Search Results (10,694)

This paper presents a real-time digital twin (DT) of the power conversion system used in offshore wind applications. The proposed DT is exploited to identify key electrical parameters of both the permanent magnet synchronous generator (PMSG) and the three-phase boost rectifier and has been developed with a Condition Monitoring (CM)-oriented approach. A Gated Recurrent Unit (GRU) neural network is adopted as a real-time digital model (RTDM) to estimate online the PMSG phase resistance and synchronous inductance, as well as the DC-link capacitance at the rectifier output. The network is trained in MATLAB using data generated by a Typhoon HIL 606 emulator, covering both balanced and unbalanced operating conditions and a wide range of parameter variations. The trained GRU is then deployed on the control board and implemented in LabVIEW Real-Time for embedded execution. Experimental tests on a PMSG-based generating unit confirm the effectiveness of the proposed RTDM, achieving low root-mean-square and mean percentage errors in parameter estimation. The results demonstrate that the enhanced neural real-time DT is a promising tool for condition monitoring and predictive maintenance of power conversion systems in offshore wind applications. Full article

Activating PIK3CA mutations occur in approximately 40% of hormone receptor-positive (HR+)/HER2-negative breast cancers and represent a major driver of endocrine resistance. The PI3Kα-selective inhibitor alpelisib, in combination with fulvestrant, significantly improves progression-free survival in patients with PIK3CA-mutant disease, as demonstrated in the SOLAR-1 trial. However, this therapeutic strategy is frequently complicated by treatment-induced hyperglycemia, a metabolic disturbance that promotes oxidative stress, mitochondrial dysfunction, and inflammatory signaling, thereby increasing cardiovascular vulnerability. Sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as cardiometabolic modulators with benefits extending beyond glucose lowering. In this study, we used a human cardiomyocyte in vitro model designed to recapitulate the hyperglycemic metabolic milieu observed in breast cancer patients receiving PI3Kα-targeted therapy, to investigate whether the SGLT2 inhibitor dapagliflozin directly protects cardiomyocytes from alpelisib- and fulvestrant-induced injury. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured under hyperglycemic conditions (25 mM glucose) to mimic the metabolic environment associated with PI3Kα inhibitor-induced dysglycemia. Cells were exposed to alpelisib (100 nM) and fulvestrant (100 nM), alone or in combination, in the absence or presence of dapagliflozin (1 μM). Cardiomyocyte viability was assessed using the MTS assay, mitochondrial function by TMRM-based mitochondrial membrane potential (ΔΨm) measurements, and apoptosis by caspase-3 quantification. Cardiomyocyte injury was evaluated by release of cardiac troponin I and heart-type fatty acid binding protein (H-FABP). Lipid peroxidation markers (MDA and 4-HNE) were measured to assess oxidative membrane damage. Intracellular inflammasome-related signaling (NLRP3 and MyD88) and secreted inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2) were quantified by ELISA. Exposure to alpelisib, particularly in combination with fulvestrant, significantly reduced cardiomyocyte viability, induced mitochondrial depolarization, and increased caspase-3-mediated apoptotic signaling. These alterations were accompanied by elevated lipid peroxidation (MDA and 4-HNE) and increased release of cardiac injury biomarkers (troponin I and H-FABP). Alpelisib-based treatments also activated inflammasome-related signaling, as indicated by increased intracellular NLRP3 and MyD88 levels and enhanced secretion of pro-inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2). Co-treatment with dapagliflozin significantly attenuated these alterations, preserving mitochondrial membrane potential, reducing apoptotic signaling, limiting oxidative membrane damage, and suppressing inflammatory cytokine release. This study provides evidence that alpelisib-based therapy under hyperglycemic conditions is associated with oxidative, mitochondrial, and inflammatory stress responses in human cardiomyocytes, recapitulating key features of cardiometabolic stress relevant to PI3Kα-targeted therapy. Importantly, dapagliflozin markedly attenuated these alterations, supporting a potential cardioprotective role that may extend beyond glycemic control. These findings provide a mechanistic rationale for further investigation of SGLT2 inhibition as a cardiometabolic protective strategy in patients receiving PI3Kα inhibitor-based cancer therapy. Full article

