Search Results (5,716)

Background: Severe asthma is a chronic, difficult-to-treat disorder that significantly affects quality of life, and oral glucocorticosteroids are usually required. Many patients suffering from severe asthma exhibit T2 inflammation and may benefit from biological treatment. This study aims to evaluate changes in cytokine concentrations during therapy with benralizumab, dupilumab, and mepolizumab in severe eosinophilic asthma. Materials and Methods: In this prospective, single-center study, 39 patients with severe eosinophilic asthma received treatment with one of the above-mentioned biologics. Parameters, such as the cytokine profile (Human Th9/Th17/Th22 Luminex, Performance Assay 18-plex Fixed Panel, R&D Systems, Minneapolis, MN, USA) and additionally the Asthma Control Questionnaire (ACQ), mini-Asthma Quality of Life Questionnaire (mini-AQLQ), spirometry (FEV1, FEV/FVC), FeNO, and functional status, were assessed at baseline and after 3–4 months of therapy. Results: The biologic therapies demonstrated diverse effects on inflammatory biomarkers. Dupilumab showed the most pronounced decreases in CD40L, IL-6, and FeNO in comparison to other drugs. In turn, the greatest decrease in TNF-α concentration was observed in the group treated with mepolizumab. Conclusion: Changes in cytokine concentrations highlight the heterogenous immunomodulatory mechanisms of biologics and support personalized strategies based on inflammatory profiles. However, the results should be interpreted with prudence, as the concentrations of cytokines in blood serum fluctuate and the study sample size is small. Full article

Accurate quantification of immune cell subpopulations is essential for understanding immune responses in research and clinical settings. Flow cytometry (FC) is widely used for immune cell phenotyping, providing rapid and quantitative single-cell resolution. However, tissue-based pathological assessment offers additional spatial and morphological context that is often necessary for a comprehensive understanding of immune cell distribution. Traditionally, these methods are applied separately to different specimens, limiting direct comparative analysis. Here, we describe a simple combined approach to immune cell quantification that integrates both FC and pathology analysis within the same tissue specimen of colon biopsies. Tissue samples were divided into two portions: one processed into a single-cell suspension for FC-based characterization of CD45⁺, CD3⁺, CD4⁺, and CD8⁺ T cells and another formalin-fixed, paraffin-embedded (FFPE), and analyzed with hematoxylin and eosin (H&E) for eosinophils and immunohistochemistry (IHC) for CD4 and CD8. A pilot analysis of 10 samples shows high concordance of the results taken from the two methods, allowing for cross-validation between methodologies and improved diagnostic accuracy. This proof-of-principle study demonstrates the feasibility of an integrated workflow that combines FC and pathology for immune cell quantification, which provides assessment of immune cell populations from the limited material of intestinal biopsies with potential for improved diagnostic accuracy. Full article

Background and Objectives: Inherited disorders of calcium metabolism are rare pediatric conditions with diverse manifestations, including seizures, growth impairment, and renal or skeletal complications. Precise molecular diagnosis is crucial for effective management and informed genetic counseling. This study aimed to develop a systematic diagnostic approach, broaden the mutational spectrum, and characterize initial clinical features. Material and Methods: We retrospectively analyzed 13 pediatric cases at a tertiary center in southern Taiwan (2020–2025). Clinical, biochemical, and imaging data were reviewed. Genetic testing followed a tiered strategy to identify copy number variations and single-nucleotide variants. Variants were classified according to the ACMG/AMP guidelines and assessed by in silico tools. Results: The pediatric cohort (8 males, 5 females) had a median diagnostic age of 2 years and a mean follow-up of 7.7 years. Hypoparathyroidism was most common (n = 7), followed by PTH resistance (n = 3), hyperparathyroidism (n = 1), calcipenic rickets (n = 1), and syndromic hypercalcemia (n = 1). Genetic diagnoses were established in 12 children and one parent, involving CASR, GNAS, PRKAR1A, CYP27B1, and KMT2D. Two novel variants were identified (CASR p.Val836Ile and GNAS c.719-30A>T). Phenotypic heterogeneity included incomplete penetrance in autosomal dominant hypocalcemia and variable multisystem involvement in syndromic cases. Conclusions: A stepwise genetic testing strategy achieved a high diagnostic yield in pediatric calcium metabolism disorders. The discovery of novel and population-specific variants expands the mutational spectrum, supporting precision medicine in pediatric endocrinology. Full article

