Search Results (3,774)

Background/Objectives: Chronic primary pain (CPP) is a new diagnostic category including chronic pain conditions lacking clinical signs or a clear etiopathogenetic origin. These disorders may share a common neural mechanism known as central sensitization, where nociceptive neurons become hyper-responsive to standard or subthreshold pain stimuli, resulting in pain hyper-sensitivity. In this context, non-invasive brain stimulation (NIBS) appears to be a promising tool for improving CPP symptoms by targeting maladaptive brain activity and connectivity. To date, the effects of NIBS on CPP symptoms remain unexplored. To fill this gap, we conducted a meta-analysis, investigating the effect of NIBS in improving the three core symptoms of CPP, namely pain intensity, emotional distress, and functional disability. Methods: Following PRISMA guidelines, we screened four databases up to February 2025 for English-language, peer-reviewed randomized clinical trials that included CPP patients treated with NIBS and reported pre/post or follow-up scores on validated measures of at least one core symptom. Quality of life was examined as an additional outcome. Results: Fifty-four studies were included, with 1371 participants receiving real stimulation and 1103 sham. Findings highlighted that real stimulation improved CPP symptoms immediately after treatment and at one-month follow-up. Meta-regressions showed that longer CPP duration reduced short-term effects on emotional distress and diminished all outcomes at one-month follow-up. Conclusions: Further research is needed to establish standardized NIBS protocols for CPP management, to investigate the effectiveness at longer follow-up periods, and to test whether combining NIBS with other interventions enhances treatment effectiveness and durability. Full article

Driven by the high-end furniture industry’s demand for skin-tactile decorative boards, UV inkjet printing shows potential for wood-based surface finishing. Using primer-treated inkjet-printed melamine-faced panels, this study compared traditional UV varnish coatings with different thicknesses and UV curing intensities and 254 nm UV excimer-cured coatings with different radiant energies. Varnish thickness significantly affected surface roughness, 20° gloss, 85° gloss, and color difference, indicating a trade-off between matte tactile appearance and color fidelity. Thinner varnish coatings exhibited higher roughness and lower gloss but larger color differences, whereas thicker coatings better preserved color fidelity but resulted in higher gloss. For the UV excimer-cured system, one-way ANOVA showed significant treatment effects on acrylate conversion, water contact angle, 85° gloss, surface roughness, and abrasion mass loss. The coating prepared at an excimer radiant energy of 827.9 mJ/cm² showed the lowest 85° gloss of 5.28 GU and a pencil hardness of 3H, but also exhibited the highest abrasion mass loss in the short-cycle abrasion screening test. For both coating systems, three independently prepared specimens were tested for each processing condition. The UV varnish system was analyzed using two-way ANOVA, whereas the UV excimer-cured system was analyzed using one-way ANOVA. Friedman tests of sensory evaluation data showed significant differences among the eight selected samples for fineness, smoothness, and elasticity, with the excimer-cured coatings generally receiving higher fineness and smoothness scores than the UV varnish coatings. These results indicate that 254 nm UV excimer curing is a promising route for producing low-gloss, micro-wrinkle-induced skin-tactile surfaces on inkjet-printed melamine-faced panels, although optimization should balance tactile quality, gloss reduction, and abrasion resistance. Full article

Ports combine clusters of operational buildings, shared energy infrastructure, and structurally critical assets requiring coordinated management to ensure safety and efficiency. Nevertheless, existing Digital Twin (DT) frameworks for building energy management rarely integrate Structural Health Monitoring (SHM) with energy performance assessment, while port-specific implementations remain scarce. This paper presents a pre-operational energy-aware DT architecture for port building clusters, structured in a unified five-layer framework integrating three capabilities: (i) EGMS/InSAR-based SHM screening with planned in situ sensing and computer-vision inspection workflows; (ii) smart metering and measurement and verification (M&V) protocols aligned with ISO 50001/50015 and IPMVP standards; and (iii) weighted multi-criteria prioritization considering structural condition, energy saving potential, service continuity, and cost. The framework is applied to the Port of Formia (Italy), a brownfield district comprising nine buildings (3371 m²), 16 high-mast lighting towers, shore power infrastructure, and 90 kWp of planned photovoltaics. In the absence of operational metering, energy and carbon values are reported as bounded ex-ante scenario estimates, not as verified performance outcomes. The analysis estimates photovoltaic generation of 116–137 MWh/year and lighting retrofit savings of 31.5–36.8 MWh/year; the related carbon values are treated as gross grid-displacement upper bounds pending measured self-consumption and export data. A four-phase validation roadmap with quantitative acceptance criteria supports the transition from feasibility assessment to verified performance. Full article

