Search Results (5,591)

Microbial inactivation is essential for extending the shelf life of raw milk. Radio frequency (RF) thermal pasteurization has emerged as a promising technology for small-scale dairy processing. This study aimed to determine optimal RF temperature–time conditions, evaluate their effects on milk quality across milk from different species of cows, and assess economic feasibility. Raw milk from Holstein Friesian, Jersey, and Brown Swiss cows was treated using a dielectric heating system (40.68 MHz) at 72–92 °C for 20–100 s. The results were compared with conventional low-temperature long-time (LTLT) pasteurization of untreated milk. The optimal condition was 92 °C for 50 s, reducing the aerobic plate count from 5.80 to 0.69 log CFU/mL (a 5.11 log reduction), with no detection of Staphylococcus aureus, Bacillus cereus, and Escherichia coli. RF treatment did not significantly affect milk composition (p > 0.05), and color changes remained within acceptable limits. Milk stored at 4 °C maintained quality and safety for up to 28 days. Economic analysis indicated a net present value of USD 134,721.78, a benefit–cost ratio of 3.25, and a payback period of 6.8 months, confirming economic feasibility. These findings demonstrate that RF pasteurization can improve processing efficiency and support sustainable dairy production. Full article

Water-soil gushing caused by tunnel leakage can induce severe ground disturbance and threaten the safety of shield tunnels, yet rapid prediction remains difficult because high-fidelity numerical simulations are computationally expensive. This study develops an interpretable machine-learning framework for predicting gushing-induced ground disturbance around shield tunnels based on a validated two-phase Material Point Method database. Six governing variables are considered, including the tunnel depth ratio, gushing location, soil friction angle, Young’s modulus, intrinsic permeability, and soil gushing mass. Three representative response variables were selected, namely the maximum ground settlement, flow-zone width, and flow-zone centroid angle. Five algorithms, including MLP, RF, XGBoost, SVR, and Ridge, were established and compared, with hyperparameters optimised using Optuna. The results show that nonlinear models consistently outperform the linear baseline, among which MLP, RF, and XGBoost achieve the best overall accuracy and robustness. Error-distribution analysis further indicates that MLP and RF yield the highest proportion of low-error predictions. SHAP interpretation shows that SGM is the dominant factor governing maximum settlement and flow-zone width, whereas gushing location primarily controls the flow-zone centroid angle. The proposed framework provides an efficient and physically interpretable surrogate for rapid hazard assessment of gushing-induced ground disturbance in shield tunnelling. Full article

Introduction: Esophagectomy has traditionally been considered mandatory after neoadjuvant therapy for locally advanced esophageal cancer. However, recent evidence has challenged this paradigm and motivated interest in organ-preservation strategies with active surveillance in patients achieving clinical complete response (cCR). Methods: A literature search was performed using PubMed/MEDLINE, ScienceDirect, and Embase databases to identify relevant studies related to non-operative management (NOM) of esophageal cancer. Evidence was synthesized qualitatively with a critical focus on the biological rationale of NOM, diagnostic limitations of response-assessment, oncologic outcomes associated with surveillance strategies and the evolving role of molecular biomarkers. Results: The safety of NOM with active surveillance is tightly linked to the diagnostic accuracy of response assessment. Although structured multimodal response assessment protocols combining endoscopy, endoscopic ultrasound, and PET-CT have shown acceptable performance, residual clinically undetectable disease might persist in some patients. Evidence from the SANO trial has suggested non-inferior short-term survival outcomes of NOM compared with immediate esophagectomy in carefully selected patients with cCR after neoadjuvant chemoradiotherapy treated within specialized centers. Nevertheless, long-term oncologic outcomes remain unknown, and uncertainty persists regarding the broader applicability of this strategy outside specialized multidisciplinary settings. Emerging biomarker-driven approaches including PD-L1 expression, microsatellite instability, and circulating tumor DNA (ctDNA) may further refine response assessment and help identify patients most suitable for organ-preservation strategies. Conclusions: Active surveillance represents a promising alternative to immediate esophagectomy in selected patients with cCR after neoadjuvant therapy. However, further studies with longer follow-up and standardized surveillance protocols are still needed to safely implement this strategy outside trial settings. Full article

