Search Results (3,157)

A-type granites represent high-temperature, highly differentiated felsic magmas formed in post-collisional and intraplate tectonic settings. While whole-rock geochemistry constrains bulk melt evolution, zircon trace element systematics provide higher-resolution insights into crystallization conditions, including temperature, oxidation state, and differentiation intensity. This study integrates whole-rock geochemical data with zircon trace element analyses to evaluate the extent to which zircon records magmatic evolution in Neoproterozoic A-type granites from Sinai, Egypt. Whole-rock compositions define a high-silica, ferroan differentiation trend characterized by enrichment in high-field-strength elements (HFSE) and pronounced negative Ba–Sr–Ti anomalies, indicating advanced fractional crystallization. Zircon trace element patterns exhibit strong heavy rare earth element (HREE) enrichment (Yb up to 1757 ppm), systematically negative Eu anomalies (mean Eu/Eu* = 0.32), and elevated Hf concentrations (up to 14,453 ppm; mean = 4763 ppm), reflecting progressive melt differentiation. Ti-in-zircon thermometry yields crystallization temperatures ranging from 562 °C to 1384 °C. However, most values cluster between 757 °C and 872 °C (mean ≈ 837 °C), indicating sustained high-temperature magmatic conditions. The broader temperature range likely reflects analytical uncertainties, assumptions in Ti activity, and possible outliers. Positive Ce anomalies indicate moderately oxidized crystallization environments. Systematic relationships among zircon Hf, Eu/Eu*, Yb/Gd, Th/U, and Ti-in-zircon temperatures demonstrate a strong coupling between zircon chemistry and whole-rock differentiation trends. These relationships are supported by statistically significant correlations, indicating that zircon trace element systematics provide a robust, semi-quantitative framework for interpreting melt evolution, while preserving independent constraints on temperature and redox state. Full article

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder that confers an increased risk of venous thromboembolism (VTE) and subsequent pulmonary embolism (PE). The risk stems from chronic systemic inflammation promoting endothelial dysfunction and hypercoagulability. Data on specific inpatient outcomes and procedural needs in patients with IBD with acute PE remains limited. This study explores these outcomes at a national level. Methods: We conducted a Nationwide Inpatient Sample (NIS) database analysis (2016–2020). Adult hospitalizations for acute PE were identified using ICD-10-CM codes and stratified based on IBD status. Multivariable regression analysis was performed to determine independent associations between IBD status and in-hospital mortality, length of stay (LOS), cardiac complications, and ICU-level interventions (intubation, central venous catheterization (CVC), arterial line placement, requirement of vasopressors), and blood transfusion. Results: Among 377,143 acute PE hospitalizations, 4123 (1.1%) had IBD. Patients with IBD were younger (58.72 vs. 62.78 years, p < 0.001) and had lower prevalence of diabetes mellitus, hypertension, end-stage renal disease (ESRD), dyslipidemia, overweight/obesity, coronary artery disease and smoking status (p < 0.05). Despite a favorable baseline profile, patients with IBD had a longer length of stay (LOS) (8.82 vs. 7.30 days, p < 0.001) but no significant association with in-hospital mortality (aOR = 0.93, p = 0.281). Multivariable analysis showed patients with IBD had higher odds of requiring CVC placement (OR = 1.42, p < 0.001), vasopressors (OR = 1.22, p = 0.05), and blood transfusions (OR = 1.78, p < 0.001). Conversely, they had lower odds of cardiac arrest (OR = 0.64, p < 0.001) and cor pulmonale (OR = 0.32, p = 0.012). Conclusions: patients with IBD with acute PE represent a complex population with high resource utilization. Future research is needed the development of IBD-specific PE risk stratification, targeted management, prophylactic and therapeutic anticoagulation guidelines. Full article

