Search Results (478)

Background/Objectives: This study investigated variations in DNA methylation patterns associated with chronic pain and propensity for recurrent pressure injuries (PrI) in persons with spinal cord injury (SCI). Methods: Whole blood was collected from 81 individuals with SCI. DNA methylation was quantified using Illumina genome-wide arrays (EPIC and EPICv2). Comprehensive clinical profiles collected included secondary health complications, in particular current PrI and chronic pain. Relationships between recurrent PrI and chronic pain and whether the co-occurrence of both traits was mediated by changes in DNA methylation were investigated using R packages limma, DMRcate and mCSEA. Results: Three differentially methylated positions (DMPs) (cg09867095, cg26559694, cg24890286) and one region in the micro-imprinted locus for BLCAP/NNAT are associated with chronic pain in persons with SCI. The study cohort was stratified by PrI status to identify any sites associated with chronic pain and while the same three sites and region were replicated in the group with no recurrent PrI, two novel, hypermethylated (cg21756558, cg26217441) sites and one region in the protein-coding gene FDFT1 were identified in the group with recurrent PrI. Gene enrichment and genes associated with specific promoters using MetaScape identified several shared disorders and ontology terms between independent phenotypes of pain and recurrent PrI and interactive sub-groups. Conclusions: DMR analysis using mCSEA identified several shared genes, promoter-associated regions and CGI associated with overall pain and PrI history, as well as sub-groups based on recurrent PrI history. These findings suggest that a much larger gene regulatory network is associated with each phenotype. These findings require further validation. Full article

Recently, the concept of subprojectivity domains for modules has been introduced as a means of quantifying the level of projectivity exhibited by a module. In this research article, we focus on the subprojectivity domain of Goldie torsion modules. In particular, we establish that a ring denoted as R is classified as right nonsingular if and only if the subprojectivity domain of each Goldie torsion module is closed under submodules. In addition, we demonstrate that a right C-ring is a right nonsingular ring if and only if every module possesses an epic ecf-flat envelope, which is further equivalent to each Goldie torsion module having an epic projective envelope. Full article

Background/Objectives: Worldwide, men experience a higher incidence of pancreatic cancer (PC) than women. Methods: To increase understanding of the underlying reasons for this sex-related difference, we analysed general and sex-related risk factors for PC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (women/men No. = 293,682/136,728; 717/577 PC-cases). Results: Cox proportional hazards models showed a 1.31-fold higher risk of developing PC for men compared to women (HR, 95% CI 1.15–1.49) after adjustment for age, smoking history, BMI, diabetes, and alcohol consumption. Associations of PC with established risk factors did not differ between men and women, with the exception of a greater risk of PC among women with greater attained body height, meat consumption and cigarettes smoked (1.12 (1.05–1.19) per 5 cm, 1.18 (1.02–1.36) per 100 g/d, 1.42 (1.27–1.59) per 10/d; respectively). Among child-bearing women, long cumulative duration of breastfeeding was inversely associated with risk of PC (HR 0.74, 95% CI 0.61–0.89) for >5.7 months of breastfeeding (median) relative to ≤5.7 months and among HRT users, cumulative duration of HRT use was inversely associated with PC risk (HR 0.71, 95% CI 0.53–0.95, >2.4 versus ≤2.4 years). Further reproductive and hormonal factors, such as age at menarche, number of full-term pregnancies, age at menopause, or use of oral contraceptives, were not significantly associated with PC risk. Conclusions: Pooled analyses of large cohort studies are needed to confirm these results, and detailed data on the type and intensity of HRT are required to better evaluate its effect. Full article

The rising prevalence of elderly obesity in developed countries poses a public health challenge, since body composition changes during aging are associated with higher risks of chronic diseases. We cross-sectionally explored the relationship between diet, physical activity, and sex-specific differences in body composition among 378 elderly previously enrolled in the Florence European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Information on dietary habits and lifestyle was collected through validated questionnaires. Adherence to the Italian Mediterranean Index (IMI), Dietary Approaches to Stop Hypertension (DASH), and Greek Modified Mediterranean Diet (GMMD) a priori dietary patterns was calculated. Anthropometric measures were taken by trained personnel, and body composition parameters were estimated via bioelectrical impedance. In age- and energy-intake-adjusted regression models, adherence to the DASH and IMI patterns was associated with healthier body composition among women, while no significant relationship emerged among men. Fitness activities and total recreational physical activity revealed positive associations with healthier body composition (lower % fat mass, higher % muscle mass, and reduced waist circumference) in both sexes. These findings highlight the synergistic effect of diet and physical activity on body composition in the elderly and underscore the need for sex-specific interventions for promoting healthy aging. Full article

