Search Results (4,001)

In this article, we present a new approximate solution for blood nanofluid having gold nanoparticles as it flows near a stretching porous cylinder in fractal space. A Casson non-Newtonian magneto-bio-nanofluid flowing through a porous medium is considered a potential application in chemotherapy for eradicating cancer cells. Without the need for the nonperturbative approach, the proposed solution uses an alternative approach to dealing with nonlinear problems. This approach transforms the nonlinear cubic jerk model resulting from the simplification of the governing fractional partial differential equations into an equivalent linear formula. This approach is known as highly efficient linear approximation (HELA) or non-perturbation technique (NPT), and this represents a significant advancement over traditional perturbation methods in the analysis of non-linear systems. As a robust mathematical approach, it excels at handling a wide range of coefficient values, particularly in cases of clear nonlinearity. This study also utilized the masking technique simultaneously with HELA, which played a crucial role, as they simplify the complex dynamics of the system, making it more amenable to analysis. The numerical solution by the Runge–Kutta fourth-order (RK-4) method integrated with a shooting technique compared favorably with graphs drawn for the analytical solution from the proposed strategy HELA. The current results show that an increase in the fractal factors enhances the resistance to fluid motion, leading to a suppression of the velocity field. Physically, this often relates to the complexity of the medium or the fractal nature of the transport process, where higher fractal dimensions or factors can lead to slower diffusion or flow rates, like the role of porous media. Therefore, the current study has significant implications in the promotion of nanotechnology fields in medicine, particularly the use of gold nanoparticles in chemotherapy for the eradication of cancerous cells. Full article

Myasthenia gravis (MG) is a rare autoimmune disorder characterized by muscle weakness and fatigue, caused by autoantibodies produced by B-cells that target proteins in the postsynaptic membrane of the neuromuscular junction. Clinical manifestations are heterogeneous and may include diplopia, ptosis, dysarthria, dysphagia, and limb muscle weakness, with severity ranging from mild symptoms to life-threatening myasthenic crisis. Despite advances in diagnostic approaches and the availability of immunomodulatory and biological therapies, there remains a need for an improved understanding of the disease mechanisms and biomarker development in MG. Blood-derived exosomes are small extracellular vesicles that carry proteins, lipids, nucleic acids, and glycoconjugates, and are involved in intercellular communication and the transfer of biological material between cells. Circulating exosomes may reflect aspects of cellular and immune status and have been proposed as a minimally invasive source of biomarkers in various diseases. In this review, we summarize current evidence on the potential role of exosomes in MG, with a focus on their involvement in disease-associated processes and their possible utility as biomarkers, as well as directions for future research. Full article

In heart failure (HF), elevated blood lactate levels, particularly during exercise or in advanced disease stages, reflect impaired tissue perfusion and altered metabolic regulation. Beyond its traditional role as a marker of anaerobic metabolism, lactate has emerged as a dynamic indicator of metabolic reserve and ventilatory control. This narrative review summarizes current evidence on lactate dynamics at rest and during exercise, highlighting their pathophysiological and clinical relevance. In HF patients, exercise-induced lactate accumulation occurs earlier and at lower workloads, reflecting impaired oxidative capacity and reduced peripheral oxygen utilization. This phenomenon is closely associated with ventilatory inefficiency, as demonstrated by the relationship between lactate levels and the VE/VCO₂ slope during cardiopulmonary exercise testing (CPET). Emerging data suggest that lactate is not only a marker of disease severity but also a potential mediator of chemoreflex activation and abnormal ventilatory responses. Furthermore, both pharmacologic and non-pharmacologic interventions may influence lactate production and utilization, supporting its role as a potential tool for therapeutic monitoring. Overall, the integration of lactate assessment, particularly during exercise, into clinical evaluation may provide additional insight into disease mechanisms, improve risk stratification, and contribute to personalized therapeutic optimization in patients with HF. Full article

