Search Results (2,605)

Impaired wound healing is a major cause of morbidity among patients with diabetes. Human α1-antitrypsin (hAAT) promotes the resolution of injured tissues. In hyperglycemic conditions, circulating hAAT is likely to undergo glycation, yet it is unknown whether its reparative properties are preserved. We hypothesized that clinical-grade hAAT treatment, but not deliberately glycated hAAT (gly-hAAT), would promote wound repair under hyperglycemic conditions. Mice were rendered hyperglycemic, excisional wounding was performed, and wounds were treated with topical albumin or hAAT every three days. The wound area was assessed, and samples were collected for histology and gene expression analysis. Gly-hAAT was generated from clinical-grade hAAT, after which in vitro RAW 264.7 macrophage responses and re-epithelialization of A549 cells were assessed. Gap closure was further assessed using sera from a human cohort (prospective samples from 10 patients with poorly controlled diabetes at Soroka University Medical Center, Beer-Sheva, Israel, 2018). Group comparisons were performed using one-way ANOVA with Tukey’s post hoc test. hAAT accelerated in vivo wound closure and in vitro A549 cell gap closure, accompanied by an anti-inflammatory IL-1Ra/IL-1β gene expression profile. In contrast, gly-hAAT inhibited normoglycemic mouse wound closure, evoked an inflammatory response in macrophages, and interfered with A549 cell gap closure; concomitant hAAT treatment improved gap closure. Similarly, patient serum inhibited A549 gap closure, and concomitant hAAT treatment improved gap closure. Importantly, inferential statistical analysis was not performed on this outcome due to the small and heterogeneous human cohort. In conclusion, hAAT accelerated wound closure in hyperglycemic mice and in A549 cells, whereas gly-hAAT promoted inflammatory responses and impaired wound closure, a trend reversed by native hAAT. These findings support the concept that glycation undermines the beneficial functions of circulating hAAT and provides a mechanistic insight into the pathophysiology of diabetic wound healing. Further studies are warranted to evaluate clinical-grade hAAT as a potential therapeutic for hyperglycemia-associated impaired wound healing. Full article

This paper developed a probabilistic framework for system level reliability and risk assessment that coupled hydraulic loading with structural response and explicitly modelled cascading interactions and statistical dependence between components. The contribution is a system-level reliability and risk modelling methodology that integrates dynamic cascading interactions, non-stationary design-life reliability accumulation, and system-level optimisation within a unified Monte Carlo architecture. Dynamic Monte Carlo simulation was used to evaluate individual, joint, conditional, and system-scale probabilities of failure across varying flood magnitudes and design lives. Model verification confirmed that discretisation and sampling errors were small relative to parameter-driven variability. Results showed that long-term system reliability arose from the combined influence of flood frequency, exposure duration, and the strength of interaction between interdependent structures. Frequent loading accelerates the accumulation of failure probability through repeated events, whereas rare events contribute more slowly but dominate extreme outcomes, indicating that cumulative reliability cannot be inferred by the linear extrapolation of annual probabilities. In an examined diversion–levee–basin configuration, strong structural coupling amplified vulnerability by contracting joint stability margins and increasing conditional failure probabilities. The system-level optimisation of structural parameters over the examined design life reduced cumulative system failure probability from 0.305 to 0.153, whereas single-component optimisation redistributed risk within the system without reducing total system risk. The framework advances beyond static risk analysis by integrating time-dependent reliability, cascading dependencies, and design-life optimisation for system-scale mitigation. Full article

Health crises hinder the provision of intensive care for critical obstetric conditions such as preeclampsia and eclampsia, where timely decision making and system capacity directly impact maternal and fetal outcomes. This study compared the clinical and epidemiological profile and care processes in the ICU for cases of preeclampsia and eclampsia before and during the COVID-19 health crisis in Alto Amazonas, Loreto (Peru), using a comparative mixed-method approach. Quantitative data were obtained from ICU medical records for two periods (2015–2019 and 2020–2022). Categorical variables were compared using exact methods (Fisher’s exact test for 2 × 2 tables and exact procedures for scatter tables with multiple categories), and continuous variables were compared using nonparametric tests where appropriate. The most notable change was an increase in the frequency of cesarean sections during the health crisis, which should be interpreted with caution given the small sample size and potential changes in admission criteria and system limitations. Other clinical indicators and discharge status showed no clear evidence of substantial differences between the periods. Qualitative findings highlighted systemic limitations affecting continuity of care, particularly those related to timely access to safe blood products and referral pathways. These results align with SDG 3 (Good Health and Well-being) and support strengthening preparedness, referral coordination, and the availability of essential resources to protect maternal health during large-scale emergencies. Full article

