Search Results (1,369)

Background and Objectives: Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. An early and accurate diagnosis is essential for effective clinical management and risk stratification. Recent advances in machine learning (ML) have provided opportunities to enhance the diagnostic performance by integrating multidimensional patient data. This study aimed to develop and compare several supervised ML algorithms for early CAD diagnosis using demographic, anthropometric, biochemical, and psychosocial parameters. Materials and Methods: A total of 300 adult patients (165 CAD-positive and 135 controls) were retrospectively analyzed using a dataset comprising 21 biochemical markers, body composition metrics, and self-reported eating behavior scores. Six ML algorithms, k-nearest neighbors (k-NNs), support vector machines (SVMs), artificial neural networks (ANNs), logistic regression (LR), naïve Bayes (NB), and decision trees (DTs), were trained and evaluated using 10-fold cross-validation. Model performance was assessed based on accuracy, sensitivity, false-negative rate, and area under the Receiver Operating Characteristic (ROC) curve (AUC). Results: The k-NN model achieved the highest performance, with 98.33% accuracy and an AUC of 0.99, followed by SVM (96.67%, AUC = 0.95) and ANN (95.33%, AUC = 0.98). Patients with CAD exhibited significantly higher levels of glucose, triglycerides (TGs), LDL cholesterol (LDL-C), and abdominal obesity, while vitamin B12 levels were lower (p < 0.001). Although emotional and mindful eating scores differed significantly between the groups, their contribution to model performance was limited. Conclusions: Machine learning models, particularly k-NN, SVM, and ANN, have demonstrated high accuracy in distinguishing CAD patients from healthy controls when applied to a diverse set of clinical and behavioral variables. This study highlights the potential of integrating psychosocial and clinical data to enhance CAD prediction models beyond traditional biomarkers. Full article

Metabolic bariatric surgery (MBS) induces substantial metabolic, inflammatory, and nutritional changes that can alter hemostatic balance through redox-dependent mechanisms. This systematic review evaluated coagulation disturbances after MBS with emphasis on oxidative stress and micronutrient deficiencies. A structured search of PubMed, Scopus, and Web of Science (2000–2025) identified 1707 records; 21 studies met inclusion criteria. Available evidence suggests that although MBS reduces obesity-related inflammation and oxidative burden in many patients, a proportion of individuals may present with persistent redox imbalance, elevated D-dimer or vWF (von Willebrand Factor), and delayed normalization of fibrinolysis. Micronutrient deficiencies—particularly vitamins K, B12, folate, selenium, zinc, and copper—are common after malabsorptive procedures and contribute to both thrombotic and hemorrhagic complications by impairing antioxidant defenses, endothelial function, and vitamin K-dependent coagulation pathways. Postoperative venous thromboembolism (VTE) incidence ranges from 0.3 to 0.5%, with higher risk after Roux-en-Y gastric bypass than sleeve gastrectomy, while bleeding is primarily associated with vitamin K deficiency, marginal ulcers, and anticoagulant exposure. The findings underscore the interdependence of oxidative stress, nutritional status, and hemostasis after MBS. Individualized thromboprophylaxis, routine detection of micronutrient deficiencies, and long-term biochemical monitoring are essential to maintain hemostatic stability. Standardized redox–hemostasis biomarker panels are needed to clarify mechanistic pathways and improve postoperative preventive strategies. Full article

Pulmonary embolism (PE) is one of the most serious complications of antiphospholipid syndrome (APS), a systemic autoimmune disorder defined by thrombotic events and persistent antiphospholipid antibodies (aPLA). PE occurs in 11–20% of patients and may constitute the initial clinical manifestation. Young and middle-aged women are most frequently affected, and triple-positive aPLA profiles markedly increase the risk of recurrence and long-term morbidity, including chronic thromboembolic pulmonary hypertension (CTEPH). This review article summarizes current evidence on the epidemiology, pathophysiology, diagnostic approach, and management of PE in APS. Key mechanisms include anti-β2-glycoprotein I-mediated endothelial and platelet activation, complement engagement, and neutrophil extracellular trap formation, resulting in immunothrombosis. Diagnostic pathways follow standard PE algorithms; however, chronically elevated D-dimer levels and lupus anticoagulant-related aPTT prolongation require careful interpretation and consideration. Long-term vitamin K antagonist therapy remains the standard of care, whereas direct oral anticoagulants are not recommended in high-risk APS. Future directions include improved risk stratification through detailed aPLA profiling and the use of emerging biomarkers, early screening for CTEPH, and the development of targeted therapies such as complement inhibition and anti-NETosis strategies. Full article

