Search Results (207)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes an immune-mediated neurological syndrome, which persists long after infection. Mechanisms for SARS-CoV-2-associated neurological complications are multifactorial, with an increased risk of drug abuse such as methamphetamine (meth). SARS-CoV-2 infection and its viral proteins play pivotal roles in coronavirus disease 2019 (COVID-19)-associated neuroinflammation, which can lead to long COVID. We hypothesize that meth augments activation of the microglial NOD-, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome by the SARS-CoV-2 nucleocapsid (N) protein, resulting in neuroinflammation. To test this hypothesis, we investigated the effect of N-protein and meth on NLRP3 inflammasome activation in primary rat microglial cultures using enzyme-linked immunosorbent assay (ELISA), Reverse Transcription quantitative Polymerase Chain reaction (RT-qPCR), western blot (WB), and immunofluorescence assay (IFA). Our results showed that meth augmented N-protein-induced microglial activation, as evidenced by increased ionized calcium-binding adapter 1 (Iba-1) expression. The addition of meth to the microglial cultures treated with N-protein increased proinflammatory cytokine production. Meth augmentation of N-protein-induced neuroinflammation was further supported by increased inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) production. The effects of meth on N-protein-associated inflammatory responses were significantly attenuated by MCC950, a specific NLRP3 inhibitor. Moreover, meth-associated NLRP3 activation was either blocked by the opioid sigma1-receptor (σ1_-R) inhibitor BD1047 or by σ1R siRNA knockdown. Taken together, these results demonstrated that meth augmented SARS-CoV-2 N-protein-induced neuroinflammation via microglial σ1_-R and the NLRP3 inflammasome, which may underlie the pathogenesis of neurological manifestations in COVID-19, such as long COVID with meth abuse. These results may also underscore the impact of drug abuse on long COVID and provide targets for the development of therapeutic strategies to control the neurological outcomes of long COVID. Full article

The dual reliance on surface-mount technology (SMT) and pin-through-hole (PTH) assembly lines in high-volume printed circuit board (PCB) manufacturing induces logistical bottlenecks, excessive operational costs, and elevated thermal stress on components. This study presents the optimization of a wireless detector terminal production line by integrating Pin-in-Paste (PiP) technology within a Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) framework. By accurately calculating the required solder volume ($V_{req}$) and stencil aperture dimensions based on pin and pad geometries, the wave soldering process was eliminated without altering existing thermal profiles. The integration consolidated the assembly into a single heat cycle, ensuring IPC-A-610 Class 2 compliance for barrel fill ratios. The results demonstrate a 97% reduction in average assembly costs, yielding annual savings of USD 92,513 while eliminating USD 44,025 in work-in-progress (WIP) inventory. Furthermore, the single-reflow approach mitigated component thermal degradation and reduced the facility’s carbon footprint by an estimated 13.32–17.76 metric tons of CO₂ equivalent annually. This research validates a comprehensive methodology for transitioning to PiP technology, offering a sustainable, cost-effective framework for operational excellence in the electronics’ manufacturing industry. Full article

Neurodegenerative diseases are targets for pridopidine therapy, which aims to improve quality of life through neuroprotective mechanisms that involve sigma-1 receptor (S1R) activation. Neurodegenerative motor and cognitive diseases are influenced by dopamine imbalance, where disruptions in pathways contribute to states that are hyperkinetic or hypokinetic, while current dopaminergic treatments are symptomatic rather than disease-modifying, especially for Huntington’s disease and Amyotrophic lateral sclerosis. This review summarizes the mechanisms underlying pridopidine-mediated neuroprotection and examines the current evidence supporting its therapeutic potential. The S1R is an endoplasmic reticulum-mitochondria-associated chaperone involved in homeostasis of calcium, stress regulation, and mitochondrial function. Pridopidine is a small lipophilic molecule that crosses the blood–brain barrier and acts as an S1R agonist, with minimal dopamine D2 receptor occupancy. Activation of S1R by pridopidine modulates calcium signaling and enhances anti-apoptotic activity. Collectively, available evidence suggests that pridopidine may improve motor outcomes and slow disease progression in Huntington’s disease and amyotrophic lateral sclerosis, supporting its promise as a disease-modifying therapeutic strategy. Full article

