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Real-world effectiveness and safety of eculizumab in AQP4-IgG-positive neuromyelitis optica spectrum disorder
No full textObjective: To evaluate the real-world effectiveness and safety of eculizumab in patients with AQP4-IgG–positive neuromyelitis optica spectrum disorder (NMOSD) and to identify predictors of disability outcomes. Methods: This multinational, retrospective cohort study analyzed data from 46 patients across 26 centers. The outcomes included the annualized relapse rate (ARR), relapse-free status, change in expanded disability status scale (EDSS) scores, and adverse events. To identify predictors of EDSS improvement or worsening, patients were stratified into subgroups (improved vs. stable/worsened) at each follow-up time point and compared based on demographic, clinical, and radiological variables. Results: This retrospective cohort study included 46 patients with AQP4-IgG-positive NMOSD from 26 centers, followed for a mean of 27.3 months. The mean ARR significantly decreased from 1.1 in the 2 years pre-treatment to 0.1 during eculizumab therapy. The relapse-free rate increased from 6.5% pre-treatment to 80.4%. Mean EDSS scores improved from 4.2 at baseline to 3.6 at 24 months. The presence of area postrema syndrome was associated with a favorable prognosis, while the presence of spinal attacks was associated with a poor prognosis at 12 months. Adverse events occurred in 7 patients (18.9%), leading to permanent discontinuation in only two. Conclusion: Eculizumab demonstrated robust real-world effectiveness in reducing relapse rates and stabilizing disability, with an acceptable safety profile. Clinical outcomes may be influenced by attack phenotype, underscoring the importance of early intervention
A multi-level and iterative feature engineering framework for deepfake audio detection
No full textThis study introduces FakeSleuthNeXt, a lightweight, fully interpretable, handcrafted feature engineering framework for deepfake audio detection. The method relies exclusively on manually designed features without any neural network training. It combines a histogram-driven binary pattern extractor applied to 7-level discrete wavelet transform sub-bands with 15 statistical descriptors per level. An iterative ensemble feature selection strategy fusing INCA, IChi2, and IReliefF algorithms produces compact and highly discriminative representations. Evaluated on six challenging and diverse deepfake audio datasets (over 72,000 segments) using only kNN and Cubic SVM classifiers, the framework achieves accuracies ranging from 89.20% to 99.21%, EER values from 0.97% to 10.85%, and min-tDCF of 0.124 (ASVspoof 2019 LA) and 0.298 (ASVspoof 2021). These results match or surpass many recent deep learning systems while offering significantly lower computational cost, full transparency, and straightforward deployment on resource-constrained devices, making FakeSleuthNeXt particularly suitable for forensic applications. FakeSleuthNeXt provides a fast, transparent, and highly resource-efficient solution, making it particularly well-suited for forensic applications and deployment on resource-constrained devices
Trolox-Mediated Alleviation of Cadmium Toxicity in Grapevines Through Enhanced Mineral Homeostasis and Metabolic Stability
No full textHeavy metal contamination poses significant challenges to sustainable viticulture, necessitating innovative approaches to protect grapevine health and productivity. However, comprehensive evaluations of antioxidant-mediated protection against cadmium toxicity in integrated physiological systems remain scarce. We assessed mineral homeostasis, organic acid metabolism, and sugar accumulation in three-year-old Vitis vinifera L. cv. Okuzgozu berries exposed to graduated cadmium (Cd) concentrations (0-20 ppm) with and without 50 mu M Trolox supplementation. Treatment effects were highly significant across all measured parameters (p < 0.001). Notably, Trolox application consistently demonstrated protective efficacy, maintaining nitrogen content at 1.53% compared to 0.65% in untreated cadmium-stressed plants, while preserving essential macronutrient (phosphorus, potassium, calcium, magnesium) and micronutrient (manganese, iron, zinc) accumulation under toxic conditions. In contrast, cadmium exposure alone severely compromised mineral nutrition, organic acid biosynthesis, and carbohydrate metabolism, with total organic acids declining from 15.27 to 4.43 mg L--(1) and reducing sugars dropping substantially across all stress levels. Multivariate analysis revealed that Trolox treatment fundamentally reorganized the metabolic network, enhancing coordination between mineral uptake, organic acid production, and sugar metabolism. Particularly, Trolox-supplemented plants formed distinct clusters with elevated beneficial compounds, including preserved tartaric, malic, citric, and succinic acid levels, alongside maintained glucose and fructose concentrations, indicating efficient stress mitigation capacity. These findings show that targeted antioxidant application plays a crucial role in improving grapevine performance under heavy metal stress. Trolox consistently protected multiple vine systems, including nutrient balance, organic acid metabolism, and carbohydrate stability. Rather than just providing support, antioxidant supplementation proved essential for maintaining vine health and metabolic function. This suggests that carefully designed antioxidant protocols adapted to specific contamination conditions could be an effective strategy for sustaining vineyard productivity and fruit quality in heavy metal-polluted areas
Hydrochar production from Izmit Gulf sludge for efficient Methylene Blue removal: A sustainable water treatment approach
No full textOff-diagonal solutions in Einstein gravity modeling f(R) gravity and dynamical dark energy vs ΛCDM cosmology
No full textModified gravity theories (MGTs) have long been studied as alternatives to general relativity (GR) and the standard ΛCDM cosmological model. For example, exponential f(R) models often yield better fits to observational data, suggesting that ΛCDM may be inadequate. In this work, we argue that the gravitational and accelerating cosmology paradigm can remain close to GR and ΛCDM if one considers broader classes of off-diagonal cosmological solutions of the Einstein equations. These solutions are constructed using the anholonomic frame and connection deformation method (AFCDM), which enables the decoupling and integration of nonlinear systems in nonholonomic dyadic variables with connection distortions. The resulting off-diagonal Einstein manifolds and cosmological models are characterized by nonholonomic constraints, nonlinear symmetries, and effective cosmological constants. Such structures allow one to approximate cosmological effects, mimic features of MGTs, and describe gravitational polarization, local anisotropies, and dark energy and dark matter phenomena within GR. We further show that these models can be endowed with relativistic versions of Perelman's thermodynamic variables for geometric flows, which we compute in general form for accelerating cosmology
