Search Results (31,066)

This study investigates the environmental stability of ferronickel slag (FNS) and primary lead slags (GCS and FCS) from historical metallurgical complexes in Greece, in rainwater and seawater media. Leaching experiments revealed that nickel is the most mobile element from FNS (43.5 μg·g⁻¹ in seawater after 90 days). Chromium release, on the other hand, is very limited, not exceeding 0.04 μg·g⁻¹. In lead slags, zinc and lead exhibit significant leaching (up to 650 and 230 μg·g⁻¹, respectively), while arsenic release reaches 22.6 μg·g⁻¹. GCS contains pores primarily in the range of 50–90 Å. The majority of pore volume in FCS is centered around 30 Å. The porosity appears to have a significant effect on the element’s leachability. Pb, Zn, As, Sb, and Cd are released in significantly higher amounts from the finely porous FCS compared to GCS. Thermodynamic modeling was used to identify the pollutant speciation in water media in relation to the oxygen concentration. The release of toxic elements such as Cr from FNS and As from lead slags is enhanced under oxic (open-air) conditions. Therefore, their land disposal poses a greater environmental threat compared to sea disposal, where anoxic conditions prevail. Full article

Primary podocytopathies, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), are caused by a circulating factor or factors injurious to the podocyte. An immunologic origin seems likely based on responsiveness to corticosteroids or other immunosuppressive agents, including calcineurin inhibitors targeting T-cells and rituximab targeting B-cells. Potential non-antibody-mediated circulating factors have been identified, including cardiotrophin-like cytokine 1, soluble urokinase plasminogen activator receptor, and angiopoietin-like 4, among others. More recent research supports a primary antibody pathogenesis, with anti-nephrin antibodies found in a significant percentage of cases. Such antibodies also predict recurrence after transplantation. Other potential antigenic targets besides nephrin include annexin, the proteosome, podocin, and CD40. Additionally, high-resolution confocal microscopy has identified punctate immunoglobulin deposits along the slit diaphragm and podocyte cell body that may or may not colocalize with abnormal punctate nephrin staining and may correlate with detectable circulating antibodies. The success of rituximab in observational studies in both native kidneys and transplants supports a primary role for autoantibodies. We discuss in detail the data supporting putative non-antibody circulating factors, as well as the recent data supporting antibody pathogenesis, which may provide some clues on treating the individual patient. Full article

In this study, we aim to provide a comprehensive analysis of the risk management potential of sectoral Credit Default Swaps (CDSs) within financial portfolios. Our objectives are threefold: (i) to investigate the safe haven properties of sectoral CDSs; (ii) to assess their hedging effectiveness and evaluate the diversification benefits of incorporating sectoral CDSs into both conventional and Islamic stock market portfolios; and (iii) to compare these findings with those obtained from alternative assets such as the VSTOXX, gold, and Bitcoin indices. To achieve this, we estimate time-varying hedge ratios using a range of multivariate GARCH (MGARCH) models and subsequently compute hedging effectiveness metrics. Conditional correlations derived from the Asymmetric Dynamic Conditional Correlation (ADCC) model are employed in linear regression analyses to assess safe haven characteristics. This methodology is applied across different subperiods to capture the impact of the crypto currency bubble and the COVID-19 pandemic on hedging performance. Full article

To identify molecular markers associated with wool traits in fine-wool sheep, we examined genetic polymorphisms in the NOTCH2 and CD1A genes in 944 Subo Merino sheep in this study. Subsequently, we performed association analyses between mutation sites in the NOTCH2 and CD1A genes and wool traits using SAS 9.4 software, followed by linkage disequilibrium (LD) analysis of different mutation sites using Haploview 4.2 software. Additionally, bioinformatics tools were employed to predict the potential impacts of missense mutations on protein secondary and tertiary structures. Finally, quantitative PCR (qPCR) was used to assess the expression levels of the NOTCH2 and CD1A genes. Genetic analysis revealed six polymorphic sites in NOTCH2 and CD1A, all of which were missense mutations. Two SNPs in NOTCH2 (SNP1 and SNP2) showed significant associations with the coefficient of variation of fibre diameter, and SNP1 was also associated with greasy fleece weight. Four SNPs in CD1A (SNP3–SNP6) were significantly associated with fibre diameter standard deviation, and SNP3, SNP4, and SNP5 were additionally associated with crimp number. LD analysis revealed that SNP3, SNP4, and SNP5 were closely linked. Bioinformatics analysis indicated that the mutations caused alterations in the secondary and tertiary structures of the NOTCH2 and CD1A proteins. qPCR results showed that the CD1A gene was highly expressed in the fine wool fibre group compared with the ultra-fine wool fibre group. In conclusion, this study revealed a genetic association between NOTCH2 and CD1A and wool traits. The results are expected to provide a theoretical foundation for breeding wool traits in Subo Merino sheep, thereby enhancing the economic value of fine wool. Full article

