Search Results (425)

Chronic kidney disease–mineral and bone disorder (CKD-MBD) is a major complication of end-stage renal disease and is associated with increased morbidity and mortality. Sclerostin, an osteocyte-derived glycoprotein that inhibits the Wnt/β-catenin signaling pathway, has been implicated in the dysregulation of bone metabolism in dialysis patients. However, comparative data on sclerostin levels and their clinical determinants between hemodialysis (HD) and peritoneal dialysis (PD) patients remain limited, particularly in Southeast Asian populations. This cross-sectional study was conducted at Hue Central Hospital, Vietnam, between June 2023 and January 2026. A total of 89 end-stage renal disease patients were consecutively enrolled (HD: n = 51; PD: n = 38). Median serum sclerostin levels were 584.21 (IQR: 301.18–1479.50) pg/mL in the HD group and 684.21 (IQR: 407.48–940.35) pg/mL in the PD group, with no significant difference between groups (p = 0.839). Serum sclerostin was inversely correlated with PTH in both HD (r = −0.444, p = 0.001) and PD patients (r = −0.341, p = 0.036). In the HD group, total femur BMD showed a significant inverse correlation with sclerostin (r = −0.304, p = 0.030). In multivariable analysis, Log_PTH remained an independent predictor of sclerostin across all three sequential models in the HD group (Model 1: B = −0.340, p = 0.001; Model 2: B = −0.270, p = 0.035; Model 3: B = −0.268, p = 0.039; adjusted R² range: 0.197–0.217) and in the combined HD + PD cohort (Model 1: B = −0.271, p < 0.001; Model 2: B = −0.263, p < 0.001; Model 3: B = −0.249, p = 0.003; adjusted R² range: 0.141–0.158). In the PD subgroup, Log_PTH was significant in Models 1 and 2 but not in Model 3; none of the models reached overall statistical significance (all p ≥ 0.081), and findings should be considered exploratory given the limited sample size. Serum sclerostin levels did not differ significantly between HD and PD patients. PTH was the most consistent independent predictor of sclerostin across dialysis modalities and analytical models, underscoring its central role in CKD-MBD pathophysiology. Larger prospective multicenter studies are warranted to validate these findings and further clarify the clinical utility of sclerostin in dialysis populations. Full article

Background/Objectives: The spectrum of chronic kidney disease—mineral and bone disorder (CKD-MBD) is changing and adynamic bone disease (ABD) is now believed to constitute the majority of CKD-MBD in the developed world. However, its prevalence and risk factors are poorly described in the literature. Its diagnosis requires bone biopsy, but biochemical criteria including parathyroid hormone (PTH) levels show good correlation. The aim of this study is to understand the prevalence of ABD in our patients with kidney failure (KF) on hemodialysis (HD), identify the risk factors for its development, and in doing so enable early intervention to modify the risk factors specific to our population. Methods: This is a retrospective cross-sectional study. A total of 201 prevalent adult patients on maintenance HD for at least 3 months were recruited. Patients with previous parathyroidectomy were excluded. Relevant data including clinical and biochemical parameters, prescribed dialysate and medications, and clinical outcomes were collected. ABD was diagnosed if any intact PTH (iPTH) level during the study period was <15 pmol/L. Results: Of the 201 patients in the study (median age 64.5 years), 35 (17.4%) patients had ABD. In the multivariable logistic regression model, the adjusted odds ratio (OR) of ABD was higher with a higher mean adjusted serum calcium level, while the concurrent use of non-calcium-based binders was associated with lower odds of ABD. Activated vitamin D use was also associated with lower odds of ABD, likely reflecting past occurrence of ABD, prompting a pre-emptive discontinuation of activated vitamin D. Overall, 17% of patients had had fractures without significant association with ABD. The mean PTH level was in the target range (15–60 pmol/L) in 41% of the cohort. Cardiovascular complications were not significantly associated with ABD. Conclusions: Approximately one in every six HD patients in our care have ABD as diagnosed by the iPTH level. Targeting a lower serum calcium level and using non-calcium-based binders may reduce the occurrence of ABD and will need to be tested in prospective studies. Full article