Alzheimer’s disease (AD) is an aging-related neurodegenerative disease characterized by an initial memory impairment that progresses to a widespread cerebrocortical failure, culminating in death. Understanding the molecular mechanisms that protect brain function during aging may help reveal novel targets for the development of effective treatments for the memory and cognitive deficits associated with AD. In this study, we analyzed a gene expression dataset generated from the prefrontal cortices of individuals showing no neurological or cognitive abnormalities. The gene expression profiles were used to identify candidate protective genes. We then compared the expression patterns of these genes in aging with their expression patterns in AD, thereby enabling us to pinpoint the genes that potentially contribute to brain resilience that delays or prevents aging-related dementia. We selected seven genes that are potentially protective for aging and AD, and have known homologues in Caenorhabditis elegans (C. elegans). Among these genes, SRPK2, AAK1, EFR3A and MAPK10 were previously implicated in attenuating AD-related cognitive decline. Our experiments demonstrated that all seven genes prioritized by our resilience model significantly extended the lifespan of C. elegans. Given the important relationship between neuronal functional integrity and lifespan (i.e., lifespan vs. brain health span), this work suggests the predicted AD resilience genes could serve as important candidate targets for therapeutic intervention. Full article

Chosen family caregivers assume caregiving roles by choice rather than by blood or legal relation. Chosen family caregivers play a critical yet often invisible role in supporting older adults living with HIV. Unlike traditional family caregivers, many chosen family members are themselves living with HIV or other chronic health conditions, creating unique dynamics of mutual support, resilience, and vulnerability. Older LGBTQ adults are disproportionately reliant on chosen family, often due to stigma, estrangement from biological family, or social marginalization, highlighting distinct challenges in caregiving relationships. Women in chosen family roles frequently experience compounded burdens, balancing emotional, physical, and logistical care responsibilities alongside broader social and structural pressures. Despite their essential contributions, chosen family caregivers remain largely unrecognized within healthcare systems, limiting their access to formal support, respite, and decision-making authority. This commentary synthesizes the existing literature and conceptual perspectives to examine the social, gendered, and health-related dimensions that distinguish chosen family caregiving. It highlights key gaps in recognition and support and outlines implications for policy, research, and practice aimed at strengthening care for older adults living with HIV. Full article

Raman spectroscopy is a non-destructive, label-free analytical technique that can probe biochemical alterations in tissues and cells. Raman spectroscopy, being sensitive to biochemical perturbations, can potentially provide early and real-time identification of changes preceding morphological changes, allowing early diagnosis as well as disease monitoring. Recent research has demonstrated its broad utility across diverse clinical domains, including cancers, neurological conditions, and infections. Raman spectroscopy combined with machine learning algorithms allows rapid assessment and automated pipelines and can act as a clinical adjunct, enhanced by integrating tools like principal component analysis (PCA), linear discriminant analysis (LDA), random forests, and deep-learning architectures. These models allow interpretation of complex spectra, and decipher meaningful biomarkers in heterogeneous clinical samples. This review highlights the earliest and most recent progress in Raman-based non-destructive diagnosis, underscoring advances in cancer diagnosis and challenges faced in clinical settings. Full article

Background: Consumption of ultra-processed foods (UPFs) continues to rise alongside a growing body of epidemiological evidence linking high UPF intake to adverse health outcomes, including cardiovascular disease and type 2 diabetes, in the general population. However, the factors underlying these associations remain incompletely understood, underscoring the need to examine components beyond traditional nutrient composition. In particular, food-processing additives are increasingly recognized as defining features of industrially formulated UPFs. Objective/Methods: In this study, we used a large food label database to cross-sectionally examine the presence and co-occurrence of selected additives (sorbates, benzoates, phosphate additives, and non-nutritive sweeteners [NNSs]) in sweetened beverages sold by the 25 top-selling U.S. food and beverage manufacturers in 2020. Results: We found that sweetened beverages marketed in the U.S. frequently contain multiple additive classes concurrently, supporting the concept that these products represent complex chemical exposure mixtures rather than simple combinations of water and sweeteners. Formulations containing multiple additives were substantially more common than simpler formulations, with many beverages simultaneously containing combinations of sweeteners, preservatives, and phosphate additives. Products containing NNS exhibited higher additive clustering compared to products containing added sugar. Conclusions: Collectively, these findings support the need for broader consideration of beverage formulation complexity in nutrition research, dietary guidance, and policy regulation. Full article