Background: Vitamin D is a key regulator of skeletal homeostasis, and hypovitaminosis D is highly prevalent among postmenopausal women, who are at increased risk of osteoporosis, sarcopenia, and related complications. Accurate assessment of serum 25-hydroxyvitamin D [25(OH)D] is therefore essential. However, substantial variability exists among analytical methods, particularly between automated chemiluminescent immunoassays (CLIA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), the latter considered the reference technique. This study aimed to compare four analytical methods, three CLIA platforms, and LC-MS/MS for measuring circulating 25(OH)D levels in a cohort of menopausal and postmenopausal women. Methods: A total of 425 serum samples from menopausal and postmenopausal women representing the real-world distribution of vitamin D levels in this population were analyzed using three automated CLIA systems and LC-MS/MS. Method comparison, agreement, precision through quality control assessment, total error, and sigma were evaluated. Results: The evaluated CLIA platforms (Abbott, Snibe, and Siemens) showed strong correlation with LC-MS/MS, with r = 0.919, r = 0.978, and r = 0.879. Furthermore, all assays showed excellent precision (CV < 5%), with good-to-acceptable total error (TE) and Sigma-metric performance. Conclusions: In conclusion, these findings demonstrate that while CLIA platforms offer a reliable and precise alternative for routine clinical use, these findings underscore the importance of method selection and result interpretation in the clinical assessment of vitamin D status in postmenopausal women. Furthermore, it highlights the ongoing need to minimize inter-assay variability and ensure consistent vitamin D assessment. Full article

In this paper, based on the Hertzian contact analysis, we determine the minimum dynamic load of a ball bearing using a Weibull probabilistic approach. The lower L₁₀ life limit was determined considering a confidence interval, the sample size that corresponds to the L₁₀ life (90% reliability), and the standard deviation of the related Weibull scale parameter η. Then, we determine a functional relationship between the normal and the Weibull distributions to determine the corresponding $1\mathsf{\sigma }$ , $2\mathsf{\sigma }$ , and $3\mathsf{\sigma }$ Six Sigma indices of the ball-bearing life. Finally, a standard method was established to determine the minimum dynamic load rating required for a ball bearing in such a way that it achieves 90% reliability at the lower bound of its ${\mathrm{L}}_{10}$ life. In the case study, the SKF 6009 ball bearing was initially selected, with a dynamic load rating of 22.1 kN, exhibiting a lower bound reliability of 0.86 under a nominal Weibull scale parameter of strength of 910 MPa. After applying the proposed analysis, it was replaced with the SKF 71909 ball bearing, which provides a nominal Weibull scale parameter strength of 1174.54 MPa, which ensures 90% reliability at the lower bound of its L₁₀ life. Its reliability indices at the $1\mathsf{\sigma }$ , $2\mathsf{\sigma }$ , and $3\mathsf{\sigma }$ Six Sigma levels were $\mathrm{R}\left(\mathrm{t}\right)=0.9174$ , $\mathrm{R}\left(\mathrm{t}\right)=0.8880$ , and $\mathrm{R}\left(\mathrm{t}\right)=0.8534$, respectively. Full article

Capacitive sensing offers a low-power, non-optical route for automated insect monitoring, but architecture-level benchmarking under shared geometry remains limited. Rather than presenting a general framework, this study proposed a configuration-specific laboratory benchmark comparing four sigma-delta and charge-transfers in a 6 mm dual-arc conduit at 25 °C, targeting six adult terrestrial arthropod species spanning a 25-fold range of the body cross-sectional area. Static measurements showed a strong linear relationship between ΔC_static and body cross-sectional area (17.96 fF/mm², r = 0.995), supporting first-pass conduit sizing and detectability screening. In contrast, transit amplitudes were not monotonic with body size because posture, motion, and gap occupancy affected waveform shape. Under chamber conditions, static sensitivity degraded by less than 3.2% across all architectures from RH 40% to 80%. However, under the deployment-oriented noise model, SNR_FR degradation was substantially higher for charge-transfer devices (64.8–66.8%) than for Σ–Δ devices (≤35.5%), because the composite noise floor amplifies the effect of humidity-induced baseline drift. These results generated a conduit-specific reference dataset for preliminary capacitance-to-digital converter (CDC) selection within the tested 6 mm dual-arc geometry. In addition, the experimental validation focused on laboratory baseline noise characterization, long-term drift, and trap-integrated testing in temperature-controlled environments and natural-locomotion trials, providing critical information on configuration-specific architectures and body-size-scaling reference. This study serves as an initial step toward real-world capacitive insect sensing. Future studies will investigate additional conduit geometries and insect species to improve the robustness of the proposed framework. Full article