Plunger pumps are widely used in high-pressure and high-flow applications and exhibit strong adaptability to different fluid media. In addition to the interaction between the valve and the fluid, a potential coupling effect may exist between the flow characteristics of the pump and the electromagnetic characteristics of the motor. To investigate the electromagnetic–mechanical–hydraulic coupling effect in a motor–pump system, a transient coupled dynamics model integrating electromagnetic fields (EMF), multi-body dynamics (MBD), and computational fluid dynamics (CFD) is developed. The motion of the valve is incorporated into the model through dynamic mesh and user-defined function (UDF) techniques. The different physical models are coupled through torque, speed, force, and displacement. Based on the proposed model, the coupling characteristics of the system are analyzed. The results show that pulsating components associated with the reciprocating frequency appear in both the rotational speed and torque of the motor, resulting in fluctuations of approximately 2.11% in speed and 29.57% in torque. These pulsations are also reflected in the stator current spectrum. In addition, the valve motion at different crank angles and the flow patterns in the pump chamber are analyzed. The electromagnetic characteristics of the motor have a limited influence on the internal flow behavior of the pump. Full article

Background/Objectives: Chronic kidney disease–mineral and bone disorder (CKD-MBD) is characterized by complex interactions between parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), phosphate, calcium, and vitamin D, yet clinical decisions are often based on static individual values. A trajectory-based approach that considers how longitudinal changes in CKD-MBD biomarkers relate to each other may provide a more integrated understanding. Methods: In 1968 adults with non-dialysis CKD (mean age 68 ± 12 years; 34% female; mean follow-up duration 3.02 ± 0.35 years), annualized slopes of CKD-MBD biomarkers (PTH, FGF23, phosphate, calcium) were derived from mixed-effects models, alongside slopes and intra-individual variability of other key features of CKD—eGFR, hemoglobin, albumin, bicarbonate, 25-hydroxyvitamin D, uric acid, urine albumin creatinine ratio (UACR). These 36 features, including baseline levels, were evaluated using Extreme Gradient Boosting regression with interpretability via SHapley Additive exPlanations (SHAP). Results: Models explained substantial variance in biomarker slopes (R²: 0.86 for PTH, 0.72 for FGF23, 0.71 for phosphate, 0.67 for calcium) without evidence of overfitting. Baseline values and eGFR slopes showed the strongest associations with biomarker trajectories. PTH and FGF23 slopes were positively correlated, while declining hemoglobin and greater hemoglobin variability were associated with steeper FGF23 and phosphate slopes. Phosphate slopes were associated with UACR slopes and bicarbonate slopes. Declining 25(OH)D slopes were linked with rising PTH slopes. Conclusions: This analysis revealed consistent relationships between CKD-MBD biomarker trajectories. Longitudinal changes in kidney function, hemoglobin, bicarbonate, UACR, and vitamin D were also associated with biomarker trajectories. Our findings confirm the multi-system nature of CKD-MBD, and provide a framework for examining potentially modifiable pathways in its progression. Full article

