Search Results (6,622)

Background: Depressive disorders are among the most common and disabling psychiatric conditions. A growing body of evidence suggests that dopaminergic dysfunction plays a key role in the pathophysiology of anhedonia, amotivation, and psychomotor slowing. This systematic review aims to determine whether bromocriptine, amantadine, and selegiline improve depressive symptoms compared to placebo or standard antidepressants, and to test the hypothesis that their antidepressant effects are mediated by dopaminergic modulation of motivational and reward circuits. Methods: The review followed PRISMA guidelines and was registered in PROSPERO. Results: Twenty-eight studies met inclusion criteria. Selegiline, particularly in transdermal form, reduced HAM-D scores by approximately 40% from baseline and by 25–30% relative to placebo. Amantadine augmentation achieved ≥50% symptom improvement in 60–70% of treatment-resistant cases. Bromocriptine yielded comparable response rates (~60%) to tricyclic antidepressants. All three agents improved anhedonia and motivational deficits. Conclusions: Findings suggest that bromocriptine, amantadine, and selegiline may represent effective dopaminergic antidepressants, particularly for treatment-resistant or atypical depression. Further large-scale, methodologically rigorous studies are needed to confirm their clinical utility. Full article

An innovative, STEAM-based educational approach uses LEGO^® robots to improve the visualisation and understanding of trochoid curves in tertiary mathematics education. The method involves a two-step process: first, the curves are drawn based on the classical definition of trochoids using a custom-designed LEGO^® robot that employs LED light to trace the shapes. Then, the same process is replicated with a marker, with the robot controlling the movement of the drawing head to reproduce the curves accurately. To deepen students’ comprehension and visualisation, Desmos dynamic geometry software was used in parallel to draw all three types of trochoids (prolate, curtate, and cusped). This hands-on technique aims to make these motion curves more tangible and engaging within a classroom setting. A quantitative experiment involving 94 first-year IT BSc students was conducted during the spring semester of the 2024/2025 academic year using a quasi-experimental design. We had one control group and two experimental groups. One of the experimental groups did not use educational robotics; participants could only see how the robots worked via video. The other experimental group gained first-hand experience by building and testing LEGO^® drawing robots. The aim was to evaluate the effectiveness of an innovative teaching method that used educational robotics to improve understanding of the mathematical properties of trochoids, compared to traditional teaching methods and presentations containing short videos. The Mann–Whitney U test was used in all cases during hypothesis testing. Only watching videos of drawing robots does not have a statistically significant effect on learning outcomes. In this case, the effect size was only 0.12. However, the results of the group performing educational robotics activities showed a statistically significant difference compared to the other two groups, with large effect sizes (0.68 and 0.7). Our results suggest that visualisation using LEGO^® robots significantly improves students’ knowledge of parametric curves. Educational robotics offers promising opportunities because it is an attractive and interactive teaching tool. Its great advantage is that it combines abstract mathematical concepts with modern technology, thus creating an effective learning environment. Full article

Background/Objectives: Chronic kidney disease (CKD) is commonly complicated by anemia resulting from impaired erythropoietin (EPO) production, iron dysregulation, and chronic inflammation. Erythroferrone (ERFE) and hepcidin are key regulators of erythropoiesis and iron metabolism, but their interaction in CKD remains incompletely understood. This study aimed to examine the associations among ERFE, hepcidin, EPO, and hemoglobin, and to determine whether these markers independently relate to anemia severity in CKD. Methods: This cross-sectional case–control study included 126 patients with CKD (stages 2–5) and 33 age- and sex-matched healthy controls. Laboratory parameters, including hemoglobin, ferritin, transferrin saturation (TSAT), EPO, ERFE, hepcidin, and renal indices (eGFR, BUN, creatinine), were analyzed. Group differences were assessed using ANOVA or Kruskal–Wallis tests with post hoc analyses, and trends were evaluated using the Jonckheere–Terpstra test. Age- and sex-adjusted correlations and multivariable linear regression identified independent associations with hemoglobin. Results: Patients with CKD were older (61.2 ± 14.8 vs. 33.4 ± 10.7 years, p < 0.001) and had lower hemoglobin (11.8 ± 1.9 vs. 13.5 ± 1.4 g/dL, p < 0.001) and higher ferritin levels (245 (110–470) vs. 105 (40–240) ng/mL, p = 0.002) compared with controls. eGFR declined progressively across CKD stages (median (IQR): 73 (64–86) to 12 (7–17) mL/min/1.73 m², p-trend < 0.001). ERFE and hepcidin showed increasing trends with advancing CKD (p-trend = 0.031 and 0.047, respectively). Hemoglobin correlated negatively with ERFE (r = −0.40, 95% CI: −0.53 to −0.26, p < 0.001) and positively with eGFR (r = 0.42, 95% CI: 0.28–0.54, p < 0.001). In adjusted regression analysis, ERFE (β = −0.29, 95% CI: −0.41 to −0.18, p < 0.001) and eGFR (β = 0.25, 95% CI: 0.13–0.37, p < 0.001) remained independently associated variables of hemoglobin (adjusted R² = 0.47). Conclusions: Anemia severity in CKD is independently associated with both renal dysfunction and higher ERFE concentrations, suggesting a disrupted ERFE–hepcidin regulatory balance. These findings provide hypothesis-generating insights into the complex interplay between iron metabolism and erythropoiesis in CKD. Validation in larger, multi-center longitudinal studies that include inflammatory markers is warranted. Full article

