Search Results (1,689)

Introduction: Oxidative stress is a key factor in the pathogenesis of many chronic diseases, especially in postmenopausal women. Xylitol, a sugar alcohol with potential antioxidant properties, may affect oxidative balance when used as a sugar substitute. Aim: This pilot study aimed to assess the effect of replacing sucrose with xylitol on serum antioxidant capacity in postmenopausal women. Methods: This study included 34 women aged 50 to 65 years who successively consumed 5 g/d, 10 g/d, and 15 g/d of xylitol. The dietary intervention lasted a total of 6 weeks, with each phase covering a 2-week period. Diet was assessed twice based on a 7-day dietary interview (Diet 6.0, NIZP–PZH, Warsaw). The material for this study was venous blood. Antioxidant capacity was determined using the DPPH radical scavenging method and the ABTS cation radical scavenging method. Results: In both methods, a significant increase in serum antioxidant potential was observed after replacing sugar with xylitol (p < 0.0001). An increase in the ability to neutralize free radicals was observed in almost all women studied. Additional analysis of the effect of selected nutrients on the obtained effects of the nutritional intervention showed that the most significant effect could potentially be exerted by manganese, maltose, sucrose, and mercury, and the strongest positive correlation was exerted by vitamin A, retinol, and vitamin E. Although the values obtained in the constructed models were not statistically significant, the large effect indicates potentially significant relationships that could have a significant impact on serum antioxidant potential in the studied group of women. Conclusions: The results suggest a potential role of xylitol in enhancing antioxidant defense mechanisms in menopausal women. Although the sample size was relatively small, this study was powered at approximately 80% to detect large effects, supporting the reliability of the observed results. Nevertheless, given the pilot nature of this study, further research with larger cohorts is warranted to confirm these preliminary observations and to clarify the clinical significance of xylitol supplementation in populations exposed to oxidative stress. Full article

The Slime Mould Algorithm (SMA) is a widely used swarm intelligence algorithm. Encouraged by the theory of no free lunch and the inherent shortcomings of the SMA, this work proposes a new variant of the SMA, called the BWSMA, in which three improvement mechanisms are integrated. The adaptive greedy mechanism is used to accelerate the convergence of the algorithm and avoid ineffective updates. The best–worst management strategy improves the quality of the population and increases its search capability. The stagnant replacement mechanism prevents the algorithm from falling into a local optimum by replacing stalled individuals. In order to verify the effectiveness of the proposed method, this paper conducts a full range of experiments on the CEC2018 test suite and the CEC2022 test suite and compares BWSMA with three derived algorithms, eight SMA variants, and eight other improved algorithms. The experimental results are analyzed using the Wilcoxon rank-sum test, the Friedman test, and the Nemenyi test. The results indicate that the BWSMA significantly outperforms these compared algorithms. In the comparison with the SMA variants, the BWSMA obtained average rankings of 1.414, 1.138, 1.069, and 1.414. In comparison with other improved algorithms, the BWSMA obtained average rankings of 2.583 and 1.833. Finally, the applicability of the BWSMA is further validated through two structural optimization problems. In conclusion, the proposed BWSMA is a promising algorithm with excellent search accuracy and robustness. Full article

Background: Exocrine pancreatic insufficiency (EPI or PEI) may be prevalent in as many as 3 of 10 people with diabetes due to exocrine pancreatic function being reduced as early as the time of diagnosis. EPI can be treated with pancreatic enzyme replacement therapy (PERT), but the symptom burden of EPI remains high and improved screening and diagnosis methods are needed. Methods: An online survey (n = 324) evaluated the gastrointestinal symptom experiences of people with (n = 155) and without (n = 169) EPI using a novel symptom tool, the Exocrine Pancreatic Insufficiency Symptom Score (EPI/PEI-SS). A large sub-group (n = 120) of people with diabetes with EPI (Type 1, n = 14, Type 2, n = 20) or without EPI (Type 1, n = 78; Type 2; n = 6) was characterized and compared to those without diabetes (n = 204) in a sub-analysis of the larger EPI/PEI-SS study. Results: The symptom burden of EPI is similar, irrespective of diabetes. Like those without diabetes, people with type 1 diabetes with EPI had a statistically significant (p < 0.001) higher mean score (range 0–225) on the EPI/PEI-SS (100.86, SD: 48.92) than people with T1D without EPI (31.59, SD: 28.25), distinct from other GI conditions (p < 0.001). Similar patterns occurred in those with T2D. Conclusions: High EPI/PEI-SS scores seem to distinguish between likely EPI and other GI conditions among people with diabetes, and the EPI/PEI-SS should be further studied as a possible screening method for EPI at a population level. It should also be evaluated as a tool to aid individuals with diabetes in tracking changes to EPI symptoms over time based on PERT titration. Full article