Under dry sowing and wet emergence conditions in Xinjiang, cotton planting with extra-wide film mulching and sowing faced challenges including low soil moisture content and poor soil plasticity. These conditions resulted in inadequate film edge laying, seed exposure, and unstable sowing depth. This study focused on an extra-wide film mulch planter, conducting operational process analysis and parameter optimization experiments. The research first analyzed the soil layer structure required for a high-quality cotton seedbed, described the structural composition and working principle of the extra-wide film mulch planter, and examined the interaction between key components and soil during operation. The primary factors affecting machine performance were identified, and a soil-deflecting device was added to mitigate rapid soil backflow. A coupled MBD-DEM model was developed to simulate the operation of key components, and simulation experiments were conducted. The optimal parameter combination obtained through optimization was as follows: furrowing disc deflection angle of 11°, primary soil-covering disc deflection angle of 20°, operational speed of 3.5 km/h, longitudinal blade height of 16 mm, and spring stiffness of 14 N/mm. Simulation validation under these parameters yielded the following results: covering soil amount ranged from 3.22 kg/m to 3.67 kg/m, with a mean of 3.43 kg/m; seeding qualification rate ranged from 94.97% to 97.52%, with a mean of 96.3%; film hole length ranged from 43.14 mm to 46.86 mm, with a mean of 45.18 mm; and cotton seed sowing depth ranged from 29.51 mm to 31.82 mm, with a mean of 31.23 mm. These simulation results met the operational requirements for extra-wide film mulching and sowing. Field validation experiments were conducted using the optimal parameter combination. The results showed a mean soil-covering thickness of 35.1 mm, mean soil-covering width of 65.3 mm, mean film hole length of 45.7 mm, and mean cotton seed sowing depth of 29.1 mm, with coefficients of variation of 5.1%, 2.6%, 4.7%, and 5.8%, respectively. The field results were generally consistent with the simulation results, confirming the reliability of the simulation model and demonstrating improved operational performance of the extra-wide film mulch planter, making it more suitable for the dry sowing with wet emergence technique. Twenty days after sowing, the mean emergence rate reached 93.3% with a coefficient of variation of 1.0%, indicating stable emergence, which preliminarily validated the effectiveness of the constructed seedbed in promoting cotton growth. Full article

Cervical cancer (CC) is an alarming global health problem, with predominantly higher incidence, lethal progression, and mortality among women of African ancestry (AA) than women of European ancestry (EA). Although persistent high-risk human papillomavirus (HPV) integration and infection are the key etiological factors, currently available evidence implicates epigenetic reprogramming as a prime contributor to ancestry-associated differences in CC pathogenesis. To address these disparities, we performed genome-wide DNA methylation profiling of HPV-positive cervical intraepithelial neoplasia (CIN) lesions from AA (n = 15) and EA (n = 15) women. Differential methylation analysis identified a distinct epigenomic landscape in AA-CIN lesions, with widespread hypermethylation and hypomethylation at promoter-associated and regulatory CpG sites. Pathway enrichment analyses highlighted dysregulation of ECM-receptor interaction, focal adhesion, PI3K-Akt, MAPK, Ras, Rap1, and RUNX-dependent transcriptional networks. Comparative analysis across CIN grades (CIN1–CIN3) revealed progressive epigenetic reprogramming affecting cell cycles, cytoskeletal dynamics, signaling, and metabolic pathways. Among hypermethylated tumor suppressor genes, SH3GL2 and ARHGAP25 showed significantly higher methylation in AA lesions, accompanied by concomitant loss of their protein expression. MBD1, a methylation-binding regulator, was upregulated in AA-CIN lesions, coinciding with global loss of 5-hydroxymethylcytosine (5hmC), suggesting enhanced transcriptional repression. In contrast, EA lesions retained protein expression and 5hmC levels. Collectively, these findings indicate that early, ancestry-specific epigenetic modifications target tumor suppressor pathways and converge on oncogenic signaling, cytoskeletal remodeling, and cell–cell adhesion. Our study provides mechanistic insight into CC health disparities, identifying SH3GL2 and ARHGAP25 hypermethylation as potential biomarkers, and highlighting epigenetic regulation as a contributor to disparate CC progression in AA women. Full article

Selecting an appropriate disc coulter is crucial for reducing the power consumption of no-till seeders, preventing straw from being pressed into seed furrows, improving the soil penetration performance of the disc coulter, and thus minimizing the weight of no-till seeders. This study utilized the quadratic regression orthogonal rotation central composite approach. With the application of EDEM and RecurDyn software, a virtual simulation model of the interaction between a toothed disc coulter and soil was developed. The angle of front serration δ, the angle of rear serration θ, and the number of serrations n were taken as experimental factors. The draft F_v and penetration resistance F_N were selected as performance evaluation indicators for parameter combination optimization simulation tests. The results indicated that δ, θ, and n have significant influences on F_v and F_N (p < 0.05). When the optimized parameter combinations δ, θ, and n were respectively determined as 16°, 39.1°, and 13, both F_v and F_N reached their minimum values. A comparative experimental study was conducted with the optimized toothed disc coulter and six existing disc coulters; under the working conditions of 14.4 km·h⁻¹, both the draft and penetration resistance of the toothed disc coulter are minimized. The draft was 227.5 ± 8.9 N and the penetration resistance was 415.9 ± 5.3 N. Meanwhile, the toothed disc coulter had the highest ratio of soil disturbance area to draft, indicating better soil loosening effects. Full article

