Search Results (310,162)

Oxidative stress appears to be implicated in both the initiation and progression of autoimmune thyroiditis. Selenomethionine, which exhibits antioxidant properties, has been shown to reduce thyroid antibody titers in patients with autoimmune thyroiditis. Recent evidence suggests that vitamin E, a fat-soluble antioxidant, may protect against the development of autoimmune thyroiditis, and that its supplementation has been associated with improvements in female sexual function. The objective of the present pilot study was to determine whether vitamin E intake modulates the effects of selenomethionine on female sexual function and depressive symptoms in individuals with thyroid autoimmunity. The study enrolled three groups of reproductive-age women with euthyroid autoimmune thyroiditis, with 26 participants in each group. The groups were matched for age, thyroid peroxidase antibody titers, and TSH levels and differed according to vitamin E intake: adequate intake (group A), low intake (group B), and high intake (group C). All participants received selenomethionine supplementation (200 µg/day) for six months. Antibody titers and hormone levels were measured, and participants completed questionnaires assessing female sexual function (FSFI) and depressive symptoms (BDI-II). At baseline, no differences in biochemical outcomes were observed between the groups, except for testosterone levels. The study groups differed in sexual desire and arousal domain scores, which were higher in group A than in the other two groups. Total FSFI scores, the remaining FSFI domain scores, and BDI-II scores did not differ between groups at baseline. Across all groups, selenomethionine reduced thyroid peroxidase and thyroglobulin antibody titers and increased SPINA-GD and the ratio of free triiodothyronine to free thyroxine; however, the effects on antibody titers were most pronounced in group A. An increase in SPINA-GT and testosterone levels following selenomethionine supplementation was observed only in group A. In this group, selenomethionine also led to significant improvements in total FSFI scores and all individual domain scores. In contrast, in the remaining groups, the effects of supplementation were limited to increases in domain scores for lubrication, sexual satisfaction, and pain. A treatment-related reduction in total BDI-II scores was observed exclusively in women with adequate vitamin E intake. These findings suggest, for the first time, that dietary intake of a natural antioxidant may influence the effects of exogenous selenomethionine on sexual function and depressive symptoms in reproductive-age women with euthyroid autoimmune thyroiditis. Full article

Microplastics (MPs) often co-occur with heavy metals (HMs), posing combined stress that inhibits plant growth. While plant growth-promoting bacteria (PGPB) are known to alleviate heavy metal toxicity, their role under MP–HM co-contamination and the differential responses of rhizosphere microbial communities remain unclear. This study evaluated the effects of cadmium (Cd) and lead (Pb), polylactic acid (PLA) MPs, and their combined contamination on spinach growth using pot experiments, and assessed the mitigation potential of two PGPB strains. PGPB inoculation significantly increased plant height and dry weight. High-throughput sequencing revealed that pollution treatments and PGPB altered rhizosphere bacterial and fungal community composition and diversity. Microbial shifts were closely associated with soil chemical properties and plant growth. Notably, bacteria and fungi exhibited distinct response patterns to combined stress and remediation. Functional prediction (PICRUSt2) indicated that microbial communities enhanced metabolic processes and nutrient (N and P) cycling to cope with stress. PGPB inoculation reduced heavy metal toxicity, improved soil nutrient status (P and K), increased microbial diversity, and regulated microbial functions, thereby supporting soil ecological stability. These findings provide insights into rhizosphere microbial mechanisms and support the application of PGPB for remediation of MP–HM co-contaminated soils. Full article

Minimal access cardiac surgery (MACS) can mitigate the increasing risk profile of cardiac surgery patients and is associated with improved postoperative outcomes. One of the ways to manage the steep learning curve of MACS is the use of surgical simulation training. We conducted a narrative review to identify the relevant literature discussing MACS simulation training. We identified 20 studies using our search strategy. Various platforms were represented: high-fidelity (n = 8), low-fidelity (n = 6), and animal studies (n = 6). Virtual reality (VR) appeared in two wet-lab studies as an adjunct. The surgical approach was video-assisted thoracoscopic surgery (VATS) in 11 and robotic-assisted thoracoscopic surgery (RATS) in nine. The most simulated procedure was minimal access mitral valve (MV) repair (n = 16). Most studies (n = 16) evaluated the impact of simulation training on the surgical skill of participants with varying baseline MACS experience. A small proportion of included studies (n = 4) carried out only fidelity testing. While some standardised assessment tools were used, there was considerable variation in how surgical skill and fidelity were assessed. There are an increasing number of publications on MACS simulation training, with equal focus on bench and animal models. MV procedures were the most simulated, suggesting a drive towards increasing the scope of minimal access MV training. Full article