In addition to products with a single component, this study examines products composed of multiple components whose lifetimes follow a one-parameter exponential distribution. An overall lifetime performance index is developed to assess products under the progressive type I interval censoring scheme. This study establishes the relationship between the overall and individual lifetime performance indices and derives the corresponding maximum likelihood estimators along with their asymptotic distributions. Based on the asymptotic distributions, the lower confidence bounds for all indices are also established. Furthermore, a hypothesis testing procedure is formulated to evaluate whether the overall lifetime performance index achieves the specified target level, utilizing the maximum likelihood estimator as the test statistic under a progressive type I interval censored sample. Moreover, a power analysis is carried out, and two numerical examples are presented to demonstrate the practical implementation for the overall lifetime performance index. This research can be applied to the fields of life testing and reliability analysis. Full article

The rapid digitalization of banking services has transformed consumer interactions, necessitating a deeper understanding of the factors influencing online banking adoption. This research investigates the factors influencing consumer adoption in a country undergoing rapid digital transformation but still facing gaps in digital skills and infrastructure—Romania. The objective of the study is to analyze how key variables such as ease of use, security, speed, usefulness, and social pressure influence online banking behavior of Romanian consumers, especially the most digitally engaged ones. The study utilizes a multi-method empirical approach, hypothesis testing, binary logistic regression for prediction modeling, and segmentation analysis to offer a comprehensive view of customer behavior. The findings identify essential adoption drivers and separate customer profiles, providing useful information for financial organizations aiming to enhance their digital strategy. Perceived ease of use and perceived security are primary factors influencing adoption; nevertheless, decision tree analysis indicates that speed and usefulness have a more significant impact than logistic regression implies, but social pressure unexpectedly serves as an impediment. These results highlight the necessity for banks to customize their digital services, harmonizing security and user-friendliness with improved efficiency and usefulness to promote broader adoption in emerging digital economies like Romania. Full article

Predicting the electric field distribution inside microfluidic devices featuring an embedded array of electrical insulating pillars is critical for applications that require the electrokinetic manipulation of particles (e.g., bacteria, exosomes, microalgae, etc.). Regularly, these predictions are obtained from finite element method (FEM)-based software. This approach is costly, time-consuming, and cannot effortlessly reveal the dependency between the electric field distribution and the microchannel design. An alternative approach consists of analytically solving Laplace’s equation subject to specific boundary conditions. This path, although precise, is limited by the availability of suitable coordinate systems and can only solve for the simplest case of a single pair of pillars and not for a rectangular array of pillars. Herein, we propose and test the hypothesis that the electric field across a longitudinal path within the microchannel can be estimated from an electric circuit model of the microfluidic device. We demonstrate that this approach allows estimating the electric field for whatever pillar shape and array size. Estimations of the electric field extracted from a commercial FEM-based software were used to validate the model. Moreover, the circuit model effortlessly illustrates the relationships between the electric field and the geometrical parameters that define the microchannel design. Full article