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked with type 2 diabetes mellitus (T2D) and obesity. Despite its growing prevalence, effective pharmacological interventions remain limited, with antidiabetic agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) showing emerging promise. This study aimed to evaluate the impact of different antidiabetic therapies on hepatic steatosis, fibrosis, and cardiometabolic risk factors in patients with T2D and MASLD from Romania. Materials and Methods: We conducted a prospective observational study involving 256 patients with T2D and MASLD followed up for 6 months. Assessed parameters included anthropometry, glycemic indices, lipid profile, renal function, liver enzymes, and non-invasive evaluation of hepatic steatosis and fibrosis. Patients were 53% women, had a median age of 63 years, a median BMI of 32.2 kg/m², a median baseline CAP of 281 dB/m, a FibroScan of 8.9 kPa, and an HbA1c of 8.0%. Results: CAP decreased significantly from 281 to 245 dB/m, p < 0.0001; FibroScan from 8.9 to 8.0 kPa, p < 0.0001. The largest changes were observed in the GLP-1 RA subgroup (CAP −50 dB/m, FibroScan −1.0 kPa, weight −8.0 kg, HbA1c −0.7%), and in the SGLT2i subgroup (CAP −30.5 dB/m, FibroScan −0.7 kPa, weight −4.0 kg, HbA1c −0.5%). In regression analysis, independent factors associated with CAP improvement included GLP-1 RA therapy (β = 44.5, 95% CI 38.3–50.6, p < 0.0001), SGLT2i therapy (β = 23.4, 95% CI 15.7–31.1, p < 0.0001), and ≥10% weight loss (β = 23.2, 95% CI 12–34.4, p < 0.0001). For FibroScan improvement, GLP-1 RA (β = 1.0, 95% CI 0.8–1.2, p < 0.0001) and SGLT2i (β = 0.5, 95% CI 0.3–0.7, p < 0.0001) therapies were both significant. Conclusions: Antidiabetic therapy, particularly GLP-1 RA, was significantly associated with improvement in hepatic steatosis, fibrosis, and cardiometabolic risk in T2D patients with MASLD beyond the weight reduction effect. However, weight loss and lipid modulation enhance these benefits, supporting the development of integrated therapeutic strategies for this high-risk population. Full article

This study presents a theoretical analysis of the effectiveness of the use of variatropic concretes in multi-layer panel structures of buildings in terms of heat transfer. Theoretical analysis was performed with the aid of the modern numerical modeling software package ELCUT 6.6 and the computer algebra system Maple, which helped improve the reliability of the calculations. The results of this study of the thermophysical parameters of multi-layer panels using variatropic concrete showed that an increase in the degree of variatropy contributes to a rise in the temperature on the inner surface of the panel from 17.94 °C (traditional panel) to 18.87 °C (the most variatropic panel, Scheme 4), which improves indoor comfort conditions and reduces the risk of condensation. Additionally, it is possible to reduce the thickness of the insulation layer without compromising thermal efficiency. The high thermal inertia (D > 7) of variatropic panels ensures the accumulation and retention of heat, which has a positive effect on energy consumption during the heating season. The moisture regime of the studied structures meets regulatory criteria for preventing moisture accumulation, thereby increasing panel durability and eliminating conditions for mold formation or structural degradation. The air permeability performance of the panels also complies with the standards, while the dense outer concrete layers provide additional protection against air infiltration, stabilizing both thermal and moisture balance. The calculated thermal resistance of variatropic panels (Schemes 3 and 4) exceeded the standard requirement (3.20 m²·°C/W) by 1.2 and 1.74 times, respectively. Thus, it was established that the application of the variatropic principle in panel design ensures a more rational distribution of temperature fields, which results in reduced heat losses and improved thermal stability of exterior enclosures. This approach develops new design solutions focused on improving the energy efficiency of buildings and reducing material costs, which is consistent with current trends in Functionally Graded Design (FGD). Full article

The present research aims to investigate the impact of various mixing techniques (centrifugal planetary mixing, ultrasonication, and high-temperature magnetic stirring) on the properties of nanocomposite epoxy resins using expanded graphite particles. Differential scanning calorimetry reveals that the curing behavior and glass transition temperature are influenced by the selected method, indicating that a suitable choice allows increasing curing degree (C.D.) and glass transition temperature up to 10% and 12%, respectively. Morphological analysis performed via Scanning Electron Microscopy and Tunneling Atomic Force Microscopy offers detailed insights into the dispersion characteristics of fillers within polymer matrices, which sensitively affect the properties of the materials. The electrical conductivity values vary by more than five orders of magnitude among the various mixing methods. Centrifugal mixing leads to a decrease in the equilibrium concentration of water (C_eq) by up to 23% compared to that of the unfilled matrix, thanks to the chemical interactions that occur between the graphitic particles and the epoxy matrix (detectable via Fourier Transform Infrared Spectroscopy). Such a reduction is strongly desired in strategic fields such as the transport sector. The analysis of the obtained results suggests choosing the dispersion method of the filler in the matrix by considering the required performance for the specific planned application. Full article