Oxidative stress is a key contributor to the pathogenesis of immune-mediated diseases through its effects on cellular metabolism, mitochondrial function, immune signaling pathways, and inflammatory tissue injury. Disruption of redox homeostasis promotes metabolic reprogramming and persistent activation of innate and adaptive immune responses, contributing to disease progression across multiple inflammatory and autoimmune disorders. Recent advances in high throughput molecular technologies have generated large scale multi-omics datasets that enable comprehensive investigation of redox-associated mechanisms at a systems level. Integration of these datasets with computational analytical approaches has facilitated the identification of multidimensional molecular signatures associated with disease development and progression. This systematic review evaluates studies applying computational frameworks to analyze redox-related molecular data in immune-mediated diseases including multiple sclerosis, systemic lupus erythematosus, lupus nephritis, rheumatoid arthritis, Sjögren’s syndrome, and inflammatory bowel disease. Across the reviewed studies, oxidative stress associated with molecular signatures were consistently linked to immune activation, mitochondrial metabolism, and inflammatory signaling pathways. Computational analyses also identified regulatory genes involved in antioxidant defense and metabolic regulation, as well as pathways associated with regulated cell death. These findings highlight the translational potential of computational redox analysis for biomarker discovery, disease stratification, and development of targeted therapeutic strategies aimed at restoring redox balance and improving clinical management of immune-mediated diseases. Full article

Background/Objectives: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Identifying reliable biomarkers that reflect the underlying immune pathophysiology of sepsis and support early risk stratification remains a major clinical priority. This prospective study aimed to evaluate the prognostic value of interleukin-6 (IL-6) measured at ICU admission in patients with sepsis and septic shock. Methods: This prospective observational study included adult patients with sepsis and septic shock admitted to the Intensive Care Unit (ICU) of the Clinical Hospital of Infectious Diseases Constanța between 2021 and 2025. Receiver operating characteristic (ROC) curve analysis with DeLong comparisons, Kaplan–Meier survival analysis, and Cox proportional hazards regression modeling were performed to assess the association between baseline IL-6 levels, in-hospital mortality, and time to death. Results: Among the analyzed biomarkers, IL-6 demonstrated the highest discriminatory performance for in-hospital mortality (AUC = 0.956; 95% CI: 0.893–0.987; p < 0.0001). The optimal cut-off value (>135.14 pg/mL) yielded a sensitivity of 87.65% and specificity of 92.86% (Youden index = 0.805). However, despite this excellent discrimination between survivors and non-survivors, baseline IL-6 levels were not significantly associated with time-to-death in Cox proportional hazards regression analysis. Conclusions: Admission IL-6 showed excellent discriminatory performance for mortality risk stratification but was not associated with survival duration in time-to-event analyses. These findings suggest that IL-6 should be interpreted primarily as an early risk stratification biomarker rather than a predictor of survival duration in patients with sepsis. Full article

The aim of this study was to shed light on activity-based prospective memory performance in children and adult patients with narcolepsy type 1 (NT1) during the first sixty minutes after morning awakening. With reference to the children (C) sample, 21 C-NT1 patients and 20 healthy controls (C-HC) were enrolled; as regards adults (A), 31 A-NT1 patients and 51 A-HC were examined. Each participant used an actigraph for one week, being asked to press the event marker button at get-up time (prospective memory task—PMT). Computing the time interval between the get-up time and the moment the event marker button was pushed, no significant differences were observed in the children’s groups. In contrast, in the adult groups, A-NT1 patients had a longer interval than A-HC. Moreover, the rate of compliant performers (those who remembered to push the event-marker button within 2 min of get-up time) and late performers was significantly different in adults only, with a low rate of compliant performers in A-NT1 patients. In C-NT1, a shorter cognitive inertia was associated with higher motor activity after awakening; in contrast, this association was not observed in A-NT1. Overall, the present pattern of results suggests that prospective memory performance is impaired only in NT1 adult patients. Full article