Aortic valve diseases affect a significant percentage of the population, and with the extension of survival expectancy, they are expected to increase furthermore. Surgical treatment of aortic valve diseases mainly includes valve replacement and, rarely, its repair. The technology of both surgical and transcatheter valves is evolving, and new prosthetic valves with improved characteristics are available, e.g., longer lifespan, faster implantation, better hemodynamic performance with better effective orifice area, suitable for small aortic annuli, etc. Minimally invasive surgical techniques are constantly evolving and spreading. New access sites are used for transcatheter valve implantation. The Heart Team determines the most appropriate intervention for each patient based on their anatomical and clinical profiles, aiming to optimize long-term outcomes. Full article

Background/Objectives: Iron deficiency without anaemia (IDNA) is common in non-dialysis-dependent chronic kidney disease (CKD) and contributes to fatigue, reduced exercise tolerance, and impaired quality of life (QoL). While intravenous (IV) iron replacement is known to benefit anaemic patients, its role in IDNA remains uncertain. This study aimed to evaluate the impact of ferric derisomaltose (FDI) on patient-reported QoL outcomes in CKD patients with IDNA. Methods: This was a post hoc analysis of the double-blind, multicentre Iron and the Heart randomised controlled trial. Fifty-four participants with IDNA (ferritin < 100 µg/L or transferrin saturation < 20% and haemoglobin 110–150 g/L) and CKD stages G3b–G5 were randomised 1:1 to receive either 1000 mg FDI (n = 26) or placebo (n = 28). An additional 10 iron-replete CKD patients served as controls. SF-36v2 QoL surveys were collected at baseline, 1 month, and 3 months. Results: SF-36v2 scores declined across all domains, but deterioration was consistently milder in the FDI group. Role physical declined by 3% in the FDI group versus 12% with placebo and 4% in controls. Bodily pain improved by 2.8% with FDI but worsened by 1.5% in the placebo group. Mental health improved by 3.4 points with FDI and declined by 2.7 points in the placebo group, creating a 6.1-point separation. While differences did not reach statistical significance, likely due to small sample size, the consistent trends favour FDI. Conclusions: IV iron may attenuate QoL decline in non-dialysis-dependent CKD patients with IDNA. These findings support the need for larger, adequately powered trials to assess patient-centred outcomes in this population. Full article

Background: The Malnutrition Screening Tool (MST) is commonly used to identify malnutrition risk; however it has demonstrated poor sensitivity to detect malnutrition in inpatients with chronic kidney disease (CKD) and kidney replacement therapy (KRT) populations. Gastrointestinal symptoms, such as poor appetite, may better detect malnutrition. The accuracy of MST or other nutrition-related parameters to detect malnutrition in ambulatory patients with CKD stages 4–5 without KRT has not been evaluated. Methods: A single site retrospective audit of outpatient records from May 2020 to March 2025 was conducted. Patients with eGFR < 25 mL/min/1.73 m² without KRT who had both MST and a 7-point Subjective Global Assessment (SGA) within 7 days were included. Sensitivity, specificity, and ROC-AUC analyses compared nutritional parameters against SGA-defined malnutrition. Nutritional parameters tested included MST, hand grip strength, upper gastrointestinal symptom burden, poor appetite and a combination of some of these parameters. Results: Among 231 patients (68.8% male, median age 69 years, median eGFR 15), 29.9% were at risk of malnutrition (MST ≥ 2) and 33.8% malnourished (SGA ≤ 5). All potential screening tools had AUC ranging from 0.604 to 0.710, implying a poor-to-moderate discriminator ability to detect malnutrition. Combining HGS ≤ 29.5 kg or MST ≥2 demonstrated high sensitivity (95.5%) and negative predictive value (93.3%), but low specificity (33.3%) for detecting malnutrition, indicating this approach is effective for ruling out malnutrition but may over-identify at-risk individuals. Conclusions: MST and other tested tools showed limited overall accuracy to identify malnutrition. Using combined nutritional markers of HGS or MST score was the most sensitive tool for detecting malnutrition in this advanced CKD without KRT population. Full article