Over the past five decades, the Tallet Alsauda district of Aleppo (Syria) has experienced multiple catastrophic collapses, attributed to a network of subsurface chalk cavities formed through historic quarrying and possible natural karstification. Yet, no comprehensive investigation has previously been conducted to characterise the cavities or clarify the governing failure mechanisms. Such assessments are particularly difficult in historic urban environments, where void geometries are irregular, subsurface data scarce, and underground access limited. This study addresses these challenges through an integrated programme of fourteen boreholes, laboratory testing, and inverse-distance interpolation to reconstruct subsurface geometry and overburden thickness. These data-informed three-dimensional finite element simulations are designed to test the hypothesis that chalk deterioration, driven by both natural and anthropogenic processes, controls the instability of cavity roofs. Rock mass parameters, particularly the Geological Strength Index (GSI), were progressively reduced and evaluated against the site’s documented collapse history. The simulations revealed that a modest decline in GSI from ~53 to 47 precipitated abrupt displacements (>300 mm) and upward-propagating plastic zones, consistent with field evidence of past collapses. These results confirm that instability is governed by threshold reductions in material strength, with sewer leakage identified as a principal trigger accelerating chalk softening and roof destabilisation. Full article

Objectives: The objective of this study was to separately examine the effects of exercise addiction and the Collagen Type I Alpha 1 Chain (COL1A1) gene rs1800012 G/T polymorphism on injury susceptibility in elite female volleyball players, and to test the hypothesis that the T allele, previously identified as a risk allele, is underrepresented in volleyball players compared to the general population. Methods: The study included 50 professional Turkish female volleyball players with documented injury data, along with 557 Turkish controls, 53 professional Russian volleyball players, and 810 Russian controls. The Turkish participants were enrolled in a case–control study, an injury study, and an exercise addiction study, whereas the Russian participants were enrolled solely in a case–control study. Results: Injured players had significantly higher scores in the Delay of Individual Social Needs and Conflict subscale of the Exercise Addiction Scale compared to their uninjured counterparts (p = 0.036). The random-effects meta-analysis revealed a significantly lower frequency of the COL1A1 T allele in volleyball players compared to controls (pooled OR = 0.63, 95% CI: 0.41–0.96, p = 0.031). Athletes who had not undergone surgery had a significantly higher frequency of the G allele compared to controls (89.2% vs. 78.7%, p = 0.037; OR = 2.23, 95% CI: 1.1–4.7). Among injured athletes, those carrying the GT genotype were significantly more likely to experience prolonged recovery (≥3 months) (57.1%) compared to those with the GG genotype (28.0%, p = 0.017). Conclusions: Exercise addiction and the COL1A1 rs1800012 T allele were associated with a higher incidence of injury in female volleyball players. The T allele was also associated with a longer recovery time following injury. Full article

Background: The interaction between probiotics and the vitamin D/vitamin D receptor (VDR) pathway has been increasingly explored as a potential mechanism for immune modulation in inflammatory bowel disease (IBD). Lactobacillus rhamnosus GG (LGG) has shown promising results in ulcerative colitis (UC) patients, but its effect on the VDR pathway remains unexplored in humans. Aim: To test the hypothesis that LGG can stimulate the vitamin D/VDR pathway and modulate mucosal-adherent microbiota. Methods: In this study, we analyzed a subgroup of 13 patients from the LGGinUC trial, in which UC patients with mild-to-moderate disease activity received LGG monotherapy for four weeks. Colonic biopsy samples were collected before and after treatment to evaluate VDR expression via RT-qPCR and immunohistochemistry. Mucosal-adherent microbiota was also analyzed by DNA extraction and next-generation sequencing (NGS). Results: LGG administration significantly increased VDR mRNA expression in colonic mucosa (p < 0.05), with a corresponding rise in VDR protein levels in both epithelial and sub-epithelial compartments. Microbiota analysis revealed a reduction in α-diversity, primarily due to a decrease in commensal bacterial species, while β-diversity remained largely unchanged. Conclusions: Although the present results have to be considered preliminary, this is the first human study demonstrating that probiotic supplementation can upregulate VDR expression in colonic mucosa. We propose that LGG may exert its beneficial effects in UC by stimulating the VDR pathway, which in turn modulates mucosal immunity and microbiota composition. Further studies with larger sample sizes and longer treatment durations are needed to validate these findings and explore their therapeutic implications. Full article