This study demonstrates that synergistic pyrolysis and water-soaking pretreatment transforms municipal solid waste incineration fly ash (MSWI FA) into high-performance alkali-activated materials when combined with ground granulated blast furnace slag (GGBS). Pyrolysis reduced chlorine content by 94.3% and increased reactive components by 44.4%, thereby shifting hydration products from Friedel’s salt to ettringite (AFt). Subsequent water-soaking eliminated expansion-causing elemental aluminum, liberating activators for enhanced reaction completeness (29% higher cumulative heat release) and enabling a denser matrix with 71.5% harmless pores (<20 nm). The dual-treated FA (T-PFA) achieved exceptional mechanical performance—295.6% higher 56-day compressive strength versus untreated FA at a 1:1 ratio—while reducing porosity by 29.1% relative to pyrolyzed-only FA. Despite 22–38% increased total heavy metal content post-pyrolysis, matrix densification and enhanced C-A-S-H/AFt formation reduced Cr/Cd/Cu/Pb leaching by 11.3–66.7% through strengthened physical encapsulation and chemisorption, with all leachates meeting stringent HJ 1134-2020 thresholds. This integrated approach provides an efficient, environmentally compliant pathway for MSWI FA valorization in low-carbon construction materials. Full article

Long-span cable-supported bridges, such as cable-stayed and suspension bridges, are highly sensitive to wind-induced effects due to their flexibility, low damping, and relatively light weight. Aerodynamic analysis is therefore essential in their design and safety assessment. This study examines the aeroelastic stability of the Oued Dib cable-stayed bridge in Mila, Algeria, with emphasis on vortex shedding, galloping, torsional divergence, and classical flutter. A finite element modal analysis was carried out on a three-dimensional model to identify natural frequencies and mode shapes. A two-dimensional deck section was then analyzed using Computational Fluid Dynamics (CFD) under a steady wind flow of U = 20 m/s and varying angles of attack (AoA) from −10° to +10°. The simulations employed a RANS k-ω SST turbulence model with a wall function of Y+ = 30. The results provided detailed airflow patterns around the deck and enabled the evaluation of static aerodynamic coefficients—drag (C_D), lift (C_L), and moment (C_M)—as functions of AoA. Finally, the bridge’s aeroelastic performance was assessed against the four instabilities. The findings indicate that the Oued Dib Bridge remains stable under the design wind conditions, although fatigue due to vortex shedding requires further consideration. Full article

Williams–Beuren Syndrome (WBS) is a rare neurodevelopmental disease caused by a microdeletion on chromosome 7 (7q11.23) and associated with behavioral disorders such as hypersociability, impaired visuospatial memory, anxiety, and motor disorders. The precise underlying neurobiological bases remain unknown. The CD mouse is a genetic model that reproduces the deletion found in WBS patients on the equivalent mouse locus. Taking into account that monoaminergic systems are known to modulate behaviors that are altered in WBS, we hypothesized that CD mice could present quantitative and qualitative changes in brain noradrenaline, dopamine, and serotonin systems compared to wild-type (WT) littermates. We sampled 10 brain regions in female mice for quantifying monoamines and related compounds by high-performance liquid chromatography coupled to electrochemical detection. We found a decrease in dopamine in the nucleus accumbens and serotonin and its metabolites in the hypothalamus. Using correlative approaches of tissue content across the brain, we found that the relationships between neurotransmitters or their metabolic ratios (metabolite/neurotransmitter) changed in CD compared to WT. Notably, compared to WT, the ratios in CD mice showed striatal correlations for the serotonin/dopamine systems interaction, and cortical, thalamic, and hypothalamic correlations for the noradrenaline/dopamine systems interaction. The data suggest specific alterations of monoaminergic systems across the brain that could sustain the abnormal behavioral responses displayed by CD mice. Full article

