Search Results (10,334)

Background/Objectives: Low-dose corticosteroids have gained popularity in the treatment of acute respiratory distress syndrome (ARDS); however, the efficacy of high-dose corticosteroids as pulse steroid therapy remains controversial. This study aimed to evaluate the efficacy of pulse steroid therapy in patients with severe ARDS requiring venovenous (V-V) extracorporeal membrane oxygenation (ECMO), where enhanced anti-inflammatory effects may be beneficial. Methods: Using data from the J-CARVE registry, which included patients with severe ARDS managed with V-V ECMO across 24 Japanese hospitals between January 2012 and December 2022, we identified 373 patients treated with corticosteroids. The patients were divided into two groups: pulse steroid therapy and non-pulse steroid therapy. Propensity score matching was performed, and all-cause hospital mortality and ECMO-free days within 28 days were compared between groups. Pulse steroid therapy was defined as methylprednisolone at a dose of 1000 mg/day. Results: After matching, 48 patients were included in each group. The all-cause hospital mortality rates were 41.7% (20/48) in the pulse steroid group and 47.9% (23/48) in the non-pulse steroid group, with no significant difference (odds ratio, 1.28; 95% confidence interval: 0.53–3.12, p = 0.68). The median ECMO-free days were 9.5 (interquartile range [IQR]: 0–17.3) in the pulse steroid group and 3 (IQR: 0–17) in the non-pulse steroid group, showing no significant difference (p = 0.69). Conclusions: Pulse steroid therapy did not improve all-cause hospital mortality or ECMO-free days in patients with severe ARDS who required V-V ECMO. Full article

Background/Objectives: Possessing red and white ecotypes, and utilized in traditional Guyanese medicine, Doliocarpus dentatus’ red ecotype is preferred locally for its purported superior therapeutic efficacy. Although therapeutic metabolites were detected in D. dentatus previously, phytohormones remain largely unexplored, until now. Cytokinins, phytohormones responsible for plant cell division, growth and differentiation, are gaining traction for their therapeutic potential in human health. This study screened and quantified endogenous cytokinins and correlated detected cytokinins with selected secondary metabolites. Methods: Liquid chromatography–mass spectrometry was used to acquire phytohormone and metabolite data. Bioinformatics tools were used to assess untargeted metabolomics datasets via statistical and pathway analyses, and chemical groupings of putative metabolites. Results: In total, 20 of the 35 phytohormones were detected and quantified in both ecotypes, with the red ecotype displaying higher free base and glucoside cytokinin concentrations and exhibited 6.2 times the total CK content when compared to the white ecotype. Pathway analysis revealed flavonoid and monoterpenoid biosynthesis in red and white ecotypes, respectively. Positive correlations between specific cytokinins and alkaloids, and between trans-Zeatin and isopentenyladenosine riboside with phenolic compounds were observed. Conclusions: These results suggest that the red ecotype’s elevated cytokinin levels coupled with flavonoid biosynthesis enrichment support its preference in Guyanese traditional medicine. Full article

Arginine kinase is a key phosphagen kinase in invertebrates that facilitates rapid ATP regeneration by reversibly transferring phosphate groups between phosphoarginine and ADP. Structural studies have shown that the enzyme adopts distinct conformations in its ligand-free and ligand-bound states, known as the “open” and “closed” forms, respectively. These conformational changes are crucial for catalytic activity, enabling precise positioning of active-site residues and loop closure during phosphoryl transfer. Transition-state analog complexes have provided additional insights by mimicking intermediate states of catalysis, supporting the functional relevance of the open/closed structural model. Furthermore, studies across multiple species reveal how monomeric and dimeric forms of arginine kinase contribute to its allosteric regulation and substrate specificity. Beyond its metabolic role, arginine kinase is also recognized as a major allergen in crustaceans. Its structural uniqueness and absence in vertebrates make it a promising candidate for selective drug targeting. By integrating crystallographic data with functional context, this review highlights conserved features and species-specific variations of arginine kinase that may inform the design of inhibitors. Such molecules have the potential to serve both as antiparasitic agents and as novel therapeutics to manage crustacean-related allergic responses in humans. Full article

Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or cause less toxicity. Methods: We retrospectively analyzed 76 patients with locally advanced EAC or AEGJ treated at our tertiary cancer center between January 2015 and March 2023. Patients received either perioperative FLOT chemotherapy (n = 36) or neoadjuvant radiochemotherapy following the CROSS protocol (n = 40), followed by surgical resection and standardized follow-up. We compared survival outcomes, toxicity profiles, treatment compliance, and surgical results between the two groups. Results: There were no statistically significant differences between FLOT and CROSS treatments in five-year loco-regional controls (LRC: 61.5% vs. 68.6%; p = 0.81), progression-free survival (PFS: 33.9% vs. 42.8%; p = 0.82), overall survival (OS: 60.2% vs. 63.4%; p = 0.91), or distant controls (DC: 42.1% vs. 56.5%; p = 0.39). High-grade hematologic toxicities did not significantly differ between groups (p > 0.05). Treatment compliance was lower in the FLOT group, with 50% (18/36) not completing all the planned chemotherapy cycles, compared to 17.5% (7/40) in the CROSS group. All the patients in the CROSS group received the full radiotherapy dose. Surgical outcomes and post-surgical tumor status were comparable between the groups. Conclusions: Although perioperative chemotherapy with FLOT has recently become a standard of care for locally advanced EAC and AEGJ, neoadjuvant radiochemotherapy per the CROSS protocol remains a well-tolerated alternative. In appropriately selected patients, both approaches yield comparable oncological outcomes. Full article

Background: Atrial fibrosis is a key contributor to atrial cardiomyopathy and can be assessed invasively using mean left atrial voltage (MLAV) from electroanatomical mapping. However, the invasive nature of this procedure limits its clinical applicability. Machine learning (ML), particularly regression tree-based models, may offer a non-invasive approach for predicting MLAV using clinical and echocardiographic data, improving non-invasive atrial fibrosis characterisation beyond current dichotomous classifications. Methods: We prospectively included and followed 113 patients with paroxysmal or persistent atrial fibrillation (AF) undergoing pulmonary vein isolation (PVI) with ultra-high-density voltage mapping (uHDvM), from whom MLAV was estimated. Standardised two-dimensional transthoracic echocardiography was performed before ablation, and clinical and echocardiographic variables were analysed. A regression tree model was constructed using the Classification and Regression Trees—CART-algorithm to identify key predictors of MLAV. Results: The regression tree model exhibited moderate predictive accuracy (R² = 0.63; 95% CI: 0.55–0.71; root mean squared error = 0.90; 95% CI: 0.82–0.98), with indexed minimum LA volume and passive emptying fraction emerging as the most influential variables. No significant differences in AF recurrence-free survival were found among MLAV tertiles or model-based generated groups (log-rank p = 0.319 and p = 0.126, respectively). Conclusions: We present a novel ML-based regression tree model for non-invasive prediction of MLAV, identifying minimum LA volume and passive emptying fraction as the most significant predictors. This model offers an accessible, non-invasive tool for refining atrial cardiomyopathy characterisation by reflecting the fibrotic substrate as a continuum, a crucial advancement over existing dichotomous approaches to guide tailored therapeutic strategies. Full article