Background and Objectives: Age-related macular degeneration (AMD) is a multifactorial retinal disease in which inflammation and blood-retinal barrier dysfunction may contribute to disease pathogenesis. Claudin-5 is a key tight-junction protein involved in endothelial barrier integrity. Hemogram-derived indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) reflect systemic inflammatory status. This study aimed to evaluate circulating claudin-5 levels and systemic inflammatory indices in patients with wet and dry AMD and to investigate their associations with visual function. Materials and Methods: This prospective case–control study included 90 participants: 30 patients with wet AMD, 30 patients with dry AMD, and 30 healthy controls. All participants underwent detailed ophthalmologic examination, including best-corrected visual acuity (BCVA) assessment and optical coherence tomography. Serum claudin-5 levels were analyzed by enzyme-linked immunosorbent assay, and NLR, PLR, MLR, and PIV were calculated from complete blood count parameters. Group comparisons, correlation analyses, and age-adjusted analyses were performed using appropriate statistical methods. Results: Age differed significantly among the groups (p = 0.032), with the highest median age in the dry AMD group. BCVA (logMAR) also differed significantly (p < 0.001), and both AMD groups had worse visual acuity than controls. Median serum claudin-5 levels were 2.42 in controls, 3.28 in the wet AMD group, and 3.10 in the dry AMD group, with no significant between-group difference (p = 0.280). NLR, MLR, and PIV were also comparable among the groups (p = 0.310, p = 0.410, and p = 0.752, respectively). PLR differed among the groups (p = 0.019), and post hoc analysis showed higher PLR values in the dry AMD group than in the wet AMD group (p = 0.013). However, this difference was no longer statistically significant after adjustment for age (adjusted p = 0.098). Serum claudin-5 was not significantly correlated with age, BCVA, NLR, PLR, MLR, or PIV. Conclusions: Circulating claudin-5 did not differ significantly across AMD phenotypes and was not associated with age, visual function, or systemic inflammatory indices. Although PLR differed between wet and dry AMD before adjustment for age, the overall findings suggest that single-point peripheral serum measurements of claudin-5 may have limited utility in reflecting local retinal barrier-related changes in AMD. Larger longitudinal studies are needed to clarify its potential biomarker role. Full article

This study re-examines the monetary “black box” in India by investigating whether monetary-policy transmission is state-dependent across different interest-rate environments. Using quarterly data spanning 1993Q1–2024Q2, it constructs a Taylor rule-based monetary-policy shock to mitigate the endogeneity of raw policy rates and estimates dynamic discrete-threshold regressions with endogenously determined regimes. The results provide strong evidence of nonlinearity and structural instability in India’s transmission process. For real output, the weighted average call money rate (WACR) emerges as the more informative threshold variable, while wholesale price inflation is more effectively segmented by the 91-day Treasury bill yield. The findings show that the contractionary effect of monetary policy on output is most evident in the intermediate-rate regime, whereas low- and high-rate regimes exhibit weaker or counterintuitive short-run responses, consistent with crisis accommodation, delayed pass-through, and state-specific frictions. For inflation, monetary tightening is associated with a short-run price puzzle in low- and intermediate-yield regimes but produces the expected disinflationary effect in the high-yield regime. Across channels, the credit and asset-price channels matter selectively for output, while the exchange-rate channel is the most relevant for inflation only in the intermediate regime. Overall, the evidence suggests that monetary-policy transmission in India is regime-dependent and that policy assessment should distinguish between operating-rate conditions and broader market-rate regimes. Full article

In the history as well as historiography of Chinese Buddhism, the tradition has often been closely associated with death-related cultural practices and ideas, an association that has frequently carried negative connotations. Early twentieth-century reformers such as Taixu famously criticized Buddhism as a religion of ghosts and funerals and sought to redirect Mahāyāna Buddhism toward engagement with an urban, modernizing society. Contemporary Taiwanese Buddhists have realized many aspects of this socially engaged vision. Yet concern with death remains deeply embedded in Buddhist life. Far from standing in contradiction to social engagement, this concern has become one of its central expressions, most visibly in the emergence of modern Buddhist palliative care. Focusing on the writings of the scholar-monk Shi Huimin, this article examines the development of Buddhist palliative care in Taiwan in response to a secular, multireligious, and rapidly aging society, with primary attention to Huimin’s conceptual work. Rather than treating death in isolation, Huimin situates dying within a broader ethical horizon that links good death to good aging, good living, and community formation. Through his reinterpretation of the Five Śīlas and his notion of a Community Pure Land, he extends prevailing concerns with dying well toward a more comprehensive reflection on everyday moral cultivation, healthy lifestyles, and communal responsibility. In this sense, the study reads Buddhist palliative care as a site that “provincializes” dominant Euro-American frameworks of spiritual and palliative care, highlighting their particular historical and Christian-inflected origins while tracing how they are reconfigured and made productive in a multireligious, secular context. By foregrounding Huimin’s conceptual contributions, this study highlights how palliative and spiritual care are localized and reworked within Taiwanese Buddhism, connecting end-of-life care to broader questions of life, aging, and community well-being. Full article