To investigate the multi-factor aging mechanisms of silicone rubber used in the outer sheath of composite bushings, this study focused on HTV silicone rubber employed in the sheath layer of 1100 kV high-voltage bushings. The samples were subjected to temperature–humidity–corona coupled aging in a multi-factor aging platform. The aged samples were characterized by scanning electron microscopy, energy-dispersive spectroscopy, Fourier-transform infrared spectroscopy, hydrophobicity measurements, hardness tests, and dielectric constant measurements. The results indicate that different aging factors affect the material differently. Corona aging primarily affects the sample surface, leading to substantial methyl group detachment, surface oxidation, and a decrease in hydrophobicity, with the local static contact angle decreasing by up to 70%. In contrast, wet heat aging affects the bulk material; under high-temperature and high-humidity conditions, the internal small-molecule chains accelerate silicon-oxide crosslinking, leading to a marked increase in hardness and a relative dielectric constant that initially decreases and then increases. Considering the complex field environment, surface performance measurements are easily influenced by external factors. Therefore, hardness and relative dielectric constant are proposed as key indicators for evaluating the aging degree of silicone rubber sheaths in service. The findings provide a valuable reference for the service-life evaluation of composite bushings. Full article

(1) Background: University food service establishments are complex environments, where high turnover and handling practices create conditions for microbial persistence. Food-contact surfaces (FCSs) and handlers’ hands (FHs) function as dynamic reservoirs, facilitating the circulation of contaminants within these institutional settings. This study aimed to characterise the microbiological contamination of FCSs and FHs in university food service establishments in Northern Portugal and to evaluate their role as interconnected environmental reservoirs within the indoor built environment. (2) Methods: A total of 590 samples were analysed from two universities in Northern Portugal (L1, L2), comprising 380 FCS and 210 FH samples. Aerobic colony counts (ACCs), Enterobacteriaceae, and Moulds and yeasts (MYs) were analysed according to ISO methods. FH samples were additionally screened for Escherichia coli and Staphylococcus spp. (3) Results: Overall, 35.5% of FCSs were classified as non-compliant, according to microbial criteria based on guideline values from the National Health Institute Dr. Ricardo-Jorge (INSA), with non-compliance primarily driven by elevated ACCs and MYs. Based on a Generalised Linear Model (GLM), establishment types (canteens vs. cafes) were associated with Enterobacteriaceae levels (p = 0.016), whereas ACCs and MYs were not significantly associated with district, establishment type, or functional surface category (p > 0.05). Differences between left and right hands showed small effect sizes, and location was a highly significant determinant of hand hygiene acceptability. (4) Conclusions: FCSs and FHs act as relevant contamination reservoirs in these settings. The results indicate that Enterobacteriaceae levels on FCSs differed between establishment types, while ACCs and MYs showed no significant variation across the evaluated environmental factors. Marked differences in hand hygiene acceptability between campuses support the implementation of targeted interventions, including the optimisation of cleaning and disinfection protocols, the structured training of food handlers, and the routine microbiological monitoring of surfaces and hands to improve institutional food safety. Full article

Background/Objectives: Diabetic small fiber neuropathy and related sensory and epidermal problems affect up to 70% of all patients with diabetes. Long-term hyperglycemia disrupts cytoskeletal organization and axonal transport; however, molecular changes within human diabetic epidermis remain understudied. Diaph1 and its cytoskeletal ligands, including β-Actin and Profilin, are key regulators of cytoskeletal dynamics and may be associated with diabetes-related alterations in skin structure and innervation. Methods: Sixteen patients with type 2 diabetes, aged 43.3 ± 9.6 years (disease duration 18.9 ± 8.7 years), and twelve non-diabetic controls, aged 43.9 ± 8.9 years, were enrolled in the study. All participants provided informed consent. Skin punch biopsies were obtained under local anesthesia and processed for staining of PGP 9.5, Diaph1, β-Actin, and Profilin. Quantitative image analysis was performed to assess stained area fraction, signal intensity, and intraepidermal nerve fiber density. Statistical comparisons and Spearman’s rank correlation analyses were used to evaluate group differences and associations between staining parameters. Results: Diabetic skin samples exhibited a significant reduction in PGP 9.5-positive intraepidermal nerve fibers, indicating reduced cutaneous innervation. In contrast, Diaph1 and Profilin showed broader and more diffuse epidermal staining, while β-Actin displayed altered staining patterns and intensity. Significant correlations between Diaph1- and β-Actin-related staining measures indicated an association consistent with altered cytoskeletal organization under chronic hyperglycemic conditions. Conclusions: Long-standing type 2 diabetes was associated with reduced PGP 9.5-positive intraepidermal nerve fibers, together with altered epidermal staining patterns of Diaph1, Profilin and β-Actin. These findings indicate coexisting cutaneous denervation and cytoskeletal alterations in diabetic skin. Full article