In this study, the free vibration characteristics of a functionally graded (FG) shear-deformable Timoshenko beam were investigated both analytically and numerically. The work is notable for its significant contribution to the literature, particularly in addressing analytically challenging problems related to complex FGM structures using advanced computer-aided finite element methods. For the analytical approach, the governing equations and associated boundary conditions were derived using Hamilton’s principle of minimum potential energy. These equations were then solved using the Navier solution method to determine the natural frequencies of the beam. In the numerical analysis, a 3D FG beam model was developed in the ABAQUS finite element software (2023, Dassault Systèmes, Providence, RI, USA)using the second-order hexahedral (HEX20/C3D20) and 1D three-node quadratic beam (B32) elements. The material gradation was defined layer-by-layer along the thickness direction in accordance with the rule of mixtures. Modal analysis was subsequently performed to extract the natural frequency values. The results show a high level of agreement between the analytical and numerical solutions. and were consistent with previously published studies in the literature. Full article

Objectives: Pleural mesothelioma (PM) is a rare cancer that often develops after a decades-long latency period and confers a grim prognosis. Novel, biomarker-based therapeutic modalities are expected to improve the outcome of patients with advanced PM. CUDC-907 (fimepinostat) is a dual inhibitor that affects both histone deacetylases and PI3K enzymes. Its antitumor activity was described in several cancer types, but it has not yet been explored in PM. Materials and Methods: The sensitivity of 22 PM cell lines—including 18 models established in our laboratory—to cisplatin and CUDC-907 was determined using a cell viability assay. BAP1, PTEN, and c-Myc expression, as well as MYC copy number variation, were measured. The effect of combination treatment with cisplatin was assessed with cell viability, cell cycle, and 3D spheroid formation assays. Results: Most PM cell lines were sensitive to CUDC-907 treatment, and the CUDC-907 response was significantly higher in cell lines with higher c-Myc expression due to MYC copy number gain or amplification. Importantly, all cisplatin-insensitive cell lines were sensitive to CUDC-907. Combination treatment with cisplatin synergistically decreased cell viability and induced G2/M arrest or cell death. We tested cisplatin-sensitive P31WT and cisplatin resistant P31cis isogeneic pair and found that in both 2D and 3D assays the cisplatin-resistant cells showed a higher sensitivity to CUDC-907 single treatment. Combining CUDC-907 with cisplatin further decreased cell growth even in cisplatin-resistant cells. Conclusions: The majority of PM cell models are sensitive to CUDC-907, which may be a potent therapeutic agent in PM. Full article

Rubber material with high elasticity and viscoelasticity has become the most widely used universal material, and the study of the aging failure mechanism of rubber has been meaningful research in the polymer materials field. Cis-polyisoprene was employed to analyze the mechanism of oxidative degradation under artificial UV irradiation, and the GQDs/g-C₃N₄ photocatalysis with a 2D layered structure prepared by the method of microwave-assisted polymerization enabled to accelerate the degradation procedure. The results showed that the oxidation of cis-polyisoprene occurred during the irradiation for 3 days and the structure of cis-polyisoprene changed. The α-H of the double bond was attacked by oxygen to form hydroperoxide. Then, aldehydes and ketones generated as the addition reaction of double bonds occurred. The content of the hydrogen of C=C reduced, and the oxidative degradation was dominant at the initial aging stage. The crosslinking reaction was dominant at the final aging stage and the average molecular weight decreased from 15.49 × 10⁴ to 8.78 × 10⁴. The GQDs could promote the charge transfer and the photodegradation efficiency and inhibit the electron–hole recombination. The light capture ability of GQDs was improved after compositing with g-C₃N₄. The free radicals ·O₂²⁻ generated after adding GQDs/g-C₃N₄ nanoparticles, and the molecular weight of cis-polyisoprene decreased to 5.79 × 10⁴, with the photocatalytic efficiency increasing by 20%. This work provided academic bases and reference values for the application of photocatalysts in the field of natural rubber degradation and rubber wastewater treatment. Full article