Background and Objectives: The vitamin K epoxide reductase complex subunit 1 (VKORC1) plays a central role in the vitamin K cycle, which is essential for γ-carboxylation of multiple bone-related proteins. Genetic variants in VKORC1 may influence bone mineral density (BMD) and osteoporosis risk. Materials and Methods: A systematic review and meta-analysis were conducted to evaluate the association between VKORC1 polymorphisms and osteopenia and osteoporosis. Relevant studies were identified through PubMed, Scopus, and Web of Science databases. Data on study characteristics, genotypes, BMD measurement, ethnicity, sex, and menopausal status were extracted. Results: Six studies comprising 7335 participants were included. All studies assessed BMD using dual-energy X-ray absorptiometry (DXA). The mean participant age ranged from 41.9 to 63.7 years. The VKORC1 variants most frequently studied, which were included in the meta-analysis, were rs9923231 and rs9934438. The overall effect of VKORC1 risk alleles on osteopenia/osteoporosis was significant with a p = 0.041 (fixed effects OR = 1.16, 95% CI = 1.01–1.35). Heterogeneity among studies was insignificant (I² = 0%, p = 0.893). Conclusions: A modest association was observed for the VKORC1 variants. The current body of evidence requires further studies to elucidate whether VKORC1 polymorphisms have a clinically meaningful role in bone health. Full article

Background: Vitamin K has emerged as a promising regulator of glucose metabolism in preclinical studies. There is, however, scant evidence to support this promising potential in a clinical setting. Aim: The aim of this study was to confirm the effects of vitamin K supplementation on glycaemic parameters such as fasting blood glucose (FBG), fasting insulin (FI), glycated haemoglobin (HbA1c), insulin resistance (HOMA-IR), and homeostatic model of beta cell function (HOMA-β) across randomised controlled trials (RCTs). Materials and Methods: This meta-analysis used evidence from PubMed, Scopus, and manual screening. Only RCTs were considered for this meta-analysis of interventional studies. The Meta online tool was used to analyse data, with the results reported as either the mean or the standardised mean difference (SMD), alongside 95% confidence intervals (CI). Results: Only eight RCTs were found relevant and analysed; the age of those in the vitamin K group was 50.58 ± 6.91 years, and in the control group, it was 48.19 ± 5.41. The evidence showed a significant reduction in FBG, SMD = −0.22 (−0.39 to −0.05), HbA1c, MD = −1.00%, 95% CI (−1.92 to −0.07), and HOMA-IR, MD = −0.63, 95% CI (−1.20 to −0.06). However, no effect was observed on insulin (SMD = −0.39, 95% CI: −0.91 to 0.13, p = 0.15) and HOMA-β (MD = 6.56, 95% CI (−3.89 to 17.01), p = 0.2184. Low doses of vitamin K2 and vitamin K1 were associated with reduced HbA1c and HOMA-IR, respectively. An intervention of less than 12 weeks was associated with reduced HOMA-IR. Conclusions: This study showed a significant decrease in FBG, HbA1c, and HOMA-IR without affecting insulin or HOMA-β. Nevertheless, the limited number of trials with moderate quality warrants larger, longer-term RCTs with rigorous methodology and direct comparisons of vitamin K isoforms to better assess therapeutic potential. Full article