The complex surface architecture of natural oyster reefs is widely considered to promote biological attachment, yet the underlying mechanisms and the relevance to the design of artificial reefs are not fully understood. Here, we combined field experiments, 3D surface characterization, and numerical modelling to quantify how reef-like roughness regulates biofouling development and near-wall flow around artificial substrates. Surface morphological characteristics of natural oyster reefs were first obtained by 3D scanning and used to fabricate concrete panels with simulated rough textures, while traditional smooth concrete panels served as controls. The two types of panels were simultaneously deployed in the target sea area for a hanging-panel experiment. Samples were collected after 3, 6, 9, and 12 months to track changes in biofouling communities. At each sampling time, the panel surfaces were quantified by canopy roughness ($R_C$), surface heterogeneity ($\sigma$), and fractal dimension ($D$), and these metrics were integrated into numerical simulations combined to resolve the flow field, turbulence kinetic, and near-wall shear stress around the colonized panels. The research results show that, after 12-month immersion, the mean thickness of the biofouling layer on rough and control panels reached 6.39 mm and 5.91 mm, respectively. Rough panels exhibited consistently higher $R_C$ and $\mathsf{\sigma }$ than controls, and these two parameters are strongly linearly correlated ($R^2=0.891)$. Numerical simulations reveal that increased $R_C$ enlarges the oyster settlement shear-stress window (OSSW), indicating more favorable hydrodynamic conditions for oyster settlement and growth on rough panels. Nevertheless, the hydrodynamic differences between the initial rough panels and control panels gradually diminish over time, suggesting that biological growth can progressively naturalize initially smooth substrates. These findings advance the mechanistic understanding of how small-scale roughness and biofouling co-evolve to shape oyster habitat quality and provide a quantitative basis for the eco-engineering design of artificial oyster reefs. Full article

Unbiased stereology represents the most accurate approach for estimating the total number of neurons of specific brain regions; however, its reliability critically depends on the use of rigorously defined and anatomically appropriate sampling parameters. The brain nucleus Locus Coeruleus (LC) plays a key role in several brain functions. LC impairment has been associated with a range of disorders affecting individuals across the lifespan, from infancy to adulthood. In animal models of these conditions, precise estimation of LC neuronal number is essential. The LC analysis poses specific methodological challenges due to its small size, indistinct anatomical boundaries, and age-dependent changes in neuronal density. In this study, we present a detailed and reproducible stereological workflow for the quantification of LC neurons in the mouse brain across the lifespan. Using C57BL/6J mice at postnatal, adult, and aged stages, we optimized all key components of the Optical Fractionator method, LC neurons were identified by immunoperoxidase staining for tyrosine hydroxylase (TH) and quantified using systematic-random sampling implemented in Stereo Investigator^® software. We show that age-specific adjustment of stereological parameters is necessary to obtain reliable estimates, particularly at early postnatal stages characterized by high neuronal packing density. With the optimized protocols described here, TH+ LC neuron counts consistently met accepted precision criteria, as assessed by the Gundersen coefficient of error. Full article

Clostridium butyricum is a well-known Gram-positive, spore-forming, obligate anaerobic, and butyrate-producing bacterium with a few species of next-generation probiotic strains. By far, the most well-known strain is Clostridium butyricum CBM588 (also known as MIYAIRI 588). This strain has gained significant attention for its therapeutic potential across a variety of human health conditions. Preclinical studies have shown its ability to stabilize gut microbiota, enhance short-chain fatty acid (SCFA) production, and modulate immune responses, which contribute to its therapeutic effects in conditions such as ulcerative colitis, allergies, and cancer. We examined 28 interventional clinical trials and 7 observational studies investigating the effect of Clostridium butyricum strains. These studies have supported the findings of preclinical trials and demonstrated symptom improvement and immune modulation in diverse conditions. Clostridium butyricum CBM588 has shown efficacy in managing gastrointestinal diseases, such as acute gastroenteritis and inflammatory bowel disease, and has also proven beneficial in immune modulation, as evidenced by its positive effects in allergic rhinitis and cancer immunotherapy. Additionally, CBM588 has been reported to have a favorable safety and tolerability profile in various patient populations, including children, adults, and critically ill patients. Despite these promising results, clinical studies face limitations such as small sample sizes, varied protocols, and short study durations. Future well-designed, large-scale trials are necessary to further validate the long-term safety and efficacy of Clostridium butyricum in clinical practice. Full article