Background: Oscillating hyperglycemia (glycemic variability) and vitamin D deficiency each damage the retinal microvasculature, yet their combined effect on sight-threatening proliferative diabetic retinopathy (PDR) is uncertain. Objective: To determine whether high GV and severe vitamin D deficiency independently, and additively, associate with retinal neovascularization in adults with diabetes. Materials and Methods: We conducted a cross-sectional study between January 2025 and June 2025 in 58 adults with diabetes at Constanța County Emergency Hospital, Romania. GV was classified as high (coefficient of variation > 36% or SMBG-SD > 50 mg/dL) or low. Serum 25-hydroxy-vitamin D [25(OH)D] was measured; severe deficiency < 10 ng/mL. Dilated funduscopy graded retinopathy as non-proliferative (NPDR) or proliferative (PDR). Multivariable logistic regression adjusted for HbA1c, diabetes duration, BMI, smoking, triglycerides and therapy. Results: From 58 adults (mean ± SD 59 ± 11 years), high GV characterized 29/58 participants (50%). Severe vitamin D deficiency was more frequent in the GV-high group (45% vs. 31%). PDR prevalence was 48% in GV-high and 31% in GV-low patients. After adjustment, high GV (adjusted OR 2.31, 95% CI 1.05–5.09) and severe vitamin D deficiency (OR 2.04, 95% CI 0.98–4.25) each predicted PDR. Concomitant exposure to both stressors conferred 3.9-fold higher odds of PDR (OR 3.88, 95% CI 1.35–11.1). No interaction term reached significance (p = 0.21), indicating additive effects. Conclusions: High GV and severe vitamin D deficiency independently and additively associate with PDR. Screening for both parameters may enhance risk stratification of PDR. Within adults with diabetes, high glycemic variability and severe vitamin D deficiency were each associated with higher odds of PDR after adjustment for HbA1c, diabetes duration, BMI, smoking, triglycerides, and treatment pattern; their effects appeared additive rather than multiplicative. These findings reflect associations within diabetes and do not imply that vitamin D deficiency produces retinopathy in euglycemic individuals. Full article

The increasing reliance on conventional coatings such as WC-Co raises serious environmental and health concerns due to the toxicity of cobalt and the ecological footprint of these materials. To address this challenge, the present study explores the development of eco-friendly multifunctional coatings via the Plasma Spray (PS) process, using titanium (Ti), silicon carbide (SiC), and tungsten carbide-cobalt (WC-Co) mixtures as alternative feedstocks. Steel substrates were coated under different deposition strategies (powder mixing, layer-by-layer) and current settings (800-900 A). The coatings were characterized by scanning electron microscopy (SEM/EDX), 3D profilometry, sliding wear testing, and potentiodynamic corrosion measurements. Results showed that Ti-WC (mix, 900 A) and Ti-SiC (layer, 900 A) coatings achieved the most favorable performance, combining excellent adhesion, uniform coverage, reduced porosity, and improved resistance to wear and corrosion compared to conventional Cr₂O₃ coatings. Notably, Ti-WC coatings provided surface roughness values comparable to Cr₂O₃, while significantly lowering the environmental impact. These findings demonstrate that PS-based Ti-WC and Ti-SiC systems can serve as sustainable and high-performance alternatives for protective applications in harsh environments, particularly in marine industries, supporting the transition toward coatings with reduced ecological footprint. Full article

Background and Objectives: Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are characterized by persistent inflammation, malnutrition, and immune dysfunction, all of which contribute to poor outcomes in hemodialysis (HD) patients. The C-reactive protein albumin lymphocyte (CALLY) index has been proposed as a novel biomarker that integrates these mechanisms. This study aimed to evaluate the prognostic value of the CALLY index together with established markers, including the C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR) for all-cause mortality in HD patients. Materials and Methods: This retrospective cohort study was conducted on 106 patients undergoing HD. Demographic, clinical, and laboratory parameters were obtained three months after the effects of HD initiation was reviewed. Results: During a median follow-up of 24.5 months, 29 patients (27.3 percent) died. Non-survivors were significantly older (65.3 vs. 52.5 years, p < 0.001), had a higher prevalence of coronary artery disease (31 percent vs. 2.6 percent, p < 0.001), or shorter dialysis duration (14 vs. 27 months, p < 0.001). They also showed lower hemoglobin (9.2 vs. 10.1 g/dL, p = 0.007), creatinine (5.3 vs. 6.3 mg/dL, p = 0.048), and albumin levels (28 vs. 34 g/L, p = 0.001), as well as a higher MLR (0.329 vs. 0.254, p = 0.014). In multivariate analysis, age, CAR, and NLR independently predicted mortality, explaining 83.8% of the variation. ROC analysis identified age and MLR as significant predictors, with MLR showing a high negative predictive value (83.9%). The CALLY index did not demonstrate independent prognostic value. Conclusions: Age, CAR, NLR, and MLR were independent predictors of mortality in HD patients, whereas the CALLY index was not prognostic in this cohort. Among these markers, MLR may be a practical biomarker with strong negative predictive power. Larger prospective studies are needed to validate these findings. Full article