Background/Objectives: Pancreatic cancer (PC) is among the most aggressive malignancies, often diagnosed at late stages. MicroRNAs (miRNAs) and proteins released from the tumor microenvironment into body fluids represent promising non-invasive biomarkers for early cancer detection. In this study, we took advantage of an innovative ultrasound (US)-based instrument (SonoWell^®, Inno-Sol srl, Rome, Italy) to treat PC cells in order to promote and amplify the release of molecules, with the aim of identifying novel putative diagnostic PC biomarkers. Methods: Three human pancreatic adenocarcinoma cell lines (T3M-4, Panc02.03, and PaCa-44) and a non-cancerous pancreatic epithelial line (HPanEPic) were subjected to US using the SonoWell instrument. MiRNAs released in the supernatants were profiled by TaqMan-based qRT-PCR microfluidic cards, while proteins were analyzed by antibody arrays. Publicly available datasets of circulating miRNAs in PC patients were also reviewed. Results: Expression levels of 22 miRNAs in T3M-4 cells, 11 in Panc02.03, and 22 in PaCa-44, none of which were identified in the non-cancerous cell line profiling, were increased in the supernatant of US-treated as opposed to control cells. Among the statistically significant miRNAs or miRNAs common to at least two tumor cell lines, the expression levels of miR-155-5p, miR-320a, miR-32-5p, and miR-93-5p were also found to be significantly upregulated in sera from PC patients compared to the results for healthy controls. With regard to proteins released after sonication, several molecules were identified as candidate biomarkers in cancer US supernatants (Beta-2 microglobulin, CA125, CA19-9, CEA, CRP, Galectin-3, TIMP-1, uPA, and VEGF-A). Conclusions: We demonstrated that US-mediated sonoporation can promote and amplify the release of small molecules, miRNAs, and proteins into cell culture supernatants for consideration as putative biomarkers, thus encouraging further studies aimed at directly validating their expression levels in sera/plasma from PC patients and at deepening their role in the treatment of PC. Full article

Background/Objectives: Stereotactic radiotherapy (SABR) is a recognized standard treatment modality for localized prostate cancer, though data is limited regarding the risk of increased toxicity when including the elective nodes (ENI) for high-risk disease. Placement of a peri-rectal spacer can decrease the risk of toxicity to the rectum when administering high-dose prostate radiotherapy. Herein we present toxicity findings for patients who underwent five-fraction prostate SABR with ENI in a setting with peri-rectal spacing. Methods: Genitourinary (GU) and gastrointestinal (GI) toxicity data was analyzed for patients with ≥12 months of follow-up who were treated with curative-intent five-fraction SABR with ENI. A radiopaque hydrogel spacer was placed for all eligible patients. The primary endpoints were the three-month toxicity, which was measured using CTCAEv5, and quality of life (QoL), which was measured using EPIC 26. Secondary endpoints included intermediate-term GU and GI toxicity between 6 and 12 months. Univariable logistic regression was used to assess associations between baseline patient characteristics and the presence of a peri-rectal hydrogel spacer and GU and GI toxicity. Results: Among the 100 patients treated, 69 had grade group 4/5 disease and 40 had evidence of T3a/3b extension. The ENI dose was 25 Gy/5, and 78.9% of the patients received 40 Gy to the prostate, while the remainder were given 36.25–37.5 Gy. A total of 70% underwent placement of a radiopaque hydrogel spacer. GU toxicities of grades 1, 2, and 3 were reported in 28/22/1% of the patients, respectively, at three months; in 18/11/0% at six months; in 11/9/0% at nine months; and in 5/3/0% at twelve months. GI toxicities of grades 1 and 2 were reported in 14/0% of the patients at three months and 8/1% at six months, with all cases resolving by nine months. MCICs in the urinary incontinence, urinary obstructive, and bowel domains were reported in 5%, 18%, and 4% at three months; by twelve months, these values decreased to 2%, 2%, and 0%, respectively. The presence of a hydrogel spacer resulted in reductions in high and intermediate doses to the rectum and had a significant inverse association with short-term GI toxicity (HR: 0.09, CI: 0.27–0.35, p: 0.0004). Conclusions: In this prospective series, five-fraction SABR including ENI was well tolerated, and the presence of a hydrogel spacer was associated with a lower risk of rectal toxicity. Full article