Background: Public healthcare systems face persistent workforce retention challenges that undermine service continuity, organizational resilience, and public value creation. Although leadership is frequently identified as a relevant lever, the literature remains theoretically fragmented and often treats leadership effects as direct and context-free. Methods: This review adopts a PRISMA-guided systematic literature review as a theory-building strategy. Searches were conducted in Web of Science, Scopus, and PubMed using combinations of terms related to leadership, organizational commitment, job satisfaction, turnover intention, and retention in healthcare settings. The review identified 640 records, removed 372 duplicates, screened 268 titles and abstracts, assessed 90 full-text records for eligibility, and retained 30 peer-reviewed studies for configurative synthesis. The analysis combined thematic synthesis with configurative mapping to identify mechanisms, recurring patterns, and contextual contingencies. Results: The review shows three consistent patterns. First, leadership is linked to retention predominantly through organizational commitment, especially affective and normative commitment, rather than through direct effects. Second, institutional and organizational conditions—particularly red tape and working conditions—shape the strength of leadership–commitment relationships. Third, workforce heterogeneity, including generational differences, affects how leadership practices and organizational environments are interpreted, although these dynamics are rarely theorized explicitly in the literature. Conclusions: The article develops a governance-sensitive integrative framework in which people-centered leadership influences turnover intentions indirectly through organizational commitment, while red tape and working conditions operate as contextual moderators. By embedding leadership within Public Administration and governance theory, the review clarifies the literature’s main explanatory gap and provides a foundation for comparative empirical testing and for more sustainable workforce strategies in public healthcare systems. Full article

Public concrete datasets often contain duplicate records, coupled variables, and cross-source distribution shifts, which may lead to overly optimistic model evaluation. Based on a deduplicated UCI high-performance concrete dataset (1005 samples), this study develops a leakage-controlled data-driven workflow with applicability-domain assessment. TabPFN, SHAP, and NSGA-II are used for compressive strength prediction, model-response attribution, and scenario-based candidate mix screening, respectively. Model evaluation follows a unified data split, inner training-set cross-validation, and an independent test-set protocol. In addition, 502 non-overlapping records from the Mendeley PCC dataset are used as an external benchmark to examine cross-source transferability and sensitivity to distribution shift. The results show that TabPFN achieves the highest R² and the lowest RMSE, MAE, and MAPE on the internal UCI test set, with values of 0.953, 3.744 MPa, 2.265 MPa, and 7.580%, respectively; however, its advantage over strong baselines such as CatBoost is limited. On the external Mendeley PCC dataset, TabPFN remains competitive, with R², RMSE, and MAE values of 0.490, 15.175 MPa, and 11.457 MPa, respectively, but its performance is close to that of random forest, XGBoost, and CatBoost. The 5NN applicability-domain stratification shows that external samples located within the 95% 5NN applicability domain achieve improved performance (R² = 0.634 and RMSE = 12.367 MPa), suggesting that external prediction errors are associated with the distance from the source-domain distribution. SHAP results indicate that cement, ground granulated blast-furnace slag, curing age, and water are the main attribution variables in the model output; their response directions should be interpreted as statistical attributions rather than material causal mechanisms. The Pareto candidate mixes generated by NSGA-II satisfy basic engineering constraints. Nevertheless, because the external benchmark reveals sensitivity to cross-source distribution shift, the resulting mix proportions should be treated as pre-experimental screening candidates rather than engineering-validated low-GWP concrete mix proportions. Full article