This study evaluated the acute toxicity of the hydroethanolic extract and the butanolic fraction of Piper marginatum Jacq., following the OECD Guideline 423. Oral and intraperitoneal exposure of CD-1 mice was used in single-dose and repeated-dose schedules. No mortality or significant behavioral alterations were observed. Body weight remained stable during treatment, and histopathological analysis revealed only mild to moderate alterations, mainly in the liver, kidneys, and lungs. These results indicate the absence of acute systemic toxicity under the conditions evaluated. Preliminary phytochemical analysis and metabolomic profile analysis by LC-QTOF/MS revealed a diverse composition of secondary metabolites, including alkaloids, flavonoids, phenylpropanoids, and sphingolipids. Compounds with known biological activity and some with potential toxicity were identified. The findings support the safe use of Piper marginatum extracts in short-term applications and suggest further subchronic toxicity studies and mechanistic evaluation. This research provides fundamental data for preclinical characterization and standardization of extracts of plant origin. Full article

Tumor necrosis factor receptor-associated factors (TRAFs) are a family of adaptor proteins that transmit signals from immunoregulatory receptors—such as TNF receptors, Toll-like receptors, and interleukin receptors—to coordinate immune and inflammatory responses. Among them, TRAF5 is highly expressed in lymphocytes and implicated in obesity-associated inflammation, but its role in secondary lymphoid organs during chronic low-grade inflammation remains unclear. We examined splenic B and T cell phenotypes in wild-type (WT) and Traf5-deficient (KO) mice fed a high-fat diet (HFD). Although lymphocyte composition was broadly comparable, KO mice showed reduced spontaneous immunoglobulin G2c (IgG2c) production ex vivo—about 1.5-fold lower than WT. Notably, despite elevated TNF-α and CD40 ligand (CD40L) expression in HFD-fed KO splenocytes, IgG2c production remained diminished—about 1.9-fold lower than WT—upon soluble CD40L stimulation, indicating impaired CD40-mediated class-switch recombination (CSR). Consistently, B cells from KO mice on a normal diet exhibited reduced activation-induced cytidine deaminase (AID) expression—about 4.4-fold lower than WT—after CD40L stimulation, and decreased IgG2c secretion—about 6.6-fold lower—upon CD40L and IFN-γ co-stimulation in vitro. Collectively, these findings suggest that TRAF5 is involved in CD40-dependent CSR in B cells under inflammatory conditions and may contribute to sustaining adaptive immune responses during obesity-associated chronic inflammation. Full article

Novel research data in different cancer types indicate that mutations within PIK3CA might serve as a biomarker of an improved response to immune therapy. Therefore, the aim of this study was to evaluate and examine possible differences in the tumor microenvironment composition and PD-L1 expression as well the prognostic significance of CD4, CD8, CD68, and CD163 in PIK3CA mutated and non-mutated hormone receptor positive and HER2 negative (HR+/HER2−) breast carcinoma. Breast carcinoma tissue was analyzed by Cobas PIK3CA mutation test for the presence of PIK3CA mutation and immunohistochemistry was applied to assess PD-L1 expression and CD4, CD8, CD68, and CD163 infiltration within tumor. Statistically significant association was observed between PD-L1 expression and the presence of PIK3CA exon 20 mutation (p = 0.044), with PD-L1–positive patients predominantly harboring this mutation. Tumors harboring PIK3CA mutations exhibited moderate to strong statistically significant positive correlations between PD-L1 expression and infiltration by CD8 cells (rs = 0.462, p = 0.0027), CD68 cells (rs = 0.398, p = 0.0134), and CD163 cells (rs = 0.617, p < 0.0001). In patients with PIK3CA mutation and exon 20 PIK3CA mutation there was statistically significant longer survival without recurrence (p = 0.026 and p = 0.041, respectively). Research regarding PD-L1 expression, immune cells and PIK3CA mutations might have an impact on how to determine therapeutic approaches for patients with HR+/HER2− breast carcinoma. Full article