Microbial fermentation is an important means to enhance the nutrition and functionality of food, and soybean fermentation has a long history and a wide variety of products. This study systematically compared the effects of fermentation and post-ripening processes of Bacillus subtilis natto JLCC513 on the nutritional components, active substances, and sensory characteristics of soybeans. The experimental results showed that, in terms of basic nutrition, fermentation led to a significant decrease in fat and reducing sugar content, followed by an initial increase and then a decrease in total protein content. In contrast, water-soluble protein continued to increase, and the total amount of free amino acids surged. The active nutritional indicators before and after soybean fermentation showed that nattokinase activity continued to increase during fermentation and post-ripening. At the same time, the number of viable bacteria decreased slightly during post-ripening. The increase in the proportion of easily absorbed aglycone-type isoflavones before and after soybean fermentation is accompanied by a sustained increase in vitamin K2 and gamma aminobutyric acid (GABA) content. In terms of sensory quality, color-difference analysis shows a decrease in brightness (L value) and an increase in redness (a value), resulting in the characteristic yellow-brown color of natto. In terms of texture characteristics, the hardness decreases, while the viscosity and elasticity are significantly enhanced. Through GC-IMS analysis of volatile aromas during soybean fermentation and post-ripening, it was found that esters (such as ethyl acetate) and pyrazines (such as 2,3-dimethylpyrazine) increased, and the product flavor shifted from grassy to fruity and nutty. In summary, natto bacteria enhance the digestibility, nutritional value, and sensory acceptance of soybeans through enzymatic hydrolysis and metabolic transformation. The post-ripening stage plays a key role in flavor maturation and further accumulation of active ingredients. Full article

Biostimulants have emerged as effective tools for enhancing both the productivity and quality of crops. In this study, we assessed the impact of the two commercial biostimulant products (Kiana Earth^® and Kiana Climate^®) on the growth, yield, and quality of lettuce (Lactuca sativa L.). Eight treatments were established, comprising six different biostimulant formulations, a normal control (no fertilizer applied), and a positive control (chemical fertilizer application). Biostimulant treatments significantly improved plant and stem diameters, fresh and dry biomass, and yield (p < 0.01). The best yields and morphological performance were obtained with samples receiving T6 (Kiana Climate^® + 75:50:75 kg ha⁻¹ N:P:K) and T7 (Kiana Earth^® + 150:100:150 kg ha⁻¹ N:P:K) applications, which comprised biostimulant–fertilizer combinations. Chlorophyll a, chlorophyll b, and total chlorophyll levels were significantly higher with than without biostimulant treatment, indicating that the biostimulants enhanced photosynthetic efficiency. Biochemical analyses further identified significant increases in vitamin C levels, total antioxidant capacity, total phenolic compounds, and flavonoid contents, especially with treatments T5 (Kiana Earth^® + 75:50:75 kg ha⁻¹ N:P:K)–T8 (Kiana Climate^® + 150:100:150 kg ha⁻¹ N:P:K). Nitrogen assimilation analysis showed that leaf NO₃⁻ levels were lower with the combined treatment than with chemical fertilizer alone, suggesting that the biostimulants improved nitrogen-use efficiency. Micronutrient (Fe, Zn, Cu, Mn, Na) and macronutrient (N, P, K, Ca, Mg, S) levels were significantly increased with biostimulant-enriched treatments, alongside a rise in soil organic matter. Biostimulants, especially when combined with mineral fertilization, significantly enhanced lettuce growth, yield, and nutritional quality, while also promoting soil fertility. These findings highlight the potential of biostimulants as valuable tools in conventional, regenerative, and organic agricultural practices, offering a sustainable approach to enhancing agricultural productivity while ensuring long-term soil fertility. Full article

The effect of heavy metals on male hormonal regulation—particularly the hypothalamic–pituitary–testicular (HPT) axis—remains poorly characterized. We aim to investigate associations between heavy metal exposure and HPT axis-related hormones. We analyzed data, including male participants aged 3–80 years, from a nationally representative survey. Five metals and twelve sex hormones were measured. We used multivariate linear regression and restricted cubic splines to assess associations and dose–response relationships. Mixture effects were quantified using quantile-based g computation. The modifying effects of vitamin D and folate were examined. The underlying mechanisms were explored through a narrative review and integrative bioinformatics analysis. A total of 6547 males were included. Metal exposure was predominantly associated with hormonal perturbations in adolescents and older adults. Specifically, metal mixture was associated with hormones in adolescent males [effect range: −5.10% (95% CI: −9.24, −0.76) to 18.12% (95% CI: 9.80, 27.07)] and older males [effect range: 3.17% (95% CI: 0.07, 6.37) to 10.94% (95% CI: 4.82, 17.43)]. Effect modifications were observed for vitamin D in children and adolescents, and for folate across all age groups. The PI3K-Akt signaling pathway was identified as a potential mechanism. Our findings provide novel insights into the association and potential pathway between heavy metals and male hormonal disturbance. Full article