Heritable thoracic aortic diseases (HTADs) comprise a genetically heterogeneous group of disorders predisposing patients to thoracic aortic aneurysm and dissection, yet current medical therapies remain limited to slowing disease progression rather than preventing aortic wall failure. Although pathogenic variants affect diverse genes encoding extracellular matrix (ECM) components, smooth muscle contractile proteins, and signaling molecules, these defects converge on disruption of the mechanobiological systems that maintain aortic wall integrity. The thoracic aorta functions as a mechanically integrated tissue in which endothelial cells, vascular smooth muscle cells, fibroblasts, immune cells and ECM continuously sense and respond to pulsatile biomechanical forces. Genetic perturbations affecting ECM architecture, contractile force generation, or growth factor signaling alter force transmission across this multicellular network, leading to maladaptive mechanotransduction, cellular phenotypic modulation, and progressive aneurysm formation. Using Marfan syndrome as a paradigmatic ECM-driven aortic disease, this review synthesizes current understanding of how altered biomechanics, biochemical signaling and immune responses reshape intercellular communication and activate disease-associated signaling pathways, including dysregulated TGF-β, nitric oxide, angiotensin receptor, calcium-dependent, and metabolic signaling. We highlight how single-cell transcriptomic analyses have elaborated changes in different cell-level functions including, ECM degradation, iron homeostasis, circadian/stress responses. Changes in iron metabolism in different cell types in the aorta suggest possible coordinated metabolic changes in aneurysm progression. These mechanistic insights enable the identification of cell-type–specific pathogenic programs and therapeutic discovery through systems-level approaches. We highlight the translational opportunities and challenges emerging from mouse models and human studies, emphasizing that therapeutic efficacy depends not only on pathway selection but also on disease stage, cellular context, and timing of intervention. Together, these findings support a model in which HTAD progression reflects dynamic, multicellular failure of mechanobiological homeostasis and provide a framework for the development of more precise, mechanism-based therapies. Full article

Platelet lipidomics offers a window into the thromboinflammatory responses to acute coronary syndromes (ACS) and chronic coronary syndromes (CCS), yet differences between the platelet lipidomes of these two coronary artery disease subtypes remain poorly characterized. In this pilot study, untargeted platelet lipidomics and miRNA transcriptomics were performed on platelets isolated from 19 ACS and 57 CCS patients undergoing coronary angiography, integrated with routine clinical and hematological traits in statistical network analyses and cross-validated machine learning models. Platelet lipidomics identified 81 lipid features significantly altered between ACS and CCS (FDR q < 0.05), predominantly involving phosphatidylcholines, lysophosphatidylcholines, and ceramides. Cer 18:2;O2/24:0 showed the strongest inverse association with ACS of any identifiable lipid (q = 0.0394, OR = 0.297, 95% CI [0.171, 0.515]), while increased Cer 18:0;O2/22:1 (q = 0.088, OR = 3.072, 95% CI [1.607, 5.878]) and Cer 18:0;O2/18:0 (q = 0.088, OR = 2.791, 95% CI [1.515, 5.145]) demonstrate nominally significant promotive effects on ACS. Differential correlation analysis further identified oxidized phospholipid species as connectivity hubs in ACS-specific lipid networks, a pattern not detectable by differential abundance approaches alone. Although untargeted lipidomics did not meaningfully outperform a routine clinical trait benchmark in ACS classification, phosphatidylcholine-trained models achieved modest gains in AUROC, and the prominent ceramide signal—platelet-specific and mechanistically distinct from plasma ceramide risk scores—supports a targeted validation strategy centered on a ceramide-enriched platelet lipid panel in prospective, adequately powered cohorts. Full article