Introduction: Multiple sclerosis (MS) is a chronic neurodegenerative disease that entails high costs, progressive disability, and reduced quality of life (QoL). Telerehabilitation (TR), supported by new technologies, is emerging as an alternative or complement to in-person rehabilitation, potentially lowering socioeconomic impact and improving QoL. Aim: The objective of this study was to evaluate the effect of TR on the QoL of people with MS compared with in-person rehabilitation or no intervention. Materials and methods: A systematic review of randomized clinical trials was conducted (March–May 2025) following PRISMA guidelines. Searches were run in the PubMed-Medline, EMBASE, PEDro, Web of Science, and Dialnet databases. Methodological quality was assessed with the CASP scale, risk of bias with the Risk of Bias 2 tool, and evidence level and grade of recommendation with the Oxford Classification. The protocol was registered in PROSPERO (CRD420251110353). Results: Of the 151 articles initially found, 12 RCTs (598 total patients) met the inclusion criteria. Interventions included (a) four studies employing video-controlled exercise (one involving Pilates to improve fitness, another involving exercise to improve fatigue and general health, and two using exercises focused on the pelvic floor muscles); (b) three studies using a monitoring app to improve manual dexterity, symptom control, and increased physical activity; (c) two studies implementing an augmented reality system to treat cognitive deficits and sexual disorders, respectively; (d) one platform with a virtual reality headset for motor and cognitive training; (e) one study focusing on video-controlled motor imagery, along with the use of a pain management app; (f) a final study addressing cognitive training and pain reduction. Studies used eight different scales to assess QoL, finding similar improvements between groups in eight of the trials and statistically significant improvements in favor of TR in four. The included trials were of good methodological quality, with a moderate-to-low risk of bias and good levels of evidence and grades of recommendation. Conclusions: TR was more effective in improving the QoL of people with MS than no intervention, was as effective as in-person treatment in patients with EDSS ≤ 6, and appeared to be more effective than in-person intervention in patients with EDSS between 5.5 and 7.5 in terms of QoL. It may also eliminate some common barriers to accessing such treatments. Full article

In this study, we discovered a new diameter-dependent carbon nanotube (CNT) hydrogel composed exclusively of CNTs and tannic acid (TA). Accordingly, we first examined the relationship between the concentrations of CNTs and TA, as well as the CNT diameter, and whether gelation occurred. As a result, we found that when the TA concentration was fixed at 0.15 wt%, the threshold CNT concentration required for gelation was 0.05 wt%, which was lower than the values reported for previously known CNT hydrogels. We also determined that a TA to CNT weight ratio of 2–3 is critical for gelation. Furthermore, we found that subjecting the CNT dispersion to hydrothermal treatment at 160 °C, followed by freezing and ambient drying, produced a CNT aerogel that retained its 3D structure. Then, we evaluated the thermoelectric properties (electrical conductivity and Seebeck coefficient) of the resulting CNT hydrogel and aerogel under a temperature gradient for application. Both materials exhibited stable and reproducible electromotive force, and the measured Seebeck coefficients were comparable to those of conventional CNT-based thermoelectric materials. These findings demonstrate that 3D thermoelectric materials can be readily fabricated from CNT dispersions via simple processes and highlight the potential of these materials for future applications in energy-harvesting devices. Full article

In this paper, a new 3D printing system based on temperature–pressure double closed-loop collaborative control is proposed to solve the problem of 3D printing accuracy of starch food. The rapid and accurate adjustment of the nozzle temperature is realized by the hybrid control of Bang-Bang and PID, and the extrusion pressure is optimized in real time by combining the adaptive fuzzy PID algorithm, which effectively reduces the influence from the change of material rheological properties and external interference. The experimental results show that the printing accuracy of the system is up to 98% at 40 °C, the pressure fluctuation is reduced by 80%, and the molding accuracy of complex structures is improved to 97%, which significantly improves the over-extrusion and under-extrusion, and provides an effective solution for stable and high-precision printing of high-viscosity food materials. Full article