Methacrylyl-CoA is a key metabolic intermediate in the valine catabolic pathway. Its accumulation has been found to be cytotoxic and associated with pathological conditions. Nevertheless, detailed biological effects of methacrylyl-CoA and methacrylate in human physiology and pathology are poorly understood. We propose that the electrophilicity of the alkene bond in the methacrylyl group can react with the cysteine residues in proteins resulting in an unexplored protein post-translational modification (PTM), cysteine S-2-carboxypropylation (C2cp). To test and validate this mechanistic hypothesis, we experimentally detected and profiled S-2-carboxypropylated proteins from the complex cellular proteome with the design and application of a bioorthogonal chemical probe, N-propargyl methacrylamide. We tested the probe in different mammalian cell models and demonstrated its versatility and sensitivity to protein cysteine S-2-carboxypropylation. We established quantitative chemical proteomics for global and site-specific profiling of protein S-2-carboxypropylation, which successfully identified 403 S-2-carboxypropylated proteins and 120 cysteine modification sites from HEK293T cells. Through bioinformatic analysis, we found that C2cp-modified proteins were involved in a variety of critical cellular functions including translation, RNA splicing, and protein folding. Our chemoproteomic studies demonstrating the proteome-wide distribution of cysteine S-2-carboxypropylation provide a new biochemical mechanism for the functional investigation of methacrylyl-CoA and understanding valine-related metabolic disorders. Full article

The placement of miniscrews in orthodontics enhances dental and skeletal movements with reduced need for patient cooperation but may lead to complications such as incorrect positioning or damage to adjacent teeth. Computer-assisted surgery techniques have shown improved accuracy and reduced risks. This study aimed to compare the accuracy of the X-Guide^® dynamic navigation system with the freehand method for orthodontic miniscrew insertion and to assess the influence of screw position and side on accuracy. The main hypothesis was that the X-Guide^® system would yield superior accuracy in the primary variable (3D apical deviation) compared to the freehand technique. Secondary hypotheses were that the X-Guide^® system would also demonstrate superior accuracy in the secondary parameters (3D entry deviation, angular deflection, apical depth, and 2D entry deviation) and that screw position and side would not significantly affect any of the outcomes. An in vitro, randomized, and blinded experimental design was used with 10 maxillary models divided into two groups: experimental (X-Guide^®) and control (freehand). In each model, six miniscrews were planned using cone beam computed tomography (CBCT): three were inserted freehand and three with navigation. A trained novice clinician performed all insertions. Post-placement CBCT scans were used to compare 3D deviations between planned and actual positions. Wilcoxon signed-rank tests and Friedman’s ANOVA were applied. In conclusion, the results supported the main hypothesis regarding the primary variable: the X-Guide^® system significantly improved miniscrew placement accuracy in terms of 3D apical deviation, even when used by a novice operator. However, the results partially rejected the secondary hypotheses related to precision, showing a significant improvement in 3D entry deviation with dCAS, but not in angular deflection or 2D measured parameters. Furthermore, the results supported the secondary hypothesis regarding screw position, which did not affect the outcomes. Nevertheless, with dCAS, a significantly greater deviation was found on the right side for 3D entry deviation, 2D entry deviation, and angular deflection. Full article

Passive design strategies incorporating phase change materials (PCM) provide effective thermal energy storage, improve indoor comfort, and reduce building energy demand. This study aimed to evaluate the effectiveness of partially filled PCM glazing systems in stabilizing indoor thermal comfort under Korean climate conditions, testing the hypothesis that partial integration can provide meaningful diurnal temperature regulation without compromising daylight access. Indoor air, interior and exterior glazing surfaces, and the PCM layer were monitored to evaluate heat transfer, while EnergyPlus simulations extended the analysis to seasonal conditions. The PCM model was developed using the Conduction Finite Difference (CondFD) algorithm and validated against experimental data, reliably reproducing dynamic phase change behavior. Field tests with a 28 °C PCM showed reductions in indoor peak temperatures of about 2.0 °C during daytime and increases of 1.5 °C at night. Under broader climatic simulations, the same PCM achieved up to 3.7 °C daytime reductions and 2.0 °C nighttime increases, depending on outdoor conditions. These findings highlight the potential of PCM-integrated glazing systems for adaptive thermal regulation in Korean climates and suggest broader applicability for passive cooling and heating strategies in buildings facing increasingly variable weather conditions. Full article