This study investigates the convergence of energy intensity in the member states of the European Union (EU) between 1993 and 2021. To assess convergence, sigma and stochastic (beta) convergence analyses are performed using conventional, Fourier transform, and quantile-based unit root tests. Unlike previous studies, this work combines Fourier transform and quantile approaches to capture both gradual structural breaks and distributional differences between EU countries. The results show that convergence was strong between 1993 and 2009 but weakened after 2009, indicating increasing structural divergence between member states. The results also show that the convergence behavior is not uniform, suggesting that linear methods alone provide an incomplete picture. These findings imply that a single EU policy may not be sufficient and that a sustainable energy transition requires coordinated yet flexible strategies that take national differences into account. All empirical analyses were performed using R (version 4.3.2) and Stata (version 18). Full article

The sigma-1 receptor (S1R) is an endoplasmic reticulum (ER)-resident protein enriched at the mitochondria-associated ER membranes (MAMs) that supports ER homeostasis, preserves mitochondrial function, and enhances cell survival under stress. Disruptions of MAM integrity and prolonged ER stress are well-recognized pathological features of amyotrophic lateral sclerosis (ALS), contributing to motor neuron dysfunction and degeneration. In this study, we evaluated the protective effects of pridopidine, a highly selective and potent S1R agonist currently in clinical development for Huntington’s disease (HD) and ALS, using neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iPSCs) from a patient with sporadic ALS. Exposure of ALS NPCs to the ER stressor tunicamycin increased the ER stress markers binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP), disrupted mitochondrial membrane potential, upregulated expression of the mitochondrial apoptotic marker, BAX, increased caspase-3 activation, and reduced cell viability. Pridopidine significantly attenuated tunicamycin-induced BiP and CHOP expression in a biphasic, dose-dependent manner (with maximal efficacy at 1 µM), consistent with the typical pharmacology of S1R agonists. Pridopidine restored mitochondrial membrane potential, reduced mitochondrial apoptotic signaling, shown by decreased BAX expression and caspase-3 activation, and improved survival of ALS-NPCs under ER stress. Co-treatment with the selective S1R antagonist, NE-100, attenuated these effects, supporting an S1R-mediated mechanism of action for pridopidine. Together, these results demonstrate that S1R activation by pridopidine mitigates ER-stress-induced mitochondrial dysfunction and cell loss in ALS-NPCs, resulting in enhanced survival of NPCs supporting the therapeutic potential of pridopidine in ALS. Full article

Background: Neuropathic pain remains a major unmet clinical challenge. Growing evidence identifies sigma receptors (σRs) as pivotal intracellular modulators of maladaptive stress signaling, positioning them as promising non-opioid targets for chronic pain management. Notably, despite the pleiotropic nature of σRs in regulating diverse cellular pathways—which might theoretically suggest a high risk of off-target effects—current selective antagonists have demonstrated remarkable safety and tolerability profiles. Sigma-1 and sigma-2 receptors (σ1R and σ2R) are molecularly and functionally distinct proteins that regulate neuronal excitability, proteostasis, and neuroimmune communication, all mechanisms that characterize neuronal excitability and cellular stress adaptation. σ1R acts as a ligand-operated molecular chaperone at the mitochondria-associated endoplasmic reticulum membrane. Extensive preclinical data demonstrate that σ1R antagonism attenuates peripheral and central sensitization, suppresses neuroinflammation, and restores opioid analgesic efficacy. These findings are supported by the advanced clinical candidate E-52862, which has shown efficacy and a favorable safety profile in neuropathic pain conditions. σ2R, identified as transmembrane protein 97 (σ2R/TMEM97), functions as a regulator of cholesterol trafficking, lysosomal integrity, and integrated stress response (ISR). σ2R modulation alleviates neuropathic pain by restoring proteostatic balance and reducing ISR-driven neuronal vulnerability rather than directly suppressing excitability. Emerging σ2R ligands such as FEM-1689, UKH-1114, and CM-398 provide compelling proof-of-concept for durable, disease-modifying analgesia. Methods: A structured literature search was conducted using PubMed, Scopus, and Web of Science to identify studies published within the last decade describing σ1R and σ2R/TMEM97 biology, ligand development, and their preclinical or clinical evaluation in neuropathic pain. Reference lists were manually screened to ensure comprehensive coverage. Conclusions: This review synthesizes pharmacology, ligand development, and translational evidence supporting σRs as next-generation targets for neuropathic pain therapy, highlighting convergent roles of σ1R and σ2R in pain chronification and outlining future directions for structure-guided therapeutic strategies. Full article

