Search Results (672)

The small heat shock protein HSPB1 is a ubiquitously expressed mechanoresponsive chaperone essential for cytoskeletal remodeling under mechanical load. Mutations in HSPB1, including S135F, cause Charcot-Marie-Tooth (CMT) peripheral neuropathy, yet the mechanisms underlying the selective vulnerability of peripheral nerves remain enigmatic. Here we demonstrate that substrate stiffness is a critical determinant of HSPB1^S135F-mediated neurodegeneration. Using stiffness-tunable polydimethylsiloxane (PDMS) substrates (1 kPa, 10 kPa, 2 MPa) and uniaxial cyclic stretch, we show that primary dorsal root ganglia (DRG) neurons and SH-SY5Y cells expressing HSPB1^S135F exhibit profound deficits in mechanoadaptation. On compliant substrates (10 kPa), HSPB1^S135F causes stretch-induced axon fragmentation and neuronal death, whereas HSPB1^WT confers robust neuroprotection. HSPB1^S135F also disrupts stiffness-directed neuritogenesis in differentiated SH-SY5Y cells: HSPB1^WT-expressing cells show optimal axonal outgrowth and βIII-tubulin expression on 10 kPa substrates mimicking muscle tissue stiffness, while HSPB1^S135F mutants display disorganized focal adhesions and complete differentiation failure. Mechanistically, we uncover that HSPB1^S135F dysregulates stage-specific transglutaminase (TGase) expression—insufficient TGase during early neuritogenesis impairs filopodia stabilization, whereas aberrant TGase persistence at late stages constrains axon extension. Our findings establish HSPB1 as a biomechanical sensor that integrates ECM stiffness signals to coordinate peripheral nerve regeneration, and identify defective mechanoadaptation as a previously unrecognized pathomechanism in CMT. These results open new avenues for stiffness-targeted therapeutic strategies in peripheral neuropathy. Full article

This study evaluated infrared thermography (IRT) as a dual-purpose, non-invasive tool for detecting limb pathology and subclinical mastitis in dairy cows. Surface temperatures were measured at the coffin, pastern, and fetlock regions of all limbs and at the teat surface of all udder quarters. Limb health status was determined by orthopedic clinical examination, and mastitis status was assessed using the California Mastitis Test (CMT). Hindlimbs were significantly warmer than forelimbs in healthy cows (p < 0.001), with confirmed bilateral symmetry (r = 0.524–0.569). Limbs with pathology showed significantly higher temperatures at all anatomical sites, with particularly large effect sizes in the hindlimbs (r around 0.80). Additional lesion-specific analyses demonstrated that both infectious and claw horn lesions exhibited significantly higher temperatures than healthy limbs. In the hindlimbs, infectious lesions showed higher thermographic values than claw horn lesions. CMT-positive quarters showed teat temperatures of 30.0–30.2 °C compared with 25.2–25.8 °C in CMT-negative quarters (p < 0.001). Receiver operating characteristic (ROC) analysis demonstrated excellent diagnostic performance for teat surface temperature in identifying CMT-positive quarters, with an area under the ROC curve (AUC) of 0.956. The optimal threshold was 29.5 °C, corresponding to a sensitivity of 0.992 and a specificity of 0.838. Each 1 °C increase in teat temperature increased the odds of CMT positivity by 5.3-fold (p < 0.001). A practical three-zone thermographic framework was established: <27 °C (healthy), 27–29.5 °C (monitoring recommended), and ≥29.5 °C (mastitis likely). Teat temperature was not associated with composite milk somatic cell count, but hindlimb pathology was independently associated with elevated teat temperatures (partial r = 0.23–0.26, p ≤ 0.001). These findings demonstrate that IRT has strong potential as an integrated screening tool for dairy cow limb health and udder health monitoring. Full article

Background: Complementary Medicine and Therapies (CMTs) are increasingly used worldwide, particularly in Saudi Arabia, due to growing interest in holistic and integrative healthcare. However, concerns regarding safety, regulatory awareness and evidence-based use persist, while comparative knowledge data between family physicians and the general population remain limited. This study aimed to compare knowledge of CMTs between family physicians and the general population in Saudi Arabia. Methods: A comparative cross-sectional analysis was conducted using two independent datasets collected in Saudi Arabia from a total of 1307 participants. Variables related to the participants’ demographic characteristics, and their knowledge of and information sources on CMTs, were harmonised prior to analysis. Between-group comparisons were performed using Chi-square and Fisher’s exact tests, with statistical significance set at p < 0.05. Results: The family physicians demonstrated significantly higher levels of knowledge of CMTs than the general population. While 35.5% of the physicians demonstrated good knowledge levels, 82.0% of the public participants exhibited poor or low knowledge. However, knowledge of regulatory and quality control measures governing CMTs remained limited among both the physicians (21.0%) and the public (24.6%). Both the physicians (66.1%) and the members of the public (34.8%) primarily relied on healthcare professionals as major sources of information on CMTs. Significant associations were observed between the participant group and the knowledge-related variables, overall knowledge levels and information sources (p < 0.001). Conclusions: Strengthening public education, physician training and regulatory awareness may support safer and more evidence-based integration of CMTs within healthcare systems. Full article

