Search Results (538)

Recent findings in nutritional epidemiology report an association between high dietary phosphorus intake and increased cancer risk. Building on the author’s analysis of breast cancer incidence in the Study of Women’s Health Across the Nation (SWAN), this paper presents a theoretical–conceptual model and a hypothesis to guide further population-study replication. To strengthen the initial SWAN analysis signal, a sensitivity analysis increased the number of controls in the nested case–control design from four to five per case. This adjustment modestly raised the relative risk (RR) of breast cancer incidence among middle-aged women consuming >1800 mg/day of dietary phosphorus (compared with 800–1000 mg/day) from RR: 2.30 to 2.38 (95% CI: 0.95–5.95; p = 0.06), improving statistical precision from the original p = 0.07. However, the result remains an exploratory pilot signal, not a confirmed association. Because clinical trials cannot ethically expose participants to potential harm from phosphate toxicity, a confirmed association relies on observational research. As in historical tobacco–cancer investigations, secondary analyses are needed across large cohort studies to examine dietary phosphorus intake and incidence of major cancer types. Relevant cohorts include the Nurses’ Health Study, Women’s Health Initiative, Health Professionals Follow-Up Study, National Health and Nutrition Examination Survey (NHANES) Epidemiologic Follow-Up Study, European Prospective Investigation into Cancer and Nutrition (EPIC), and the Canadian Study of Diet, Lifestyle and Health. Effect estimates can be synthesized using meta-analytic methods following PRISMA-P 2015 guidelines. Dietary phosphate modification may offer a cancer prevention strategy with substantial public health impact and clinical implications. Full article

Objectives: The present study aimed to examine the relationship between dietary habits and anthropometric characteristics of high school adolescents. Participants and Methods: This cross-sectional study involved randomly selecting 104 students (34 boys and 70 girls) who were 17–19 years old. To evaluate dietary habits, a validated and standardized EPIC-Norfolk frequency food questionnaire was used, and anthropometric characteristics of the participants were assessed. Results: The most often consumed foods during the week were meats and fruits, while the least frequently consumed were fish and vegetables. For all participants, intake below the recommended levels was for alpha-carotene, total carbohydrate sugars, vitamin D, milk, dairy products, nuts, and seeds. Intake of proteins and iron was below the recommended levels in girls. Boys had a lower intake of proteins and fruits compared to girls. No differences were observed in the consumption of macronutrients. The median of all anthropometric values was within the reference values. Boys were slightly older and had significantly higher values of body weight and height, BMI, waist circumference, and waist-to-hip-ratio (WHR) compared to girls. In addition, systolic blood pressure (SBP) was significantly higher in males than in females. Participants with increased arterial blood pressure (ABP) showed significantly higher energy intake from fat, sodium intake, and total fat intake compared to those with normal ABP. Participants with increased WHR had significantly higher energy intake, intake of sodium, and total carbohydrates compared to those with normal WHR. Conclusions: This study shows that adolescents’ eating habits (particularly intake of fat and sodium) were associated with anthropometric values, ABP, and WHR, which present risks for cardiometabolic diseases in adulthood. Full article

Octopuses of the genus Scaeurgus inhabit upper bathyal benthic habitats and are composed of five recognized species. In this study, we conducted morphological and molecular phylogenetic analyses of two individuals of Scaeurgus and provided additional field observations of the genus in seamounts of the Nazca and Salas y Gómez ridges (southeast Pacific Ocean) over the last six years. Specifically, two specimens of Scaeurgus were collected at 234 m depth in 2019 during the EPIC oceanographic cruise onboard the R/V Mirai (JAMSTEC, Japan), and five other specimens were video recorded at depths between 210 and 340 m during three oceanographic expeditions in 2024 onboard the R/V Falkor (too) (Schmidt Ocean Institute). Both specimens collected during 2019 corresponded to medium-sized females (18 and 38 mm mantle length). Each arm presented 108–132 biserial suckers, nine to ten lamellae per demibranch, and a W-shaped funnel organ. Morphological traits evidenced a closer resemblance of these specimens to S. patagiatus from the NW Pacific; however, phylogenetic evidence did not clearly differentiate them from S. unicirrhus from the Atlantic and the Mediterranean. Although molecular evidence supports the hypothesis of the monophyly of Scaeurgus, further morphological and genetic analysis are needed to delimit and validate the different species proposed along the global distribution of the genus. Full article