Background/Objective: This study explores a novel approach for diagnosing common middle ear pathologies using Pressure-Less Acoustic Immittance (PLAI™), a non-invasive alternative to conventional tympanometry. Methods: A total of 516 ear measurements were collected and stratified into three age groups: 0–3, 3–12, and 12+ years, reflecting key developmental stages. PLAI™-derived acoustic parameters, including resonant frequency, peak admittance, canal volume, and resonance peak frequency boundaries, were analyzed using Random Forest classifiers, with SMOTE addressing class imbalance and SHAP values assessing feature importance. Results: Age-specific models demonstrated superior diagnostic accuracy compared to non-stratified approaches, with macro F1-scores of 0.79, 0.84, and 0.78, respectively. Resonant frequency, ear canal volume, and peak admittance consistently emerged as the most informative features. Notably, age-based stratification significantly reduced false negative rates for conditions such as Otitis Media with Effusion and tympanic membrane retractions, enhancing clinical reliability. These results underscore the relevance of age-aware modeling in pediatric audiology and validate PLAI™ as a promising tool for early, pressure-free middle ear diagnostics. Conclusions: While further validation on larger, balanced cohorts is recommended, this study supports the integration of machine learning and acoustic immittance into more accurate, developmentally informed screening frameworks. Full article

Background and Objective: Adverse pathology to high-risk prostate cancer (PCa) after radical prostatectomy (upgrading) poses a threat to risk stratification and treatment planning. The impact on sexual function, urinary continence, and health-related quality of life (HRQOL) remains unclear. Methods: From 2004 to 2024, 4189 patients with preop low-/intermediate-risk PCa (Gleason score 6 or 7a, PSA ≤ 20 ng/mL) underwent radical prostatectomy at our department and were analyzed. Primary endpoint was HRQOL, erectile function, and urinary continence. Secondary endpoint was rate of salvage therapies and biochemical-free survival. Propensity score matching was performed using “operative time”, “robot-assisted surgery”, “blood loss”, “nerve-sparing surgery”, “age”, and “BMI” to represent comparable surgical approach. Median follow-up was 39 months (Interquartile-range (IQR) 15–60). Key Findings and Limitations: Patients who were upgraded to high-risk PCa showed a higher rate of postoperative radiotherapy and androgen-deprivation therapy compared to patients who were not upgraded (21% vs. 7%, p < 0.001; 9% vs. 3%, p = 0.002). Five-year biochemical recurrence-free survival was 68% in the upgrading group vs. 84% in the no-upgrading group (p < 0.001). We saw no difference in patient-reported HRQOL, urinary continence, or erectile function. Multivariable analysis showed that postoperative upgrading was a significant risk for not achieving good overall HRQOL (OR: 0.77, 95% CI: 0.61–0.97, p = 0.028) during the follow-up. Conclusions and Clinical Implications: Although postoperative upgrading to high-risk PCa leads to worse oncologic outcomes and higher salvage therapy rates, this study indicates that its impact on health-related quality of life is minimal and should not deter a cautious approach to radical prostatectomy. Full article

Background: RiBi is integral to cell proliferation, and its dysregulation is increasingly recognized as a hallmark of aggressive cancers. We sought to develop and validate a composite “PanRibo-515 score” reflecting RiBi activity across multiple tumor types, assess its prognostic significance, and explore its relationship with immune checkpoint therapy outcomes. Methods: We curated 515 RiBi–associated genes (PanRibo-515) and used a LASSO regression-based strategy on a training dataset (GSE202203) to select the prognostically most relevant subset of 68 genes (OncoRibo-68). Directionality (positive or negative impact on survival) was assigned based on the sign of the LASSO coefficients. We integrated a forward selection approach to identify a refined subset of genes for computing the OncoRibo-68 score. For validation, patients in The Cancer Genome Atlas (TCGA) were stratified into high or low OncoRibo-68 score groups for survival analyses. Additional validation for immunotherapy response was conducted using bioinformatic platforms used for immunotherapy response analysis. Results: A higher OncoRibo-68 score consistently correlated with poorer overall and progression-free survival across multiple cancers. Elevated OncoRibo-68 score was linked to an immunosuppressive tumor microenvironment, but interestingly to increased response to checkpoint inhibitors. Conclusions: Our findings highlight RiBi as an important determinant of tumor aggressiveness and identify the OncoRibo-68 score as a promising biomarker for risk stratification and therapy selection. Future research may evaluate whether targeting RiBi pathways could enhance treatment efficacy, particularly in combination with immunotherapy. Full article