The Rio Grande Rise (RGR) is the largest oceanic plateau in the South Atlantic and represents a key natural laboratory for understanding oceanic plateau formation, deep-sea circulation, ecosystem functioning, and ferromanganese crust development. This study presents a critical synthesis of current scientific knowledge on the RGR, integrating geological, geophysical, oceanographic, biological, and geochemical evidence published over the last two decades. Geophysical data reveal a complex tectono-magmatic evolution involving Late Cretaceous plume-related volcanism, crustal thickening, rifting, and subsequent subsidence. The structural framework of the plateau is dominated by the Cruzeiro do Sul Rift, which plays a central role in controlling sedimentation, magmatism, and seawater circulation. Oceanographic studies demonstrate that the interaction between the southern branch of the South Equatorial Current and the complex topography of the RGR generates intense internal tides and bottom currents, strongly influencing sediment transport and benthic habitats. Biological investigations indicate that the RGR hosts diverse deep-sea communities, including sponge grounds, cold-water corals, and associated fauna, whose distribution is tightly linked to geomorphology and hydrodynamics. Ferromanganese crusts occurring on the plateau preserve valuable geochemical records of oceanographic and redox conditions, although their spatial distribution, thickness, and metal budgets remain incompletely constrained. Despite major advances, significant knowledge gaps persist regarding crustal structure, sedimentary evolution, ecosystem functioning, and mineral formation processes. This review highlights these uncertainties and outlines research priorities necessary to improve understanding of oceanic plateaus and deep-sea systems in the South Atlantic. Full article

The present narrative review reports the main preclinical and clinical results obtained by using supplementation of saffron or its pure components in neurodegeneration, with special emphasis on age-related macular degeneration. Beyond that, this article will address shared pathways between neurodegenerative diseases of the eye and the brain. It will be shown that saffron treatment might counteract oxidative damage in the retina and brain, as well as inflammation and inflammatory mediators that induce neuronal degeneration and death. The ways of action are multiple, and saffron chemical components appear to act in a synergistic manner, inducing tissue resilience. These effects critically depend upon the saffron chemical composition and structure. A well-defined ratio among molecules is linked to a patented batch known as Repron^® and offers the maximum protection against neurodegeneration. Full article

Heating, ventilation, and air conditioning (HVAC) systems are essential for indoor air quality and thermal comfort but can simultaneously act as vectors for microbial contamination, particularly bacteria and fungi. While the COVID-19 pandemic intensified focus on airborne viral transmission, bacterial and fungal contamination in indoor environments remains a persistent and significant health risk. This study presents a detailed case study of a restaurant HVAC system, analysing the impact of different ventilation strategies on bacterial contamination, infection transmission risk, energy consumption, and thermal comfort. By focusing on a real-world application, the research evaluates practical challenges and trade-offs associated with HVAC operation modifications aimed at mitigating microbial risks while maintaining acceptable energy and comfort levels. The research compares three operational scenarios: normal operation with air recirculation, 24 h operation with 100% outdoor air, and extended operation periods. Results demonstrate that while strategies emphasizing outdoor air intake and extended operation reduce infection probability by up to 60–65%, they simultaneously increase energy consumption by over 1700% and compromise thermal comfort parameters. In the h24 case, the pre-heat coil rises from 2421.7 to 43,923.7 kWh and the post-heat coil from 24,812.8 to 152,970.4 kWh, while the Plus 2 h strategy reduces the energy penalty by roughly 42–51% with respect to the h24 case. The findings are contextualized within current research on bacterial and fungal risks in HVAC systems, highlighting the critical need for balanced ventilation strategies that integrate health protection, energy efficiency, and comfort considerations. Full article