This article argues that racism did not originate with the modern invention of race but crystallized out of a much older imperial grammar that had already learned how to naturalize domination through embodied difference. Long before race emerged as a named category, ancient and medieval empires developed durable ways of converting historically produced hierarchies into features of nature, the cosmos, and divine order. Through a comparative genealogy spanning early Mesopotamian epic, Near Eastern imperial inscriptions, Egyptian visual regimes, Greek philosophy and historiography, biblical scripture, South Asian metaphysics, late antique encyclopedism, and medieval Marian devotion, the article shows how inequality was repeatedly anchored in the body, in genealogy, in geography, and in moral psychology. Across these traditions, political authority is consistently masculinized, while subordination is feminized, animalized, or rendered reproductively vulnerable. Patriarchy and racialization thus emerge as co-constitutive imperial technologies rather than as separate or sequential phenomena. Modern racism did not invent hierarchy; it rendered an ancient logic portable, inheritable, and globally scalable by fastening domination to visible human difference. By situating race within a longue durée history of empire and male domination, the article reframes contemporary debates on racism as questions of imperial continuity rather than modern deviation. Full article

Purpose: Whether medical cannabis reduces opioid use during early chemotherapy remains unclear. We examined cannabinoid and opioid prescribing among patients with GI cancers initiating chemotherapy. Methods: Patients with GI cancers initiating chemotherapy (2016–2025) were identified from the Epic COSMOS database. Cannabis exposure was defined as prescriptions for FDA-approved cannabinoids recorded in the EHR; non-prescription cannabis obtained through dispensaries were not captured. Patients with any cannabis or opioid use in the prior year or death within 90 days were excluded. Multivariable logistic regression evaluated factors associated with cannabinoid use. Results: Among 144,981 patients, 2.4% received cannabinoids within 90 days of chemotherapy initiation. Cannabinoid recipients were more likely to receive opioids than nonrecipients (60.6% vs. 31.1%, p < 0.01). In adjusted analyses, cannabinoid prescribing was more common among Black patients (aOR 1.45; 95%CI 1.30–1.61), women (aOR 1.11; 95%CI 1.03–1.19), and individuals with pancreatic cancer (aOR 3.26; 95%CI 2.97–3.58). Prescribing varied by region and declined over time, relative to 2017. Conclusions: Early cannabinoid prescribing was not associated with reduced opioid use. Use was more common among patients with pancreatic cancer and among Black patients, highlighting clinical and structural variation in supportive-care practices. Full article