Chronic kidney disease (CKD) is a progressive condition associated with metabolic disturbances, systemic inflammation, and the accumulation of gut-derived uremic toxins. Increasing evidence highlights the role of gut microbiota dysbiosis in the progression of CKD through the gut–kidney axis. Consequently, microbiome-targeted nutritional strategies, including probiotics, prebiotics, and synbiotics, have emerged as promising complementary approaches to modulate intestinal microbial composition and metabolic functions. This review summarizes and critically evaluates the current clinical evidence regarding the use of these interventions in CKD patients. Clinical studies indicate that supplementation with probiotics, prebiotics, and synbiotic formulations may promote beneficial shifts in the composition of the gut microbiota, enhance saccharolytic fermentation, and increase the production of short-chain fatty acids (SCFAs). These changes have been associated with reduced circulating levels of gut-derived uremic toxins such as indoxyl sulfate and p-cresyl sulfate, as well as with the attenuation of systemic inflammation and oxidative stress. However, available trials remain heterogeneous in terms of study design, probiotic strains, prebiotic substrates, dosing regimens, and patient populations, and are frequently limited by small sample sizes and short intervention durations. As a result, evidence for improvements in renal function and long-term clinical outcomes remains inconclusive. While synbiotics may offer theoretical advantages by combining microbial supplementation with targeted substrates that support microbial growth and metabolic activity, current evidence does not consistently demonstrate superior clinical efficacy. Overall, these interventions often improve surrogate biomarkers, but their effects on renal function and hard clinical outcomes remain uncertain. Larger, longer-duration multicenter randomized controlled trials with standardized formulations are needed to establish their clinical utility and to better elucidate microbiota–host interactions in CKD. Advancing this field may support the development of personalized microbiome-based therapeutic strategies aimed at modulating the gut–kidney axis and ultimately improving clinical outcomes in CKD patients. Full article

Background: Temporomandibular disorders (TMDs) are multifactorial conditions frequently encountered in orthodontic practice, and the independent associations of occlusal and structural variables remain unclear. This case–control study constructed a multivariable model integrating clinical, cephalometric, panoramic, and functional variables to examine their associations with TMD, diagnosed according to the DC/TMD Axis I protocol. Fifty patients with TMD and 50 non-TMD controls were consecutively recruited between October 2024 and December 2025. Occlusal characteristics, lateral cephalometric measurements, and Kjellberg panoramic symmetry indices (SI1/SI2) were assessed using standardized protocols. Candidate variables were initially explored using univariable analyses with false discovery rate adjustment, followed by multivariable Firth penalized logistic regression to reduce small-sample bias and separation. Mandibular deflection (OR = 3.57, 95% CI 1.54–9.09) and deviation (OR = 4.35, 95% CI 1.69–12.50) demonstrated the strongest independent associations with TMD, while SI1 asymmetry (<90%) became significant after multivariable adjustment (OR = 3.57, 95% CI 1.08–14.29). The final model showed apparent discrimination within the study sample (AUC = 0.822; 95% CI: 0.742–0.902). However, this value was calculated using the same dataset and should not be interpreted as validated model performance or compared to other studies. The observed SI1 effect should be interpreted cautiously, as it may reflect model instability due to the relatively small sample size. Within the limitations of this case–control design, functional disturbances showed stronger associations with TMD than static structural variables; however, external validation is required before clinical application. Full article