Background/Objectives: We examined the association between dietary intake and blood concentrations of one-carbon metabolism (OCM)-related nutrients in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Blood concentrations and dietary intake of the vitamins riboflavin (B2), Pyridoxal 5′-phosphate (PLP and B6), folate (B9), B12, and methionine, concentrations of homocysteine, and dietary intake of betaine, choline, and cysteine were pooled from 16,267 participants in nine EPIC nested case–control studies. Correlation analyses between dietary intakes and blood concentrations were carried out. Principal component (PC) analysis identified latent factors in the two sets of measurements. Results: Pearson correlations between dietary intakes and blood concentrations ranged from 0.08 for methionine to 0.12 for vitamin B2, 0.15 for vitamin B12, 0.17 for vitamin B6, and 0.19 for folate. Individual dietary intakes showed higher correlations (ranging from −0.14 to 0.82) compared to individual blood concentrations (from −0.31 to 0.29). Correlations did not vary by smoking status, case–control status, or vitamin supplement use. The first PC of dietary intakes was mostly associated with methionine, vitamin B12, cysteine, and choline, while the first PC of blood concentrations was associated with folate and vitamin B6. Conclusions: Within this large European study, we found weak to moderate associations between dietary intakes and concentrations of OCM-related nutrients. Full article

Background/Objectives: DNA methylation profiles have emerged as robust biomarkers of ageing, leading to the development of “epigenetic clocks” that estimate biological age. Most established clocks (e.g., Horvath’s 353-CpG pan-tissue clock and Hannum’s 71-CpG blood clock) require dozens to hundreds of CpG sites. This study presents a novel saliva-specific epigenetic clock built on 10 sites identified from Illumina MethylationEPIC (850 k) array data. Methods: Saliva DNA methylation was analysed from 3408 individuals (age range 15–89 years, 68% male, 32% female, no diagnosed disease) from the Muhdo Health Ltd. dataset (2022–2024), and 10 CpG sites were selected where methylation levels showed the strongest positive correlations with chronological age (Pearson r = 0.48–0.66, p < 1 × 10−20). These CpGs map to genes involved in developmental and metabolic pathways (including ELOVL2, CHGA, OTUD7A, PRLHR, ZYG11A, and GPR158). A linear combination of the 10 methylation sites was used to calculate a “DNA methylation age”. Results: The 10-CpG clock’s predictions were highly correlated with chronological age (r = 0.80, R2 = 0.64), with a mean absolute error of ~5.5 years. Its performance, while slightly less precise than Horvath’s or Hannum’s multi-CpG clocks, is notable given the minimal marker set. It was observed that all 10 clock CpGs undergo age-related hypermethylation. The biological significance of these loci is discussed, along with the potential health and forensic applications of a saliva-based epigenetic age predictor. Conclusions: This study demonstrates that a saliva-specific epigenetic clock using only 10 CpG sites can capture a substantial portion of age-related DNA methylation changes, providing a cost-effective tool for age estimation. Full article

This article explores Greco-Roman mythology through the lens of ecocriticism, focusing on how sacred landscapes and natural elements were imagined as animate, divine, and morally instructive forces. In ancient Mediterranean cultures, nature was not merely a passive setting for human action but a dynamic presence—rivers that judged, groves that punished, and mountains that sheltered or revealed. Texts such as Ovid’s Metamorphoses, Virgil’s Georgics, and Homer’s epics present nature as both sacred and sentient, often intervening in human affairs through transformation, vengeance, or protection. Forests, springs, and coastlines functioned as thresholds between human and divine, civilization and wilderness, mortal and eternal. By analyzing these representations, this article reveals a rich tradition in which nature teaches, punishes, guides, and transforms, long before ecological consciousness became a formalized discipline. Drawing connections between classical literary landscapes and contemporary environmental concerns, the article argues that myth can inform today’s ecological imagination, offering an alternative to extractive, anthropocentric paradigms. Recovering the reverence and narrative agency once granted to nature in classical thought may help us rethink our ethical relationship with the environment in the age of climate crisis. Full article