Understanding complex systems requires analytical tools capable of covering nonlinear dynamics, structural complexity, and informational uncertainty simultaneously. In this context, chaos theory, fractal analysis, and entropy measures provide complementary perspectives for examining any irregular behavior in natural and socio-economic systems. This paper examined the relation between the Geopolitical Risk Index and the World Uncertainty Index to the volatility of West Texas Intermediate crude oil, gold, and Bitcoin over the period October 2010–February 2026. The analysis was motivated by the recent intensification of geopolitical tensions, particularly conflicts involving Iran, the United States, and Israel, which have significantly heightened uncertainty in global energy and financial markets. The empirical analysis first investigated the underlying complexity of the variables using entropy, chaos, and fractionality measures. Results from the Shannon, R-T entropy, Kolmogorov–Sinai complexity, Hurst, H-M and Lo’s R/S statistics, Phillips, and GPH fractionality tests consistently indicate entropy, fractal persistence, and long-range dependence across the series. In addition, the largest Lyapunov exponents and Hurst coefficients confirmed the presence of chaotic dynamics. The results reveal strong regime heterogeneity with geopolitical shocks exerting significantly stronger effects during high-uncertainty periods. Forecast comparisons show that regime-switching models outperform linear specifications, highlighting the importance of fractal and nonlinear dynamics in understanding financial market responses to geopolitical risk. Full article

While bacterial skin infections are highly prevalent worldwide, their eradication with conventional topical medications remains highly challenging. Cinnamic acid (CA) is a naturally occurring molecule with interesting antibacterial properties, but its efficacy is hindered by poor aqueous solubility and skin permeability. To overcome these challenges, CA was encapsulated within novasomes, which are multilamellar vesicles composed of fatty acids, cholesterol, and nonionic surfactants. The novasomes were optimized using a 2³ factorial design and the optimized formulation was incorporated in a carbopol gel base and evaluated for spreadability, rheological properties, drug release, ex vivo skin permeation and deposition, and antibacterial efficacy. The optimized novasomes featured desirable properties, including high drug entrapment (94.75 ± 0.05%), nanometric particle size (123.80 ± 1.44 nm), and negative zeta potential (−36.63 ± 0.61 mV). CA novasomal gel exhibited shear-thinning behavior, coupled with thixotropic properties. It also achieved approximately 1.7-fold higher flux through rat skin compared with the free CA gel. Moreover, the novasomes showed a two-fold reduction in the minimum inhibitory concentration of the drug against E. coli compared with the drug suspension. These findings support the potential of CA novasomal gel to enhance its antibacterial activity and skin permeability, making it a promising approach for topical delivery of this naturally occurring compound. Full article

High-fat diet (HFD)-induced hyperlipidemia is an experimental metabolic condition characterized primarily by dysregulated serum lipid levels and hepatic lipid accumulation, with associated oxidative, inflammatory, mitochondrial, and cardiovascular alterations. This study investigated the therapeutic efficacy of epigallocatechin gallate (EGCG)-functionalized selenium nanoparticles (EGCG-SeNPs) against HFD-induced metabolic and hepatic injury, in comparison with free EGCG, sodium selenite (Na₂SeO₃), and Lipanthyl. EGCG-SeNPs were characterized by dynamic light scattering, zeta potential analysis, transmission electron microscopy, X-ray diffraction, and UV–visible spectrophotometry. Forty-two adult male rats were allocated into six groups: control, HFD, HFD/Lipanthyl, HFD/EGCG, HFD/Na₂SeO₃, and HFD/EGCG-SeNPs. High-fat diet (HFD) feeding induced pronounced dyslipidemia, elevated hepatic enzymes, increased cardiac injury biomarkers, enhanced lipid peroxidation and nitrosative stress, depletion of antioxidant defenses, and disruption of the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) regulatory axis. HFD also increased nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while altering mitochondrial apoptotic markers, including B-cell lymphoma 2 (Bcl-2), cytochrome c, and caspase-3. At the transcriptional level, HFD increased lipogenic gene expression and reduced the expression of genes related to fatty-acid oxidation, metabolic regulation, and mitochondrial homeostasis. EGCG-SeNPs showed the greatest overall improvement among the tested interventions, as indicated by an improved lipid profile, hepato-cardiac injury biomarkers, antioxidant status, inflammatory markers, apoptotic markers, hepatic architecture, and Nrf2 immunoreactivity. Collectively, EGCG-SeNPs may mitigate HFD-induced hepatic lipotoxicity and associated cardiac stress through coordinated modulation of lipid metabolism, redox balance, inflammation, and mitochondrial homeostasis. Full article