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation and oxidative stress, increasingly implicated in cancer biology. However, its molecular regulation across breast cancer subtypes and its potential systemic manifestations remain incompletely understood. The aim of this study was to identify ferroptosis-associated molecular alterations that are largely shared across subtypes and to evaluate their systemic reflection following localized tissue injury. Tumor and matched normal breast tissues representing major molecular subtypes were analyzed. Global mRNA and miRNA expression profiling was performed using microarrays, followed by validation of selected genes using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Functional enrichment and protein–protein interaction analyses were conducted to characterize associated pathways. In addition, systemic responses were assessed in patients undergoing fibroadenoma cryoablation through longitudinal blood sampling. Six ferroptosis-related genes (SLC7A11, GPX4, FTH1, NQO1, NFE2L2, SQSTM1) demonstrated consistent upregulation across all breast cancer subtypes, with higher expression observed in more aggressive tumors. These genes are functionally linked to antioxidant defense, iron metabolism, and oxidative stress regulation, and their coordinated expression pattern is consistent with activation of NRF2-dependent cytoprotective pathways. Downregulation of selected miRNAs may contribute to this expression profile but likely represents a secondary regulatory mechanism. Survival analysis revealed heterogeneous and subtype-dependent associations, with limited and gene-specific prognostic relevance. Cryoablation induced transient increases in circulating levels of the analyzed proteins, reflecting systemic responses to localized tissue injury. In conclusion, breast cancer is characterized by a largely shared ferroptosis-associated molecular signature across subtypes; however, its clinical impact appears to be variable and context-dependent. Systemic detection of related molecular signals suggests potential utility as indicators of tissue stress responses, although their role as specific biomarkers of ferroptosis requires further validation. Full article

Non-invasive assessment of oocyte quality remains a challenge in assisted reproductive technology (ART). Through their bidirectional communication with the gamete, cumulus cells (CCs) act as a functional mirror of oocyte competence; however, the specific angiogenic signature within this microenvironment is still poorly understood. In the present study, we performed RNA-seq on CCs from healthy oocyte donors and infertile patients, utilizing a multi-pipeline bioinformatic approach (STAR-Cufflinks, TopHat-HTSeq, and HISAT2-StringTie) to establish a high-confidence, exploratory transcriptomic profile. A set of 234 differentially expressed genes (DEGs) consistently identified across pipelines was obtained, with functional enrichment highlighting blood vessel morphogenesis and angiogenesis as primary drivers of transcriptomic divergence between groups. RT-qPCR validation in individual samples confirmed statistically significant differences for ANKRD22 (upregulated) and E2F7 (downregulated) in infertile patients, while other angiogenesis-related genes, including ANGPT1, ANGPT2 and THBS1, showed consistent but non-significant expression trends, suggesting alterations in angiogenesis-related processes within the follicular microenvironment. These findings support the presence of coordinated angiogenesis-related alterations in cumulus cells and provide a basis for future studies exploring their potential relevance in oocyte competence and ART outcomes. Full article

Background/Objective: The identification of novel non-invasive diagnostic and prognostic biomarkers is urgently needed in pleural mesothelioma (PM). While soluble mesothelin-related peptides (SMRP) are the most established circulating biomarker, their prognostic value is limited. A wide range of microRNAs (miRs) play diverse roles in regulating gene expression in PM. MiR-21 has been shown to be upregulated in mesothelioma tissue; nevertheless, the diagnostic and prognostic utility of miR-21 in the circulation and its association with survival in PM have not been extensively investigated to date. The objective of the current study was to evaluate miR-21 as a potential blood-based diagnostic and prognostic biomarker in PM. Methods: Plasma samples from PM patients (n = 94) were collected at the time of diagnosis, prior to treatment. Sex- and age-matched healthy individuals (n = 30) served as controls. MiR-21 levels were measured using quantitative RT-PCR and normalized to miR-16, and potential correlations with clinicopathological data were analyzed. Serum SMRP levels were measured in matched patients (n = 84), and a direct comparative analysis of miR-21 and SMRP was conducted. In situ hybridization (ISH) was used to confirm the presence of miR-21 in tumor cells. Results: Plasma miR-21 levels were significantly elevated in PM patients compared to healthy controls (p < 0.001), demonstrating good diagnostic performance (AUC 0.81). The localization of miR-21 in PM cells was confirmed by ISH. High miR-21 levels were associated with significantly shorter median overall survival (12.4 vs. 24.3 months, p < 0.001). Elevated SMRP levels were also associated with reduced survival (12.4 vs. 19.5 months, p = 0.032); however, SMRP did not retain independent prognostic significance in multivariable analysis. In contrast, high-circulating miR-21 was confirmed as an independent predictor for poor survival (HR 3.12, p < 0.001). Conclusions: Our findings highlight that circulating miR-21 is a potential non-invasive biomarker with both diagnostic and independent prognostic value in pleural mesothelioma and outperforms SMRP in multivariable survival analysis. Further research is warranted to validate its role in the biology of this disease and to assess its correlation with outcome and treatment responses. Full article