Mastitis is a major and costly dairy disease that reduces milk yield and quality and harms animal welfare. This study evaluated infrared thermography (IRT) combined with machine learning (ML) for non-invasive mastitis screening in dairy cows and explored links with biological and feeding-system variables in Egyptian farms. A total of 976 thermal udder images obtained from 488 Holstein cows were used, including 708 healthy and 268 mastitic images. Images were captured before milking, processed with CLAHE, resized to 224 × 224 pixels, and split using cow-level grouping before augmentation to prevent animal-level data leakage. The training set contained 780 original images and was augmented to a balanced 4708-image set (2354 per class), while the held-out test set remained unaugmented, with 196 original images (142 healthy and 54 mastitic). EfficientNetB3 with global average and max pooling extracted 3072 thermal features, and ten ML classifiers were evaluated. In the image-level hold-out evaluation, MLP achieved the best performance (accuracy = 86.22%, AUC = 0.9184, sensitivity = 74.07%, specificity = 90.85%), followed by SVM (accuracy = 83.67%, AUC = 0.8963). A separate group-based five-fold cross-validation yielded a more conservative AUC of 0.6812 ± 0.1323 and accuracy of 0.6244 ± 0.0642. Logistic regression analyses did not identify statistically significant associations between model predictions and somatic cell count (SCC), California Mastitis Test (CMT), blood biomarkers, or nutritional variables at p < 0.05. Ration A (Delta Misr) showed a higher observed mastitis incidence (20/40; 50.0%) than Ration B (Copenhagen; 16/45; 35.6%), but nutritional predictors were not statistically significant, indicating that farm-level confounding should be considered. Overall, IRT with ML remains a promising non-invasive screening approach, but broader multicenter datasets and independent external validation are needed before routine farm deployment. Full article

The demand for large-scale high-performance components with tailored properties in the aerospace and automotive industries has increased interest in multi-material additive manufacturing (AM). Among AM techniques, the Wire Arc Additive Manufacturing (WAAM) process is preferred for bimetallic fabrication due to high deposition rates, low equipment costs, and efficient material utilization. However, differences in metallurgical and thermal properties between dissimilar alloys can cause heat accumulation, leading to thermal stresses, cracking, and weak interfacial bonds. To the best of the authors’ knowledge, no study has reported the fabrication and characterization of a 17-4PH SS/Inconel 625 joint using the large-scale CMT-WAAM Process. To fill this gap, this study characterizes the microstructure and elemental distribution of the joint using scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray Microscopy (XRM) and energy dispersive spectroscopy (EDS). Microstructural analysis revealed a martensitic matrix with retained δ-ferrite in the 17-4PH region, a fully austenitic γ-phase in the Inconel 625 region, and a mixed BCC–FCC transition zone at the interface. EDS results demonstrated a Fe–Ni compositional gradient across the interface. Radiographic inspection confirmed a defect-free build, and XRM results showed a porosity of less than 0.003% only in the 17-4PH region. Tensile testing confirmed joint integrity, with fracture occurring in the Inconel 625 region, and average yield and ultimate tensile strengths of 391 ± 7 MPa and 676 ± 9 MPa, respectively. The simplified Johnson-Cook constitutive model successfully predicted the ultimate tensile strength (UTS), with a prediction error of 9.3% compared to the experimental result. Furthermore, a novel 3D-structured light scanner technique was developed and validated with an extensometer to provide insight into localized strain behavior. Full article