Background: Cancer treatment-induced ulcerative mucositis (UM) is a debilitating toxicity in patients with cancers of the lip, oral cavity, and pharynx (CLOP). This study evaluated the association of chemotherapy-induced (CT-UM) and radiotherapy-induced ulcerative mucositis (RT-UM) with burden of illness (BOI), focusing on hospital length of stay (LOS) and total charges, and examined disparities in outcomes. Methods: This retrospective cohort study analyzed 2019 National Inpatient Sample (NIS) data. Adult patients (≥18 years) hospitalized with CLOP (ICD-10-CM C00–C14) undergoing inpatient surgery, chemotherapy, or radiotherapy were included. CT-UM (K12.31) and RT-UM (K12.33) were identified as secondary diagnoses. Survey-weighted generalized linear models (negative binomial for LOS; gamma for charges) adjusted for demographics, comorbidities (Elixhauser score), insurance, income, and Diagnosis-Related Groups (DRG; surgical vs. medical) were used. Results: Among 59,710 weighted CLOP hospitalizations, 820 had CT-UM and 1010 had RT-UM. Patients with UM were younger and had varying comorbidity burdens. Unadjusted analyses showed prolonged geometric mean LOS for CT-UM (5.66 vs. 3.81 days, p < 0.001) and RT-UM (4.95 vs. 3.81 days, p = 0.001), with lower total charges ($48,645 and $42,938 vs. $56,267). Multivariable analyses confirmed RT-UM was associated with increased LOS (adjusted coefficient 1.33, 95% CI 1.14–1.55) but lower charges (0.67, 95% CI 0.56–0.81). In patients >50 years, CT-UM showed stronger effects (LOS 1.80, 95% CI 1.49–2.15; charges 0.79, 95% CI 0.65–0.98). Significant disparities were observed: females, Black and Hispanic patients, and Medicaid beneficiaries experienced greater BOI (prolonged LOS and/or higher charges in subgroups). Associations persisted in DRG- and procedure-stratified sensitivity analyses, suggesting treatment interruptions as a key driver. Conclusions: Ulcerative mucositis in hospitalized CLOP patients is associated with prolonged LOS but lower charges, likely due to treatment modifications, and disproportionately affects vulnerable populations. These findings highlight the need for proactive oral care protocols, multidisciplinary integration, and equity-focused interventions to reduce the burden of this toxicity and improve cancer treatment outcomes. Full article

Background: Gastroparesis presents with frequently debilitating symptoms of nausea, vomiting, abdominal pain, bloating and early satiety, resulting in high healthcare utilization. Resilience, defined as the inherent and modifiable ability of an individual to adapt and recover positively to stress, is crucial for patients with chronic diseases but has not been studied in gastroparesis. We aimed to investigate if resilience correlates with acute care utilization and symptom severity in patients with gastroparesis. Methods: We conducted a single-center prospective observational study of patients with gastroparesis. Resilience was assessed using the 10-item Connor–Davidson Resilience scale (CD-RISC). Symptom severity was assessed through the Gastroparesis Cardinal Symptom Index (GCSI). Gastric emptying severity using scintigraphy or wireless motility capsule was categorized as mild, moderate, or severe based on consensus recommendations. Acute care utilization and hospitalizations in the last 12 months, comorbidities, medications, and demographic information were collected. Count outcomes were modeled using negative binomial regression due to overdispersion. Models were adjusted for age, sex, and symptom severity. Results: Among 40 consecutive patients (mean age 39 ± 16, 88% female), gastric emptying severity was mild in 35%, moderate in 15%, severe in 30%, and unknown in 20%. Mean resilience score was 29 ± 8 and mean GCSI was 2.96 ± 1.14. Gastroparesis symptoms did not correlate with gastric emptying severity (p = 0.5). In a linear regression model, no statistically significant correlation was observed between resilience and mean GCSI score in unadjusted or adjusted models. In negative binomial regression models, greater symptom severity was strongly associated with higher Emergency Department (ED)/urgent care visits (IRR 3.12; 95% CI 1.60–6.98; p < 0.001) and hospitalization rates (IRR 3.36; 95% CI 1.62–8.57, p = 0.006). Resilience was not a significant predictor of either (IRR 1.07; 0.95–1.22; p = 0.2 and IRR 1.02; 0.89–1.18; p = 0.7). Conclusions: Among patients with gastroparesis, no statistically significant association was detected between resilience and symptom severity, gastric emptying, or acute-care utilization after accounting for clinical and demographic factors. Symptom severity was the dominant predictor of ED visits and hospitalizations. These findings suggest that symptomatic disease burden, rather than objective gastric emptying severity, is the primary driver of acute healthcare utilization in this cohort. Full article