The accumulation of histamine in fish products represents a significant food safety issue, particularly in skipjack tuna (Katsuwonus pelamis), due to its elevated histidine content. This study sought to isolate histamine-producing bacteria from skipjack tuna and assess the inhibitory effects of six plant-derived essential oils on bacterial proliferation and histamine synthesis. Seven bacterial isolates were obtained and screened, with histamine concentrations quantified via high-performance liquid chromatography (HPLC) following dansyl chloride derivatization. The isolate exhibiting the highest histamine production (1.2 ± 0.2 mM) was identified as Aeromonas hydrophila through 16S rDNA sequencing. Essential oils were administered to bacterial cultures prior to histamine quantification, and their minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined in vitro. Among the tested oils, oregano and cinnamon demonstrated the strongest antibacterial activity, with MIC and MBC values below 1 mg/mL. Scanning electron microscopy analysis revealed pronounced structural damage to bacterial cells treated with these oils. At the MBC, histamine production was entirely suppressed; at half the MBC, histamine synthesis was reduced by more than 90%, whereas lower concentrations yielded moderate inhibition ranging from 15% to 22%. These findings suggest that selected essential oils, notably oregano and cinnamon, possess considerable potential as natural preservatives to reduce histamine formation in skipjack tuna. However, further investigation is necessary to confirm their effectiveness under practical storage conditions. Full article

Quantitative structure–activity relationship and quantitative structure–property relationship (QSAR/QSPR)-based molecular toxicity prediction provides an in silico strategy for prioritizing environmental contaminants when longer-duration bioassay data are sparse. However, many Simplified Molecular-Input Line-Entry System (SMILES)-based machine learning models treat exposure duration as an unconstrained numerical covariate and provide limited information on whether predictions are supported by the observed temporal domain. Here, we evaluated an applicability-domain-aware chemoinformatics framework that combines transformer-derived molecular representations with toxicokinetic-informed temporal encoding and evidential uncertainty estimation. The approach replaces conventional ${log}_{10}$-transformed time encoding with a bounded first-order toxicokinetic saturation feature and combines this representation with Deep Evidential Regression to support a joint chemical–temporal view of the QSAR/QSPR applicability domain. Using experimentally derived U.S. EPA Ecotoxicology Knowledgebase (ECOTOX) fish EC50 mortality records, models were trained on 48,728 acute-duration observations and evaluated retrospectively on 2090 temporally separated longer-duration observations. The combined toxicokinetic and evidential model reduced temporal extrapolation error relative to conventional time encoding while maintaining comparable within-domain validation performance. The learned population-level timescale converged to 221 ± 3 h, consistent with accumulation timescales extending beyond standard acute fish test durations. Epistemic uncertainty was positively associated with absolute prediction error across all 10 folds, suggesting that the uncertainty estimates retained sample-level information relevant to applicability-domain-aware molecular toxicity screening. Cross-species analyses further showed that model behavior depended on training time coverage, with greater convergence when available assays covered a larger fraction of the learned timescale. These results suggest that toxicokinetic-informed temporal encoding can improve uncertainty-aware QSAR/QSPR modeling of environmental contaminant toxicity and support prioritization of compounds for further testing, while complementing rather than replacing chronic bioassays. Full article