Background/Objectives: Diabetes mellitus (DM) is associated with a doubled prevalence of elevated intraocular pressure (IOP) caused by trabecular meshwork (TM) dysfunction. Chronic hyperglycaemia leads to oxidative stress and fibrotic remodeling of the TM. We previously identified the Sigma-1 receptor (S1R) as a novel anti-fibrotic target by demonstrating that its agonist, fluvoxamine (FLU), is protective in diabetes-related renal fibrosis. Here, we investigate its potential to mitigate ocular fibrosis. Methods: First, we wanted to verify in different in vivo models (high-fat diet/streptozotocin (HFD/STZ) rats, db/db mice) that type 2 DM (T2DM) leads to fibrotic remodeling of the TM. Then, in vitro, we assessed the effect of FLU (15 µM) on hyperglycaemia-induced (HG, 25 µM) fibrosis, oxidative stress and endogenous nitric oxide (NO) production. Results: In T2DM models, excessive accumulation of collagen, α-smooth muscle actin (αSMA), fibronectin (Fn) and F-actin was observed in the eyes. Ocular fibrosis was accompanied by IOP elevation (13.7 vs. 18.7 mmHg) in db/db mice. In human TM cells (HTM5), FLU decreased HG-induced cell proliferation (14% vs. 24%) and upregulated S1R protein expression. Furthermore, FLU suppressed the expressions of key fibrotic elements, including transforming growth factor-β2 (TGF-β2) by 37%, Fn by 49%, collagen type 1 (COL1A1) and type 4 (COL4A1) by 24% and 45%, respectively. FLU also reversed HG-induced F-actin accumulation by 39% and enhanced intracellular NO levels by 34%. Crucially, FLU decreased ROS generation by half, demonstrating its protective effect against HG-induced oxidative stress. Conclusions: These findings highlight the potential of S1R activation as a promising therapeutic target to alleviate hyperglycaemia-induced injury to the TM by modulating multiple molecular pathways. Full article

Bacillus anthracis displays susceptibility to penicillin despite harboring a β-lactamase gene, a phenotype governed by the anti-sigma factor RsiP. While RsiP represses σ^P-dependent β-lactamase expression, its broader roles in physiology and virulence remain unclear. This study aimed to define the global regulatory functions of RsiP beyond antibiotic resistance. Deletion of rsiP significantly upregulated the nprR gene, which is an important quorum-sensing (QS) system regulator and enhanced protease secretion. The ΔrsiP mutant caused higher mortality in cellular and Galleria mellonella models and triggered elevated inflammatory cytokines (IL-6, IL-1β, TNF-α, MIP-2) in macrophages models. Surprisingly, in DBA/2 mice models, ΔrsiP was attenuated, with increased host survival and reduced bacterial loads. Competitive indices (CI) confirmed fitness defects in mice (spleen CI = 0.39; liver CI = 0.42). These defects were not due to altered oxidative stress tolerance but were attributed to impaired macrophage internalization of ΔrsiP spores, reducing early colonization. Our findings indicate that RsiP not only modulates β-lactam resistance but also influences extracellular protease activity and host adaptation. Full article