Ultra-precision thinning of hard and brittle materials like monocrystalline silicon demands high dynamic stability in thinning spindle. To address the challenge of accurately detecting subtle spindle chatter anomalies in industrial environments characterized by high noise and limited data, this paper proposes a physics-guided dual-stream attention fusion transfer network (PG-AFNet). First, a physics-guided signal preprocessing method was developed. Using variational mode decomposition (VMD) and continuous wavelet transform (CWT) masking, one-dimensional dynamic features and high-frequency regions of interest (ROIs) rich in transient impact features were extracted. Second, the PG-AFNet architecture was designed. By introducing an attention mechanism, it achieves deep integration of one-dimensional purely dynamic sequences with two-dimensional spatiotemporal visual textures to capture surface damage features caused by subtle vibrations. Finally, systematic validations were conducted using a real silicon wafer thinning dataset with 197 real samples. By overcoming small-sample limitations via physical augmentation, PG-AFNet achieved an 82.45% (86.64% after data augmentation) diagnostic accuracy, significantly outperforming traditional baselines. Furthermore, a large-scale cross-load validation on the diverse CWRU dataset yielded an exceptional 99.68% accuracy under mixed-load conditions, conclusively verifying the model’s robust domain generalization. Lastly, a rigorous ablation study explicitly quantified the indispensable contributions of the physics-guided dual-stream architecture and attention fusion. This research provides a feasible theoretical foundation for intelligent surface quality monitoring in semiconductor hard-brittle material processing. Full article

This study examined temporal scalp electroencephalography (EEG) absolute power and brief self-reported psychological state measures before and after participation in a Life Story Program (LSP) in older adults. Five older women participated in the study. For each participant, pre- and post-assessments were scheduled at approximately the same time of day and included a brief four-item questionnaire and biosignal acquisition in a controlled seated environment. EEG was recorded at 500 Hz from T5 and T6 during an eyes-closed resting condition. For EEG analysis, only non-speaking segments were used; the initial 3–5 min stabilization period was excluded, and the subsequent 10 min of data were analyzed. One participant was excluded after outlier screening, resulting in a final EEG sample of four participants. EEG preprocessing included linear detrending, 60 Hz notch filtering, 0.5–50 Hz band-pass filtering, artifact rejection, and Welch-based estimation of absolute power in the delta, theta, alpha, beta, and gamma bands. Given the small sample size, all analyses were treated as exploratory. Questionnaire responses remained generally stable across assessments. No statistically significant pre–post differences were observed after false discovery rate correction, although small reductions, particularly in the gamma band, were observed. These findings should be interpreted as preliminary observations requiring confirmation in larger controlled studies with broader multichannel EEG coverage and more robust recording configurations. Full article

This paper investigates frequentist prediction methods for the Burr X distribution under Type II censored data. To address the challenges of small sample sizes and high censoring rates commonly encountered in survival analysis, we derive four point prediction methods: best unbiased prediction (BUP), maximum likelihood prediction (MLP), conditional median prediction (CMP), and median unbiased prediction (MUP). For interval prediction, we examine four approaches—the pivotal method, the Wald method, the highest conditional density (HCD) method, and the shortest-length method to construct prediction intervals. The finite-sample performance of these methods is evaluated through Monte Carlo simulations and illustrated using three real-world datasets. The results demonstrate that CMP provides the most stable point predictions, with its advantage being particularly pronounced in small samples due to the conditional median’s robustness to extreme values. For interval prediction, the pivotal method yields the most consistently reliable coverage. The shortest-length method exhibits high accuracy and efficiency. Analyses of three real datasets further validate the applicability of these methods to both complete and right-censored data. Full article

This study addresses the instability of statistical modeling for small-sample maximum friction torque data under multiple temperature conditions. Within the Weibull distribution framework, a sample-aggregation method is proposed, and a unified modeling scheme separating central tendency from dispersion structure is established. This approach enables equivalent aggregation of data across different temperature levels while preserving structural consistency, thereby improving parameter estimation stability and statistical efficiency. To overcome the tendency of single-criterion optimization to fall into local optima under small-sample conditions, a secondary identification criterion combining residual minimization with a Levene-based statistical consistency test is introduced, and a dual-level search strategy is used to obtain a more robust global optimal solution. The parameter estimation results indicate that direct estimation based on small samples produces unstable parameters, with the coefficient of variation of the shape parameter reaching approximately 7.4%. In contrast, the sample-aggregation method shows that the scale parameter increases with temperature, while the location parameter first decreases and then increases due to the combined influence of central tendency and dispersion. The parameters obtained by the aggregation method exhibit more stable and regular variation trends with temperature. The results demonstrate that the proposed method significantly improves parameter stability and statistical efficiency for small-sample maximum friction torque data and provides a practical statistical modeling approach for multi-condition small-sample engineering data. Full article