Acute Lymphoblastic Leukemia (ALL) is a highly prevalent hematological malignancy, especially in children, for whom precise and prompt subtype identification is essential to establish suitable treatment protocols. Current deep learning-based computer-aided diagnosis (CAD) methods for identifying ALL are hindered by numerous drawbacks, such as a dependence on solely spatial feature depictions, elevated feature dimensions, computationally extensive deep learning architectures, inadequate multi-layer feature utilization, and poor interpretability. This paper introduces LUMINA-Net, a custom, lightweight, and interpretable deep learning CAD for the automated identification and subtype diagnosis of ALL using microscopic blood smear pictures. LUMINA-Net makes four principal contributions: first, it integrates a self-attention module within a lightweight custom Convolution Neural Network (CNN) to effectively capture long-range spatial relationships across clinically pertinent cytological patterns while preserving a compact design. Second, it employs a Discrete Wavelet Transform (DWT)-based wavelet pooling layer that decreases feature dimensions by up to 96.875% while enhancing the obtained depictions with spatial-spectral information. Third, it utilizes a multi-layer feature fusion strategy that combines wavelet-pooled features from two deep layers with a third fully connected layer to create a discriminating multi-scale feature vector. Fourth, it incorporates Gradient-weighted Class Activation Mapping as a dedicated explainability process to furnish clinicians with apparent visual explanations for each classification decision. Withoit the need for image enhancement or segmentation preprocessing, LUMINA-Net outperforms the competing state-of-the-art methods on the same dataset, achieving a peak accuracy of 99.51%, specificity of 99.84%, and sensitivity of 99.51% on the publicly available Kaggle ALL dataset. This demonstrates that LUMINA-Net has the potential to be a dependable, effective, and clinically interpretable CAD tool for ALL diagnosis. Full article

Background: Hyperparathyroidism is a common endocrine disorder, and its diagnosis can be complex. Various indices based on blood biomarkers have been proposed to improve diagnostic accuracy. The objective of this systematic review was to analyze the diagnostic utility of different indices in primary hyperparathyroidism. Methods: A systematic review was performed with searches up to January 2026. Risk of bias was assessed, and a meta-analysis was conducted for indices with two or more studies, calculating sensitivity, specificity, and other accuracy measures. The certainty of the evidence was evaluated using the GRADE system. Results: Twelve studies were included. The calcium–phosphorus ratio demonstrated a sensitivity of 91.6%, specificity of 89.3%, and an area under the curve of 0.957. The parathyroid function index showed a sensitivity of 94.4% and specificity of 94.2%; however, this finding is based on only two studies and requires validation in larger cohorts. The Wisconsin index also showed good performance. Other indices, including the Ca × Cl/P ratio (evaluated in a single study), yielded promising results but with very limited evidence that precludes firm conclusions. All indices performed poorly in cases with normal calcium. Certainty assessment indicated moderate evidence for the main indices and low or very low evidence for the others. Conclusions: The calcium–phosphorus ratio and the parathyroid function index are valid and useful tools for the diagnosis of primary hyperparathyroidism, with excellent performance. The calcium–phosphorus ratio is especially valuable due to its simplicity and accessibility for screening. No index should be used in isolation; integration with clinical evaluation remains essential. Full article

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has revealed a complex interplay between respiratory and neurological manifestations. This study utilized K18-hACE2 transgenic mice to investigate the morphological, ultrastructural, and transcriptomic changes induced by SARS-CoV-2 infection in both lungs and brain tissues. Histopathological analysis at seven days post-infection revealed significant pulmonary damage characterized by interstitial pneumonia, alveolar septal thickening, with a marked inflammatory infiltrate predominantly consisting of neutrophils and lymphocytes, and an abnormal profile of type II pneumocytes. Concurrently, in the brain, we observed vasculitis, gliosis, and edema, indicating an inflammatory response and vascular compromise that can disturb the blood–brain barrier. In addition, gene expression in lung tissue presented increased CCL2, IL10, and GDDA45D in infected mice and the downregulation of proinflammatory genes. However, in brain tissue, the increased expression of CCL2, CASP1, IL6, IFNB1, and GDDA45G inflammatory genes was observed in infected K18-hACE2 mice. Full article