Archaeological sites located on the edge of growing cities often struggle to reconcile heritage protection with rapid development. To understand this tension, we examined a 50.83 km² zone around the Western Han Imperial Mausoleums in the Qin-Han New District. Using Landsat images from 1992, 2002, 2012, and 2022, this study applied supervised classification, land-use transfer matrices, and dynamic-degree analysis to trace three decades of land-use change. From 1992 to 2022, built-up land expanded by 29.85 percentage points, largely replacing farmland, which shrank by 35.64 percentage points and became fragmented. Forest cover gained a modest 5.78 percentage points and migrated eastward toward the mausoleums. Overall, urban growth followed a “spread–integrate–connect” pattern along major roads. This study interprets these trends through five interrelated drivers, including policy, planning, economy, population, and heritage protection, and proposes an integrated management model. The model links archaeological pre-assessment with land-use compatibility zoning and active community participation. Together, these measures offer a practical roadmap for balancing conservation and sustainable land management at imperial burial complexes and similar urban fringe heritage sites. Full article

The Tree–Seed Algorithm (TSA) is a symmetry-driven metaheuristic algorithm that shows potential for complex optimization problems, but it suffers from local optimum entrapment and slow convergence. To address these limitations, we propose the ADTSA algorithm. First, ADTSA adopts a symmetry-driven dual-layer framework for seed generation, which promotes effective information exchange between subpopulations and accelerates convergence speed. In later iterations, ADTSA enhances the population’s exploitation ability through a population fusion mechanism, further improving the convergence speed. Moreover, we propose a historical optimal solution archiving and replacement mechanism, along with a t-distribution perturbation mechanism, to enhance the algorithm’s ability to escape local optima. ADTSA also strengthens population diversity and avoids local optima through convex lens symmetric reverse generation based on the optimal solution. With these mechanisms, ADTSA converges more effectively to the global optimum during the evolutionary process. Tests on the IEEE CEC 2014 benchmark functions showed that ADTSA outperformed several top-performing algorithms, such as LSHADE, JADE, LSHADE-RSP, and the latest TSA variants, and it also excelled in comparison with other optimization algorithms, including GWO, PSO, BOA, GA, and RSA, underscoring its robust performance across diverse testing scenarios. The proposed ADTSA’s applicability in solving complex constrained problems was also validated, with the results showing that ADTSA achieved the best solutions for these complex problems. Full article

Background: Short-stem hip replacements are designed to provide improved load distribution and to mimic natural biomechanics. The interplay between implant design, positioning, and resulting bone biomechanics in individual patients remains underexplored, and the relationship between radiographically assessed bone remodeling around short stems and biomechanical predictions has not been previously reported. Methods: This study evaluated three short-stem hip implant designs: Proxima, Collo-MIS, and Minima. Postoperative bone remodeling patterns were analyzed, categorizing remodeling as bone gain, bone loss, or no observable activity, with changes tracked over time. Patient-specific biomechanical models were generated from 6-week postoperative radiographs. Finite element simulations incorporated body weight and gluteal muscle forces to estimate stress and strain distributions within the proximal femur. Strain energy was then applied to a mechanostat-based remodeling algorithm to predict bone remodeling patterns. These biomechanical predictions were compared to observed radiographic remodeling at 2 years post-surgery. A validated biomechanical model was further used to simulate different postoperative positions of the three types of stems. Results: No differences in bone remodeling patterns were observed among the three short-stem designs. Computational modeling demonstrated a statistically significant correlation between predicted remodeling and radiographic measurements at 2 years (p < 0.001). Proxima stems showed a tendency towards increased cortical bone loading under pronounced varus or valgus position in comparison to other two stems, although this observation requires further validation. Conclusions: This exploratory study demonstrates the feasibility of using biomechanical modeling to estimate bone remodeling around short-stem hip implants based on early postoperative radiographs. While the results are promising, they should be interpreted with caution due to the limited cohort size. The proposed modeling approach may offer clinical value in evaluating implant behavior and informing patient-specific treatment strategies. However, further research with larger populations is necessary to refine and validate these predictive tools. Full article