Background/Objectives: Azathioprine (AZA) is widely used for maintaining remission in inflammatory bowel disease (IBD), but the implications of its withdrawal remain unclear. This study evaluates relapse rates after AZA discontinuation in adult IBD patients in remission and identifies predictors of relapse. Methods: A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines and registered in PROSPERO (CRD420251016594). Databases were searched from inception to 4 January 2025, including RCTs and cohort studies involving adult IBD patients who discontinued AZA in clinical remission. The main outcome assessed was relapse incidence, with additional outcomes covering time until relapse, predictors of relapse, and management following relapse. Random-effects meta-analysis, subgroup analyses, and meta-regression were performed. Results: Twenty-two studies comprising 3057 patients were included. The pooled relapse rate after AZA withdrawal was 32.5% (95% CI: 28.2–37.2%; I² = 94.2%). UC patients exhibited higher relapse rates (41.3%) than CD patients (24.7%, p = 0.003). Shorter AZA duration, elevated CRP, and absence of mucosal healing were associated with increased relapse risk. Meta-regression identified AZA duration as a significant predictor (β = −0.18, p = 0.009). Post-relapse management often involved AZA reintroduction or escalation to biologics, with low surgery rates. The GRADE assessment revealed that the certainty of evidence for the majority of primary outcomes was classified as low to very low. Conclusions: While this meta-analysis suggests that relapse after AZA withdrawal occurs frequently in IBD patients, the low to very low certainty of evidence limits definitive recommendations. The significant heterogeneity indicates that relapse risk varies across different patient populations and different settings. Full article

Background: Perianal Crohn’s disease (pCD) is one of the most disabling complications of inflammatory bowel disease, characterized by fistulas and abscesses that demand precise imaging for diagnosis, treatment planning, and follow-up. Magnetic resonance imaging (MRI) is considered the reference standard, but endoanal ultrasound (EAUS) with high-frequency 360° probes provide a readily available, cost-effective, and repeatable alternative. Methods: We performed a narrative review of the literature, evaluating studies on the EAUS technique, diagnostic applications, distinguishing features of Crohn’s-related fistulas, and comparative analyses with MRI. Consensus documents and structured reporting initiatives were also included. Results: EAUS provides high-resolution visualization of the anal sphincter complex and intersphincteric space, enabling the reliable detection of fistulas and abscesses. Characteristic features such as tract width > 4 mm, bifurcation, hyperechoic debris, the Crohn’s Ultrasound Fistula Sign (CUFS), and the rosary sign assist in differentiating Crohn’s from cryptoglandular fistulas. EAUS is well-suited for serial monitoring, perioperative seton guidance, and therapeutic decision-making. Emerging tools such as Doppler and shear wave elastography provide additional information on activity and fibrosis. MRI remains indispensable for supralevator disease, deep pelvic sepsis, and standardized activity indices. Comparative studies indicate similar sensitivity for simple fistulas, with MRI superior in complex cases; combining both modalities maximizes accuracy. Conclusions: EAUS is a practical and repeatable imaging tool that complements MRI in the multidisciplinary management of perianal Crohn’s disease. Advances such as 3D imaging, contrast enhancement, and elastography may enable validated activity scoring—for example, a future PEACE (Perianal Endosonographic Activity in Chron’s Evaluation) Index—further strengthening its role in longitudinal care. Full article

Vitamin D deficiency is highly prevalent in the Middle East despite abundant sunlight; however, most genetic studies have focused on common variants in Europeans only. We analyzed whole-genome sequences from 13,808 Qatar Biobank participants, evaluating rare variants (minor allele frequency 0.01–0.0001) for associations with serum 25-hydroxyvitamin D (25(OH)D) levels and deficiency risk (≤20 ng/mL) in independent discovery (n = 5885) and replication (n = 7767) cohorts, followed by meta-analyses. In quantitative analyses, the discovery cohort identified 41 genome-wide significant signals, including CD36 rs192198195 (p = 2.48 × 10⁻⁸), and replication found 46, including SLC16A7 rs889439631 (p = 2.19 × 10⁻⁸), implicating lipid metabolism pathways. In binary analyses, replication revealed POTEB3 rs2605913 (p = 2.8 × 10⁻⁸), while meta-analysis (n = 13,652) uncovered SLC25A37 rs952825245 (p = 5.15 × 10⁻¹²), a locus associated with cancer and vitamin D signaling. Rare-variant polygenic scores derived from discovery significantly predicted continuous (R² = 0.146, p = 9.08 × 10⁻¹²) and binary traits (AUC = 0.548, OR = 0.99, p = 9.22 × 10⁻⁶) in replication. This first rare-variant GWAS of vitamin D in Middle Easterners identifies novel loci and pathways, underscores the contribution of ancestry-specific rare alleles, and supports integrating rare and common variants to guide precision management in high-burden populations. Full article