Active packaging systems have emerged as a promising strategy to control microbial spoilage without direct incorporation of preservatives into food matrices. In this context, this study evaluated bacterial nanocellulose (BNC) as a nanostructured carrier for vapor-phase delivery of natural antifungal compounds in bread preservation. Cinnamaldehyde (CIN), cinnamon extract and clove extract were screened against Aspergillus niger, Penicillium chrysogenum, and Rhizopus microsporus using minimum inhibitory concentration (MIC) and inverted halo assays. CIN demonstrated complete fungal inhibition at 0.19% (v/v), corresponding to approximately 2.0 mg/mL, outperforming plant extracts, which exhibited limited and concentration-dependent activity. When incorporated into BNC at a 1:1 ratio (50% reduced loading), CIN maintained inhibition halos comparable to the free compound, indicating effective release and preserved bioavailability. The performance of the system was further evaluated in a bread model using a non-contact active packaging approach. Fungal growth in control samples was detected by day 6 (>10⁵ CFU/g), while incorporation of plant extracts into BNC delayed spoilage to day 9 (≈50% shelf-life extension). In contrast, breads treated with CIN, either free or BNC-incorporated, showed no detectable fungal growth throughout 21 days of storage, corresponding to a shelf-life extension of at least 15 days. These results demonstrate that antifungal efficacy in vapor-phase systems depends primarily on the intrinsic potency of the active compound, while BNC acts as an effective carrier matrix that promotes sustained retention and functional availability of CIN. The use of BNC-based active packaging for cinnamaldehyde delivery represents a promising clean-label strategy to control fungal spoilage and extend the shelf life of bread without direct incorporation into the food matrix. Full article

Heparanase 1 (HPSE1) is the only mammalian endoglycosidase that cleaves heparan sulfate (HS), a glycosaminoglycan (GAG), and is frequently upregulated in cancers, thereby promoting tumor progression. Despite extensive efforts to develop inhibitors of its HS-degrading activity, its non-enzymatic functions limit therapeutic efficacy and pose a major challenge for therapeutic development. Thus, inhibiting HPSE1 expression is critical for controlling its enzymatic and non-enzymatic functions; however, no FDA-approved inhibitors are currently available. Here, we identify auranofin (AUF), an oral gold-containing drug used to treat rheumatoid arthritis, as a potent inhibitor of HPSE1 promoter activity. High-throughput screening revealed that an atypical protein kinase C (aPKC)–NF-κB signaling axis is a key regulator of HPSE1 expression. Notably, AUF treatment reduced HPSE1 expression and significantly suppressed the invasive capacity of MDA-MB-231 cells in a Transwell migration assay. We then investigated the role of HPSE1 in the invasive activity of MDA-MB-231 cells, which produce higher levels of hyaluronan (HA) and HS than non-invasive cells. Neither HS degradation, HA supplementation in Matrigel during Transwell migration, nor HPSE1 overexpression alone was sufficient to drive invasion, suggesting that invasive capacity depends on mesenchymal features and coordinated induction of HPSE1 and GAGs rather than HS degradation. Collectively, our findings demonstrate that AUF-mediated inhibition of aPKC suppresses HPSE1 expression, thereby inhibiting both its enzymatic and non-enzymatic functions and limiting cancer progression, metastasis, and angiogenesis. These results highlight the therapeutic potential of AUF for targeting HPSE1-driven tumor progression and support its repurposing for cancer treatment. Full article

Transitioning from conventional wastewater treatment to circular wastewater management requires novel technologies that enable resource recovery, energy efficiency, and resilience under variable conditions. Within the NAMOR project, hybrid microalgae–bacteria Membrane PhotoBioReactors (MPBRs) are assessed as a sustainable solution for decentralized wastewater treatment and reuse. This study focuses on screening and optimizing mixed microalgae–bacterial consortia to treat municipal wastewater streams in the Mediterranean region, with an emphasis on achieving high nutrient removal, biomass productivity and robustness. A diverse set of strains will be evaluated under controlled temperature, light and nutrient regimes to enhance the symbiotic synergy between photosynthetic microalgae and heterotrophic bacteria, while minimizing aeration demand. Based on these results, a pilot demo in Lagadas, Greece, will integrate the optimized consortia into a moving-bed PBR equipped with polymeric carriers and membrane filtration for advanced effluent polishing, intended to produce reclaimed water for irrigation and biomass for valorisation into fertilizers or biogas. Full article