Flavonoids constitute a broad class of naturally occurring chemical compounds classified as polyphenols, widely present in various plants, fruits, and vegetables. They share a common flavone backbone, composed of two aromatic rings (A and B) connected by a three-carbon bridge forming a heterocyclic ring (C). One representative flavonoid is chrysin, a compound found in honey, propolis, and passionflower (Passiflora spp.). Chrysin exhibits a range of biological activities, including antioxidant, anti-inflammatory, anticancer, neuroprotective, and anxiolytic effects. Its biological activity is primarily attributed to the presence of hydroxyl groups, which facilitate the neutralization of free radicals and the modulation of intracellular signaling pathways. Cellular uptake of chrysin and other flavonoids occurs mainly through passive diffusion; however, certain forms may be transported via specific membrane-associated carrier proteins. Despite its therapeutic potential, chrysin’s bioavailability is significantly limited due to poor aqueous solubility and rapid metabolism in the gastrointestinal tract and liver, which reduces its systemic efficacy. Ongoing research aims to enhance chrysin’s bioavailability through the development of delivery systems such as lipid-based carriers and nanoparticles. Full article

Poly(vinyl chloride) (PVC) undergoes thermal degradation during processing and operation, which necessitates the use of effective thermal stabilizers. The purpose of this work is to comprehensively evaluate the potential of new hierarchically structured titanium phosphates (TiP) with controlled morphology as thermal stabilizers of plasticized PVC, focusing on the effect of morphology and Ti/P ratio on their stabilizing efficiency. The thermal stability of the compositions was studied by thermogravimetric analysis (TGA) in both inert (Ar) and oxidizing (air) atmospheres. The effect of TiP concentration and its synergy with industrial stabilizers was analyzed. An assessment of the key degradation parameters is given: the temperature of degradation onset, the rate of decomposition, exothermic effects, and the carbon residue yield. In an inert environment, TiPMSI/TiPMSII microspheres demonstrated an optimal balance by increasing the temperature of degradation onset and the residual yield while suppressing the rate of decomposition. In an oxidizing environment, TiPR rods and TiPMSII microspheres provided maximum stability, enhancing resistance to degradation onset and reducing the degradation rate by 10–15%. Key factors of effectiveness include ordered morphology (spheres, rods); the Ti-deficient Ti/P ratio (~0.86), which enhances HCl binding; and crystallinity. The stabilization mechanism of titanium phosphates is attributed to their high affinity for hydrogen chloride (HCl), which catalyzes PVC chain scission, a catalyst for the destruction of the PVC chain. The unique microstructure of titanium phosphate provides a high specific surface area and, as a result, greater activity in the HCl neutralization reaction. The formation of a sol–phosphate framework creates a barrier to heat and oxygen. An additional contribution comes from the inhibition of oxidative processes and the possible interaction with unstable chlorallyl groups in PVC macromolecules. Thus, hierarchically structured titanium phosphates have shown high potential as multifunctional PVC thermostabilizers for modern polymer materials. Potential applications include the development of environmentally friendly PVC formulations with partial or complete replacement of toxic stabilizers, the optimization of thermal stabilization for products used in aggressive environments, and the use of hierarchical TiP structures in flame-resistant and halogen-free PVC-based compositions. Full article

