0.05), but GLM analysis showed that sampling year (p = 0.0024) and province (p = 0.0490) significantly influenced antibody intensity. A significant temporal increase in antibody intensity was observed towards 2025 (p = 0.037), suggesting an intensification of infection pressure. Conclusions: Our results confirm that Brucella canis is an endemic pathogen in the shelter dog population of southern Italy. The high seroprevalence and significant increase in antibody magnitude (GMT) over the study period indicate rising infection pressure, highlighting the urgent need for mandatory screening and a coordinated One Health surveillance strategy to manage zoonotic risk effectively. Full article

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation and systemic inflammation, with the cardiovascular (CV) system representing a major yet frequently under-recognized target. Cardiac involvement spans from subclinical myocardial inflammation to overt pericardial disease, myocarditis, valvular abnormalities, coronary microvascular dysfunction, and accelerated atherosclerosis. Given that CV disease remains a leading cause of morbidity and mortality in SLE, early detection of silent cardiac injury is crucial. Aim: This review aims to provide a comprehensive and clinically oriented overview of CV involvement in SLE, focusing on the role of multimodal cardiac imaging in the detection, characterization, and risk stratification of cardiac abnormalities, as well as its potential implications for clinical management and preventive strategies. Methods: This narrative review is based on a structured, non-systematic search of PubMed (2013–2026), combining the term “systemic lupus erythematosus” with imaging-related keywords including “transthoracic echocardiography,” “cardiac magnetic resonance,” and “cardiac computed tomography.” English-language studies in adult populations were screened and selected according to clinical relevance, methodological robustness, and contribution to understanding SLE-related cardiac involvement. Discussion: Multimodal cardiac imaging plays a central role in the evaluation of SLE-related cardiac disease. Transthoracic echocardiography (TTE) represents the first-line modality for the assessment of ventricular function, pericardial disease, and valvular abnormalities, while deformation imaging enables the detection of subtle myocardial dysfunction. Cardiac magnetic resonance (CMR) provides comprehensive tissue characterization, allowing differentiation between active inflammation and chronic fibrosis. Cardiac computed tomography (cCT) identifies subclinical coronary atherosclerosis and high-risk plaque features, whereas nuclear imaging techniques offer insight into inflammatory activity and microvascular dysfunction. Conclusions: An integrated, imaging-based approach enables early diagnosis, refined CV risk stratification, longitudinal monitoring, and personalized therapeutic strategies. Multimodal imaging thus represents a key pillar of precision medicine in lupus-associated CV disease. Full article

The ratio of high-sensitivity C-reactive protein (hs-CRP) to Serum albumin (SA) (hs-CRP/SA) is emerging as a new potential biomarker capable of stratifying cardiovascular risk in patients with chronic HF (CHF), particularly the risk of major adverse cardiovascular events (MACEs). Objectives: The aim of this study was to evaluate the long-term prognostic value of the hs-CRP/SA ratio on the risk of MACEs in a population of outpatients with CHF. Methods: In this retrospective observational study, 500 patients were enrolled and were stratified into two groups based on the median value of the hs-CRP/SA ratio: 249 patients with hs-CRP/SA < 1.19 and 251 patients with hs-CRP/SA ≥ 1.19. Results: During median follow-up of 5.2 years, 3.6 MACEs/100 patients/year were detected; patients with hs-CRP/SA ≥ 1.19 had a MACE incidence of 5.9 events per 100 patient-years, compared with 1.2 events per 100 patient-years in those with hs-CRP/AS < 1.19 (p < 0.001). Multivariate analysis confirmed that hs-CRP/SA ≥ 1.19 was associated with an approximately 6.5-fold increased risk of new MACEs (HR 6.513, 95% CI 3.928–10.797; p < 0.001). Conclusions: The hs-CRP/SA ratio is confirmed as a powerful prognostic marker in patients with CHF, associated with a significantly increased risk of MACEs. Full article

In recent years, applications with robots collaborating actively with humans have been increasing. The transition from Industry 4.0 to 5.0 rearranges the focus of fully automated processes to a human-centered system that allows more customization and flexibility. In human-centered systems, the robot is expected to safely assist or provide support to the human operator, avoiding any unintentional harm, while the latter is focused on tasks that require human reasoning, since current decision-making systems still have some limitations. This survey reviews all the main functionalities required to make a robot (collaborative or not) act as an assistant for human operators, analyzing and comparing solutions proposed by the authors (based on previous works) and/or the ones available in the literature. In this way, it is possible to combine those functionalities and build a complete framework enabling safe mobile manipulation while interacting with humans. In particular, a mobile manipulator is used to receive requests from a user, navigate in a human-shared environment, identify the requested object, and grasp and safely deliver such an object to the user. The framework, which is completed by a user interface designed using Android Studio, is developed in ROS1, tested, and validated on a real mobile manipulator in real-world conditions. Full article