Overhead transmission conductors are flexible cable structures. Their initial equilibrium configuration is affected by self-weight, tension, boundary constraints, and material deformation, and is required for force analysis, sag calculation, and safety assessment. Existing studies use catenary theory or numerical iterative methods. The direct iterative method is used in conductor form-finding. However, its geometric update ratio is assigned in segments based on empirical thresholds. This may cause unsmooth updates, low efficiency, and numerical instability in sensitive cases. This study investigates a single-span conductor within a nonlinear finite element form-finding framework. The direct iterative method is analyzed in terms of control variables, implementation process, and update-ratio control mode. A continuous error-driven adaptive geometric update strategy is proposed and an adaptive direct iterative method is developed. The two methods are compared under the same finite element model, parameters, loads, constraints, convergence threshold, and maximum iterations. Three factors are selected: element number, nonlinear substep number, and initial strain coefficient. A total of 27 full-factorial cases are calculated. Convergence efficiency, final error, and abnormal case distribution are evaluated. The results show that the proposed method reduces iterations, improves computational efficiency, and enhances numerical stability in sensitive cases without changing the finite element solution framework. Full article

The ski-jump spillway is an energy-dissipating structure that discharges extra water beyond the dam’s capacity. The scour process occurs below spillways due to the collision of the water jet with high energy. It is critical to acquire information on scour holes to improve the dam’s safety and related components. Machine learning (ML) techniques have successfully demonstrated their effectiveness for modeling scour in hydraulic engineering. The present research considers novel approaches of ML models for estimating the scour hole geometries below ski-jump bucket spillways. This study investigates the capability of two novel feature-engineering approaches, namely Stronger Variable Creator Machine (SVCM) and High Correlated Variables Creator Machine (HCVCM), along with Gene Expression Programming (GEP) and their hybrid forms (SVCM+GEP and HCVCM+GEP), which were employed to predict normalized scour depth, scour length, and scour width below ski-jump spillways. Statistical metrics, graphical analyses, the Rank Mean (RM) method, the cross-validation approach, and $U_{95}$ index were used for the evaluation and reliability assessment of the proposed ML models. The results showed that hybrid ML models consistently outperformed individual algorithms. The results indicated that the SVCM+GEP method with $\mathrm{R}\mathrm{M}=1.83$ and $1.50$ had the highest performance compared to other methods for the prediction of ${\displaystyle \frac{Ds}{Dw}}$ and ${\displaystyle \frac{L_s}{D_w}}$, respectively. In addition, the HCVCM+GEP method with $\mathrm{R}\mathrm{M}=1.33$ was the best model for the prediction of ${\displaystyle \frac{Ws}{Dw}}$. In comparison with the conventional regression-based equations and previously reported ML methods, the proposed hybrid approaches improved the prediction results. In addition, the cross-validation method confirmed the robustness and generalization capability of the suggested hybrid ML models. The superior performance of the hybrid models is attributed to their ability to capture complex nonlinear interactions among hydraulic and geometric variables. The developed SVCM/HCVCM+GEP models provide accurate approaches for predicting scour parameters in hydraulic structures. Full article

Stroke is a leading cause of morbidity and long-term disability worldwide. This study evaluated the feasibility, safety, and preliminary clinical effects of phonotherapy (PHT) as an adjunct to standard care in patients with acute ischemic stroke. This prospective observational study enrolled 140 patients, who were assigned to receive either phonotherapy in addition to standard care (PHT group, n = 70) or standard care alone (control group, n = 70). Phonotherapy consisted of twice-daily 528 Hz sound stimulation administered for 3 months. Neurological (NIHSS), functional (mRS), and cognitive (MoCA) outcomes were assessed at days 10 and 90. At day 10, patients receiving PHT showed significantly better neurological, functional, and cognitive outcomes compared to the controls. However, these differences were not sustained at 90 days. Phonotherapy was not an independent predictor of favorable functional outcome at 90 days. Recurrent stroke occurred in three patients (4.3%) in the PHT group and nine (12.9%) in the control group (p = 0.07). No intervention-related adverse events were observed. Phonotherapy appears to be a safe adjunct intervention in acute ischemic stroke and may be associated with short-term improvements in selected outcomes. Overall, phonotherapy appeared safe as an adjunctive intervention in patients with acute ischemic stroke and showed possible short-term associations with improvements in selected outcomes, although these preliminary findings require confirmation in randomized controlled trials. Full article