This study presents the synthesis and physicochemical characterization of coordination compounds formed between chrysin, a natural flavonoid, and transition metal ions: Mn(II), Co(II), and Zn(II). The complexes were obtained under mildly basic conditions and analyzed using elemental analysis, thermogravimetric analysis (TGA), silver-assisted laser desorption/ionization mass spectrometry (SALDI-MS), FT-IR spectroscopy, and ¹H NMR. The spectroscopic data confirm that chrysin coordinates as a bidentate ligand through the 5-hydroxyl and 4-carbonyl groups, with structural differences depending on the metal ion involved. The mass spectrometry results revealed distinct stoichiometries: 1:2 metal-to-ligand ratios for Mn(II) and Co(II), and 1:1 for Zn(II), with additional hydroxide coordination. Biological assays demonstrated that Co(II) and Mn(II) complexes exhibit enhanced antibacterial and anti-biofilm activity compared to free chrysin, particularly against drug-resistant Staphylococcus epidermidis, whereas the Zn(II) complex showed negligible biological activity. Full article

The correlation between fermented vinegar’s physicochemical properties and functional characteristics, particularly skin-related functionalities, remains unclear. We analyzed the quality of widely consumed Korean fermented vinegars, including grain and persimmon vinegars, and their correlation with skin-related functionalities to establish quality control criteria linked to functional properties. Fifteen traditional Korean grain vinegars and fourteen persimmon vinegars were collected; distilled white vinegar was used as the control group. Grain vinegars showed 3.57–100.00% collagenase and 62.38–77.03% tyrosinase inhibition; persimmon vinegars showed 0.00–94.50% and 30.75–71.54%, respectively. To determine which quality characteristics are high in fermented vinegar with high skin-related functionality, a correlation analysis was conducted. In grain vinegar, total nitrogen and free amino acids were strongly associated with skin-related functionalities. In persimmon vinegar, organic acids, particularly lactic acid, were correlated with skin-related effects; thus, both demonstrated the importance of quality assessment. Insights into relationships between the composition and functional properties of fermented vinegar were gained. Specific quality markers for managing skin-related functionality of Korean fermented vinegar established a scientific basis for standardizing quality control, developing high-value functional vinegar products, and ensuring consistent product quality. Full article

Objective: This retrospective observational study evaluated the efficacy and safety of an ovarian stimulation protocol for embryo banking that involves continuous administration of clomiphene citrate (CC) in combination with gonadotropins, without the use of GnRH antagonists. Methods: Conducted at the Serum IVF Clinic in Athens, Greece, the study included 250 women aged 25–45 who underwent IVF for embryo banking. The protocol involved administering 150 mg of CC daily from day 2 of the menstrual cycle until the day before hCG trigger, alongside 150 IU/day of Meriofert. Outcomes assessed included oocyte yield, fertilization rates, incidence of ovarian hyperstimulation syndrome (OHSS), and hormonal correlations. Comparative and regression analyses explored differences between age groups and predictors of success. Results: The protocol demonstrated a favorable safety profile with no cases of OHSS and yielded a mean of 10.25 oocytes per patient. Group analysis showed significantly more oocytes retrieved in women under 40 (mean: 12.5) versus those over 40 (mean: 8.43), while fertilization rates were paradoxically higher in the older cohort (59.16% vs. 30.68%, p < 0.0001). Regression models revealed basal FSH to be a significant inverse predictor of oocyte yield, but it was positively associated with fertilization rate. Continuous CC use effectively suppressed premature LH surges without compromising oocyte or embryo quality, allowing flexible and cost-effective stimulation with minimal monitoring. Conclusions: Continuous administration of clomiphene citrate in combination with gonadotropins presents a promising, antagonist-free ovarian stimulation protocol for embryo banking. The approach is economically efficient, reduces monitoring requirements, and maintains safety and effectiveness and is particularly notable in women over 40. Further studies are warranted to validate these findings and refine protocol mechanisms. Full article