Multiple sclerosis (MS) is a chronic neuroinflammatory and autoimmune disorder of the central nervous system (CNS) whose cause remains unknown. Disease-modifying therapies (DMTs) are the current standard of care, yet growing evidence highlights the importance of complementary lifestyle-based interventions, including nutrition, in modulating disease activity. Given the influence of diet on immune function, several studies have examined its effects in MS, with particular attention to specific dietary patterns and macronutrients. However, fewer studies have focused on micronutrients, bioactive compounds, and minerals and their influence in MS. In this narrative review, we report the latest evidence on micronutrients such as vitamins and essential metals, along with polyphenols and minerals like salt, in both experimental autoimmune encephalomyelitis (EAE) and MS. We also discuss how these dietary components may influence the gut microbiota, which is considered a contributor to disease onset due to its interaction with the immune system in the gut–brain axis. While findings for vitamins B, C, E, and K remain heterogeneous, vitamins A and D show the most consistent immunological and clinical effects, with immunomodulatory, antioxidative, and neuroprotective effects in both EAE and MS. Polyphenols also display anti-inflammatory and neuroprotective properties in EAE and, to a lesser extent, in clinical studies. Lastly, evidence suggests the importance of balanced salt intake and adequate levels of essential metals, as dysregulation may contribute to comorbidities or enhance inflammatory pathways relevant to MS. Although only a limited number of studies have explored these aspects, the gut microbiota appears to be differentially affected by these dietary factors. Overall, advancing our understanding of how these components interact with immune and microbial pathways may support the development of personalized nutritional strategies to complement current therapies and improve patient outcomes. Full article

Background/Objectives: Hemorrhagic complications are among the most common adverse events of anticoagulant therapy in patients with atrial fibrillation (AF). Non-vitamin K antagonist oral anticoagulants (DOACs) are known to be more effective than vitamin K antagonists (VKAs) in preventing thromboembolism. The aim was to identify clinical factors associated with hemorrhagic events in AF patients treated with DOACs and to develop a simple, clinically applicable bleeding risk score. Methods: Data were derived from the multicenter CRAFT trial (NCT02987062). We conducted a retrospective analysis of hospital records of 1435 AF patients (median age: 67 years; 44.8% female) treated with dabigatran or rivaroxaban. The main study endpoints were the occurrence of a bleeding episode, thromboembolic episode, or all-cause death during a mean four-year follow-up (1531 [1062–2140] days). Results: The rates of bleeding episodes, thromboembolic episodes, and all-cause death were 17.4%, 13.5%, and 23.9%, respectively. Nine factors were identified as predictors of bleeding complications: male sex, history of major bleeding, history of cancer, COPD, CRT, rivaroxaban therapy, statin therapy, age, and absence of heart failure. Based on these, the CRAFT bleeding score was developed to predict the risk of hemorrhagic events in individual patients. Conclusions: The CRAFT bleeding score may be implemented in AF patients as an additional tool for evaluating DOACs safety prior to initiating anticoagulant therapy, and for guiding closer monitoring of high-risk individuals to minimize bleeding complications. Full article

