Search Results (62,794)

Background/Objectives: Laryngeal cancer remains a global health burden, particularly in regions with high tobacco and alcohol consumption. This study aimed to provide a comprehensive epidemiological overview of laryngeal cancer in Western Greece and to assess overall survival (OS), disease-specific survival (DSS), and key prognostic factors over a 21-year period. Methods: A retrospective cohort study was conducted, including patients diagnosed and treated for laryngeal cancer at the Otorhinolaryngology Department of the University General Hospital of Patras between 1997 and 2017. Demographic, clinical, histopathological, and treatment data were collected. Survival outcomes were estimated using Kaplan–Meier analysis and compared using the log-rank test. Multivariable Cox proportional hazards regression was performed to identify independent prognostic factors. Significance was set at p ≤ 0.05. Results: A total of 211 patients were included (mean age 62.7 years; 95.3% male). Active smoking was reported in 97.6% of cases. Most patients (88.6%) were diagnosed at advanced stages (III–IV), with glottic tumors being the most common (61.1%). The 5-year OS and DSS rates were 47.0% and 55.6%, respectively. Larger tumor size, nodal involvement, and advanced stage were significantly associated with reduced DSS in univariable analysis (p < 0.001). Cox regression confirmed tumor size (HR = 1.665, 95% CI: 1.187–2.336) and nodal status (HR = 1.546, 95% CI: 1.176–2.031) as independent predictors of DSS. Conclusions: The findings highlight the impact of advanced disease at diagnosis and the central prognostic role of tumor burden in laryngeal cancer in Western Greece. Early detection and timely management remain essential to improve patient outcomes. Full article

Coronavirus infections pose a significant threat to both human and animal health, causing widespread morbidity, mortality, and substantial economic losses. While vaccines are crucial for prevention, their efficacy is often limited by the high mutation rate of these viruses. This underscores the urgent need for anti-coronavirus drugs, particularly broad-spectrum antiviral agents. In this study, we demonstrated for the first time that Biochanin A (BCA), a bioactive isoflavonoid found in legumes, exhibits broad-spectrum antiviral activity against coronaviruses. BCA potently inhibits porcine epidemic diarrhea virus (PEDV), as well as human coronaviruses HCoV-OC43 and HCoV-229E in vitro, with EC₅₀ values of 6.90, 2.80 and 15.4 μM, respectively. In a lethal mouse model of HCoV-OC43-induced encephalitis, oral administration of BCA (40–60 mg/kg) significantly improved animal survival and reduced cerebral viral loads. Mechanistic studies revealed that BCA upregulates the AMPK/Nrf2 signaling pathway, thereby increasing expression of the glutamate-cysteine ligase catalytic subunit (GCLC) and enhancing glutathione (GSH) biosynthesis. Our findings identify BCA as a promising host-directed antiviral agent and highlight its therapeutic potential against coronavirus infections. Full article

Background/Objectives: Central Nervous System (CNS) relapse represents a severe and often fatal complication of Diffuse Large B-Cell Lymphoma (DLBCL). This study aimed to evaluate clinical, biological, and treatment-related factors associated with progression-free survival (PFS) until CNS relapse in patients with DLBCL. Methods: A retrospective cohort study was conducted using clinical data from adult DLBCL patients evaluated and treated at the Regional Institute of Oncology, Iași, Romania, between 2015 and 2023. Associations between clinical, biological, and treatment-related variables and CNS relapse were evaluated using univariate and multivariable Cox proportional hazards models, Fine–Gray competing-risk analyses, and propensity score-based methods to address confounding by indication for CNS prophylaxis. Results: Twenty-six CNS relapse events (6.3%) and 72 deaths without prior CNS relapse occurred over a median follow-up of 12 months. In the prespecified reduced multivariable Cox model, non-R-CHOP regimens (HR 4.57, 95% CI 1.67–12.52; p = 0.003) and high CNS-IPI scores (HR 4.70, 95% CI 1.14–19.46; p = 0.033) were independently associated with CNS relapse. The 20-month cumulative incidence of CNS relapse was 7.0% in the R-CHOP-like group versus 35.2% in the non-R-CHOP group (Gray’s test p < 0.001). Fine–Gray modeling confirmed the association for non-R-CHOP regimens (SHR 3.38, 95% CI 1.21–9.45; p = 0.02). Cell-of-origin subtype, double-expressor phenotype, and Ki-67 were not significantly associated with CNS relapse. Conclusions: High CNS-IPI and treatment with non-R-CHOP regimens independently predicted earlier CNS relapse. Future multicenter studies with molecular profiling are needed to refine CNS risk stratification. Full article