In people-centered urban planning, enhancing the well-being of residents and tourists is one of the core objectives. Tourist emotion serves not only as a key indicator of the tourism experience but also indirectly reflects the quality of a city’s public spaces and built environment. In recent years, user-generated content has provided abundant data for understanding human emotional responses in urban environments, while deep learning models offer new technological pathways for extracting spatial–emotional associations from such data. However, existing research lacks a systematic evaluation of emotion analysis models from an urban spatial perspective and their application to uncover the relationship between emotional distribution and spatial characteristics in specific urban contexts. Based on a dataset of 9419 manually annotated travel reviews from Harbin, this study developed a multi-level evaluation framework and conducted a systematic comparison of seven emotion analysis models. This study then screened for the optimal model combinations based on two dimensions—spatial location and emotion polarity—to create a model matching matrix for mapping Harbin’s emotion map. Subsequently, a regression analysis was performed to examine the relationship between emotions and built environment elements. The results show that the ERNIE model demonstrated the best overall performance. Road density, green space density, and accommodation facility density were positively correlated with emotion, while POI diversity showed a negative correlation. This study demonstrates that emotion analysis technology can serve as a valuable analytical tool for identifying spatial patterns of sentiment, thereby offering empirical support for optimizing spatial design parameters and advancing a more people-centered approach to urban development. Full article

Background: Neuroinflammation is recognized as a key contributor to Parkinson’s disease (PD), but the relationships between inflammatory signaling, immune-state alterations, and cell-type-specific transcriptional programs remain unclear. Methods: Public transcriptomic datasets, including GSE20141 (discovery cohort) and the substantia nigra subset of GSE114517 (external validation cohort), were analyzed. Genes identified by exploratory differential-expression screening in the discovery cohort were intersected with predefined inflammation- and chemokine-related gene sets to define a candidate space for downstream prioritization. Protein–protein interaction, Gene Ontology, KEGG, and immune-signature analyses were performed, followed by machine learning-based feature prioritization using Elastic Net, support vector machine-recursive feature elimination, and random forest. Prioritized candidates were further evaluated by cross-platform validation, single-nucleus transcriptomic mapping, and a hypothesis-generating in silico perturbation analysis in PD astrocytes. Results: Seventeen genes were retained at the intersection of PD-related differentially expressed genes and inflammation-/chemokine-associated gene sets. These candidates formed a response module enriched in mitochondrial organization, oxidative phosphorylation, and mitophagy pathways. Immune-signature analysis suggested an altered transcriptome-derived immune landscape in PD, with changes in NK cell-related signatures and significant correlations between immune-state scores and the candidate genes. Machine learning-based prioritization yielded five shared candidates, of which only CCL2 and PAK6 showed same-direction support with nominal significance in the external validation cohort. Single-nucleus transcriptomic analysis localized CCL2 predominantly to astrocytes, whereas PAK6 was more strongly associated with neuronal populations, particularly OTX2-positive ventral midbrain neurons. In silico perturbation analysis further predicted that CCL2 suppression in PD astrocytes may be associated with translational- and ribosome-related regulatory programs. Conclusions: CCL2 and PAK6 emerged as prioritized candidate biomarkers associated with PD-related inflammatory and chemokine-linked transcriptional alterations in the substantia nigra. More broadly, this study provides a multi-layered framework for candidate prioritization, cross-platform validation, and cell-type-level contextualization in PD neuroinflammation. Because the study is computational and the perturbation analysis is predictive, orthogonal experimental validation will be required to determine whether CCL2 and PAK6 are biomarkers of disease-associated transcriptional states, functional contributors to PD pathogenesis, or both. Full article