Vitamin D, traditionally regarded as a nutrient, is increasingly recognized as a pharmacologically active secosteroid with pleiotropic effects extending beyond calcium homeostasis and bone integrity. Together with vitamin K2, it participates in the fine-tuning of mineral metabolism and vascular health, potentially modulating cardiometabolic risk through intertwined endocrine and paracrine pathways. Despite widespread fortification and supplementation, vitamin D deficiency remains a major global health concern, driven by limited sun exposure, obesity, and metabolic dysfunction. Observational and mechanistic studies consistently link low serum 25(OH)D concentrations with hypertension, insulin resistance, heart failure, and increased cardiovascular mortality. At the molecular level, vitamin D exerts pharmacological actions—modulating the renin–angiotensin–aldosterone system, exerting anti-inflammatory and antifibrotic effects, and influencing endothelial and cardiomyocyte signaling. While experimental and epidemiological evidence suggests potential cardiovascular benefits, large randomized controlled trials (RCTs) provide conflicting results, particularly regarding hypertension and heart failure. However, these often-neutral results do not preclude a targeted action. On the contrary, clinical efficacy is strongly dependent on baseline deficiency status and the presence of metabolic cofactors. In this context, high-dose supplementation of Vitamin D, in combination with Vitamin K2 to prevent vascular calcification, elevates the supplement to a genuine pharmacological agent, with a distinct therapeutic potential for modulating cardiometabolic risk in selected patient subgroups. Emerging evidence supports the concept that vitamin D, when appropriately dosed and combined with K2, may act more as a low-potency pharmacological modulator than a simple nutritional supplement. This review synthesizes current mechanistic, observational, and interventional evidence, aiming to clarify whether vitamin D should be reclassified—from a micronutrient to a pharmacologically relevant agent—in cardiometabolic prevention and therapy, proposing a paradigm shift toward personalized and targeted dosing strategies, characteristic of precision pharmacology. Full article

This study evaluated the energy-dependent effects of pulsed electric field (PEF) treatment on the physicochemical properties, bioactive compounds, antioxidant activity, and microstructure of red bell pepper (Capsicum annuum L.). Red bell pepper tissue was treated at specific energy inputs ranging from 1 to 10 kJ/kg and compared with a fresh (untreated sample). The cell disintegration index (CDI) increased progressively with PEF energy, confirming enhanced membrane permeabilization and structural disruption. Structural analyses (SEM and micro-CT) confirmed the formation of pores and interconnected channels, particularly at moderate and high energies. PEF treatment caused a decrease in total polyphenols and flavonoids, whereas vitamin C and total carotenoid contents increased at intermediate energies. Antioxidant activity (ABTS, DPPH, FRAP) declined overall but remained at comparable levels for mild PEF exposure. A significant reduction in firmness was observed (from 17% to 27% compared with the untreated control), and color changes were dependent on the energy input, while microstructural degradation intensified as the energy level approached 10 kJ/kg. PEF treatment improved microbial stability, resulting in a measurable reduction in total viable counts and yeast and mold counts, particularly at higher energy inputs. FTIR, TGA, and NMR data confirmed molecular alterations without degradation of major components. Multivariate analysis (dendrogram, PCA) distinguished four characteristic response groups: fresh, low-energy (1–2 kJ/kg), moderate-energy (4–5 kJ/kg), and high-energy (10 kJ/kg). PEF treatment selectively modified red bell pepper tissue, enhancing permeabilization and carotenoid/vitamin C release while preserving visual quality at mild–moderate energies. These results demonstrate the potential of PEF as a nonthermal technique for tailoring the structural and functional properties of plant-based products. Full article

This study aimed to investigate the effects of dietary manganese deficiency and compare the impact of manganese macroparticles (MnCO₃) and nanoparticles (Mn₂O₃NPs) on bone remodeling and metabolism. Twenty-seven male Wistar rats were divided into three groups (n = 9): control (standard MnCO₃, 65 mg Mn/kg), manganese-deficient, and Mn₂O₃NPs-supplemented (65 mg Mn/kg). After a 12-week feeding period, bone-related markers and gene expression were analyzed in the femur and blood. Mn-deficient rats showed reduced plasma levels of bone-specific alkaline phosphatase (BALP), tartrate-resistant acid phosphatase 5b (TRAP5b), interferon-β (IFN-β), RANKL glycoprotein, 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃), vitamin K₂, and collagen turnover markers (PINP, CTX-1, NTX). Femur levels of BALP, TRAP5b, interferon-γ (IFN-γ), osteonectin, calcitonin, PICP, PINP, and CTX-1 were also decreased. Replacing MnCO₃ with Mn₂O₃NPs increased IFN-γ but lowered IFN-β and 1,25-(OH)₂D₃ levels in plasma. This treatment also decreased the femur level of BALP and calcitonin, and the RANKL:OPG ratio, while increasing the expression level of Sp7 and Ctsk genes. To conclude, our results suggest that manganese deficiency is associated with suppressed bone turnover and altered mineral metabolism. Furthermore, replacing MnCO₃ with Mn₂O₃ nanoparticles did not yield the anticipated benefits for bone remodeling, as evidenced by the observed imbalances in osteogenic and resorptive markers, indicating a need for cautious evaluation of nanoparticle-based supplementation. Full article