Despite advances in surgical technique and perioperative care, pancreatic ductal adenocarcinoma (PDAC) remains associated with poor survival. Sarcopenia is highly prevalent in PDAC and is consistently associated with inferior survival and reduced tolerance of systemic therapy. However, interventions primarily aimed at increasing muscle mass through nutritional supplementation and resistance-based exercise have yielded limited improvements in clinically meaningful postoperative outcomes. This has prompted increasing interest in sarcopenia as a marker of broader biological vulnerability rather than isolated physical deconditioning. Emerging clinical, translational, and experimental evidence demonstrates that skeletal muscle and adipose tissue function as active immunometabolic organs, and that cancer-associated inflammatory pathways drive early muscle loss, immune dysfunction, and impaired physiological recovery. Across multiple clinical cohorts, sarcopenia is reproducibly associated with worse overall survival and failure to complete adjuvant therapy, but not consistently with increased postoperative complications, suggesting that its prognostic relevance lies in impaired recovery and oncological fitness rather than immediate surgical risk. Translational studies further indicate that sarcopenia identifies patients with reduced antitumor immune competence, particularly in early-stage disease. This review synthesizes current evidence linking sarcopenia, immune dysfunction, and surgical outcomes in PDAC and examines implications for perioperative care. We propose that immunometabolic-informed prehabilitation, integrated with existing nutritional and exercise strategies, may represent a more effective approach to improving recovery, treatment tolerance, and durable oncological outcomes following PDAC resection. Full article

Background: Cutaneous adverse events (cAEs) are among the most frequent immune-related toxicities associated with immune checkpoint inhibitors (ICIs). Previous clinical trials have reported higher rates of dermatologic toxicity with anti-CTLA-4 agents compared to Programmed Cell Death (PD-1)/ Programmed Cell Death-1 Ligand (PD-L1) inhibitors. However, real-world data may differ due to evolving clinical experience and improved AE management strategies. Methods: We conducted a retrospective analysis of patients treated with ICIs to assess the incidence and severity of cAEs —specifically rash and pruritus—across different treatment regimens and PD-L1 expression subgroups, 285 patients treated with ICIs at Soroka Medical center during the years August 2018–November 2025. Results: Regarding dermatologic toxicity, 57 out of 285 patients (20%) experienced a rash. Among them, 46 patients (16% of total; 81% of those with rash) had grade 1, 7 patients (2% of total; 12% of those with rash) had grade 2, and 4 patients (1% of total; 7% of those with rash) had grade 3 reactions. No grade 4 or life-threatening cases were observed. Additionally, 47 patients (16.5%) developed pruritus, all grade 1–2. When stratified by treatment type, PD-L1 expression and the occurrence of immune-related adverse events, specifically rash and pruritus, were significantly associated with survival outcomes (p < 0.001). Patients with expressions of PD-L1 ≥1% had longer median overall survival (34.0 months) compared to those with expressions of PD-L1 < 1% (20.0 months), and longer progression-free survival (22.0 vs. 13.0 months). When considering rash, overall survival ranged from 19.0 months (PD-L1 < 1% with rash) to 36.0 months (PD-L1 ≥1% without rash), and progression-free survival ranged from 12.0 to 27.0 months. The presence of pruritus was associated with the most favorable outcomes, with median overall survival reaching 48.0 months and progression-free survival 31.0 months in patients with PD-L1 ≥1% and pruritus. All comparisons showed statistically significant differences (p < 0.001). Conclusion: These findings highlight that higher PD-L1 expression and the presence of immune-related adverse events—particularly pruritus—may serve as important prognostic indicators and could help inform personalized treatment strategies. The incidence and severity of cAEs in our study were consistent with prior clinical trials. The low frequency of grade ≥ 3 events may reflect increased familiarity with ICIs, leading to earlier recognition of adverse events, better patient education, and more effective management of skin toxicities. Full article