Background: Dopamine participates in the cognitive cerebellar role and in cerebellum development. The trace amine-associated receptor (TAARs, TAAR1-TAAR9) system contributes to dopamine signaling tuning. So, the aim of the present study is the analysis of the TAARs’ gene expression and functional associations in prenatal and neonatal mouse cerebellums. Methods: The transcriptomic data represented in the GEO repository was performed to identify Taars expression and co-expression patterns in embrionic and postnatal mouse cerebellum. Results: Open transcriptomic data analysis showed cerebellar expression of the Taar5 gene mRNA both in prenatal and early postnatal samples. The identified Taar5 expression was confirmed by RT-PCR in P5 mice. We identified the association between Taar5 expression and the expression of proliferation-related genes in late prenatal E13.5 samples, which was replaced by co-expression with genes involved in metabolism in P5–6 samples. These associations are suggested to mirror the previously identified Taar5 expression in Purkinje cells, which proliferate at the E13.5 and mature in the postnatal period. However, the analysis of TAAR5 co-expression with markers of different cell populations revealed the pronounced co-expression of TAAR5 in the P5–6 cerebellum with microglial markers, which is shifted to the association with astroglial markers in P10. Conclusions: The Taar5 gene was found to be active in the cerebellum samples taken around birth, and its co-expression pattern differs in the embryo stage and the early days after birth. We suggest that the Taar5 receptor may be involved in cerebellum development; however, further research is necessary to elucidate its role in this process. Full article

Perfluorooctanoic acid (PFOA) and its replacement, GenX, are per- and polyfluoroalkyl substances (PFASs) widely used in industrial and consumer applications. Pregnant women are a vulnerable population to environmental pollutants. The maternal effects of GenX and PFOA exposure during pregnancy have not been fully elucidated. In this study, pregnant mice received daily oral doses of GenX (2 mg/kg/day), PFOA (1 mg/kg/day), or Milli-Q water (control) throughout gestation. Histopathological analyses revealed significant liver abnormalities in both exposure groups, including hepatocyte swelling, cellular disarray, eosinophilic degeneration, karyopyknosis, lipid vacuolation, and increased inflammatory responses. Through transcriptomics analyses, it was found that multiple metabolic and inflammatory pathways were enriched in both exposure groups. In the GenX group, overexpression of CYP4A, c-Myc, and Oatp2 proteins and decreased expression of EGFR and β-catenin in the liver suggested disruption of lipid and bile acid metabolism. In the PFOA group, significantly upregulated protein levels of NLRP3, GSDMD, caspase-1, IL-18, and IL-1β indicated hepatic pyroptosis. Despite these distinct pathways, both compounds triggered inflammatory cytokine release in the liver, consistent with the results of the transcriptomics analysis, suggesting shared mechanisms of inflammatory liver injury. Taken together, our findings provided novel insights into the hepatotoxicity mechanisms of GenX and PFOA exposure during pregnancy, underscoring the potential health risks associated with PFAS exposure. Full article

Thyroid hormones (thyroxine, T₄, and triiodothyronine, T₃) are indispensable for sustaining vertebrate life, and their deficiency gives rise to a wide range of symptoms characteristic of hypothyroidism, affecting 5–10% of the world’s population. The precursor for thyroid hormone synthesis is thyroglobulin (Tg), a large iodoglycoprotein consisting of upstream regions I-II-III (responsible for synthesis of most T₄) and the C-terminal CholinEsterase-Like (ChEL) domain (responsible for synthesis of most T₃, which can also be generated extrathyroidally by T₄ deiodination). Using CRISPR/Cas9-mediated mutagenesis, we engineered a knock-in of secretory ChEL into the endogenous TG locus. Secretory ChEL acquires Golgi-type glycans and is properly delivered to the thyroid follicle lumen, where T₃ is first formed. Homozygous knock-in mice are capable of thyroidal T₃ synthesis but largely incompetent for T₄ synthesis such that T₄-to-T₃ conversion contributes little. Instead, T₃ production is regulated thyroidally by thyrotropin (TSH). Compared to cog/cog mice with conventional hypothyroidism (low serum T₄ and T₃), the body size of ChEL-knock-in mice is larger; although, these animals with profound T₄ deficiency did exhibit a marked elevation of serum TSH and a large goiter, despite normal circulating T₃ levels. ChEL knock-in mice exhibited a normal expression of hepatic markers of thyroid hormone action but impaired locomotor activities and increased anxiety-like behavior, highlighting tissue-specific differences in T₃ versus T₄ action, reflecting key considerations in patients receiving thyroid hormone replacement therapy. Full article