A universal HPLC method with diode array detection was developed for the separation and determination of the lactone and acid forms of monacolin K in the presence of other active ingredients (vitamins B₁, B₆, B₁₂, and folic acid) found in selected dietary supplements. The method also enables the quantitative determination of citrinin in monacolin K. Chromatographic separation was performed on an ACE 5 C18-PFP column (250 × 4.6 mm) thermostated at 25 °C. The mobile phase consisted of 0.005 M phosphate buffer (pH 2.60) and acetonitrile under linear gradient elution conditions. Detection was carried out spectrophotometrically at 230 nm for monacolin K and 325 nm for citrinin. The total run time was 28 min. The method was validated and met the acceptance criteria for specificity, linearity, sensitivity, accuracy, and precision. Linearity was achieved over a broad concentration range: 12.48–37.44 μg·mL⁻¹ for MK and 3.48–5.22 μg·mL⁻¹ for CTN. The method is sufficiently sensitive, with LOD and LOQ values of 0.91–2.85 μg·mL⁻¹ and 2.18–3.48 μg·mL⁻¹ for MK and CTN, respectively. Good precision (RSD < 0.70%) and intermediate precision (RSD < 1.33%) were observed. The accuracy of the method, expressed as percentage recovery at three concentration levels, ranged from 98.73% to 100.64%. The analysis revealed that the monacolin K content in randomly selected dietary supplements did not comply with the manufacturer’s declaration in any case. Full article

Background/Objectives: Unusual-site venous thrombosis (USVT) lacks robust evidence guiding anticoagulant selection between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). This study aimed to evaluate recanalization, recurrence, and major bleeding outcomes in real-world USVT patients and to replicate these findings through a validated digital twin model with Monte Carlo simulation. Methods: We conducted a retrospective study of 90 USVT patients (72% VKAs, 28% DOACs). A conditional generative adversarial network was used to generate digital twins matched on age, sex, thrombosis site, and malignancy. Logistic regression was applied to estimate treatment-specific outcome probabilities for recanalization, recurrence, and major bleeding. A nested stochastic simulation framework simulated 500 iterations across clinical scenarios, including increased DOAC use, cancer prevalence, cerebral vein thrombosis proportion, and optimized VKA control. Results: The mean age was 67.5 years, and 54.4% were female. 61.1% of splanchnic vein thrombosis, 36.7% of upper extremity deep vein thrombosis, and 2.2% of cerebral vein thrombosis were included. In the real cohort, complete recanalization occurred in 40.0% of patients with DOACs and 36.0% with VKAs. Recurrence was 8.0% with DOACs and 7.7% with VKAs, and major bleeding occurred in 8.0% and 10.8% of cases, respectively. All-cause mortality was 20% in DOAC-treated patients and 60% in those receiving VKAs. Digital Twin-based predictions replicated these results (recanalization 40.3% versus 38.0%; recurrence 10.9% versus 8.6%; bleeding 7.6% versus 9.1%). Simulated scenarios preserved the directionality effect, with the most significant differences observed in high-cerebral vein thrombosis and cancer-enriched patients. Conclusions: DOACs showed comparable efficacy and slightly lower bleeding risk than VKAs in USVT. Digital twin and Monte Carlo modeling provided robust, reproducible simulations of treatment effects under varying clinical conditions. Separating empirical and simulation-based findings, the digital twin supported the internal consistency of real-world observations and demonstrated the potential of in silico modeling as a complementary tool in rare thrombotic diseases. Full article