This study investigated the biosynthesis of magnetite nanoparticles mediated by chia mucilage (CM-Fe₃O₄ NPs) and their application in the co-encapsulation of Lactobacillus rhamnosus GG (LGG) using spray drying. CM-Fe₃O₄ NPs were synthesized by combining CM extract with iron salts, in which hydroxyl and carbonyl groups of CM acted as natural ligands for Fe²⁺/Fe³⁺ ions. A response surface design was applied to optimize synthesis parameters, focusing on size distribution and zeta potential, and confirming the influence of pH on colloidal stability. Characterization by FE-SEM, DLS, XRD, UV-Vis, and FTIR revealed spherical particles with an inorganic core (50–300 nm) and a hydrated organic coating (600–900 nm), consistent with a spinel structure functionalized by CM. Spray-drying encapsulation tests showed that incorporating CM-Fe₃O₄ NPs did not compromise bacterial viability, maintaining optimal moisture content and survival. Growth curves and confocal microscopy corroborated the physiological compatibility of the nanoparticles, with no alterations in LGG morphology or growth dynamics. Under simulated gastrointestinal conditions, co-encapsulated microcapsules exhibited slightly improved survival in the gastric phase and significantly greater viability in the initial intestinal phase. These results suggest that CM-Fe₃O₄ NPs modulate matrix degradation and promote controlled release, ensuring therapeutic concentrations of LGG in the intestine. Overall, the CM-Fe₃O₄ nanocomposite system integrates the protective properties of biopolymers with the functional advantages of iron nanoparticles, offering dual functionality: probiotic stabilization and potential iron supplementation. This innovative, food-grade approach supports the development of next-generation functional foods with combined therapeutic and nutritional benefits. Full article

Background: Inflammation is central to myocardial injury and repair after ST-segment elevation myocardial infarction (STEMI). C-reactive protein (CRP) is an established biomarker of systemic inflammation, but its prognostic thresholds across patient subgroups are not well defined. Methods: In this retrospective cohort study, admission CRP was analyzed in 958 consecutive STEMI patients admitted to University Hospital Salzburg 2018–2020 and categorized into four groups (Serum CRP < 5.0, 5.0–9.9, 10.0–15, and >15.0 mg/dL). Mortality was assessed during short- (30, 90, and 180 days) and long-term (1, 3, and 5 years) follow-up. Kaplan–Meier analyses compared survival, Cox regression tested associations, and receiver operating characteristic (ROC) curves determined discriminatory value and optimal cut-offs. Results: Elevated admission CRP was associated with larger infarct size, impaired left ventricular function, and increased mortality. Kaplan–Meier curves showed progressively poorer survival with higher CRP, with worst outcomes at >15 mg/dL. At 30, 90, and 180 days, CRP demonstrated moderate discrimination (AUC 0.628, 0.653, and 0.654; all p < 0.001), with predictive cut-offs 11–15 mg/dL in the overall cohort. Subgroup analyses revealed markedly lower thresholds in vulnerable populations. Diabetic patients showed cut-offs 5–6 mg/dL with the highest AUC values (up to 0.714). Younger patients and smokers exhibited thresholds near 9–10 mg/dL, while subacute STEMI presentations demonstrated lower cut-offs compared with acute infarction. These findings indicate that the prognostic value of CRP is context-dependent rather than uniform. Conclusions: Admission CRP predicts short-term mortality after STEMI, with subgroup-specific cut-offs emerging below conventional thresholds, highlighting profiles where modest inflammatory activation carries disproportionate risk. Full article