Background: mRNA vaccines, first approved in December 2020, have been used globally to prevent infectious diseases, and those for treating cancers are being developed. Safety-related labelling changes of Comirnaty and Spikevax were made in June 2025; however, concerns remain. This study assessed the potential risks associated with mRNA vaccines on the indications previously approved, utilizing Real-World Data (RWD) of Adverse Events Following Immunization (AEFIs) derived from the Vaccine Adverse Event Reporting System (VAERS) and Academic Literature Databases (ALD). Methods: A Disproportionality Analysis (DPA) was performed using the Reporting Odds Ratio (ROR) and the Bayesian Confidence Propagation Neural Network (BCPNN) algorithm on spontaneous case reports from VAERS. Statistical positive signals were cross-validated with literature case reports from ALD to provide more comprehensive medical descriptions and clearer causal assessments, and compared with safety information documented in clinical trials and on vaccine labelling. Time-to-onset, stratified, and immunization schedule analyses were conducted to characterize the safety profiles of mRNA vaccines. Results: In total, 5,040,725 spontaneous case reports and 4,387 literature case reports were analyzed. In both VAERS and ALD, new signals involving blood and lymphatic system disorders (e.g., thrombotic thrombocytopenic purpura) and ear and labyrinth disorders (e.g., deafness) were detected from Comirnaty as Designated Medical Events (DMEs), while blood and lymphatic system disorders (e.g., thrombotic thrombocytopenic purpura) from Spikevax in ALD only. No new signals were detected from other vaccines on the DMEs list. In VAERS, Serious Adverse Events (SAEs) were more common in females, while death risk was higher in males. In ALD, SAEs were more common in males for most mRNA vaccines, except Comirnaty. Medical history emerged as a key risk factor for SAEs, particularly among older adults. Conclusions: Statistically significant safety signals were detected across all mRNA vaccines based on five-year cumulative RWD, indicating the need of intensified monitoring of specific populations, including older adults and individuals with medical histories, alongside further optimization of vaccination strategies. Full article

Background: Cognitive changes after minor surgery may affect patient safety, functional recovery, and readiness for hospital discharge, even after low-risk procedures with early discharge protocols. In this regard, patients require neuropsychological assessment at discharge, which may have important clinical implications for return to daily activities and postoperative decision-making. Our study investigated postoperative cognitive changes after minor surgery under general anesthesia using a neuropsychological assessment and a non-surgical group. Methods: Patients undergoing laparoscopic cholecystectomy received propofol or sevoflurane anesthesia. A non-surgical control group was included. Cognitive performance was assessed at baseline and discharge using the Computerized Visual Attention Test (CVAT), the controlled oral word association test (COWAT), and the symbol digit modalities test (SDMT). Relative change scores were calculated as ((baseline − postoperative performance)/baseline). Group differences were analyzed using two-tailed multivariate analysis of variance (MANOVA), followed by ANOVAs and Bonferroni-adjusted pairwise comparisons. Results: A total of 105 participants were included (37 non-surgical, 34 propofol, 34 sevoflurane). MANOVA showed a significant group effect (Pillai’s trace = 0.332, p < 0.001, η² = 0.196). The ANOVAs revealed significant differences in sustained attention (CVAT), verbal fluency (COWAT) and executive function (SDMT). The propofol group showed evident decline in sustained attention compared to non-surgical. In verbal fluency, non-surgical improved at day after, whereas both surgical groups showed no improvement, indicating worse performance. In SDMT the sevoflurane group had worse performance. Conclusions: Minor surgery under general anesthesia may lead to transient impairments in attention and learning at discharge, supporting the need for postoperative cognitive monitoring and individualized discharge decisions. Full article