Background/Objectives: Hearing impairment is a highly prevalent sensory disorder resulting from a variety of causes. A high proportion of autosomal recessive non-syndromic hearing impairment is linked to the GJB2 (OMIM 121011) gene which encodes for a gap junction protein, connexin-26. Alterations of genes that encode for connexins can lead to changes in cell ion content and cause hearing impairment. Methods: GJB2 gene polymorphisms (c.71G>A, p.Trp24*rs104894396; c.457G>A, p.Val153Ile, rs111033186; c.380G>A, p.Arg127His, rs111033196; c.109G>A, p.Val37Ile, rs72474224; and c.269T>C, p.Leu90Pro, rs80338945) were analyzed in the Roma population of Croatia. Loci were genotyped using the KASP method. Results: Altered alleles were detected on the loci c.71G>A, c.457G>A and c.380G>A and statistically significant differences in allele frequencies were noticed. Furthermore, in comparison to worldwide populations, the Roma population also shows statistically significant difference in allele frequency of these loci. Conclusions: This study reveals marked genetic differentiation among Croatian Roma particularly with respect to the c.71G>A variant. Characterizing such population-specific mutational heterogeneity is crucial for the accurate prevention, diagnosis, and clinical management of autosomal recessive nonsyndromic hearing loss. Full article

Objectives: To investigate clinical and imaging predictors of short- and long-term outcomes in patients with posterior circulation stroke (PCS), with particular focus on infarct topography and ischemic burden. Methods: We conducted a retrospective multicenter observational study including 251 consecutive patients with acute PCS. All patients underwent CT angiography within 24 h and follow-up CT/MRI at 48–72 h. Clinical data, vascular risk factors, stroke severity (NIHSS), and functional outcome assessed by modified Rankin Scale (mRS), were collected. Short-term outcome was defined as mRS at discharge and long-term outcome as mRS at 3 months. Favorable outcome was defined as independence, graded as mRS 0–1. Imaging analysis included pc-ASPECTS, collateral scores, and quantitative ischemic volume assessment. Multivariable logistic regression was performed to identify independent predictors of outcome. Results: Among 251 patients, 105 (41.8%) had LVO. Patients with LVO presented with higher NIHSS scores, larger infarct volumes, and more frequent multiregional involvement. Basilar artery occlusion was associated with the most severe clinical and radiological profile. Infarct location, ischemic volume, baseline NIHSS, and pre-stroke mRS were independently associated with short-term outcome. For long-term outcome, age, infarct location, diabetes, and pre-stroke mRS remained significant predictors. LVO status and treatment variables were not independently associated with outcome. Conclusions: In PCS, outcome is primarily influenced by infarct topography and clinical factors rather than LVO status alone. Multiregional involvement and baseline disability are key determinants of prognosis. These findings underscore the need for PCS-specific prognostic models and highlight the importance of detailed imaging assessment beyond vessel occlusion. Full article

Background and Objectives: Enhanced Recovery After Surgery (ERAS) pathways are increasingly used in spine surgery, but uptake in adolescent idiopathic scoliosis (AIS) remains heterogeneous across institutions. Evidence in pediatric deformity surgery supports shorter recovery with protocolized care, yet real-world comparative data combining ERAS and the erector spinae plane block (ESPB) remain limited. This study aimed to compare early postoperative outcomes between a historical standard-care pathway and a structured ERAS+ESPB pathway in adolescents undergoing posterior spinal fusion for AIS. Materials and Methods: A single-center retrospective time-based comparative cohort study design included consecutive AIS patients (<18 years) treated between 1 January 2024 and 31 December 2025. The standard-care pathway was applied to patients operated on before 1 June 2025 (n = 34), whereas the ERAS+ESPB pathway was applied to those operated on from 1 June 2025 onward (n = 35), following formal institutional implementation. Outcomes included postoperative pain assessed using the visual analog scale under two functional conditions—at rest in the supine position and during standing/mobilization—at POD0, POD1, POD2, POD3, discharge, and 2-week follow-up; postoperative nausea at POD0–POD3; and length of stay (LOS). Between-group pain comparisons used Welch’s t-test; nausea used Fisher’s exact test; LOS used the Wilcoxon rank-sum test. Results: At POD0, supine pain was lower in ERAS+ESPB (1.50 ± 0.55) than in standard care (3.20 ± 1.50; p < 0.001). From POD1 onward, supine pain did not differ significantly between groups. Among assessable patients, standing pain was lower in ERAS+ESPB at POD2 (3.05 ± 1.53 vs. 4.50 ± 1.05; p = 0.020), POD3 (2.82 ± 1.62 vs. 4.17 ± 1.03; p = 0.006), and 2-week follow-up (1.45 ± 0.80 vs. 2.26 ± 0.93; p = 0.006). Nausea was lower in ERAS+ESPB at POD0 (11.4% vs. 35.3%; p = 0.024) and POD2 (8.6% vs. 32.4%; p = 0.018), with no significant differences at POD1 or POD3. LOS was shorter in ERAS+ESPB (5.41 ± 1.10 vs. 8.32 ± 2.06 nights; p < 0.001). Conclusions: In adolescents undergoing posterior spinal fusion for AIS, an ERAS-based perioperative pathway incorporating ESPB was associated with improved early postoperative recovery, particularly in terms of immediate postoperative pain, pain during mobilization, early postoperative nausea at selected time points, and length of hospital stay. Prospective multicenter studies are needed to confirm these findings and clarify the independent contribution of individual pathway components. Full article