Wire-arc directed energy deposition (arc-DED) of maraging 250 (M250) steel is of growing interest for aerospace, tooling, and defense applications, yet systematic process characterization data remain limited. This study presents a mixed quantitative–qualitative factorial comparison of three Fronius synergic transfer modes, GMAW-CMT-Mix, GMAW-CMT-Universal, and GMAW-Pulsed-Arc, for single-bead M250 deposition across wire feed speeds of 4.45 to 8.26 m/min and travel speeds of 0.3 to 1.5 m/min. Bead geometry and process behavior are characterized using non-contact optical profilometry and destructive methods (i.e., metallographic sectioning, optical microscopy, and Vickers microhardness). The material feed rate ratio, R_wt, is introduced as a unifying process descriptor; heat input and cross-sectional area scale linearly with R_wt, while travel speed primarily governs bead height and wire feed speed primarily governs bead width. At the highest travel speed tested, GMAW-CMT-Mix and GMAW-Pulsed-Arc exhibit bead humping, rendering those conditions unsuitable, while GMAW-CMT-Universal maintains stable deposition with consistent dilution and the lowest heat input at equivalent R_wt. GMAW-CMT-Mix yielded the highest dilution and hardness. Linear regression of process responses against R_wt gives $R^2$ exceeding 0.83 for both height and width across all modes. These results establish a characterization baseline supporting future multi-layer studies. Full article

Fungal iterative non-reducing polyketide synthases (NR-PKS) contain a unique product template (PT) domain for aromatic cyclization. Among them, some NR-PKSs, such as the sorbicillin NR-PKS (SorB), have an apparently inactive PT. It is unknown what role such PT plays in NR-PKS programming. In this study, the PT domain of SorB was first dissected and engineered. Removal of the PT domain from SorB did not change the product profile, but the yield decreased. Meanwhile, a significantly lower transcriptional level of the ketoacyl synthase (KS) domain was observed in the knockout mutant (UvSorB∆PT). Phylogenetic tree analysis and multiple sequence alignments revealed this PT belongs to group I (C2–C7, monocyclic ring), and mutations were found at catalytic dyad sites when compared with functional fungal PTs. However, mutating these residues back to the conserved ones did not give rise to products corresponding to a functional PT, but rendered the NR-PKS unproductive. Likewise, removal of the C-methyltransferase (CMT) domain from SorB destroyed the polyketide production. Furthermore, in an attempt to alter the methylation pattern, mutations of the key substrate-binding sites of the CMT domain were made. Site-directed mutations of the C-MT led to cessation of the polyketide production. This reveals CMT is vulnerable to engineering in a collaborating NR-PKS (SorB). These results provide additional insights for catalytic reprogramming in fungal NR-PKS. Full article

This study investigates whether female representation on corporate boards and carbon emissions disclosure (CED) are interrelated in an emerging market. Using critical mass theory (CMT), which posits that female directors can surely impact the decisions of boards once they reach critical mass, we examine whether the presence of three women on the board or approximately 30% board membership is necessary in Indonesia. This context is important since (i) boards are still a long way from representing the demographics of Indonesians due to low female representation on boards; (ii) in many cases board sizes are too small for meaningful communication between two directors; and (iii) regulations surrounding environmental disclosure barely exist relative to more developed markets. Based on panel data from Indonesian manufacturing firms, the study demonstrates that the effect of board gender diversity on CED is nonlinear and contextually dependent. The results demonstrate that the core idea of CMT is not fully supported in this setting. The presence of even a single female director is linked to higher levels of carbon emissions disclosure, signaling that female directors likely play a substantive role and serve more than just symbolic purposes. That said, improvements associated with having women on the board do not increase progressively with more females taking a seat around the table. However, the positive effect is diminished and becomes statistically insignificant at higher levels of female representation. The results also imply that firms whose board of directors contain moderate levels of gender diversity (with 20–40% women on the board) engage in Type I CED to the highest extent. However, boards nearing a gender balance do not seem to garner any further benefits from disclosure. Full article

Purpose: This study investigates the multifaceted dynamics of institutional sustainability (IS) within the higher education sectors of Saudi Arabia and Egypt. It examines the direct influence of cultural, technological, and economic factors, alongside change management techniques (CMT), on the sustainability of universities in these two nations. Methodology: Employing a comparative, mixed-methods approach, the research collected data from 427 university staff members across Saudi Arabia and Egypt. Structural Equation Modeling (PLS-SEM) was utilized for data analysis, complemented by Multiple Group Analysis (MGA) to explore variations across different demographics, including gender, geographical location, and institution type (public vs. private). Findings: The study reveals that Change Management Techniques (CMT), cultural norms, technological infrastructure, and economic factors all significantly and directly influence institutional sustainability. Effective CMT is crucial for successful technological integration and mitigating staff resistance. Cultural norms, particularly in high power distance and collectivist societies, profoundly impact the adoption of innovations. A robust technological infrastructure is foundational for operational efficiency and educational outcomes, while strategic economic planning and diversified funding streams are vital for long-term stability and growth. Originality: This research offers actionable insights for policymakers and academic leaders by providing a nuanced understanding of how to build resilient, sustainable, and technologically advanced educational institutions in the Middle East. It emphasizes the necessity of context-specific strategies that acknowledge the unique regional socio-cultural and economic realities of Saudi Arabia and Egypt, bridging the gap between global sustainability paradigms and local implementation challenges. Full article