The fatigue failure of railway axles is directly associated with the operational safety of trains. As 25CrMo4 steel is commonly employed for high-speed train axles, precise evaluation of its fatigue life is essential for transportation reliability. This study compared six machine learning models following hyperparameter optimization via a differential evolution algorithm. The DE-optimized Gaussian process regression (DE-GPR) model exhibited superior predictive performance, achieving a coefficient of determination (R²) of 0.8020 and a root mean square error (RMSE) of 0.1250 on the most significant outer test fold. Furthermore, an interpretable analysis of the model utilized a combination of SHapley Additive exPlanations (SHAP) and partial dependence plots (PDP) to elucidate feature importance. The results indicate that the applied stress level is the predominant feature affecting fatigue life predictions and that it slightly interacts with surface residual stress and full width at half maximum to influence the predicted fatigue life. This study can provide valuable insights into the fatigue life assessment and process optimization of 25CrMo4 steel components. Full article

Background: Multiple sclerosis (MS), an autoimmune disease, involves peripheral immune activation followed by CNS inflammation in a compartmentalized manner. Although high-efficacy disease-modifying therapies (HE-DMTs) have been effective in suppressing relapses in MS patients, they fail to effectively target chronic microglial activation and smoldering lesions in MS patients. Bruton’s tyrosine kinase inhibitors (BTKis), which are orally active and capable of crossing the blood–brain barrier, have been found to be effective in modulating B cells and CNS-resident myeloid cells. Objective: The objective was to assess the efficacy and safety of Bruton’s tyrosine kinase inhibitors in patients with relapsing, secondary, and primary progressive MS. Methods: We performed a systematic review and meta-analysis according to the Cochrane and PRISMA guidelines (PROSPERO registration number: 1323474). We included randomized controlled trials (RCTs) that assessed fenebrutinib, evobrutinib, or tolebrutinib in adult MS patient populations. The main outcome measures were annualized relapse rate, MRI lesion activity, disability progression (EDSS), and hepatotoxicity. The quality of the included trials was assessed for bias by the RoB2 tool. Results: Six RCTs with 3616 participants were included. BTK inhibitors significantly reduced ARR compared with control therapy (pooled RR 0.24; 95% CI 0.15–0.39). MRI activity was reduced (mean difference −1.45 new/enlarging T2 lesions; 95% CI −2.08 to −0.82). Disability progression was unchanged in short-term relapsing MS trials. Serious hepatotoxicity was reported in 11.0% of BTKi-treated patients compared with 13.7% of control patients (pooled RR 0.80; 95% CI 0.66–0.96). However, increased transaminase elevations were reported in placebo-controlled trials, which indicates that hepatotoxicity remains a clinically relevant safety concern for the class. Conclusions: BTK inhibitors reduce inflammatory disease activity in relapsing MS and have emerging efficacy in progressive MS phenotypes; however, continued monitoring for hepatotoxicity is warranted. Optimization of CNS penetrance and pharmacologic selectivity may influence long-term clinical positioning. Full article