Background/Objectives: The aim of the present investigation was to validate the diagnostic performance of the AI-based dental cloud software Diagnocat^® AIS (Version 1.0 (UDI: 860010268018), DGNCT LLC, Miami, FL, USA) regarding the detection possibilities of seven different endodontic findings on cone-beam computed tomography (CBCT) against a multi-rater consensus reference standard, and to characterize its calibration, threshold-optimized performance and clinical utility. Methods: 358 root-canal-treated teeth from 167 CBCT scans (167 patients) were retrospectively evaluated at a single private dental practice. From initially included 383 root-canal-treated teeth from 177 patients, 358 (93.5%) were recognized by the AI tool and entered the primary analysis. Two experienced dentists with a clinical focus on endodontics independently graded each tooth and disagreements were adjudicated by a senior expert. Seven different endodontic findings were evaluated: (i) apical (periapical) lesion; (ii) short root-canal filling (apical filling end >2 mm short of the radiographic apex); (iii) voids/lacunae in the root-canal filling; (iv) missed (un-instrumented/un-filled) canal; (v) overfilled root-canal filling (apical extrusion); (vi) apicoectomy (resected root apex with or without retrograde filling); and (vii) coronal restoration with a full-coverage crown. Diagnocat^® output was binarized at the manufacturer-fixed 0.50 probability threshold; sensitivity, specificity, predictive values, accuracy, area under the curve AUC (ROC), Cohen κ and Gwet AC1 were computed with 95% cluster-bootstrap confidence intervals (cluster = scan). Threshold optimization, probability calibration, GEE-based subgroup analyses, and decision-curve analysis were pre-specified. Results: Diagnostic performance varied by finding. AUCs were 0.984 for missed canal, 0.917 for overfilled root canal, 0.902 for short root filling, 0.893 for crown, 0.864 for apical lesion, 0.857 for apicoectomy and 0.761 for voids in the root filling. Apical-lesion sensitivity rose from 33.6% for sub-millimeter lesions to ≥80% for lesion measuring 1–5 mm. Re-tuning the decision threshold raised missed-canal sensitivity from 69.6% to 97.5%. Decision-curve analysis confirmed positive benefits for missed canal and root-filling-quality findings. Conclusions: The AI tool Diagnocat^® can be recommended as a focused screening adjunct in CBCT-based endodontic interpretation for missed canals, crowns, and gross root-filling-quality flaws. Sub-millimeter apical lesions and several less common findings (resorption, instrument fragment, retrograde filling) remain outside the reliable performance envelope of the current platform. Full article

Background: To investigate the protective effects of Phellodendron amurense Rupr. polysaccharides (PAP), alkaloids, and flavonoids in alleviating diabetic kidney disease (DKD) and to elucidate the role of the PI3K/AKT/GSK-3β/Nrf2 signaling pathway. Methods: Active components were extracted and quantified. In vitro, high-glucose (HG)-induced human kidney-2 (HK-2) cells were used to screen the optimal fraction via CCK-8, reactive oxygen species (ROS), TdT-mediated dUTP Nick-End Labeling (TUNEL), and Western Blot (WB) assays. In vivo, a DKD rat model was established using 2% Streptozotocin (STZ) and a high-fat with high-sugar diet. Rats were treated with PAP and LY294002. Renal damage and signaling pathway proteins were evaluated using histological staining and WB. Results: Among the tested components, PAP conferred the most pronounced cytoprotection against HG-induced injury in HK-2 cells. PAP significantly reduced glomerular damage, collagen deposition, and glycogen accumulation in the kidneys of DKD rats. Mechanistically, PAP activated the PI3K/AKT/GSK-3β/Nrf2 pathway, upregulating HO-1 and NQO1, while inhibiting the TGF-β1/Smad2 pathway and Bcl-2/Bax-mediated apoptosis. These protective effects were significantly attenuated by LY294002. Conclusions: Among the tested fractions under the present experimental conditions, PAP exhibited the most pronounced protective activity. These protective effects were partially mediated through the PI3K/AKT/GSK-3β/Nrf2 pathway, which enhanced antioxidant capacity while reducing fibrosis and apoptosis. Full article