Background: Whether there are differences in clinical outcomes between segmentectomy and lobectomy in patients with early-stage lung adenocarcinoma (LUAD) remains uncertain. This study aimed to compare all-cause mortality and lung cancer-specific mortality in patients with lung tumors ≤ 20 mm undergoing these two procedures. Methods: Patients with stage IA lung adenocarcinoma (≤20 mm) who underwent segmentectomy or lobectomy were identified from the SEER database (2008–2022). Propensity score matching (PSM) was applied to balance baseline characteristics. Kaplan–Meier curves depicted overall survival and lung cancer-specific survival. Multivariable Cox proportional hazards models were used to evaluate associations between surgical procedures and mortality, reporting hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Among 9641 patients, 1065 (11.0%) underwent segmentectomy. After 1:1 PSM, 2028 patients had well-balanced covariates. The median follow-up was 43.0 months. In the lobectomy group, 158 all-cause deaths (35.1 per 1000 person-years) and 66 lung cancer-specific deaths (14.7 per 1000 person-years) occurred, compared with 176 and 80 events in the segmentectomy group (39.9 and 18.1 per 1000 person-years, respectively). Multivariable Cox regression demonstrated that segmentectomy, compared with lobectomy, was not associated with a higher risk of all-cause mortality (adjusted HR [aHR], 1.07, 95% CI 0.86–1.34) or lung cancer-specific mortality (aHR, 1.18, 95% CI 0.84–1.64). The results were consistent across tumor differentiation subgroups. Conclusions: Among patients with early-stage (≤20 mm) LUAD, segmentectomy was not associated with an increased risk of all-cause or lung cancer-specific mortality compared with lobectomy. Further studies with larger sample sizes are warranted to validate these findings. Full article

Background and Objectives: Serum carcinoembryonic antigen (CEA) is a widely used biomarker in non-small cell lung cancer (NSCLC). However, its association with oncogenic driver alterations and prognostic significance across molecular subtypes in metastatic disease remains insufficiently defined. Materials and Methods: This retrospective multicenter study included 332 patients with metastatic NSCLC harboring oncogenic alterations (EGFR, ALK, ROS1, KRAS, and others) from eight oncology centers in Türkiye. Baseline serum CEA levels measured at metastatic diagnosis were analyzed on the natural logarithmic scale. Associations between CEA levels, molecular subtypes, clinical features, and overall survival (OS) were evaluated using generalized linear models and Cox proportional hazards regression. Results: Baseline CEA levels differed significantly across molecular subtypes (p = 0.001), with EGFR-mutant tumors showing the highest median levels. Multivariable analysis identified driver alteration, histology, and metastatic burden as independent determinants of baseline CEA. Higher baseline CEA and metastatic site count were independently associated with increased mortality risk (HR 1.151 and 1.279 per unit increase, respectively; p < 0.001), while female sex was protective (HR 0.626; p = 0.004). KRAS mutations were associated with poorer survival compared with EGFR (HR 2.370; p < 0.001). Kaplan–Meier analyses showed a consistent trend toward longer OS in patients with CEA < 5 ng/mL, with significance only in the rare alteration subgroup. Conclusions: Baseline CEA may reflect underlying tumor biology across molecular subtypes and are associated with survival outcomes in metastatic NSCLC. However, given the variability across subgroups and modest effect sizes, these findings should be interpreted with caution. Prospective studies evaluating longitudinal CEA dynamics are warranted. Full article

Chrysaora pacifica, a scyphozoan jellyfish widely distributed in East Asian waters, has recently shown signs of range expansion along the coasts of Korea, Japan, and China. However, ecological information on its early planktonic stage, the ephyra, remains limited. In this study, we experimentally investigated the effects of seawater temperature on the growth, feeding, and survival of C. pacifica ephyrae under controlled laboratory conditions. Five temperature treatments (12, 16, 20, 24, and 28 °C) were selected based on the species’ natural occurrence period. The results showed that ephyrae exhibited stable growth and feeding at 20–24 °C, with a high survival rate of approximately 90%, indicating that this range represents the optimal thermal condition for the ephyra stage. At 28 °C, growth and feeding were highest among all treatments; however, survival declined sharply to 22.5%, suggesting that elevated temperature may impose physiological stress. In contrast, at 12 °C, both growth and feeding activity were markedly reduced, and survival decreased to 32.5%. These findings demonstrate that temperature is a key environmental factor influencing the physiological performance and survival of C. pacifica ephyrae. This study provides essential baseline data for understanding the early life-stage ecology of this species and contributes to improving predictions of jellyfish population dynamics and potential distribution shifts in East Asian marine ecosystems under future environmental change. Full article