Background: Early and accurate risk stratification of patients suspected of serious infection is essential for improving outcomes, but existing diagnostic and predictive tools have limited accuracy. The objective was to compare the performance of an FDA-authorized AI diagnostic test, the Sepsis ImmunoScore, against widely available biomarkers and clinical tools for diagnosis of sepsis and prediction of in-hospital mortality and intensive care unit (ICU) admission. Methods: This multicenter observational study included 6027 adult patients suspected of infection across 7 U.S. hospital sites. The Sepsis ImmunoScore’s predictive performance was compared to the sequential organ failure assessment (SOFA) score, procalcitonin (PCT), C-reactive protein (CRP), Systemic Inflammatory Response Syndrome (SIRS) score, National Early Warning Score (NEWS), and quick SOFA (qSOFA). Primary outcomes included sepsis as defined by Sepsis-3 criteria, in-hospital mortality, and ICU admission. Predictive accuracy was assessed using area under the receiver operating characteristic curve (AUC), and 95% confidence intervals were generated and hypothesis testing conducted using the bootstrap method. Results: The Sepsis ImmunoScore demonstrated statistically significant superior performance across all outcomes. For sepsis prediction, the Sepsis ImmunoScore achieved an AUC of 0.82, compared to SOFA (0.72), procalcitonin (PCT) (0.70), C-reactive protein (CRP) (0.61), SIRS (0.59), NEWS (0.69), and qSOFA (0.67). For in-hospital mortality prediction, the Sepsis ImmunoScore achieved an AUC of 0.80, outperforming SOFA (0.72), PCT (0.67), CRP (0.58), SIRS (0.60), NEWS (0.72), and qSOFA (0.69). For ICU admission, the Sepsis ImmunoScore reached an AUC of 0.74, superior to SOFA (0.63), PCT (0.64), CRP (0.54), SIRS (0.60), NEWS (0.70), and qSOFA (0.65). All differences between the Sepsis ImmunoScore and comparators were statistically significant. Conclusions: The Sepsis ImmunoScore significantly improved predictive accuracy for sepsis, in-hospital mortality, and ICU admission compared to six conventional clinical scores and biomarkers. This AI-based tool may enhance risk stratification and clinical decision-making, potentially leading to more timely sepsis interventions and improved outcomes. Full article

Background/Objectives: Single-stranded oligonucleotides (ssODNs) are used as donor templates for therapeutic gene editing by CRISPR-Cas9 cleavage and homology-directed repair (HDR). Although ssODN sequence fidelity is critical to the safety and efficacy of editing, standard quality control methods cannot resolve individual nucleotide errors. Methods: We performed deep sequencing of ssODNs from three manufacturers and amplicons from edited hematopoietic stem/progenitor cells. Results: We find that synthesis errors are present in all ssODNs tested at rates that vary more than two-fold among manufacturers, at positions that are dependent on sequence context. These synthesis errors are propagated into the genome by HDR at frequencies proportional to their abundance in the ssODN. In our sickle cell mutation correction protocol, the most prevalent SNEs are predicted to produce benign β-globin variants, while the less frequent frameshift deletions are predicted to generate β-thalassemia-like alleles. Conclusions: Current quality control standards are insufficient to detect these errors, and deep sequencing of ssODNs should be incorporated into regulatory submissions for clinical gene editing programs. Full article