Background/Objectives: Epigenetic modifications, particularly DNA methylation, contribute to tumor progression and therapy resistance. Guadecitabine, a hypomethylating agent (HMA), has shown promising clinical activity when combined with carboplatin in preclinical models. We evaluated the combination of guadecitabine with carboplatin as a second-line treatment for extensive-stage small-cell lung cancer (SCLC; NCT03913455), one of the deadliest malignancies. Here, we report methylome changes in peripheral blood mononuclear cells (PBMCs) collected at baseline and during treatment from patients on the trial. Methods: PMBC DNA was analyzed using Infinium HumanMethylationEPIC v1.0 bead chips. Data were processed, and differentially methylated positions (DMPs) were identified and analyzed for pathway enrichment using bioinformatic approaches, and immune deconvolution analyses were conducted to investigate the impact on immune cell composition. Results: Direct comparison of PBMCs between cycle 2 day 5 (C2D5; post-treatment) vs. cycle 1 day 1 (C1D1; pre-treatment) revealed a greater number of hypomethylated DMPs (380 DMPs in C2D5 vs. C1D1 PBMCs; p < 0.05, |β| > 20%). Moreover, when first compared with normal PBMCs from cancer-free controls, the number of hypomethylated DMPs was even greater in C2D5 than in C1D1 (1771 vs. 237 DMPs, respectively; p < 0.05, |β| > 20%). Long interspersed nucleotide elements-1 (LINE-1) were significantly hypomethylated in PBMCs after HMA treatment (C2D5 vs. C1D1). Pathway analysis of hypomethylated DMPs revealed significant alterations in key signaling pathways, including NF-κB, Rho GTPase, and pulmonary fibrosis in C1D1 vs. C2D5. Normal PBMCs to C1D1 PBMCs revealed changes in IL-3 signaling, Fcγ receptor-mediated phagocytosis, and molecular mechanisms of cancer. Deconvolution analysis revealed a greater percentage of monocytes in C1D1 vs. normal PBMCs; after HMA treatment, percentages of monocytes and B cells decreased, while the eosinophil percentage increased in C1D1 vs. C2D5. Conclusions: HMA treatment has a global impact on PBMC methylomes in cancer patients. DNA methylation changes were associated with biological pathways related to PBMC function, and shifts in distinct immune cell populations were observed. Full article

Background/Objectives: Lifestyle behaviors such as smoking, vaping, and physical activity can induce epigenetic modifications that influence health trajectories and may provide forensic value. DNA methylation signatures linked to these behaviors offer potential for behavioral inference, personalized health assessment, and improved investigative practices. This study aimed to characterize methylation patterns associated with nicotine exposure and exercise using buccal cell DNA profiling, and to evaluate the extent to which these patterns differentiate harmful and protective lifestyle habits. Methods: Buccal epithelial DNA was analyzed using the Illumina Infinium MethylationEPIC v2 BeadChip to assess genome-wide methylation. Participants were categorized by smoking status, vaping behavior, and exercise activity. Differentially methylated regions (DMRs) and CpG sites were identified through pairwise comparisons among smokers, vapers, non-smokers/non-vapers, athletes, and sedentary individuals. A threshold of p < 1 × 10⁻⁴ was applied for significant differentially methylated CpG sites. Results: Distinct epigenetic profiles were associated with smoking/vaping and physical activity. Five DMRs differentiated smokers from non-smokers/non vapers, while 11 DMRs distinguished vapers from the same reference group. Twenty-eight DMRs displayed divergent methylation patterns between smokers and vapers. Exercise also showed measurable epigenetic influence: control athletes exhibited 26 significantly differentially methylated CpG sites relative to non-athletes, and smoker athletes demonstrated 126 suggestive differential sites compared to sedentary smokers. Additionally, 63 sites differentiated smoker athletes from non-smoker/non-vaper non-athletes, indicating interactions between risk-associated and health-promoting behaviors. Conclusions: Buccal cell DNA methylation profiling effectively captured signatures associated with smoking, vaping, and physical activity. These findings underscore the potential of epigenetic markers for lifestyle assessment in both personalized medicine and forensic investigations. Full article

Background: Small nucleolar RNAs (snoRNAs) are emerging regulators of tumorigenesis, yet their pan-cancer landscape and immunological roles remain poorly defined. This study investigates the expression pattern, prognostic significance, and immune correlation of SNORA12 across cancers, with mechanistic validation in osteosarcoma. Methods: We integrated RNA-seq data from the TCGA, TARGET, and GTEx databases to evaluate SNORA12 expression and its prognostic value using Cox regression and Kaplan–Meier analyses (progression-free survival, PFS). The correlation between SNORA12 and the tumor immune microenvironment was assessed using six independent algorithms (TIMER, EPIC, CIBERSORT, IPS, MCP-counter, xCELL). In vitro, the regulatory effect of SNORA12 on the immune checkpoint TIGIT was validated by overexpression and knockdown experiments in osteosarcoma cell lines (SW1353, U2OS) and NK cells. Results: SNORA12 expression exhibited significant tumor-type specificity. High SNORA12 expression was associated with poor prognosis in glioma (HR = 1.31, p = 0.006) but favorable outcomes in pancreatic (HR = 0.51, p = 0.01) and breast cancer (HR = 0.56, p = 0.02). Immunologically, SNORA12 showed robust positive correlations with CD8+ T cell infiltration in thyroid carcinoma (THCA) and lung adenocarcinoma (LUAD) across multiple algorithms. Notably, SNORA12 expression was positively correlated with m6A modifiers METTL3 and YTHDF1, and negatively correlated with the demethylase FTO. Experimentally, overexpression of SNORA12 in osteosarcoma cells and primary NK cells significantly upregulated TIGIT at both the mRNA and protein levels, while SNORA12 knockdown in NK92 cells reduced TIGIT expression. Conclusions: This pan-cancer analysis positions SNORA12 as a tumor type-specific prognostic biomarker and reveals its novel role as a positive regulator of TIGIT in osteosarcoma, offering a potential mechanistic link between snoRNA dysregulation and immune evasion. Full article