This article proposes a sustainable approach to producing eco-friendly paper from fibers derived from water hyacinth (Eichhornia crassipes), an invasive aquatic species with potential high lignocellulose content. The research evaluated the possibility of using its biomass as a non-wood raw material for papermaking through an industrial-oriented processing framework. About 10 groups of water hyacinth samples were analyzed by separating their components (roots, leaves, and stems) to determine moisture content, dry biomass yield, fiber distribution, and performance in papermaking. Mechanical pulping and mild alkaline treatment with sodium hydroxide were compared to evaluate their effects on fiber behavior and paper quality. The results showed a high moisture content in the biomass, averaging approximately 88%, while the remaining dry matter represented the usable fibrous material fraction. After fiber classification, it was revealed that the long fibers predominated over the short fibers and the fine fibers (waste), favoring the hydrogen bonding and structural anchoring during sheet formation. Mechanical quality analyses were conducted using the Corrugating Medium Test (CMT), Concora Crush Test (CCT), Ring Crush Test (RCT), and Short Compression Test (SCT). Untreated water hyacinth paper demonstrated mechanical properties comparable to those of an industrial reference paper, including consistent compression resistance and corrugating performance. In contrast, the alkaline-treated sample showed greater structural uniformity but lower mechanical strength due to fiber fragmentation and increased fine production. Overall, the findings showed that Eichhornia crassipes represents a viable and sustainable alternative to non-wood fibers for paper production, offering potential environmental benefits by serving as an invasive species and reducing dependence on wood-based raw materials. Full article

Background/Objectives: This study compared choroidal morphological changes, including choroidal vascularity index (CVI) and layer-specific choroidal thickness, between aflibercept 8 mg and faricimab-svoa in treatment-naïve polypoidal choroidal vasculopathy (PCV) and pachychoroid neovasculopathy (PNV). Methods: This retrospective study included 66 eyes treated with aflibercept 8 mg (n = 32) or faricimab-svoa (n = 34). Following three monthly loading injections, a pro re nata regimen was employed for 6 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachment (PED) height, and CVI were assessed. Results: Both groups demonstrated significant improvements in BCVA, CMT, SFCT, and PED height at 6 months (all p < 0.05), with no between-group differences. Dry macula rates were 75.0% and 79.4%, respectively. Faricimab-svoa was associated with a significantly greater CVI increase (0.037 vs. 0.018, p = 0.003), driven by a numerically greater reduction in choriocapillaris/Sattler’s layer thickness (−18.9 ± 16.4 μm vs. −13.8 ± 15.8 μm, p = 0.153). Conclusions: Both agents achieved comparable functional and anatomical outcomes in treatment-naïve PCV and PNV. Faricimab-svoa was associated with a greater CVI increase, reflecting differential choroidal remodeling. CVI may serve as a biomarker for differentiating the choroidal effects of second-generation anti-VEGF therapies in pachychoroid spectrum disease. Full article

In practical imaging applications, low-light and overexposure are two common types of image degradation problems with inherent conflicts, and existing methods struggle to achieve accurate restoration of both degradations within a unified framework. To address this challenge, this paper proposes DFE-Net based on explicit frequency decoupling. The network adopts a symmetric U-Net architecture and embeds discrete wavelet transform (DWT) and inverse discrete wavelet transform (IWT) to construct an explicit dual-frequency processing mechanism, which optimizes the low-frequency information carrying global illumination and the high-frequency information containing detailed textures, respectively. In the encoder, DWT decouples features into low-frequency and high-frequency sub-bands and feeds them into dedicated enhancement modules. The low-frequency enhancement block integrates SS2D and a gated convolutional feed-forward network to efficiently model global contextual dependencies with linear complexity and accurately restore image illumination and contrast; the high-frequency enhancement block adopts CMT attention combined with a matching convolutional feed-forward network, enabling the detail restoration process to be guided by the optimized low-frequency information and ensuring the collaborative optimization of global structure and local textures. The decoder completes the reconstruction and fusion of the processed sub-bands through IWT. The quantitative and qualitative experimental results on the MSEC, SICE, and LOLv1 datasets demonstrate that DFE-Net achieves or surpasses existing state-of-the-art methods in various metrics while maintaining low model complexity. Full article