Background: Generative artificial intelligence (AI) can produce realistic human faces that are shared on social media, from where younger generations often derive body image norms. Aesthetic bias in these systems may promote unrealistic standards of beauty. This study examines whether generative AI produces facial images that are perceived by humans as more attractive than real human faces. Thus, we examine AI-generated facial imagery as a contemporary site of consumer culture, where beauty may become biased, unrealistic, and commodified: generating an algorithmically optimized product circulating through social media and digital platforms without proper regulation. Methods: Fifty AI-generated female faces were prospectively compared with 50 photographs of female models from a model agency. Facial attractiveness was rated by plastic surgeons, using a Likert scale and Mann–Whitney U for analysis. Results: AI-generated images received higher mean aesthetic scores than real photographs (7.79 vs. 6.88, p < 0.05), despite prompts requesting unattractive features. Conclusions: The AI model showed a small but consistent bias toward enhanced facial attractiveness. As AI-generated imagery increasingly shapes visual culture, this bias may contribute to unrealistic beauty standards, highlighting the need for AI literacy, responsible use of AI, and ethical oversight, especially when shared on social media. Full article

Complex psychosis (CP) remains one of the most challenging conditions in mental health, characterized by persistent symptoms, cognitive impairment, functional disability, and reduced autonomy. Traditional rehabilitation approaches, although essential, are often insufficient to address the multidimensional needs of these individuals. Over the past decade, rapid advances in digital health have opened new opportunities to enhance psychosocial rehabilitation, improve engagement, and personalize treatment pathways. This narrative review synthesizes current evidence on the use of digital and immersive technologies in the rehabilitation of people with CP, including virtual reality (VR), augmented reality (AR), telerehabilitation platforms, mobile health (m-Health) applications, digital phenotyping, and AI-assisted cognitive remediation. We examine clinical trials, feasibility studies, and real-world implementations published between 2015 and 2025, highlighting the efficacy of VR-based social cognition training, remote cognitive remediation, ecological momentary interventions, and hybrid digital–in-person rehabilitation models. Mechanisms of action, transfer to real-world functioning, and predictors of engagement are described. Barriers such as digital literacy, access disparities, privacy concerns, and clinical integration are critically discussed. We also outline future directions, including adaptive algorithms, biosensor integration, and the development of multimodal digital ecosystems tailored to individual recovery trajectories. By integrating technological innovation with recovery-oriented care, digital rehabilitation tools have the potential to transform the treatment landscape for people with CP. This review offers a roadmap for clinicians, researchers, and policymakers seeking to incorporate evidence-based digital solutions into modern psychiatric rehabilitation. Full article

This paper extensively explores the concept of dark atoms, hypothetical stable lepton-like particles with a charge of $-2n$ (where n is any natural number) that form neutral bound states with n primordial helium nuclei. The discussion begins with the introduction of multiply charged stable particles. Next, the formation and evolution of dark atoms are examined, followed by a review of related constraints. The capture of dark atoms by the Earth and implications for direct dark matter search are subsequently discussed. Then, the quantum-mechanical description of bound states between dark atoms and ordinary nuclei is addressed. Moreover, procedures for systematic comparisons with this model, which have general interest, are presented considering the DAMA published results on the dark matter annual and diurnal modulation signatures as a benchmark. Full article