Surgical Management of Large Sacral Spine Chordomas
No full textChordomas are rare malignant tumors arising from notochord remnants, predominantly in the sacral region. Due to their size and location, achieving R0 resection is challenging, with larger tumors (> 50 mm or > 25 cc) linked to worse outcomes. This study examines the surgical management and outcomes of large sacral chordomas, focusing on tumor size, resection strategy, and postoperative results. This retrospective study reviewed 14 male patients with sacral chordomas ≥ 50 mm or ≥ 25 cc. Data on demographics, tumor characteristics, surgical approaches, complications, and survival were analyzed using descriptive statistics and Kaplan–Meier survival curves. The study analyzed 14 male patients (mean age: 63.1 years) with sacral chordoma. Tumor size averaged 98.4 mm, and preoperative embolization was performed in two cases. Total sacrectomy was required in 14.3%, with spinopelvic fixation in both. Negative margins were achieved in 92.9%. Complications included wound issues (50%) and neurological deficits (57.1%)(7/12), mainly in high-level sacrectomies. High-level resections had significantly higher neurological complications (p = 0.005). Kaplan–Meier analysis estimated survival above 75% postoperatively. Surgical resection of large sacral chordomas is challenging but feasible, with high rates of R0 resection. Negative margins, tailored surgical strategies, and effective complication management are critical for optimizing outcomes
Surgical outcomes in oncological sacrectomy: a detailed analysis of surgical site infections (SSI).
No full textNovel alpha-functionalized nickel(ii) phthalocyanines: photochemical, antioxidant, antibacterial, cytotoxicity studies and theoretical insights
No full textIn this study, novel nickel(ii) phthalocyanines (1a-4a) with functional groups containing different atoms such as fluorine, sulfur, and oxygen connected through oxygen bridges from their non-peripheral positions were synthesized and characterized. Singlet oxygen generation, antioxidant and antibacterial activities, and cytotoxicity of the phthalocyanines (1a-4a) were evaluated. The synthesized phthalocyanines (1a-4a) exhibited solvent-dependent singlet oxygen generation, demonstrating their potential as photosensitizers and providing useful insights into their photochemical behavior. Moderate antioxidant activity was found when compared to the previous studies. The synthesized phthalocyanines (1a-4a) showed antibacterial activity against S. aureus. Molecule (2a) showed the highest antibacterial activity with a 12 mm inhibition zone. The phthalocyanines (1a-4a) did not exhibit cytotoxic activity in the MTT assay against HEK 293 cells. In conclusion, Gaussian calculations were used to investigate the synthesis of target nickel(ii) phthalocyanines (1a-4a). These computations were performed at the B3LYP, HF, and M062X levels, and the basis set utilized was 6-31++G(d,p). Proteins such as zinc superoxide dismutase protein (PDB ID: 1CB4), human peroxiredoxin 5 protein (PDB ID: 1H2D), and FabH inhibitor protein (PDB ID: 4Z8D) were among those that were subjected to molecular docking calculations
Peripheral Perfusion vs Standard Management in Sepsis/Septic Shock: A Prospective Randomized ED Study
No full textObjective: Despite the restoration of macro-hemodynamic parameters in sepsis treatment, microcirculatory changes can lead to organ failure. This study aims to investigate the effect of patient management guided by PPI in assessing microcirculation on the survival of patients with sepsis and septic shock. Materials and methods: The study was conducted as a single-center, prospective, randomized controlled trial in the emergency department. The control group was managed according to SSC guidelines using macrohemodynamic parameters, aiming to maintain MAP >= 65 mmHg. In the study group, patient management was carried out under the guidance of PPI measurement. Patients with PPI <1.4 were rapidly brought to a euvolemic state when macro-hemodynamic parameters were maintained. If adequate perfusion was not achieved with fluid resuscitation, vasopressor and/or inotropic support was used without regard to the MAP target. The target in this group was to increase PPI above 1.4. The 30-day mortality rate, length of hospital stays and in the intensive care unit were evaluated. Results: The study included 100 patients in the control group and 100 in the study group. The 30-day mortality rate was significantly lower in the study group (p = 0.03). Lactate clearance was significantly better in the study group (p < 0.001). No significant difference was found between the groups in terms of hospital and ICU length of stay (p = 0.26 and p = 0.68, respectively). Conclusion: Our study has demonstrated that peripheral perfusion-targeted resuscitation is an innovative and effective approach with the potential to reduce mortality compared to standard methods in the management of sepsis and septic shock. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies
A comprehensive study of generalized Simpson-type inequalities via new conformable fractional integral operators
No full textIn this paper, we establish generalized Simpson-type inequalities by conformable fractional integral operator. Utilizing functions with bounded second derivatives, we derive upper and lower bounds for these inequalities. This approach extends and generalizes existing results in the literature by providing more flexible conditions and broader applicability. Furthermore, we present special cases of the derived results to demonstrate their connection with existing inequalities in the literature. Numerical examples and graphical illustrations are provided to validate the theoretical findings and highlight the utility of the new operator. This study paves the way for further exploration in the field of fractional calculus and its applications in mathematical analysis and optimization