Background/Objectives: Vascular calcification and arterial stiffness are common in chronic kidney disease (CKD). Gla-rich protein (GRP) is a vitamin K-dependent protein implicated in mineral biology, but clinical evidence across CKD stages is limited. We evaluated associations of serum GRP with vascular calcification (VC) burden and arterial stiffness across CKD stages, including hemodialysis, compared with controls. Methods: In this prospective observational study, 185 adults were enrolled: controls (n = 61), individuals with CKD stage IIIb–IV (n = 61), and individuals with CKD stage V on hemodialysis (HD) (n = 63). Abdominal aortic calcification was assessed by the Kauppila score, and arterial stiffness was assessed by oscillometric pulse wave velocity (PWV). Serum GRP, FGF-23, and β-Klotho (KLb) were measured by ELISA. Non-parametric group comparisons and Bonferroni-corrected Spearman correlations were used. Results: GRP differed across groups (p < 0.001), showing a non-linear pattern with the lowest values in CKD IIIb–IV. PWV and Kauppila score increased across CKD stages (both p < 0.001). After Bonferroni correction, GRP correlated with KLb (ρ = 0.720) and FGF-23 (ρ = 0.625), but not with PWV or Kauppila score. In multivariable analyses, GRP showed a statistically significant but modest association with PWV and Kauppila score. Conclusions: In this CKD spectrum cohort, serum GRP was associated with CKD-MBD biochemical markers (KLb and FGF-23) much more strongly than with vascular phenotypes; its associations with vascular calcification burden and arterial stiffness were modest in multivariable modelling, supporting GRP as a marker of the CKD-MBD biochemical profile rather than a strong surrogate of vascular phenotype. Full article

Model-Based Diagnosis (MBD) is widely used to identify minimal conflicts and repair actions in constraint-based systems. Recent advances in parallel reasoning have significantly reduced runtime in large-scale models through speculative and multicore execution strategies. However, existing approaches primarily focus on computational efficiency and implicitly assume that minimal diagnoses are inherently suitable explanations for human decision makers. In complex configuration environments, minimality does not necessarily imply interpretability, as diagnoses may involve structurally dispersed or semantically heterogeneous constraints. To address this limitation, this paper introduces a multi-objective explainability-aware framework for parallel MDB. Diagnosis selection is formulated as a Pareto optimization problem balancing total computational cost and a formally defined interpretability penalty. Interpretability is quantified using graph-based structural dispersion, semantic entropy, hierarchical complexity, and ambiguity metrics. The proposed E-ParetoDiag algorithm computes non-dominated diagnoses and identifies balanced knee-point solutions without modifying correctness guarantees of underlying diagnosis algorithms. Experimental evaluation on large-scale benchmark datasets demonstrates a measurable trade-off between runtime and interpretability, particularly in dense constraint systems. Comparative analysis against classical selection strategies shows that the proposed approach reduces structural dispersion by up to 18% while increasing computational cost by only 7%. Statistical validation confirms that these improvements are significant (p < 0.01) in medium- and high-density scenarios. The results indicate that aggressive parallelism may improve computational efficiency while increasing explanation complexity, highlighting the need for multi-objective selection strategies. Overall, the proposed framework extends scalable symbolic reasoning toward a human-centered diagnosis paradigm and establishes a principled foundation for explainability-aware optimization in constraint-based systems. Full article