Background: Malocclusion can influence not only oral function, but also adolescents’ perception of dental appearance, psychosocial status, and oral health-related quality of life. The present cross-sectional study aimed to examine the association between the clinical severity of malocclusion and adolescents’ self-perception, as well as to assess the level of agreement between clinician and patient ratings of aesthetic impairment. Methods: The study included 160 consecutive adolescents aged 12 to 17 years who were referred for orthodontic evaluation. Malocclusion severity was determined using the Index of Orthodontic Treatment Need (IOTN), considering both the Dental Health Component (DHC) and the Aesthetic Component (AC). Patients’ perceptions of malocclusion severity, aesthetic concerns, and functional limitations were collected through numeric rating scales, while psychosocial impact was measured using the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ). Correlations were examined with Spearman’s coefficients, agreement between clinician- and self-rated AC scores was evaluated with weighted kappa statistics, and multivariable regression analyses were used to identify independent predictors of patient-reported outcomes. Results: Moderate positive correlations emerged between IOTN-DHC and self-perceived malocclusion severity (rho = 0.42, p < 0.001), and between clinician-rated IOTN-AC and self-perceived severity (rho = 0.47, p < 0.001). Associations were stronger for aesthetic and psychosocial measures than for functional complaints, with the highest correlation observed between clinician-rated IOTN-AC and perceived aesthetic impact (rho = 0.58, p < 0.001). Greater clinical severity was also associated with increased psychosocial burden, as reflected by higher PIDAQ total scores. Agreement between clinician and patient evaluations of aesthetic impairment was fair to moderate (weighted kappa = 0.34) but improved when AC scores were grouped into broader categories (weighted kappa = 0.46). Overall, adolescents tended to perceive their dental aesthetic impairment as more severe than did clinicians. In the multivariable models, clinician-rated IOTN-AC remained an independent predictor of perceived severity, aesthetic impact, and psychosocial burden. Conclusions: Clinical measures of malocclusion severity and adolescents’ self-perception were significantly related, although they reflected partly different aspects of orthodontic treatment need. Combining normative clinical indices with patient-reported outcomes may allow a more complete and patient-centred evaluation of malocclusion. Full article

Background: Airway mucus plugging is a key but long-overlooked mechanism of persistent airflow obstruction in both asthma and chronic obstructive pulmonary disease (COPD). Type 2 (T2) cytokines, particularly interleukin (IL)-4 and IL-13, drive goblet cell metaplasia, MUC5AC overexpression, and impaired mucociliary clearance, while eosinophil-derived products increase mucus viscosity and promote plug persistence. Methods: A comprehensive narrative review was conducted by searching PubMed and ClinicalTrials.gov databases from inception to February 2026. Search terms included “mucus plugs,” “mucus plugging,” “biologics,” “dupilumab,” “tezepelumab,” “mepolizumab,” “benralizumab,” “IL-4,” “IL-13,” “MUC5AC,” “quantitative CT,” “functional respiratory imaging,” “asthma,” and “COPD.” Studies were included if they reported original data or systematic evidence on mucus plug quantification, biologic-mediated changes in mucus plug scores, or imaging modalities for mucus assessment in asthma or COPD. Editorials, case reports with fewer than three patients, and studies not available in English were excluded. Two authors (P.-V.M. and A.C.) independently screened titles and abstracts; discrepancies were resolved by consensus. Randomized controlled trials, observational studies, and preclinical studies evaluating mucus plug outcomes and T2-targeted therapies were included. Reference lists of retrieved articles were hand-searched for additional relevant publications. Results: A recent systematic review identified multiple randomized controlled trials and observational studies that showed CT-assessed mucus plug scores go down with biologic therapies targeting the T2 pathway in asthma. Observational data extend this evidence to anti-IL-5/IL-5Rα agents. The VESTIGE trial provided the first functional respiratory imaging evidence of mucus plug resolution with dupilumab. In COPD, the BOREAS/NOTUS and MATINEE trials established the efficacy of dupilumab and mepolizumab in eosinophilic phenotypes; however, differences in inclusion criteria—particularly regarding FeNO thresholds and prior exacerbation burden—may explain divergent effects on lung function endpoints. Mucus plug outcomes have not been evaluated in COPD biologic trials. Quantitative imaging modalities, including HRCT mucus plug scoring, functional respiratory imaging, and hyperpolarized gas MRI, now enable objective assessment of mucus burden. Conclusions: Mucus plugging meets the definition of a treatable trait: it can be measured with CT scoring, it matters clinically, and it responds to T2 cytokine blockade. Adding mucus plug assessment to routine clinical evaluation, together with mucolytic strategies where needed, could move treatment decisions from empirical to biology-based across the asthma–COPD spectrum. Further studies are needed to confirm that mucus plug scoring works as a biomarker of treatment response in COPD and to test whether combining biologics with mucolytics improves outcomes. Full article