Background/Objectives: Intraoperative fluorescence imaging (FI) with tumor-targeted tracers offers a promising approach to improve surgical precision in cancer surgery. cRGD-ZW800-1, an integrin-targeted fluorescent tracer, has previously demonstrated safety, tumor specificity, and utility in detecting inadequate margins in oral cancer. During this study, we observed variability in background fluorescence between different subsites of the oral cavity. Therefore, this study aimed to systematically evaluate intraoperative in vivo and ex vivo mucosal contrast ratios across various oral cavity subsites using FI with cRGD-ZW800-1. Methods: Thirty-one patients with oral squamous cell carcinoma underwent intraoperative FI following intravenous injection of cRGD-ZW800-1 at least 18 h preoperatively. In vivo imaging was performed using the Quest Spectrum platform. In addition, ex vivo FI of the resected specimen was performed using the Pearl Trilogy Small Animal Imaging System. As these ex vivo images were obtained under uniform and controlled acquisition conditions, they allow for direct comparison with the intraoperative fluorescence signals. Fluorescence intensities and tumor-to-background ratios (TBRs) were assessed per oral subsite using manually drawn regions of interest (ROIs) on the tumor and adjacent healthy mucosa using Quest’s Spectrum Software, version 4.8.2, (in vivo images) and the Pearl’s integrated software ImageStudio version 6.2 (ex vivo images). A TBR ≥ 1.5 was considered sufficient. Results: Under uniform imaging settings, all samples exhibited adequate contrast (TBR ≥ 2.3), allowing clear tumor visualization and precise evaluation of mucosal margins on final histopathology. Notably, intraoperative in vivo contrast in the posterior located maxillary alveolar process was comparatively lower, which was attributable to suboptimal imaging conditions and subsite-specific background fluorescence. Conclusions: Our findings indicate that, although contrast varies across different oral subsites, all specimens exhibited sufficient ex vivo mucosal contrast to allow reliable tumor delineation. As in vivo imaging may be affected by subsite-specific background fluorescence and inherent limitations of intraoperative imaging geometry, fluorescence signals should be interpreted in conjunction with standard visual and tactile assessment. Due to anatomical constraints, different oral subsites may appear within the same field of view, which can influence perceived signal intensity. Therefore, intraoperative ex vivo fluorescence evaluation is recommended for signal interpretation. Full article

The vitamin D receptor (VDR) plays a pivotal role in maintaining epidermal barrier homeostasis and regulating cutaneous inflammatory responses. However, the cosmetic application of vitamin D and its active metabolites is limited by photoinstability, formulation challenges, and regulatory considerations. In this study, we evaluated a synthetic VDR-activating peptide (VDR-Pep) as a potential functional cosmetic ingredient capable of modulating VDR-associated signaling pathways in human keratinocytes. In situ proximity ligation assays (PLAs) demonstrated that VDR-Pep enhanced the heterodimerization of VDR and retinoid X receptor (RXR), indicating activation of canonical VDR signaling. Treatment with VDR-Pep significantly increased the expression of S100A3 and key terminal differentiation markers, including filaggrin, involucrin, and loricrin, in a dose-dependent manner. In addition, VDR-Pep stimulated intracellular calcium mobilization at levels comparable to or exceeding those induced by 1,25-dihydroxyvitamin D₃. Under UVB-induced stress conditions, the peptide attenuated the expression of the pro-inflammatory cytokine interleukin-6 (IL-6) and enhanced NRF2-associated transcriptional engagement, as evidenced by increased interaction between NRF2 and RNA polymerase II. Collectively, these findings suggest that VDR-Pep supports epidermal homeostasis through coordinated modulation of VDR/RXR signaling, calcium-mediated differentiation, barrier-related protein expression, inflammatory responses, and antioxidant-associated pathways. The results indicate that VDR-targeting peptides may represent a promising non-hormonal strategy for cosmetic formulations aimed at reinforcing skin barrier function and improving resilience to environmental stress. Future studies should focus on validating these effects in in vivo human skin models, assessing long-term safety and efficacy, and optimizing formulation stability for practical cosmetic applications. Full article

Concrete cracks are ubiquitous in practical engineering structures and continuously affect structural safety and durability. Crack images provide important visual evidence of damage evolution; however, crack images alone are insufficient to determine the residual load-bearing capacity of concrete members. Although the development of deep learning algorithms has significantly improved the automatic detection of concrete surface cracks, most existing methods remain limited to the extraction of crack geometric features and lack a direct connection with mechanical performance. To explore the relationship between image-based crack geometry and mechanical response, this study combines U-Net-based crack segmentation, OpenCV-based crack geometry extraction, and phase-field fracture simulation to establish a preliminary visual–mechanical framework for plain concrete beams. In this framework, surface crack images are first segmented using a U-Net model, and crack length, average width, and propagation path are extracted from the predicted binary masks. The extracted crack length is then used as the primary variable to match the observed crack state with the phase-field crack evolution sequence. Once the corresponding simulation stage is identified, the associated load level and residual load-bearing capacity can be obtained from the simulated load–crack mouth opening displacement (Load–CMOD) response. Through a mixed-mode I–II fracture test, the crack geometric features extracted by deep learning are compared with the phase-field simulation results. The results show that the error in crack length is within 2.5%. Meanwhile, the relative error between the simulated peak load and the experimental value was 1.57%, which preliminarily verified the correlation between image-based crack information and the load-bearing capacity of plain concrete beams. The method is further applied to a Mode I fracture test without recorded load-bearing capacity data. By mapping the crack length identified from the image, namely 36.89 mm, to the phase-field evolution sequence, the load-bearing capacity of the member at this stage is estimated to be 74.4% of the peak load. The results indicate that the crack geometry extracted from images can be correlated with phase-field crack evolution, thereby supporting preliminary residual load-bearing capacity assessment of plain concrete beams. However, the proposed framework should be regarded as a case-level feasibility study rather than a general structural assessment method. Before broader engineering application, further validation using synchronized crack image sequences, crack mouth opening displacement (CMOD) measurements, and load records is required. Full article