The gut–skin axis is increasingly implicated in psoriasis pathogenesis, yet the cross-compartment convergence of molecular programs remains incompletely defined. We constructed a conceptual “Triple-Hit” multi-omics framework by integrating five independent public datasets spanning gut microbial functional remodeling (shotgun metagenomics), systemic immune cell methylomes (PBMC and CD8+ T-cell EPIC 850K), and lesional skin regulatory layers (miRNA and bulk RNA-seq). In the gut compartment, functional profiles exhibited a selective reduction in microbial lipid catabolic potential, including decreased fatty acid degradation and a lowered composite lipid degradation score, alongside heterogeneous shifts across SCFA-associated metabolic pathways. Systemically, PBMC methylomes revealed widespread regional remodeling (45,396 DMRs) enriched for membrane-proximal signaling and cytoskeletal programs, while CD8+ T cells showed specific epigenetic alterations in lipid- and glycosphingolipid-associated loci, suggesting a systemic metabolic–epigenetic alignment. In the skin, we identified a compact miRNA signature (168 DE-miRNAs) and a mechanistically interpretable, directionality-constrained miRNA–mRNA bridge that aligns with an AMP-dominant inflammatory transcriptome, consistent with reduced post-transcriptional restraint. Collectively, these findings support a convergent multi-omics framework linking putative microbial metabolic remodeling, systemic immune priming, and cutaneous effector programs. This study provides a systems-level perspective on psoriasis pathogenesis, highlighting the metabolic–epigenetic–transcriptional convergence as a potential avenue for therapeutic intervention. Full article

The Soil and Water Assessment Tool (SWAT) model has been widely used to simulate ecohydrological processes in watersheds. However, the SWAT model uses a simplified Environmental Policy Impact Climate (EPIC) model to simulate the leaf area index (LAI), creating a critical gap in accurately simulating evapotranspiration (ET) and runoff in semi-arid regions. This work aims to fill this gap by modifying the SWAT source code to integrate high-resolution Global Land Surface Satellite (GLASS) leaf area index (LAI) data. The modified version was applied to the semi-arid Wuding River Basin and calibrated using a Fortran-based dynamic dimension search (DDS) algorithm. The results show a relatively significant improvement in the accuracy of the daily-scale runoff simulation (R² from 0.52 to 0.71 and NSE from 0.52 to 0.7 for the calibration period, and R² from 0.21 to 0.58 and NSE from 0.2 to 0.51 for the validation period). The improved version also corrects the unrealistic default LAI peak (from >5.0 to 1.5–3.0), correcting the multi-year average ET from 251.7 mm to 341.8 mm. The improved vegetation growth module of the SWAT model effectively improved the accuracy of hydrologic simulation in the semi-arid region and enhanced the structural robustness of SWAT for water management. Full article