Black Soldier Fly larvae (BSFL) bioconvert a wide variety of organic waste into value compounds including the residual frass, a by-product exploitable as compost for plant growth. The use of a non-standardized waste diet that varies in terms of properties does not ensure the maintenance of a highly fertile and healthy BSF colony able to produce viable inoculum (5–7-day-old larvae) for waste bioconversion. The Gainesville diet (GD) is a balanced formulation to ensure full larval development in fertile adults, resulting in a stable rearing colony. On a large scale, the bioconversion supply chain can produce different types of frass. Frass derived from the Gainesville diet (GDf), from fruit and vegetable waste (FVWf), and from milled fruit and vegetable waste (MWf) was composted and then compared to evaluate its fertilizing effect on lettuce growth in two pot-growing experiments. Each compost was added at concentrations of 2.5, 5, and 10%. The growth of lettuce improved significantly with the addition of composted frass in a dose-dependent manner when compared to unfertilized soil. GDf 10% gave the significantly best performance in terms of plant height (20.8 cm versus 17.9 cm) and fresh weight (113.5 g versus 87.7 g) compared to FVWf. In the experiment, the combined use of composted frass at 10% of both GDf and FVWf with a double mineral fertilizer application showed no significant differences compared to triple application. However, GDf provided significantly greater chlorophyll content than FVWf. These results highlight how, under the conditions tested in the present work, the frass of the entire productive chain of BSF is a high value by-product. Full article

The use of olive by-products in livestock farming is a valuable resource, given their high levels of bioactive compounds with antioxidant and health-promoting properties. This preliminary study adopted an integrated approach to evaluate the influence of dietary Olea europaea L. polyphenols on animal welfare, physiological stress response, intestinal morphofunctional traits, and meat quality in Neroametà finishing pigs, a novel Casertana × Large White genetic line (Neroametà). Thirty pigs reared under extensive farming conditions were randomly allocated to two groups (n = 15): a control group fed a standard diet (C) and a treatment group (OL) supplemented with 300 mg/head/day of olive polyphenolic extract for 90 days. The study focused on the systemic correlation between host health and product quality. Meat composition, rheological properties, meat antioxidant activity, stress parameters, and fatty acid profiles of the longissimus lumborum and psoas major muscles were analyzed. Results showed that the OL diet significantly modulated the HPA axis, as evidenced by a marked reduction in plasma ACTH and cortisol levels, alongside improved antioxidant status. These physiological changes were positively associated with a trophic effect on the intestinal mucosa, characterized by increased villus height and a more favorable villus/crypt ratio. Regarding meat quality, the OL group exhibited superior oxidative stability, optimized pH decline, and an improved intramuscular fatty acid profile (increased MUFA and n-3 PUFA, reduced SFA). Despite the pilot scale of 30 animals, these findings provide a solid foundation for characterizing the Neroametà breed. In conclusion, Olea europaea L. polyphenols act as a multi-level modulator, enhancing physiological resilience and meat quality, offering a sustainable strategy for high-quality pork production in line with circular economy and One Health principles. Full article

Objectives: This study aims to define the surgical anatomy, technical feasibility, advantages, and limitations of the TPPA through detailed cadaveric dissection and a representative clinical case, evaluating its potential as a safe and effective alternative to traditional approaches to the mesiotemporal lobe. Methods: A cadaveric dissection was performed on one adult head injected with colored latex, using standard microsurgical instruments and high-definition video documentation. Each procedural step was recorded and illustrated with cadaveric photographs. Additionally, a clinical case of mesiotemporal cavernous hemangioma resected via TPPA is presented, including an operative video. Results: The dissection demonstrated a direct and safe trajectory to the amygdala and hippocampal head, with clear identification of key vascular and white matter landmarks. In the clinical case, the lesion was completely resected with no postoperative neurological deficits. Conclusions: The TPPA represents a novel microsurgical corridor to the mesiotemporal region, minimizing cortical disruption, Sylvian fissure dissection, and manipulation of middle cerebral artery branches. Although its exposure is limited posteriorly, the TPPA could offer an optimal balance between functional preservation and surgical accessibility, constituting a valuable addition to the modern microsurgical armamentarium. Full article

This paper presents the H-CoRE (Heterogeneous Cooperative Multi-Robot Execution) framework designed to enable autonomous multi-robot operations in GNSS-denied environments. Built on an ROS 2-based architecture, H-CoRE enables collaborative, structured task execution through standardized software stacks. Each robot’s stack combines a high-level executive system with an agent-specific motion layer and leverages multi-sensor fusion for localization and mapping. The framework is inherently reconfigurable, allowing individual agents to operate autonomously or as part of a multi-robot team for collaborative missions. In the considered scenario, the system integrates aerial and ground vehicles, a fixed pan–tilt–zoom camera, and a human supervisory interface within a unified, modular infrastructure. The proposed system has been deployed in indoor, GNSS-denied environments, demonstrating autonomous navigation, cooperative area coverage, and real-time information sharing across multiple agents. Experimental results confirm the effectiveness of H-CoRE in maintaining general awareness and mission continuity, paving the way for future applications in search-and-rescue, inspection, and exploration tasks. Full article