Background/Objectives: Diabetes is major metabolic disorder and rapidly increasing public health problem globally. The greatest way to reduce diabetic complications is adequate knowledge about the condition. Hence, the primary objectives of this study were to evaluate the psychometric properties of the Simplified Diabetes Knowledge Test—Arabic version (SDKT-A) among Iraqi insulin-dependent diabetic patients. Additionally, the secondary objectives were to assess the associated independent variables and the risk of atherosclerosis and cardiovascular risk event by using atherogenic indices and lipid ratios with the SDKT-A. Methods: A cross-sectional, descriptive study was conducted in primary healthcare clinics. The SDKT was translated into Arabic using forward–backward translation, reconciliation, and pilot testing. Thereafter, psychometric properties of the SDKT-A were evaluated depending on different criteria. Atherogenic indices of Castelli risk indices I and II (CRI-I and II), triglyceride/HDL ratio, non-HDL-C ratio, atherogenic coefficient (AC), and triglyceride–total cholesterol–body weight index (TCBI) were calculated using specific formulas. Results: The SDKT-A questionnaire showed acceptable readability and validity. Cronbach’s alpha test (95% confidence interval) was 0.662 (0.59–0.73). The Pearson correlation coefficient of reliability for test–retest was found to be 0.659. The item difficulty index for most items was between 0.237 and 0.877. The point biserial correlation values ranged from 0.028 to 0.535 with Ferguson’s sigma value equal to 0.962. The content validation results showed a significant content validity ratio (CVR) value for most of the questions, ranging from 0.8 to 1. The content validity index (CVI) value for SDKT-A was found to be 0.98, which showed good agreement between experts. In addition, the exploratory factor analysis with promax rotation identified four domains for the final 20 items of the SDKT-A that explained 41.83% of the scale total variance. The mean score of the SDKT-A was 11.09 ± 3.40. The total score of the SDKT-A was positively and significantly correlated with education level (r = 0.322, p < 0.01). In addition, the total scores of the SDKT-A were negatively and significantly correlated with glycemic control, age, CRI-I, CRI-II, triglyceride/HDL ratio, AC, non-HDL-C ratio, and TCBI. Furthermore, the glycemic control (HbA1c) was positively and significantly correlated with the preventive measures factor (r = 0.175, p < 0.05), and were negatively and significantly correlated with the lifestyle and modification factor (r = −0.169, p < 0.05), diet and monitoring factor (r = −0.158, p < 0.05), and awareness factor (r = −0.149, p < 0.05). Conclusions: This study showed acceptable psychometric properties for the SDKT-A, with low levels of knowledge of diabetic disease in the sample population. Finally, comprehensive and interactive educational programs regarding lifestyle and modification, diet, and monitoring and awareness in primary healthcare centers in Iraq are warranted. Full article

This study assesses the innovation performance and convergence dynamics across 237 European regions (NUTS 2 level) from 2016 to 2023, explicitly accounting for the structural and behavioural changes triggered by the COVID-19 pandemic. The article provides a novel regional-level assessment of how an unprecedented external shock reshaped innovation trajectories before and after the pandemic. To this end, the analysis combines Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), sigma-convergence measures, and a Difference-in-Differences (DiD) framework within an integrated multi-method empirical approach to evaluate shifts in regional innovation patterns over time. The results reveal a highly uneven distribution of innovation activities, with increasing polarization in the post-pandemic period. Northern and Western European regions strengthened their competitive advantage through robust digital infrastructure, strong human capital, and substantial R&D investments. In contrast, many Southern and Eastern European regions faced heightened structural barriers, leading to a widening innovation gap. Nevertheless, several regions exhibited notable resilience and achieved significant innovation catch-up, providing new empirical evidence on heterogeneous regional adaptive dynamics supported by targeted regional policies and improved local capabilities. The sigma-convergence analysis indicates a general increase in overall disparities, as reflected by rising dispersion in the Regional Innovation Index (RII) during 2020–2023. However, according to the DiD estimation, regions most severely affected by COVID-19 experienced a statistically significant relative increase (approximately 2.17%) in innovation performance, highlighting the pandemic’s role as a catalyst for accelerated digital transformation and innovation adjustment at the regional level. Full article