Background: Hepatocellular carcinoma (HCC) stands as a prevalent global health issue with increasing incidence and mortality rates. Hepatocellular carcinoma (HCC) exhibits profound molecular and clinical heterogeneity, which limits the effectiveness of current therapeutic strategies. Circadian rhythm disruption has been implicated in metabolic reprogramming, proliferation, and immune modulation in cancer, but its role in shaping HCC heterogeneity remains poorly defined. Methods: Four public HCC transcriptomic cohorts (TCGA-LIHC, CHCC, LIRI, LICA) were integrated using RMA normalization and ComBat for batch correction. Consensus clustering based on 31 core circadian clock genes (CCGs) identified robust molecular subtypes. Multi-omics characterization—including genomic alterations, pathway activity (GSEA/GSVA), immune microenvironment profiling (CIBERSORT, EPIC, MCP-counter, xCell), and drug-sensitivity prediction (pRRophetic/oncoPredict)—was performed to delineate subtype-specific biological properties. A nine-gene CCG-based RiskScore model was constructed using LASSO Cox regression to internally validate subtype robustness and intra-subtype risk stratification. Results: Using consensus clustering of 31 core CCGs in TCGA-LIHC and three independent validation cohorts (CHCC, LIRI, LICA), we identified three reproducible subtypes—Cluster-1 (metabolic–quiescent), Cluster-2 (transition–intermediate), and Cluster-3 (proliferation–inflammatory)—which were recapitulated across cohorts and showed distinct overall survival (Cluster-3 worst; log-rank p values significant across datasets). Multi-omic characterization revealed that Cluster-3 exhibits the highest tumor mutational burden and CNV burden with enrichment of TP53/AXIN1/TERT alterations, strong activation of cell-cycle, E2F, and G2M programs, and an immune-hot yet immunosuppressed microenvironment enriched for TAMs, Tregs and MDSCs. By contrast, Cluster-1 shows relative genomic stability, dominant hepatic metabolic signatures (fatty-acid oxidation, bile-acid and xenobiotic metabolism) and an immune-cold phenotype. Single-cell mapping linked ALAS1 expression to malignant hepatocytes predominating in Cluster-1, whereas NONO and CSNK1D localized to stromal (CAFs/TECs) and both malignant/immune compartments respectively in Cluster-3, providing a cellular mechanism for subtype-specific metabolism, angiogenesis and immune modulation. Finally, a nine-gene CCG-based RiskScore validated prognostic stratification and drug-sensitivity predictions indicated subtype-specific therapeutic vulnerabilities (notably increased predicted TKI sensitivity in Cluster-3). Conclusion: In conclusion, this study proposes a robust circadian rhythm-based molecular classification of hepatocellular carcinoma, revealing three biologically and clinically distinct subtypes characterized by divergent genomic alterations, metabolic programs, immune microenvironment states, and prognostic patterns. By integrating bulk and single-cell transcriptomic data, we identify subtype-specific roles of key circadian regulators—including ALAS1, NONO, and CSNK1D—in shaping tumor metabolism, proliferation, stromal remodeling, and immune suppression. These findings highlight circadian dysregulation as a potential upstream factor associated with HCC heterogeneity and provide a conceptual framework for developing subtype-tailored mechanistic studies and circadian-informed therapeutic strategies. Full article

Polyphenols represent the largest and most diverse class of dietary antioxidants. Epidemiological evidence linking specific (poly)phenol classes, such as flavonoids and lignans, to breast cancer (BC) risk remains limited and largely inconclusive in prospective studies. The aim of this study is to examine the association between the intake of total (poly)phenols—and its classes and subclasses—and BC risk—overall and by subtypes (estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2))—in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The EPIC cohort includes 257,960 adult women from seven European countries. During a mean follow-up of 14 years, there were 10,722 incident overall BC cases. Associations were computed using Cox regression models adjusted for potential confounders. No significant associations were found between total (poly)phenol intake and overall BC risk (HR_{Q5 vs. Q1} = 1.02; 95% CI: 0.95–1.11). In addition, null associations were mostly found between classes and subclasses of (poly)phenols and BC subtypes. After stratifying by menopausal status, no significant associations were observed. In conclusion, this study found no evidence of associations between the intake of any class or subclass of (poly)phenols and BC risk in the European population. Full article