The management of large and heterogeneous building stocks requires decision-support tools capable of prioritising interventions under limited technical and financial resources. In this framework, the role of structural deterioration is rarely integrated within a unified prioritisation framework. This study proposes a rapid deterioration-based assessment for prioritising maintenance within heterogenous portfolios. The assessment is articulated into two levels. A Project Level (PL) is based on visual inspections and component-level condition ratings, while a Network Level (NL) introduces contextual and functional modifiers related to the relevance of each structural unit within the building stock. A seismic assessment procedure is integrated in proposed decision-making system for optimising intervention planning. The two assessments are integrated through a decision-tree logic providing an overall classification of buildings within portfolios. The proposed framework is applied to an industrial-oriented building stock located in Italy, comprising 79 structural units characterised by significant typological heterogeneity, including masonry, reinforced concrete, precast reinforced concrete, and steel buildings. The application illustrates the internal consistency of the proposed framework and its ability to support a transparent and articulated prioritisation process for maintenance and risk mitigation within heterogeneous building portfolios. Further applications to different building stocks are required to explore the general applicability of the methodology. Full article

Light spectral composition plays a central role in regulating plant growth, morphology, nutrient uptake, and pigment biosynthesis, particularly in controlled-environment agriculture. This study investigated the effects of targeted LED spectral modulation, focusing on green light deprivation and different red-to-blue (R:B) ratios at constant photon flux density, on morphological traits, mineral composition, and photosynthetic pigments in Salvia officinalis L. and Cannabis sativa L. grown under controlled conditions. Plants were cultivated under three LED treatments providing equal light intensity but differing in spectral composition. Morphological parameters, mineral nutrients, inorganic anions, and photosynthetic pigments were assessed at harvest. Total biomass production was not significantly affected by the light treatments in either species; however, clear species-specific responses were observed. In S. officinalis, higher R:B ratios promoted stem elongation without affecting leaf number or fresh weight, whereas in C. sativa, the higher R:B ratio significantly increased leaf number. Green light deprivation and red–blue enrichment generally enhanced mineral accumulation and nitrogen content, although the magnitude and direction of these effects varied between species. Photosynthetic pigment responses were more pronounced in hemp, with increased chlorophylls and carotenoids under green light deprivation, while salvia showed a selective increase in carotenoids under higher R:B ratios. Overall, these findings emphasize the importance of species-specific LED spectral optimization to improve physiological performance and nutritional quality in indoor cultivation of medicinal plants. Full article

Inherited cardiomyopathies represent a major cause of ventricular arrhythmias (VA) and sudden cardiac death (SCD), frequently occurring in the absence of advanced systolic dysfunction. Traditional strategies for the primary prevention of SCD have relied predominantly on left ventricular ejection fraction (LVEF), an approach that fails to capture the substantial biological and clinical heterogeneity of non-ischemic cardiomyopathies. Over the past decade, advances in cardiac genetics and cardiac magnetic resonance imaging have identified specific genotypes associated with a disproportionate arrhythmic risk, which often precedes overt ventricular remodeling. The 2023 European Society of Cardiology (ESC) Guidelines on cardiomyopathies formalize this paradigm shift by integrating etiology, myocardial substrate, and electrical phenotype into contemporary risk stratification. In this narrative review, we focus on cardiomyopathy-associated genotypes consistently linked to high arrhythmic risk—LMNA, truncating variants in FLNC, RBM20, PLN p.Arg14del, and desmosomal genes—and examine their molecular mechanisms, phenotypic trajectories, and arrhythmogenic profiles. We discuss how genotype-specific patterns of myocardial fibrosis, conduction disease, and VA inform implantable cardioverter-defibrillator (ICD) decision-making beyond LVEF-based thresholds. By synthesizing genetic, imaging, and clinical evidence in light of ESC 2023 recommendations, this review highlights the evolving role of genotype-informed strategies in the personalized prevention of SCD and underscores remaining gaps in evidence and risk prediction. Full article

Urtica dioica L. and Parietaria judaica L. subsp. judaica are two members of the Urticaceae family well-known for their sensitization and allergenic potential. Nevertheless, both species were used in traditional medicine, and various pharmacological properties have been described so far. Here, the dried aerial parts from Southern Italy were extracted through maceration, and a preliminary comparative study focused on the in vitro antioxidant and anti-denaturation properties, as well as on the pancreatic lipase inhibitory effects, was carried out. The most apolar constituents were extracted by means of liquid–liquid extraction, and the phytochemical profile of the two species was verified with gas chromatography–mass spectrometry (GC–MS) analyses and compared using principal component analysis (PCA). The correlation between detected phytochemicals and observed biological properties was also verified. A positive correlation was observed between lipase inhibition and the compounds mainly abundant in the U. dioica dichloromethane fraction, which showed the best activity (IC₅₀ = 1.67 ± 0.01 mg/mL). The two P. judaica fractions instead showed the best anti-denaturation effects (IC₅₀ = 321.6 ± 3.3 and 424.4 ± 1.8 μg/mL). Further studies are needed to optimize the solvent partitioning method and to deeply study the interesting biological properties of investigated species. Full article