This exploratory study evaluated plasma atrial natriuretic peptide (ANP) concentrations in four species of captive cetaceans and their associations with physiological and environmental factors, including husbandry conditions, diet, and management practices. Twenty-six individuals were voluntarily sampled, and blood samples were analyzed using a human-based chemiluminescent immunoassay. Transthoracic echocardiography was also attempted in several individuals but was technically challenging due to interference from the lung tissue and the sternum. The mean plasma ANP concentration in clinically healthy young animals was 44.12 ± 14.62 pg/mL, with no significant differences observed according to age, sex, species, or the presence of mild chronic disease. ANP was detectable across all species using human reagents. In addition, brain natriuretic peptide (BNP), a commonly used cardiac biomarker in humans and other animals, was evaluated for comparison; however, BNP concentrations remained below the detection threshold, possibly reflecting species-specific differences. Importantly, ANP concentrations were not evaluated in animals with clinically significant disease, and therefore the relevance of these findings to diseased populations remains unknown. These results demonstrate that plasma ANP can be measured using existing clinical assays and provide preliminary baseline data for multiple cetacean species. Overall, ANP may offer preliminary insights into physiological variation in managed cetaceans; however, its utility as a biomarker for cardiovascular or systemic health assessment remains to be determined. Full article

Background: Early vascular aging (EVA) is a common complication of type 2 diabetes mellitus. Early identification is crucial in middle-aged individuals with T2DM, as vascular stiffness can occur gradually for years before cardiovascular disease. However, EVA is rarely considered in routine care. Adropin is a vasoprotective peptide that may counter-regulate endothelin-1 (ET-1). Therefore, this study aims to examine the association between circulating adropin, ET-1, oxLDL, MMP-2, VEGFA, and EVA. Methods: This observational study included 300 adults aged 25–55 years (150 T2DM; 150 age/sex-matched controls). ePWV was calculated from age and mean blood pressure. EVA was classified using a residual-based, age-specific ePWV threshold derived from controls. Associations were tested using correlation and logistic regression. ROC and decision curve analyses were performed to evaluate diagnostic performance and clinical utility. Results: EVA prevalence was 38.6% overall, occurring in 7.3% of controls and increasing across T2DM with good and poor glycemic control (56.1% and 80.95%, respectively, p < 0.001). Compared with normal vascular aging, EVA showed lower adropin and higher ET-1, oxLDL and MMP-2, with lower VEGFA (all p < 0.05). In fully adjusted models, adropin (OR 0.991 per pg/mL; p < 0.001) and ET-1 (OR 1.017 per pg/mL, p = 0.005) remained independently associated with EVA. A combined adropin + ET-1 predictor improved discrimination (AUC 0.901, 95% CI 0.868–0.934), at a predicted-probability cutoff of 0.607, 78.7% sensitivity and 87.0% specificity. Conclusions: In middle-aged T2DM, EVA was associated with lower adropin and higher ET-1 in T2DM. These findings support an association between these biomarkers and the EVA phenotype. Full article

Background: Metal elements have been reported to be associated with Alzheimer’s disease (AD). The available epidemiological evidence for these associations is often inconsistent and prone to confounding and reverse causation. We aimed to explore the causal effects of varying metal element levels on AD and investigate potential underlying mechanisms. Methods: To investigate the causal link between multiple metals and AD risk, we employed a bidirectional two-sample Mendelian randomization (TSMR) approach and used single nucleotide polymorphisms (SNPs) as instrumental variables. And the participants were extracted from large GWAS databases in the European Cohort. Our analysis primarily utilized methods including inverse variance weighted (IVW), weighted median, and MR-Egger, and used sensitivity analyses to assess pleiotropy and heterogeneity. To verify the mechanism, we further used the metal element-related genes and disease-related genes to construct a protein–protein interaction (PPI) network. Results: The IVW method results from Mendelian randomization (MR) analysis showed that blood zinc was negatively associated with AD risk (OR = 0.96, 95%CI: 0.93–0.99, p = 0.016) in the forward MR analysis, whereas AD was negatively associated with serum transferrin levels (OR = 0.89, 95%CI: 0.81–0.98, p = 0.015) in the reverse MR analysis in Europeans, which was adjusted for BMI, smoking, education, and coffee intake. However, no causal links were found between blood Cu, Mg, Se, and other iron states in serum and AD risk in Europeans. The PPI network suggested that SLC39A1 played a key role in the zinc–AD relationship, and transferrin might interact with ALB, LTF, HFE, TFRC, TF, and SLC40A1 in the context of AD. Conclusions: Our TSMR study suggested that in European populations, higher blood zinc levels might exert a protective effect against AD, whereas pathology of might lead to decreased serum transferrin levels. These findings provided evidence for metal dysregulation in AD, though further validation through randomized controlled trials is required. Full article