The design process of complex systems, such as hybrid aircraft, consists of several stages that depend on each other. The product is virtually validated by simulations in various disciplines. Each of these stages and simulation disciplines is carried out by different experts and they can choose from different tools in their field. The models created during this process are highly interdependent but are typically managed independently by each team. In this paper the first implementation of an open digital platform (ODP) is presented to provide a common data backbone for models from various tools and enable traceability across domains. An open data schema is used to ensure an open interface for the platform. This is implemented with SysML v2. In a proof of concept, two tools from different domains, simulation process and data management (SPDM) and product lifecycle management (PLM) using Teamcenter^® Simulation software and model-based design (MBD) using Simcenter™ Amesim™ software, are connected through this open standard. Full article

This paper presents an iterative graph-analytical procedure for determining the roll center height, one of the most critical design parameters influencing vehicle dynamic behavior during cornering. The conventional approaches generally determine roll center locations from suspension kinematics and then evaluate vehicle behavior using multibody or numerical vehicle dynamics models. By contrast, the proposed method is intended for the preliminary design stage and provides a direct correlation between front and rear target roll center heights using tire test data, load transfer and axle-level equilibrium conditions. The main advantage of the method is that it helps define a feasible design space before detailed geometry optimization or MBD validation is performed. The objective is to achieve stable and neutral handling (avoiding intrinsic understeer or oversteer tendencies) during steady-state cornering at a predefined target lateral acceleration. The methodology integrates (i) lateral force equilibrium at the axle level, (ii) a dynamic load transfer model based on axle roll stiffness and roll center heights, and (iii) experimental tire grip characteristics (lateral force–slip angle curves under varying vertical loads), processed through numerical interpolation. The procedure is demonstrated using a vehicle model with specific geometric and mass parameters. The results indicate that the methodology does not yield a single unique solution, but rather a set of correlated roll center heights, allowing the designer to select the most feasible geometric configuration while maintaining neutral handling. As an example, the paper presents a convergent solution for the front and rear roll center heights that satisfy neutrality conditions at a slip angle of approximately 4°. This study provides a fundamental framework for the geometric design of suspension systems and serves as a basis for subsequent numerical and experimental validation. Full article

High-pressure grinding rolls (HPGRs) are critical in mineral processing, making comprehensive research and analysis of their performance of great significance. This study focuses on the HPGR-3516 test prototype and develops an analytical model that combines the discrete element method (DEM) with multi-body dynamics (MBD). The influences of feed top size, roll speed, and specific press force on equipment performance were examined using analysis of variance (ANOVA) in conjunction with response surface methodology (RSM). A performance prediction model was established through regression analysis, followed by multi-objective optimization and experimental validation. The results indicate that increasing roll speed under high specific press force significantly reduces the roll gap, while the effect is negligible under low specific press force. Increasing roll speed improves throughput more substantially for fine feed than for coarse feed. The optimal process parameters were determined to be a feed top size of 8 mm, a roll speed of 0.37 m/s, and a specific press force of $4.84 \mathrm{N}/{\mathrm{m}\mathrm{m}}^2$. In comparison to the original parameters, throughput increased by 15.81%, qualified particle size passing rate (QPR) improved by 7.85%, and roll gap decreased by 10.24%. This study offers valuable insights into predicting the dynamic performance of HPGRs and has significant engineering implications. Full article

Osteocalcin (OCN) is increasingly recognized as a multifunctional hormone whose actions extend far beyond its traditional role as a marker of bone turnover. This review provides an integrated examination of the molecular, endocrine, and translational dimensions of osteocalcin biology, with emphasis on its bioactive undercarboxylated form (ucOCN), which links skeletal remodeling to systemic physiological processes. The structural determinants, biosynthetic pathways, and vitamin K-dependent carboxylation mechanisms underlying OCN isoform diversity are summarized, together with analytical limitations arising from assay variability and differences between N-MID and ucOCN-specific measurements. Mechanistic evidence demonstrates that ucOCN signals through GPRC6A and GPR158 to modulate insulin secretion, muscle glucose uptake, adipokine production, testosterone synthesis, neurocognitive function, hepatic lipid metabolism, and acute stress response. These receptor-level pathways position osteocalcin as a central regulator at the intersection of bone metabolism and whole-body homeostasis. The review synthesizes data across major clinical contexts, including metabolic syndrome, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease–mineral and bone disorder (CKD-MBD), cardiovascular dysfunction, and neurodegeneration, highlighting the modifying influence of vitamin K status, circadian rhythms, renal clearance, and local tissue microenvironments. The need for biomarker standardization, methodological harmonization, and receptor-targeted translational strategies is emphasized, alongside emerging therapeutic concepts involving vitamin K supplementation and exercise-induced activation of OCN. Collectively, the evidence reframes osteocalcin as a versatile endocrine mediator at the interface of bone physiology, systemic metabolic regulation, and disease mechanisms. Full article