Background: Erectile dysfunction is a common late effect of prostate radiotherapy. Hydrogel spacers aim to reduce radiation exposure to nearby structures by increasing the distance between the prostate and surrounding tissues, potentially preserving sexual function. Methods: In this retrospective cohort study of 117 prostate cancer patients who received hydrogel spacers, we compared pre- and post-insertion radiation dose and anatomical positioning of erectile structures using paired t-tests. Longitudinal sexual function, assessed via EPIC scores, was modeled using linear mixed-effects regression with natural splines (df = 3), incorporating random intercepts and slopes to account for within-subject variability. Results: Spacer insertion significantly reduced radiation dose to the left and right neurovascular bundles (mean reductions: 1.66 Gy, 95% CI: 1.32–2.00; and 1.64 Gy, 95% CI: 1.28–2.01, respectively; p < 0.01) and the right perineal artery (1.33 Gy, 95% CI: 0.57–2.09; p < 0.01). No significant dose changes were observed for the penile bulb or left perineal artery, nor in anatomical distances. However, spatial displacement was confirmed by significant overlap and integrated volume changes. Longitudinal modeling showed a significant decline in sexual function between 12 and ≥36 months post-treatment (Spline 2: β = –12.72, 95% CI: −18.52–−6.92 and Spline 3: β = –6.68, 95% CI: −10.96–−2.40; p < 0.01). Conclusions: Hydrogel spacer insertion was associated with significant reductions in radiation dose to erectile structures, most notably the neurovascular bundles and the right perineal artery. However, longitudinal analyses revealed no corresponding preservation of sexual function. These findings suggest that while hydrogel spacers effectively reduce radiation exposure to key anatomical structures, their clinical benefit for maintaining erectile function remains uncertain. Full article

Background/Objectives: We assessed the changes in the quality of life (QOL) of patients with localized prostate cancer who were treated with IMRT, either with or without Androgen Deprivation Therapy (ADT), using the Expanded Prostate Index Composite (EPIC). Methods: Changes in EPIC summary and subdomain scores were evaluated using longitudinal analyses at eight time points up to three years after IMRT. Results: The urinary score and four subdomain scores decreased significantly four weeks after the start of IMRT but returned to the baseline level three months after IMRT. This pattern of change remained consistent, regardless of whether ADT was administered or not. The longitudinal changes in bowel score were the same as those in the urinary score. The recovery of the bowel bother subdomain score was rapid, occurring as early as one month after IMRT. Regardless of whether ADT was administered, there was no difference in longitudinal changes in bowel scores. The sexual score remained consistently low throughout the survey period, ranging from 33 to 35. The baseline score for the sexual bother subdomain was 94.44, but the score for the sexual function subdomain was extremely low at 8.24. The hormonal score at the start of IMRT was 87.37 but increased significantly at two and three years after IMRT. The hormonal bother subdomain score decreased significantly six months after IMRT initiation but subsequently increased, becoming significantly higher three years after IMRT. Conclusions: IMRT has made it possible to minimize deterioration in the quality of life of patients with localized prostate cancer by reducing adverse events. Full article

This article rereads Odysseus’s encounter with the Sirens in the Odyssey through the lens of sound, arguing that the episode stages a foundational tension between knowledge and alterity in Western thought. Drawing on Emmanuel Levinas’s notion of the “temptation of temptation,” the essay shows how Odysseus’s famous stratagem—hearing the Sirens while bound to the mast—models a form of mediated proximity that allows sound to be collected without ethical exposure. Close readings of Homeric Greek, especially the Sirens’ claim to knowledge of ὅσσα γένηται, reveal that their song gestures not merely toward retrospective epic knowledge but toward natality and coming-into-being, a dimension Homer pointedly withholds. By placing the Sirens alongside early colonial soundscapes and modern reflections on cartography, the article argues that Western listening practices privilege mastery over vulnerability. Against this tradition, the Sirens’ unheard song marks a suppressed alternative: listening as openness, risk, and ethical relation. Full article