This study proposes an improved retinal blood vessel segmentation method to enhance the diagnosis of microvascular retinal complications. The proposed method extracts local shape features from retinal images utilizing a fractional Hessian matrix, which models blood vessels as surface structures characterized by ridges and valleys resulting from variations in curvature. The methodology integrates adaptive principal curvature estimation with a new framework leveraging the fractional Hessian matrix with nonsingular and nonlocal kernels. The effectiveness of the suggested method is assessed using publicly accessible datasets, including DRIVE, HRF, STARE, and some real images obtained from a local hospital. The proposed segmentation achieves 96.77% accuracy and 98.82% specificity on the DRIVE database, 96.91% accuracy and 98.69% specificity on STARE, and 95.90% accuracy and 98.36% specificity on the HRF database. Optimal parameters for the fractional order and Gaussian standard deviation were empirically determined by maximizing segmentation accuracy. Our findings show that the proposed approach achieves competitive performance compared to the listed methods, including several deep learning approaches, while maintaining significant computational efficiency. The output of the suggested method can be further utilized with deep learning techniques, which will be applied in the clinical context of diabetic retinopathy and glaucoma to identify abnormalities likely related to disease progression and different stages. Full article

Background: As life expectancy increases, more elderly patients require a pancreaticoduodenectomy (PD). While minimally invasive approaches are preferred, data indicating the safety of robotic PD in elderly patients remains limited. This study compares operative outcomes of robotic PD in elderly versus younger patients to define its oncological role. Material and Methods: A systematic search of PubMed, Embase, Web of Science, and Scopus identified studies comparing robotic pancreaticoduodenectomy in elderly versus younger patients. Robotic-exclusive cohorts were analyzed for perioperative outcomes, complications, and mortality. A meta-analysis was performed using R to calculate pooled prevalences, Odds Ratios (ORs) and Weighted Mean Differences (WMDs). Results: Elderly patients experienced significantly longer operative times (MD = 11.4 min) and hospital stays (MD = 7.76 days). They demonstrated higher odds of severe complications (Clavien–Dindo ≥ III: OR = 2.20), delayed gastric emptying (DGE) (OR = 2.34), and mortality (OR = 3.42). There were no significant differences in blood loss, transfusions, overall complications, pancreatic fistulae, bile leakage, hemorrhage, infection, readmission, or reoperation. Notably, age-stratified subgroup analyses revealed a distinct risk divergence: studies using an 80-year cutoff reported significantly higher odds of mortality and DGE, whereas 70-year-threshold studies demonstrated more pronounced odds for severe and overall complications. Conclusions: While robotic pancreaticoduodenectomy is feasible in elderly patients with comparable intraoperative blood loss and overall complication rates to younger patients, it does not eliminate all age-related risks. Elderly patients remain at significantly higher risk for severe complications and mortality. Therefore, robotic application in this demographic requires rigorous preoperative assessment, utilizing age as an initial risk-stratifier while allowing physiological reserve to determine final surgical candidacy. Full article

Intracranial atherosclerosis (ICAS) is a distinct, inflammation-dominant vasculopathy and a leading cause of global stroke morbidity. Unlike extracranial atherosclerosis (ECAS), which often utilizes compensatory positive remodeling to maintain patency, ICAS is characterized by a unique architecture and a localized antioxidant gap that favor maladaptive negative remodeling. We critically analyze the molecular cascade initiated by the breakdown of the Piezo-type mechanosensitive ion channel component 1 (PIEZO1) and the Krüppel-like factor 2/4 (KLF2/4) mechanotransduction axis, which triggers endothelial nitric oxide synthase (eNOS) uncoupling and establishes a state of chronic inflammation. This environment facilitates the subendothelial lipid retention of oxidized low-density lipoprotein (oxLDL), a process exacerbated by the intracranial deficiency of Apolipoprotein A-I (ApoA-I) and impaired glymphatic clearance. Crucially, we evaluate how these metabolic and mechanical insults drive vascular smooth muscle cell (VSMC) phenotypic switching; the transdifferentiation of contractile VSMCs into macrophage-like foam cells accounts for up to 60% of the plaque’s lipid-laden pool and destabilizes the fibrous cap. This vascular failure directly compromises the neurovascular unit (NVU), leading to pericyte dropout and blood–brain barrier breakdown. Beyond environmental stressors, we highlight the ring finger protein 213 (RNF213) variant as a critical genetic determinant of this susceptibility. Shifting the clinical paradigm from simple luminal narrowing toward the identification of the vulnerable plaque, we discuss how High-Resolution Vessel Wall Imaging (HR-VWI) and microRNA biomarkers can identify unstable lesions. By integrating these molecular and imaging signatures, we propose a precision medicine framework centered on the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the NVU to effectively mitigate the high residual recurrence risk that persists under conventional therapy. Full article