Experimental studies published to date on the effects of silver nanoparticles (AgNPs) on plants have yielded highly contradictory results: reported outcomes range from growth inhibition to stimulation. The objective of this research was to test the hypothesis that the ontogenetic stage at the time of exposure to AgNPs is a key determinant of both the qualitative profile and quantitative magnitude of plant responses. For this purpose, laboratory seed priming and small-plot field experiments with wheat plants (Triticum aestivum L.) treated with stabilized dispersions of AgNPs at 1–100 mg∙L⁻¹ were conducted. It was shown that seed priming with low concentrations of AgNPs (1–5 mg∙L⁻¹) did not affect wheat seedling growth, whereas dispersions at ≥25 mg∙L⁻¹ suppressed development. In agreement, antioxidant enzyme activities (POD, CAT, PPO) increased at 1–5 mg·L⁻¹ and decreased at 100 mg·L⁻¹. By contrast, foliar treatments of field-grown wheat increased plant population density, plant height, spike structure metrics, and grain yield. The optimal regimen—three foliar applications at 5 mg·L⁻¹—increased grain yield by 12.1% from 5.89 t·ha⁻¹ to 6.60 t·ha⁻¹. At low doses of AgNPs, activities of peroxidase, catalase, and polyphenol oxidase in seedlings tissues increased, indicating activation of nonspecific defense mechanisms; at higher concentrations, activities of these enzymes decreased, indicating antioxidant system exhaustion and dysfunction. The findings demonstrate dose- and stage-dependent effects and corroborate the central role of the developmental stage of wheat in determining responses to AgNPs, indicating opportunities to optimize stage-aware, low-dose application regimes to enhance productivity while minimizing phytotoxic risk. Full article

The Poisson distribution is a discrete probability model, widely used in science and engineering to describe various natural and man-made phenomena. It possesses an important feature, namely being inherently asymmetric, but as its parameter becomes large, the distribution becomes approximately symmetric. To broaden its use, multiple extensions and variations have been developed. Determining whether a data set follows a Poisson distribution involves hypothesis testing at a chosen significance level. When sampling from a Poisson distribution, confidence intervals provide an estimated range instead of a single value. Due to the discrete nature of the Poisson distribution, confidence intervals cannot be derived from a simple formula, and are therefore computed using specialized algorithms. In this paper, three alternatives are given and discussed. Full article

Cardiopulmonary bypass (CPB) can lead to cardiac damage due to oxidative stress (OS) and inflammation in heart failure (HF). We tested the hypothesis that preoperative HF patients with reduced ejection fraction (HFrEF) subjected to CBP have higher levels of OS and NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) in heart and plasma and in those that develop postoperative AF (pAF) as a clinical outcome. HF was categorized for preoperative left ventricular EF: preserved (HFpEF > 50%, n = 27) and reduced EF (HFrEF ≤ 40%, n = 25). Samples of atrial tissue, pericardial fluid, and plasma were collected at surgery to assess NLRP3 expression; 3-nitrotyrosine (3-NT), thiobarbituric acid reaction (TBARS), and nuclear factor erythroid 2-related factor 2 (Nrf2) in atrial tissue; NLRP3, IL-1β, and IL-18 expression in pericardial fluid; and antioxidant capacity, 8-isoprostanes, and malondialdehyde (MDA) in plasma. Reactive oxygen species, 3-NT, and NLRP3 in atrial tissue were determined by immunohistochemistry in a subset of pAF patients. Plasma and atrial tissue 3-NT and MDA were higher in HFrEF compared with HFpEF. Lipid peroxidation products were higher in both plasma and atrial tissue in pAF (n = 29), compared to sinus rhythm (SR) (n = 23). In HFrEF patients, the values of tissue ROS, 3-NT, and NLRP3 were higher than in HFpEF patients. In addition, the expression levels of NLRP3, IL-1β, and IL-18 were higher in atrial tissue and pericardial fluid in HFrEF. Patients with preoperative HFrEF showed higher OS in plasma and the expression of NLRP3, ROS, and 3-NT in atrial tissue biopsies and pericardial fluid. This finding suggests a potential pharmacologic therapy for pAF and clinical complications due to CPB. Full article