Earthquake-induced landslides are a major hazard in mountainous regions, where complex topography and near-surface conditions jointly control ground-motion amplification and slope instability. In this context, ground-motion models used as triggering inputs for landslide analyses must accurately represent site effects in complex terrain. This study develops a geomorphometry-informed ground-motion model based on predictors derived from global remote sensing Digital Elevation Models (DEMs), conceived as a triggering component for earthquake-induced landslide applications. The model is based on the eXtreme Gradient Boosting (XGBoost) regression algorithm and predicts peak ground acceleration, peak ground velocity, and spectral accelerations by integrating seismic source parameters, finite-fault source-to-site metrics, and geomorphometric site proxies derived from global DEMs. The model is trained on an extended Italian strong-motion dataset comprising about 8300 recordings from 90 earthquakes with finite-fault rupture models and is evaluated using a strict leave-one-event-out validation scheme. Results show that finite-fault parameterization reduces prediction errors by about 11% compared to point-source formulations, while DEM-derived site proxies improve predictive performance by approximately 5% relative to V_S30 and 12% relative to the fundamental frequency f₀. Residual analysis yields inter-event variability of 0.19–0.22 and intra-event variability of 0.23–0.26. The proposed framework demonstrates how global remote sensing products provide value-added predictors for ground-motion triggering in complex terrain, suitable for integration with earthquake-induced landslide susceptibility models. Full article

Teacher well-being and performance represent critical challenges for educational systems worldwide. While organizational compassion has been identified as a protective resource, it remains unclear for whom compassion is most beneficial. Drawing on Job Demands–Resources (JD-R) theory and Conservation of Resources (COR) theory, we examined whether teachers’ self-efficacy moderates the relationship between workplace compassion and performance perceptions, testing differential patterns for individual versus organizational performance evaluations. Italian public-school teachers (N = 218; 82% female; M teaching experience = 11.6 years) completed an online survey measuring compassion at work, self-efficacy, and perceptions of individual and organizational performance. We employed a two-stage approach, first validating the measurement model through Confirmatory Factor Analysis (CFA), then testing moderation hypotheses using path analysis with mean-centered variables. Bootstrap confidence intervals (5000 iterations) verified the reliability of interaction effects. Self-efficacy significantly moderated the effect of compassion on individual performance perceptions (β = −0.006, p = 0.006; bootstrap 95% CI: [−0.010, −0.002]), revealing a compensatory pattern. Teachers with lower self-efficacy benefited substantially from workplace compassion (simple slope β = 0.31, p < 0.001), whereas teachers with high self-efficacy showed no significant benefit (β = 0.06, ns). The hypothesized synergistic effect on organizational performance perceptions was not supported (β = 0.006, p = 0.027; bootstrap CI included zero). Organizational compassion functions as a compensatory resource, most powerfully supporting teachers who lack personal resources. This challenges assumptions that organizational interventions uniformly benefit all employees and suggests that compassion-based interventions should be strategically targeted toward teachers experiencing lower self-efficacy. The study advances theoretical understanding of resource substitution mechanisms and provides actionable guidance for optimizing limited organizational resources in educational settings. Full article