Chatuphalatika is a traditional Thai polyherbal formulation whose metabolically active fraction has not been identified. This study fractionated the aqueous extract (CPT) by sequential liquid–liquid partitioning to obtain solvent fractions. The ethyl acetate fraction (CPTX) had the highest total phenolic content and was enriched in hydrolyzable tannins, particularly chebulagic acid. CPTX showed the strongest inhibitory activity against HMG-CoA reductase in vitro. In vivo, C57BL/6 mice were fed a high-fat diet for 12 weeks, then treated with CPT, CPTX, or silymarin for 8 weeks while high-fat diet feeding continued. Both CPT and CPTX improved serum lipid profiles. High-dose CPTX (500 mg/kg) additionally reduced fasting blood glucose, serum ALT, and relative liver weight, without affecting body weight or adipose tissue weights. These findings indicate that phenolic enrichment concentrates the hepatic and lipid-lowering activity of Chatuphalatika. HMG-CoA reductase inhibition was used as a screening criterion to identify CPTX as the active fraction; the in vivo hepatometabolic improvements are consistent with, but do not directly confirm, modulation of cholesterol biosynthesis and hepatic lipid metabolism. Full article

Background/Objectives: Immunotherapy has emerged as an important field of research in non-small-cell lung cancer (NSCLC) and has demonstrated promising results in clinical practice. In recent years, multiple studies have been conducted, increasing the amount of available data. Therefore, the aim of this systematic review is to assess the combination of perioperative immunotherapy with chemotherapy compared to chemotherapy only in patients with resectable NSCLC in terms of survival, pathological response, and adverse events. Methods: The clinical databases PubMed, Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) were systematically searched, up to March 2026. A two-step selection process served as the screening for eligibility, in which the assessment was based on pre-defined inclusion and exclusion criteria. This process was visualized via a PRISMA diagram. For each included study, the risk of bias was assessed with the help of the Cochrane Risk of Bias 2.0 tool and the Newcastle Ottawa Scale. A narrative synthesis was performed due to heterogeneity. Data were extracted into tables. Results: A total of 16 studies, involving 4646 patients in total, met the eligibility criteria, and their data on study population, intervention, comparison, and outcome were extracted into tabular form. Survival and pathological response rates are continuously higher in patients treated with immunochemotherapy. Findings on adverse events differed across the individual studies, though the results indicate an increased risk of treatment-related adverse events (TRAEs) in patients undergoing the combined treatment approach. Discussion/Conclusions: Chemoimmunotherapy leads to superior clinical outcomes in terms of survival and pathological response rates, though the trend towards a higher incidence and severity of TRAEs warrants further research. The interpretation of findings is limited by differences in study characteristics, mechanism of conduct, and endpoints between the individual studies. Full article

Background: Sarcopenia is an age-related disorder characterized by loss of muscle mass, strength, and function, driven by oxidative stress, chronic inflammation, and protein imbalance. Broccoli-derived peptides (BDP) exert anti-inflammatory and myofiber-protective effects, while leucine regulates energy metabolism and redox balance. Methods: We established a D-galactose aging mouse model and treated mice with BDP alone, leucine alone, or their combination for 8 weeks. Lean mass, muscle index, grip strength, endurance, and treadmill capacity were detected, and atrophic, disorganized myofibers were observed through histology. RNA-seq was applied to screen differential signaling pathways, and qPCR was used to verify related gene expression levels. Results: D-galactose caused marked deficits in lean mass, muscle index, grip strength, endurance, and treadmill capacity, accompanied by atrophic and disorganized myofibers. Single BDP or leucine partially reversed these deficits, but the combination produced the most robust improvements. RNA-seq revealed that BDP enriched actin, chemokine, and TNF pathways; leucine enriched Apelin and ECM pathways; while the combination uniquely regulated MAPK signaling. qPCR confirmed that co-administration optimally upregulated myogenic drivers (Myod1, Myog, Mef2c), suppressed catabolic/inflammatory mediators (Mstn, Tnf, Cxcl10), and restored metabolic/adhesive regulators (Sirt3, Aplnr, Icam1). Conclusions: BDP and leucine show superior efficacy in ameliorating sarcopenia, through multimodal regulation of multiple signaling pathways, offering a promising plant-based nutritional strategy against age-related muscle decline. Full article