Background: Dental caries is a chronic disease mediated by biofilm, which is caused by Streptococcus mutans, and enamel genetics modulates susceptibility. The variants of ENAM might alter the adhesion of enamel and bacteria. One important anti-viral target is sortase A (SrtA), which restricts colonization but does not have an impact on bacterial survival. Aim: The aim of this study was to find out the relationship between ENAM rs3796704 and dental caries vulnerability among adult Iraqi Arab females and to assess the antibiofilm capacity of eugenol and cinnamic acid against S. mutans SrtA using molecular docking, ADMET prediction, and molecular dynamics modeling. Methods: A case–control study was done on 240 women (aged 25–30 years; 120 caries, 120 controls). HRM real-time PCR was done to genotype ENAM rs3796704. An analysis of allelic and genotypic distributions was done using chi-square tests and odds ratios (p < 0.05). An in silico docking analysis aimed at SrtA (PDB: 4TQX) was performed in AutoDock Vina, and this was followed by ADMET profiling and a 50 ns molecular dynamics simulation (OPLS4/TIP3P, NPT 300 K/1 atm). Results: The level of the G allele was found to be lower in the cases than in the controls (60% vs. 70; OR = 0.6429; p = 0.02), but the level of the A allele was found to be higher in the cases (40% vs. 30; OR = 1.5556; p = 0.02). Docking showed a minor difference in binding affinities with eugenol (−4.961 kcal/mol) and cinnamic acid (−4.939 kcal/mol) as compared with chlorhexidine (−4.692 kcal/mol). Both compounds showed stable binding for more than 50 ns as well as desirable predicted pharmacokinetics. Conclusions: The caries vulnerability in this sample was associated with ENAM rs3796704. Eugenol and cinnamic acid undergo stable dissociative interactions with SrtA and were found to have favorable safety profiles in silico. Therefore, they may be considered as adjunctive anti-virulence agents in the prevention of caries. Full article

Background: Menopausal hormone therapy (MHT) effectively relieves vasomotor symptoms, but its cardiovascular safety remains influenced by timing, formulation, and route of administration. Methods: This narrative review summarizes evidence from major randomized trials (WHI, HERS, ELITE, DOPS) and observational studies, along with mechanistic data on the vascular and metabolic effects of MHT. Results: Although early studies suggested cardioprotection, randomized trials showed no cardiovascular benefit, and in some cases, increased risks of coronary events, stroke, and venous thromboembolism, particularly in older women or those with established cardiovascular disease. The “timing hypothesis” indicates that early initiation after menopause may have neutral or modestly favorable effects, whereas late initiation is associated with adversity. Oral estrogen is linked to higher thromboembolic and stroke risk compared with transdermal formulations. Evidence on atrial fibrillation and heart failure remains limited. Conclusions: MHT should not be used for cardiovascular disease prevention. Current evidence suggests that younger women in the early postmenopausal period may derive the greatest benefit with the lowest risk from individualized hormone therapy regimens, particularly those using transdermal estrogen. Treatment decisions should be guided by careful cardiovascular risk assessment and targeted to symptom relief and osteoporosis prevention. Full article