Chronic kidney disease (CKD) is a progressively worsening condition that erodes renal function over time, reduces quality of life, and can ultimately culminate in kidney failure with far-reaching systemic complications. In addition to reduced filtration, worsening kidney function disrupts mineral homeostasis and leads to CKD–mineral and bone disorder (CKD-MBD). Dysregulated calcium handling and maladaptive endocrine responses contribute to bone pathology and increase cardiovascular calcification risk; therefore, serial calcium monitoring remains clinically relevant for longitudinal CKD management. Conventional calcium measurements are typically obtained with centralized analyzers or laboratory assays (e.g., colorimetry and electrode/optical readouts). Despite high accuracy, the required instrumentation, controlled operating conditions, and pretreatment steps complicate rapid point-of-care deployment, especially when only microliter-scale biofluids are available. Accordingly, this study develops a finger-actuated microfluidic colorimetric platform capable of determining calcium ion concentrations in human biofluids, such as whole blood, serum, and urine. The platform integrates a three-dimensional PMMA/paper microchip with a compact reader that maintains stable temperature control while enabling CMOS-based optical detection. With just 6 μL of sample, a brief finger press propels the biofluid across an internal filtration layer, generating serum or cleaned urine that subsequently reacts with a pre-deposited murexide reagent. Under optimized conditions (1.6% reagent, 50 °C, 3 min), the signal follows a strong logarithmic relationship with calcium concentration (Y = 47.273 ln X + 28.890; R² = 0.9905), supporting quantification over 1–40 mg/dL and a detection limit of 0.2 mg/dL. Across 80 clinical CKD specimens spanning serum, whole blood, and urine, results aligned closely with the NM-BAPTA reference assay, with R² values exceeding 0.97. Full article

Background: Nephrolithiasis is a significant global health and economic challenge, with an increasing prevalence and a high recurrence rate. However, there is limited knowledge regarding the potential associations between calcium nephrolithiasis risk and Chinese Han populations currently. Methods: To identify the genetic factors for calcium nephrolithiasis, we presented a genome-wide association study (GWAS) using a total of 1006 calcium nephrolithiasis cases and 1200 controls of Chinese Han ethnicity. Suggestive loci (p < 1.0 × 10⁻⁶) were replicated in 445 cases and 1008 controls. We also assessed the association of GWAS-level significant single-nucleotide polymorphisms (SNPs) with quantitative traits, including metabolic, kidney-related, and electrolyte traits. Results: Here we found three novel loci for calcium nephrolithiasis: SORBS2 on 4q35.1 (rs3736194; p = 2.84 × 10⁻¹³, OR = 0.6279), CXXC5 on 5q31.2 (rs356450; p = 6.09 × 10⁻¹⁶, OR = 2.0312), and MBD2 on 18q21.21 (rs55826947; p = 6.29 × 10⁻¹⁰, OR = 0.6017). Subsequent analyses revealed the association of SNP rs3736194 with higher serum carbon dioxide (p = 0.04666), rs356450 with lower serum chloride (p = 0.02992), and rs55826947 with higher BMI (p = 0.03174), respectively. Conclusions: We performed the first GWAS on calcium nephrolithiasis in a Chinese Han population cohort and identified three novel susceptibility loci on 4q35.1, 5q31.2, and 18q21.2. Further research into the molecular mechanisms underlying these variations in nephrolithiasis is warranted. Full article