Background: Pleural mesothelioma (PM) is a type of cancer that is difficult to diagnose and treat. Patients may have vastly varying prognoses, and prognostic factors may help guide the clinical approach. As a recently identified biomarker, the pan-Immune-Inflammation-Value (PIV) is a simple, comprehensive, and peripheral blood cell-based biomarker. Methods: The present study represents a retrospective observational analysis carried out within a single-center setting. Ninety-five patients with PM stages I–IV were enrolled in the study. We analyzed the correlation between patients’ demographic characteristics, clinicopathological factors such as histological subtypes, surgery status, tumor thickness, blood-based parameters, and treatment options with their prognoses. PIV was calculated by the following formula: (neutrophil count × monocyte count × platelet count)/lymphocyte count. Additionally, blood-based parameters were used to calculate the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune inflammation index (SII). Results: We categorized the patients into two groups, low PIV group (PIV ≤ 732.3) and high PIV group (PIV > 732.3) according to the determined cut-off value, which was defined as the median. It was revealed that high PIV was associated with poor survival outcomes. The median follow-up period was 15.8 months (interquartile range, IQR, 7.1 to 29.8 months). The median overall survival (OS) was significantly longer in patients in the low PIV group (median 29.8 months, 95% confidence interval (CI), 15.6 to 44) than the high PIV group (median 14.7 months, 95% CI, 10.8 to 18.6 p < 0.001). Furthermore, the study revealed that patients with low PIV, NLR, and SII values were more likely to be eligible for surgery and were diagnosed at earlier stages. Additionally, these markers were identified as potential predictors of disease-free survival (DFS) in the surgical cohort and of treatment response across the entire patient population. Conclusions: In addition to well-established clinical factors such as stage, histologic subtype, resectability, and Eastern Cooperative Oncology Group (ECOG) performance status (PS), PIV emerged as an independent and significant prognostic factor of overall survival (OS) in patients with PM. Moreover, PIV also demonstrated a remarkable independent prognostic value for disease-free survival (DFS) in this patient population. Additionally, some clues are provided for conditions such as treatment responses, staging, and suitability for surgery. As such, in this cohort, it has outperformed the other blood-based markers based on our findings. Given its ease of calculation and cost-effectiveness, PIV represents a promising and practical prognostic tool in the clinical management of pleural mesothelioma. It can be easily calculated using routinely available laboratory parameters for every cancer patient, requiring no additional cost or complex procedures, thus facilitating its integration into everyday clinical practice. Full article

Introduction: Oxidative stress is a key factor in the pathogenesis of many chronic diseases, especially in postmenopausal women. Xylitol, a sugar alcohol with potential antioxidant properties, may affect oxidative balance when used as a sugar substitute. Aim: This pilot study aimed to assess the effect of replacing sucrose with xylitol on serum antioxidant capacity in postmenopausal women. Methods: This study included 34 women aged 50 to 65 years who successively consumed 5 g/d, 10 g/d, and 15 g/d of xylitol. The dietary intervention lasted a total of 6 weeks, with each phase covering a 2-week period. Diet was assessed twice based on a 7-day dietary interview (Diet 6.0, NIZP–PZH, Warsaw). The material for this study was venous blood. Antioxidant capacity was determined using the DPPH radical scavenging method and the ABTS cation radical scavenging method. Results: In both methods, a significant increase in serum antioxidant potential was observed after replacing sugar with xylitol (p < 0.0001). An increase in the ability to neutralize free radicals was observed in almost all women studied. Additional analysis of the effect of selected nutrients on the obtained effects of the nutritional intervention showed that the most significant effect could potentially be exerted by manganese, maltose, sucrose, and mercury, and the strongest positive correlation was exerted by vitamin A, retinol, and vitamin E. Although the values obtained in the constructed models were not statistically significant, the large effect indicates potentially significant relationships that could have a significant impact on serum antioxidant potential in the studied group of women. Conclusions: The results suggest a potential role of xylitol in enhancing antioxidant defense mechanisms in menopausal women. Although the sample size was relatively small, this study was powered at approximately 80% to detect large effects, supporting the reliability of the observed results. Nevertheless, given the pilot nature of this study, further research with larger cohorts is warranted to confirm these preliminary observations and to clarify the clinical significance of xylitol supplementation in populations exposed to oxidative stress. Full article