Visual search behavior, influenced by expertise, prior knowledge, training, and visual fatigue, is crucial in ophthalmic diagnostics. This study investigates differences in eye-tracking strategies between novice and experienced eye care practitioners during fundus image interpretation. Forty-seven participants, including 37 novices (first- to fourth-year optometry students) and 10 experienced optometrists (≥2 years of experience), viewed 20 fundus images (10 normal, 10 abnormal) while their eye movements were recorded using an Eyelink1000 Plus gaze tracker (2000 Hz). Diagnostic and laterality accuracy were assessed, and statistical analyses were conducted using Sigma Plot 12.0. Results showed that experienced practitioners had significantly higher diagnostic accuracy (83 ± 6.3%) than novices (70 ± 12.9%, p < 0.005). Significant differences in oculomotor behavior were observed, including median latency (p < 0.001), while no significant differences were found in median peak velocity (p = 0.11) or laterality accuracy (p = 0.97). Diagnostic accuracy correlated with fixation count in novices (r = 0.54, p < 0.001), while laterality accuracy correlated with total dwelling time (r = −0.62, p < 0.005). The experienced practitioners demonstrated systematic and focused visual search patterns, whereas the novices exhibited unorganized scan paths. Enhancing training with visual feedback could improve fundus image analysis accuracy in novice clinicians. Full article

Background: Chemokine CCL5 may drive inflammation and vascular risk in advanced liver disease, but its cardiovascular implications are unclear. Secreted by hepatic, endothelial, macrophage, and lymphocytic cells, CCL5 is involved in cytokine regulation. Its serum levels rise in acute liver injury and hepatocellular carcinoma (HCC), but decline with fibrosis progression in end-stage liver disease (ESLD). CCL5 has also been linked to atherosclerosis. This study aimed to evaluate serum CCL5 levels in ESLD patients listed for liver transplantation (LT) and to assess their potential role as markers of cardiovascular (CV) risk and portal hypertension. Methods: We conducted an observational cohort study. Between 2019 and 2022, patients with ESLD evaluated for LT were enrolled. Data on liver pathology, CV risk, and laboratory parameters were collected. Serum CCL5 concentrations were measured using Sigma Aldrich^® CCL5 ELISA kits (MilliporeSigma, St. Louis, MO, USA). The database was analyzed with IBM^® SPSS^® Statistics version 20 (Chicago, IL, USA). Results: Overall, 46 patients were included, 50% with viral hepatitis and 28.3% with alcohol-related liver disease. HCC was present in 37% of cases. The median CV risk scores (CAD_LT = 7, mCAD_LT = 7, CAR_OLT = 18) placed the population at moderate CV risk. Serum CCL5 levels did not vary significantly between viral vs. non-viral cirrhosis (5511.8 vs. 6272.5 pg/mL, p = 0.15) and were not influenced by the presence of HCC (6098.4 vs. 5771.3 pg/mL, p = 0.55). We did not detect a correlation with MELD score (p = 0.21) or CV risk scores (CAD_LT: p = 0.58; mCAD_LT: p = 0.70; CAR_OLT: p = 0.22). Patients with thrombocytopenia (<100,000/µL, 54.3%) or a history of esophageal variceal ligation had lower CCL5 levels (5170.9 vs. 6750.8 pg/mL, p = 0.002 and 4252.0 vs. 6237.5 pg/mL, p = 0.003, respectively). Similarly, patients with a history of previous variceal bleeding and spontaneous bacterial peritonitis (SBP) had lower levels of CCL5 (4373.8 vs. 6119.9 pg/mL, p = 0.02 and 3404.3 vs. 6606.7 pg/mL, p = 0.01, respectively). We found a negative correlation between CCL5 and QTc interval duration (τ = −0.216, p = 0.037), left ventricle size (LV: τ = −0.235, p = 0.027), and pulmonary artery pressure (RV/RA gradient: τ = −0.225, p = 0.03). CCL5 correlated positively with the inflammatory markers C-reactive protein (CRP) (τ = 0.246, p = 0.018) and fibrinogen (r = 0.216, p = 0.04). Conclusions: In liver transplant candidates, serum CCL5 is not associated with cardiovascular risk scores or coronary atherosclerotic burden, but is inversely associated with clinical markers of portal hypertension severity. These findings suggest that CCL5 may serve as a potential non-invasive surrogate marker of portal hypertension rather than a cardiovascular risk biomarker in ESLD. Full article