The invasive yellow-legged hornet Vespa velutina nigrithorax has spread across Europe following its accidental introduction into France in 2004. This species adversely affects biodiversity, apiculture, pomiculture and viticulture, and human health. Current management relies predominantly on nest destruction; however, manual removal is often logistically challenging and costly because nests are typically located high in trees (up to 30 m), frequently necessitating vehicle-mounted lifts. Ground-based application of biocides using long injection lances is comparatively rapid and inexpensive, but in many countries, insecticides are not permitted because the products are not specifically authorized for hornet control. Consequently, alternative approaches are needed. Here, we evaluated the efficacy of activated charcoal for nest destruction in V. v. nigrithorax. We injected 145 nests with 50–100 g of activated charcoal and subsequently destroyed the nests. One week later, we assessed worker survival and the establishment of new nests. Emergency nest construction by surviving workers was observed in three of 145 cases (2.1%). This rate was comparable to that observed following insecticide treatment (two of 136 cases; 1.5%). Activated charcoal therefore appears to be similarly effective to insecticide-based control while offering advantages in terms of environmental compatibility, user safety, ease of handling, and legal applicability in Europe. Activated charcoal may represent a practical alternative to manual nest removal and unauthorized insecticide use. Full article

Background: Obesity, type 2 diabetes mellitus, and hypertension are increasingly prevalent components of metabolic syndrome and major contributors to cardiovascular disease and chronic kidney disease progression; however, in end-stage kidney disease an “obesity paradox” has been described, with higher body mass index (BMI) sometimes associated with improved survival on hemodialysis. Material and methods: This retrospective, single-center Eastern European cohort study aimed to characterize mortality and its causes around hemodialysis initiation in the contemporary era of cardiometabolic prevention and to test whether the obesity paradox persists at this high-risk transition. Adult patients initiating dialysis at the “Pius Brânzeu” Emergency Clinical Hospital (Timișoara, Romania) between January 2022 and December 2025 (n = 268; median age 66 years; 61% male; median eGFR 6.4 mL/min/1.73 m²) were analyzed using Kaplan–Meier methods and Cox regression, with comprehensive baseline clinical, laboratory, echocardiographic, medication, infection, and vascular access data; follow-up was obtained at 3, 6, 12, 24, and 36 months. Results: Late referral was common (61% < 3 months of nephrology follow-up), dialysis initiation was predominantly urgent (only 16% scheduled), and central venous catheters were the main access (81%), with substantial comorbidity burden (cardiovascular disease 71%, hypertension 90%) and frequent infections at initiation. BMI categories were non-obese (<25 kg/m², 30%), overweight (25–29.9 kg/m², 48%), and obese (≥30 kg/m², 22%); diabetes prevalence rose with BMI (32% to 58%). Unadjusted mortality did not differ by BMI (19.8%, 18.8%, 15.3%; log-rank p = 0.622), yet multivariable Cox models showed overweight status independently reduced mortality (HR 0.22 at 3 months, 0.29 at 1 year, 0.31 at 3 years vs. non-obese), whereas obesity was not protective. Early mortality was driven mainly by age ≥ 65 years, while diabetes and chronic obstructive pulmonary disease predicted later mortality; longer pre-dialysis follow-up time was strongly protective (HR per year 0.70 at 3 years), and higher intact parathyroid hormone showed an inverse association with 1-year mortality. Conclusions: These findings show a modified obesity paradox at dialysis initiation in which moderate excess weight, but not obesity, is associated with improved adjusted survival, underscoring the clinical importance of earlier nephrology engagement and individualized nutritional and risk-factor management during the pre-dialysis and early dialysis periods. Full article