Sampling with replacement occurs when drawing without removing individuals from finite populations. It is a common distribution technique used in physics, biology, and medicine. It is used in state analysis of qubits, the physics of particle interactions, studies of genetic variation and variability, and analyzing the treatment effects from clinical trial analyses. When applied, sample statistics should be accompanied by confidence intervals. The major difficulty in expressing the confidence intervals in sampling with replacement consists of discreetness regarding the probability distribution. As a result, no mathematical formula can handle an optimum solution. Using a simple algorithm is proposed in order to obtain confidence intervals for sampling with replacement variables (x from m trials with replacement) and their proportion ($x/m$). A question-based discussion is presented. Traditional confidence intervals often require large sample sizes. Confidence intervals, constructed in a deterministic way provided by the proposed algorithm for sampling with replacement, allow constructing intervals without constraints. Full article

Gaucher disease (GD) is an autosomal recessive disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Although enzyme replacement therapy (ERT) remains the standard of care for non-neuropathic GD patients, its high cost significantly limits accessibility. To enhance production efficiency, we developed a lentiviral system encoding a codon-optimized GCase gene driven by the human elongation factor 1a (hEF1α) promoter for stable production in human cell lines. A functional lentiviral vector, LV_EF1α_GBA_Opt, was generated at a titer of 7.88 × 10⁸ LV particles/mL as determined by qPCR. Six transduction cycles were performed at a multiplicity of infection of 30–50. The transduced heterogeneous human cell population showed GCase-specific activity of 307.5 ± 53.49 nmol/mg protein/h, which represents a 3.21-fold increase compared to wild-type 293FT cells (95.58 ± 16.5 nmol/mg protein/h). Following single-cell cloning, two clones showed specific activity of 763.8 ± 135.1 and 752.0 ± 152.1 nmol/mg/h (clones 15 and 16, respectively). These results show that codon optimization, a lentiviral delivery system, and clonal selection together enable the establishment of stable human cell lines capable of producing high levels of biologically active, synthetic recombinant GCase in vitro. Further studies are warranted for the functional validation in GD patient-derived fibroblasts and animal models. Full article

Background: Tobacco use is disproportionately high in rural areas, contributing to elevated cancer mortality, yet it often goes untreated due to limited access to care, high poverty and uninsured rates, and co-occurring substance use disorders (SUDs). This study explored the utility of using rapid qualitative analysis (RQA) to guide the adaptation of a tobacco-free workplace program (TFWP) in Texas healthcare centers serving adults with SUDs in medically underserved areas. Methods: From September–December 2023 and May–July 2024, we conducted 11 pre-implementation, virtual semi-structured group interviews focused on adapting the TFWP to local contexts (N = 69); 7 with providers (n = 34) and managers (n = 12) and 4 with patients (n = 23) in 6 healthcare centers. Two qualified analysts independently summarized transcripts, using RQA templates of key domains drawn from interview guides to summarize and organize data in matrices, enabling systematic comparison. Results: The main themes identified were minimal organizational tobacco cessation support and practices, and attitudinal barriers, as follows: (1) the need for program materials tailored to local populations; (2) limited tobacco cessation practices and partial policies—staff requested guidance on enhancing tobacco screenings and cessation delivery, and integrating new interventions; (3) contradictory views on treating tobacco use that can inhibit implementation (e.g., wanting to quit yet anxious that quitting would cause SUD relapse); and (4) inadequate environmental supports—staff requested treating tobacco-use training, patients group cessation counseling; both requested nicotine replacement therapy. Conclusions: RQA identified key areas requiring capacity development through participants’ willingness to adopt the following adaptations: program content (e.g., trainings and tailored educational materials), delivery methods/systems (e.g., adopting additional tobacco care interventions) and implementation strategies (e.g., integrating tobacco cessation practices into routine care) critical to optimizing TFWP fit and implementation. The study findings can inform timely formative evaluation processes to design and tailor similar intervention efforts by addressing site-specific needs and implementation barriers to enhance program uptake. Full article