Large-scale language models can produce anomalous outputs that cannot be explained solely by the quality of input data. This article presents a systematic review and descriptive quantitative synthesis of published evidence on reasoning anomalies in LLMs. The study does not report original experiments, does not evaluate new model outputs, and does not implement the proposed framework. Instead, it consolidates numerical results manually extracted from published papers, public benchmarks and official system cards, with the derived datasets and figure-generation scripts. The review organizes reasoning-related anomalies into a taxonomy that distinguishes factual hallucinations, self-contradictions, unfaithful Chain-of-Thought traces, semantic rollback, snowball errors, distractor susceptibility and sycophancy bias. Published evidence indicates that irrelevant context can reduce accuracy below 30% in controlled mathematical reasoning settings, and that knowledge and reasoning tasks can differ by more than 12 percentage points in reported biomedical benchmarks. Existing mitigation techniques, including self-consistency, semantic entropy, process reward models and formal verification, are compared descriptively across heterogeneous studies and domains. Formal verification results, such as the 91.7% reported for VERGE on AR-LSAT, are explicitly limited to structured logical reasoning and should not be generalized to open-domain natural language reasoning. Finally, the article proposes a four-layer conceptual architecture grounded in access-consciousness and monitoring-consciousness operators, C_A(t) and C_M(t), for filtering context, generating reasoning paths, monitoring inferential discrepancies and activating selective correction. The framework is presented as an implementable research roadmap whose empirical validation, computational overhead and activation thresholds remain future work. Full article

Objectives: This study aimed to assess longitudinal changes in aniseikonia following pars plana vitrectomy (PPV) in patients with idiopathic epiretinal membrane (ERM). Methods: This meta-analysis was conducted in accordance with the PRISMA guidelines. The PubMed, EMBASE, and Cochrane Library databases were searched from inception to March 2024 to identify studies evaluating aniseikonia outcomes after PPV for idiopathic ERM. Studies involving secondary ERM or those lacking aniseikonia assessments were excluded. Correlations between aniseikonia and best-corrected visual acuity (BCVA) and central macular thickness (CMT) were analyzed. Results: Ten studies comprising 456 eyes were included. PPV was associated with a statistically significant reduction in aniseikonia at all evaluated postoperative time points, including 1 month (−1.09%, p = 0.04), 3 months (−0.81%, p = 0.02), 6 months (−0.89%, p = 0.002), and 12 months (−1.13%, p < 0.001). Meta-analysis of outcomes at the final follow-up of each study also demonstrated a significant overall improvement in aniseikonia (−1.09%, p < 0.001). Subgroup analysis revealed a statistically significant improvement only in studies with long-term follow-up (≥12 months), whereas studies with short-term follow-up (≤6 months) did not show significant changes. No significant correlations were found between changes in aniseikonia and changes in BCVA, CMT, or other structural parameters. Conclusions: Aniseikonia showed a statistically significant but modest reduction after PPV for idiopathic ERM. However, the magnitude and consistency of improvement varied across studies, and its clinical significance remains uncertain. Improvements appeared gradual and more evident with longer follow-up, suggesting that longer-term follow-up may be necessary to adequately assess postoperative changes in aniseikonia. Full article

Neurofilaments (NFs) are the predominant type IV intermediate filaments in differentiated neurons, functioning not just as static scaffolds, but as active drivers of radial axonal growth and nerve conduction velocity. While their physical properties are well characterized, a critical gap remains in synthesizing how their dynamic assembly and developmental subunit switching directly dictate neurodegenerative outcomes. This review breaks down the molecular architecture and stepwise kinetic assembly of NFs, detailing their role in polarized transport and the formation of a protective viscoelastic gel network within axons. We specifically highlight the physiological expression switching of early subunits, such as alpha-internexin and peripherin, during neuronal maturation, a process often overlooked in traditional structural reviews. By examining how specific gene mutations and aberrant hyperphosphorylation trigger axonal transport jams and protein aggregation, we map the direct pathways leading to amyotrophic lateral sclerosis (ALS) and Charcot–Marie–Tooth (CMT) disease. Finally, we emphasize that a precise mechanistic decoding of NF structural dynamics and their pathological disruption is essential for understanding the fundamental etiology of these neurodegenerative conditions. Full article