Background/Objectives: The COVID-19 pandemic has been associated with significant increases in mental-health-related concerns in adolescents, including eating disorders. Disparities in screening, diagnosis, and treatment impact adolescents with eating disorders. This study aimed to describe the patterns in the prevalence and the associations between eating disorder diagnoses and demographic factors in adolescent patients since the start of the COVID-19 pandemic. Methods: We performed a retrospective cohort study examining adolescent patients (aged 12 to 21) with an eating disorder (ED) diagnosis documented between January 2019 and July 2023 using Epic Systems Corporation’s Cosmos, a de-identified dataset aggregated from electronic health record (EHR) data. We examined the differences in demographic factors by utilizing chi-square and Kruskal–Wallis rank sum tests. Results: A total of 82,435 distinct adolescent and young adult patients with eating disorder diagnoses were included in the analytical dataset. The overall prevalence of EDs has increased since 2019. The median age of patients with an ED decreased between 2019 and 2023. There was a decrease in other eating disorder diagnoses and an increase in avoidant-restrictive food intake disorder (ARFID) during the study period. There was a decrease in the proportion of individuals who identified as White and an increase in the proportion of adolescents from historically minoritized racial and ethnic groups (i.e., African American or Black and Hispanic). There was also an increase, during this study period, in the proportion of adolescents with an ED diagnosis who were from more socially vulnerable communities. Conclusions: Our study describes the changes in the prevalence of sociodemographic factors in adolescent patients with EDs since the start of the COVID-19 pandemic. Further studies should address screening, diagnostic, and treatment barriers for EDs in historically underserved communities. Full article

Background/Objectives: The human insula is a key structure implicated in integrating internal states and external food cues, yet its precise role remains unclear, in part due to the temporal limitations of neuroimaging techniques like fMRI. To address this gap, we conducted an exploratory study using an intracranial EEG (iEEG) to investigate how the insula encodes both the subjective and objective properties of food-related stimuli, and how this encoding is modulated by hunger and satiety. Methods: Eight patients with drug-resistant epilepsy undergoing a pre-surgical evaluation between 2017 and 2023 participated in this study. Depth electrodes implanted in the insular cortex recorded event-related potentials (ERPs) in response to visual food cues. The sessions were conducted in two prandial states (hungry and satiated). The subjective ratings (appetite and palatability) and objective nutritional values (e.g., calories, carbohydrates) were collected and analyzed using paired t-tests, MANOVAs, and partial correlations. Results: Hunger increased the ERP amplitudes within the 350–450 ms interval, consistent with the EPIC model and positive alliesthesia, while satiety unexpectedly enhanced the early responses (150–250 ms). Importantly, the neural activity related to nutritional values was largely uncorrelated with the subjective ratings, suggestive of distinct processing streams. The mid- and posterior insula showed greater sensitivity to both subjective and nutritional information than the anterior insula. Conclusions: These findings offer novel electrophysiological insights into how the insula differentiates between implicit and explicit food-related signals, depending on the homeostatic state. This work supports a dual-route model of food cue processing, and may inform interventions targeting insular activity in disordered eating. Full article

Background/Objectives: Sepsis is a costly and life-threatening condition caused by a dysregulated host response to infection. Lack of a reliable, timely diagnostic for sepsis leads to under- and overdiagnosis, suboptimal outcomes, and strained hospital resources. Our Lady of the Lake Regional Medical Center (OLOLRMC) implemented a sepsis learning health program to evaluate and improve outcomes through standardized ED workflows and the incorporation of a novel sepsis diagnostic test. Methods: We report the results of the first year of experience following the implementation of the learning health initiative and sepsis testing. Data from the Epic EHR were analyzed across two groups: pre-implementation (April 2023–July 2023) vs. post-implementation (August 2023–July 2024), and temporally matched cohorts (April–July 2023 vs. April–July 2024). We assessed clinical outcomes (sepsis-associated mortality, hospital length of stay, or HLOS), and resource utilization (antibiotic use, blood cultures). Results: Post-implementation, sepsis-associated mortality dropped from 10.9% to 6.6% in the temporally matched group (p < 0.001). There was also a 0.76-day reduction in mean HLOS among sepsis DRG patients (p < 0.05). Blood culture utilization fell from 50.8% to 45.7%, driven by reductions in blood culture utilization among patients receiving a Band 1 IntelliSep score. Conclusions: The FMOLHS experience demonstrated significant benefits to patient outcomes and resource utilization after implementing a sepsis QI initiative including protocolized and standardized ED workflows via a nurse-driven triage system with sepsis testing for the early risk stratification of patients who present to the ED with signs and symptoms of infection. Full article