Ceramides are central bioactive sphingolipids that regulate diverse cellular processes, including membrane organization, energy metabolism, and stress signaling. Emerging evidence has implicated that ceramide dysregulation is associated with the onset and progression of heart failure. This review introduces the understanding of ceramide metabolism, focusing on its biosynthesis, and functional roles in cardiomyocytes. In addition, the contribution of systemic ceramides derived from circulating lipoproteins and peripheral tissues to cardiovascular risk is also discussed. In parallel, it is highlighted that cardiomyocyte-intrinsic ceramide synthesis plays physiological and pathological roles in the heart. Particularly, excessive ceramide accumulation is detrimental for cardiac function, through multiple mechanisms, such as lipotoxic effects, mitochondrial impairment, inflammation, and cell death. The current review discusses the potential diagnostic and therapeutic strategies targeting ceramide metabolism, as well as the open questions about ceramide association with heart disease. Full article

Detection of pre-seismic ionospheric electric field perturbation remains an open challenge in the scientific community, hindered by methodological biases and a lack of reproducible frameworks. In this study, we investigate the existence of ionospheric perturbations associated with earthquakes by developing a deep learning framework for detecting anomalous patterns in global ionospheric electric field measurements provided by the DEMETER satellite and evaluating their statistical relationship with global seismicity. We developed an unsupervised LSTM autoencoder framework trained under a rolling-window scheme with two alternative optimisation strategies. The iterative rolling-window approach enabled the preservation of long-term temporal continuity while adapting to the non-stationary ionospheric background. Anomalies detected by the model were subjected to a seismic association and evaluated statistically. Findings were consistent across multiple network configurations, independent training optimisation strategies and different segments of the dataset, demonstrating strong methodological robustness. Our study suggests that modern sequential deep-learning models, when combined with an adaptive temporal training approach and statistical evaluation, provide an effective tool for the systematic detection and statistical quantification of associations between ionospheric electric field perturbations and seismic events. Full article

Purpose: To investigate the association between COVID-19 infection and the 1-year risk of acute urinary retention (AUR) and related urological complications in patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTs). Materials and Methods: Using the TriNetX global network, patients with BPH and LUTs between January 2020 and January 2024 were identified. Participants were classified into a COVID-19 cohort (N = 32,948) and a non-COVID control cohort (N = 434,123). Propensity score matching (1:1) balanced demographics, comorbidities, medications, and laboratory parameters. The primary outcome was AUR within one year. Secondary outcomes included Foley catheterization, urinary tract infection (UTI), gross hematuria, bladder stones, and prostate-related surgery. Results: After matching, 32,918 patients remained in each cohort. The COVID-19 group showed a significantly higher 1-year incidence of AUR compared with controls (2.18% vs. 0.32%; aHR 6.89, 95% CI 5.62–8.45; p < 0.0001). Increased risks were also observed for Foley catheterization (aHR 4.10), UTI (aHR 3.52), and prostate-related surgery (aHR 6.02). Kaplan–Meier analysis demonstrated persistent divergence in AUR-free survival. Conclusion: COVID-19 infection is independently associated with a markedly increased risk of AUR and urological complications in patients with BPH, highlighting the need for closer post-infection monitoring. Full article

Background: Left ventricular (LV) thrombosis after blunt trauma is uncommon and is most often attributed to traumatic coronary artery injury; however, it can also arise from severe myocardial contusions. Here, we report a case of LV thrombosis due to severe myocardial contusion without coronary artery injury. Case Presentation: A 36-year-old man struck by industrial fan fragments presented with hemorrhagic shock. Focused Assessment with Sonography for Trauma revealed cardiac tamponade. An emergent sternotomy was performed under cardiopulmonary bypass via the femoral vessels, which exposed severe contusion-associated hemorrhage with epicardial–myocardial dissection at the LV apex. On postoperative day (POD) 5, transthoracic echocardiography showed apical akinesia with mural thrombi; prophylactic anticoagulation was escalated and later transitioned to warfarin. Coronary computed tomography on POD 21 and invasive angiography at 6 months revealed negative findings. The thrombi resolved within 3 months; however, apical akinesia persisted. After discontinuing anticoagulation, a transient ischemic event occurring at 9 months prompted direct oral anticoagulant therapy. Apical akinesia persisted for over 7 years without recurrent thrombosis. Conclusion: This case underscores the importance of vigilance for intracardiac thrombosis in severe contusions, as well as the value of stepwise imaging (contrast echocardiography) and cautious, individualized discontinuation of anticoagulation when regional dysfunction persists. Full article