The high incidence of thrombosis in lymphoma is largely due to chronic inflammation and endothelial dysfunction. To elucidate the mechanisms underlying thrombus formation and fibrinolysis, we investigated interactions between circulating endothelial cells and peripheral blood mononuclear cells (MNCs), along with inflammatory signaling pathways, in patients with follicular lymphoma (FL), Hodgkin lymphoma (HL), and diffuse large B-cell lymphoma (DLBCL), independent of the presence of thrombosis, compared to healthy controls by flow cytometry, immunoblotting, and fluorometric assays. We observed increased tissue factor (TF) expression on CD31+ endothelial cells in DLBCL and FL. In DLBCL, inducible nitric oxide synthase expression was elevated in MNCs, while reduced nitrite levels correlated with an advanced clinical stage in patients with thrombosis. In lymphoma, nuclear factor kappa B (NFκB) signaling was activated in MNCs, while signal transducer and activator of transcription 3 (STAT3) activation was increased in DLBCL with thrombosis. Trans-endothelial migration of MNC was enhanced in HL, FL and DLBCL with thrombosis and reduced by inflammatory cytokine tumor necrosis factor alpha (TNF-α) that promoted platelet aggregation like interleukin-6 (IL-6) in HL and FL. Fibrinolytic analyses showed reduced tissue type plasminogen activator in lymphoma, whereas increased urokinase-type plasminogen activator (uPA) was linked to poorer total survival in DLBCL with thrombosis, suggesting a compensatory role in early thrombus resolution. These findings indicate that chronic inflammation promotes endothelial activation, dysregulated fibrinolysis, and increased vascular permeability, contributing to heightened thrombotic risk. This study provides mechanistic insight into lymphoma-associated thrombosis and identifies TF, uPA, and the inflammatory signaling pathways as potential biomarkers and therapeutic targets. Full article

Against the backdrop of intensifying global population aging, ensuring the sustainable provision of age-friendly spaces has become an important domain of urban policy intervention. A close examination of the supply–demand matching of age-friendly spaces is therefore essential for policymakers seeking to achieve social and environmental sustainability in an aging society. However, existing approaches to assessing this alignment primarily rely on quantitative analyses of geographical spatial distribution, lacking methods to evaluate the structural alignment of spatial functional types. To address this gap, this study proposes and validates a type-based quantitative approach to examining the alignment between policy supply and everyday demands for age-friendly spaces. By integrating policy text analysis, questionnaire surveys, activity logs, and behavior snapshots, the study identifies the types of age-friendly spaces mentioned by policies and those demanded in daily life, and quantitatively evaluates their alignment using a matching model. The results show that the older adults’ spatial demands shift progressively from life-oriented spaces to survival-oriented spaces as age increases and health declines. More importantly, a significant structural imbalance is evident: survival-oriented spaces are oversupplied, while life-oriented spaces remain in short supply. This study provides a diagnostic method for assessing the provision of age-friendly spaces and provides practical implications for local governments in formulating more balanced, responsive, and sustainable supply strategies. Full article

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals associated with a wide range of adverse health effects, yet individual PFAS compounds may exert distinct toxicological mechanisms. In this study, we investigate the toxic effects of perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) in Drosophila melanogaster using survival assays and measurements of acetylcholinesterase (AChE) activity as indicators of systematic toxicity and neurotoxicity, respectively. Male flies were exposed to PFOA and PFNA under different feeding conditions, concentrations, and temperatures. Both compounds reduced fly viability and impaired neuronal function, but with markedly different toxicological profiles. PFNA caused a pronounced, concentration-dependent reduction in lifespan under all tested conditions, indicating a strong systemic toxicity. In contrast, PFOA exerted a comparatively weaker effect on survival but induced a more pronounced reduction in AChE activity, consistent with enhanced neurotoxicity. PFOA-induced neurotoxicity in Drosophila may represent early molecular events that predispose neurons to degeneration, contributing to conditions such as dementia. Together, these findings demonstrate that structurally similar PFAS compounds can induce distinct toxicological outcomes and highlight the importance of evaluating individual PFAS using complementary assays. Moreover, this study underscores the utility of Drosophila melanogaster as a sensitive and mechanistically informative model for dissecting compound-specific PFAS toxicity. Full article