This study examines the critical role of institutional quality in driving corporate adaptation to climate change within the EU-27 member states from 2006 to 2023. It aims to investigate how governance factors—control of corruption, government effectiveness, rule of law, and regulatory quality—influence business strategies for environmental resilience and sustainability, focusing on environmental investments and industrial production. Employing fixed and random effects regression models on a balanced panel dataset, we analyze two dependent variables: environmental protection investment corporations (EPIC), measuring investments in pollution prevention and environmental degradation reduction, and industrial production (IP), reflecting output in mining, manufacturing, and utilities. A composite institutional quality index, derived through principal component analysis (PCA) from the four governance indicators, captures their collective impact, reducing multicollinearity and enhancing analytical robustness. Control variables, including final energy consumption, environmental tax revenues, expenditure on environmental protection, and a Paris Agreement dummy, are incorporated to test the institutional quality effect. Results demonstrate that higher institutional quality significantly enhances EPIC, particularly in countries with greater environmental tax revenues, indicating that robust governance and fiscal policies incentivize sustainable corporate investments. Conversely, the effect on IP is less consistent, with higher fossil energy consumption and lower environmental tax revenues driving production, suggesting a reliance on high-polluting industries. The Paris Agreement positively influences IP, reflecting stronger climate-focused industrial strategies post-2015. These findings underscore the pivotal interplay between institutional quality and environmental fiscal policies in fostering corporate adaptation to climate change. Over the long term, strong governance is essential for aligning business practices with sustainability goals, reducing environmental degradation, and mitigating climate risks across the EU. This study highlights the need for cohesive policies to support green investments and transition industries toward renewable energy sources, addressing disparities in environmental performance among EU member states. Full article

Cross-calibration is an essential technique for calibrating Earth observation satellite sensors, which involves taking nearly simultaneous images of a ground target to compare an uncalibrated sensor to a well-calibrated reference sensor. This study introduces the hyperspectral Trend-to-Trend (T2T) cross-calibration technique utilizing EPICS Cluster 13 Global Temporally Stable (Cluster 13-GTS) as the calibration target, offering better temporal stability than previous targets used in T2T cross-calibration by an absolute difference of 0.4%, between coefficients of variation across all bands excluding CA band. A multispectral sensor-specific normalized hyperspectral profile was developed using the EO-1 Hyperion hyperspectral profile over Cluster 13-GTS to improve Spectral Band Adjustment Factor (SBAF) estimation, capturing sensor-specific Relative Spectral Response (RSR) variations and introducing the ability to use the multispectral sensor-specific hyperspectral profile for calibrating future satellite sensors like Landsat Next with super-spectral bands. SBAFs were derived from EO-1 Hyperion normalized to multispectral sensors, which were interpolated to 1 nm, ensuring precise spectral band adjustments following a Monte Carlo simulation approach for uncertainty quantification. Results show that reference sensor-specific hyperspectral profiles at 1 nm spectral resolution improve SBAF accuracy and exhibit total uncertainty within 5.8% across all bands and all sensor pairs with L8 as the reference sensor. These findings demonstrate that integrating reference sensor-specific high-resolution hyperspectral data and stable calibration targets improves T2T cross-calibration accuracy, supporting future super-spectral missions such as Landsat Next. Full article

Pancreatic cancer (PC) is highly aggressive, with a 5-year survival rate of 12.8%, making early detection vital. However, non-specific symptoms and precursor lesions complicate diagnosis. Existing tools for the early detection of PC are limited. CAFs are crucial in cancer progression, invasion, and metastasis, yet their role in PC is poorly understood. This study analyzes mRNA data from PC samples to identify CAF-related genes and drugs for PC treatment using algorithms like EPIC, xCell, MCP-counter, and TIDE to quantify CAF infiltration. Weighted gene co-expression network analysis (WGCNA) identified 26 hub genes. Our analyses revealed eight prognostic genes, leading to establishing a six-gene model for assessing prognosis. Correlation analysis showed that the CAF risk score correlates with CAF infiltration and related markers. We also identified six potential drugs, observing significant differences between high-CAF and low-CAF risk groups. High CAF risk scores were associated with lower responses to immunotherapy and higher tumor mutation burdens. GSEA indicated that these scores are enriched in tumor microenvironment pathways. In summary, these six model genes can predict overall survival and responses to chemotherapy and immunotherapy for pancreatic cancer, offering valuable insights for future clinical strategies. Full article