Long COVID (LC), also known as post-acute sequelae of COVID-19 infection (PASC), is a heterogeneous and debilitating chronic disease that currently affects 10 to 20 million people in the U.S. and over 420 million people globally. With no approved treatments, the long-term global health and economic impact of chronic LC remains high and growing. LC affects children, adolescents, and healthy adults and is characterized by over 200 diverse symptoms that persist for months to years after the acute COVID-19 infection is resolved. These symptoms target twelve major organ systems, causing dyspnea, vascular damage, cognitive impairments (“brain fog”), physical and mental fatigue, anxiety, and depression. This heterogeneity of LC symptoms, along with the lack of specific biomarkers and diagnostic tests, presents a significant challenge to the development of LC treatments. While several biological abnormalities have emerged as potential drivers of LC, a causative factor in a large subset of patients with LC, involves reservoirs of virus and/or viral RNA (vRNA) that persist months to years in multiple organs driving chronic inflammation, respiratory, muscular, cognitive, and cardiovascular damages, and provide continuous viral antigenic stimuli that overstimulate and exhaust CD4⁺ and CD8⁺ T cells. In this review, we (i) shed light on persisting virus and vRNA reservoirs detected, either directly (from biopsy, blood, stool, and autopsy samples) or indirectly through virus-specific B and T cell responses, in patients with LC and their association with the chronic symptomatology of LC; (ii) explore potential mechanisms of inflammation, immune evasion, and immune overstimulation in LC; (iii) review animal models of virus reservoirs in LC; (iv) discuss potential T cell immunotherapeutic strategies to reduce or eliminate persistent virus reservoirs, which would mitigate chronic inflammation and alleviate symptom severity in patients with LC. Full article

Introduction: Cushing syndrome (CS) is a medical condition resulting from prolonged hypercortisolemia. The most common reason for endogenous CS is ACTH overproduction by pituitary adenoma, and then it is called Cushing disease (CD). The gold standard of CD diagnostic remains bilateral inferior petrosal sinus sampling (BIPSS); nevertheless, non-invasive diagnostic methods are being sought to provide a higher safety profile. The aim of this study was to evaluate whether [¹¹C]C-MET PET/CT can serve as a non-invasive alternative to BIPSS and MRI in CD diagnosis. Methods: This prospective study included 21 patients with CD who underwent BIPSS, MRI of the pituitary, and [¹¹C]C-MET PET/CT. Results: Sensitivity of BIPSS, MRI and [¹¹C]C-MET PET/CT was 100%, 59% and 24%, respectively, while specificity was 100%, 75%, and 13%. Next, we retrospectively compared PET/CT results for patients with corticotrope pituitary adenomas (n = 18) with those for individuals with no pituitary pathology (n = 18), and the results showed significantly higher SUV_max in the study group (3.74 ± 0.90 vs. 1.87 ± 1.17; p < 0.001). In ROC curve analysis, the area under the curve (AUC) was 0.889 (p <0.001; 95% CI 0.784–0.994). For SUV_max 2.60, the calculated sensitivity and specificity were 89% and 78% respectively, and for SUV_max 3.56, sensitivity and specificity were 67% and 89%, respectively. Conclusions: [¹¹C]C-MET PET/CT seems not to be a reliable diagnostic option in the diagnosis of pituitary corticotropic adenomas. BIPSS proved still to be the best diagnostic option for CD. Nevertheless, a higher than normal pituitary accumulation of the radiotracer may suggest the presence of increased amino acid metabolism, thus, the presence of adenoma. Full article