Search Results (5,777)

Background: Renal cell carcinoma (RCC) is a common malignancy with a rising global incidence. While cytoreductive nephrectomy (CRN) was historically a cornerstone in the management of metastatic RCC (mRCC), its role has been questioned following pivotal trials such as CARMENA and SURTIME. With the advent of immune checkpoint inhibitors (ICIs) and targeted therapies, the contemporary relevance of CRN coupled with first-line immunotherapy and targeted therapy combination regimens warrants re-evaluation. Methods: This retrospective cohort study utilized the TriNetX research network to identify patients aged 18–90 years diagnosed with mRCC between 2005 and 2024 who received first-line systemic therapies. Patients were stratified into two cohorts based on receipt of CRN status within one year of diagnosis. Propensity score matching (1:1) was done to adjust baseline characteristics. Kaplan–Meier survival analysis and Cox proportional hazards modeling were used to compare five-year overall survival between the groups. Results: Among 5960 eligible patients, 1776 (888 CRN matched to 888 who did not) formed the cohort of analysis. The CRN group demonstrated significantly higher five-year survival (57.7% vs. 45.0%, p < 0.0001) with a hazard ratio of 1.56 (95% CI: 1.33–1.83). Subgroup analyses showed consistent survival benefits across all four NCCN-recommended first-line regimens—Axitinib + Pembrolizumab: 64.0% (CRN) vs. 53.3% (no CRN), p = 0.01; Cabozantinib + Nivolumab: 50.1% vs. 40.4%, p = 0.004; Lenvatinib + Pembrolizumab: 37.4% vs. 22.8%, p = 0.012; Nivolumab + Ipilimumab: 56.4% vs. 46.1%, p = 0.005. Conclusions: In the era of modern immunotherapy and targeted agents, CRN remains associated with improved survival in patients with mRCC receiving NCCN-recommended first-line regimens. These findings support the continued evaluation of CRN as a component of multimodal therapy, particularly in patients with favorable risk profiles. Full article

Metro carriages, as enclosed transport microenvironments, have been understudied regarding pollution characteristics and health risks from ACs, especially during high-temperature summers that amplify exposure. This study applied NTS techniques for the first time across three major Chengdu metro lines, systematically identifying sixteen ACs, including hazardous species such as acetophenone, benzonitrile, and benzoic acid that are often overlooked in conventional BTEX-focused monitoring. The TAC concentration reached 41.40 ± 5.20 µg/m³, with half of the compounds exhibiting significant increases during peak commuting periods. Source apportionment using diagnostic ratios and PMF identified five major contributors: carriage material emissions (36.62%), human sources (22.50%), traffic exhaust infiltration (16.67%), organic solvents (16.55%), and industrial emissions (7.66%). Although both non-cancer (HI) and cancer (TCR) risks for all population groups were below international thresholds, summer tourists experienced higher exposure than daily commuters. Notably, child tourists showed the greatest vulnerability, with a TCR of 5.83 × 10⁻⁷, far exceeding that of commuting children (1.88 × 10⁻⁷). Benzene was the dominant contributor, accounting for over 50% of HI and 70% of TCR. This study presents the first integrated NTS and quantitative risk assessment to characterise ACs in summer metro environments, revealing a broader range of hazardous compounds beyond BTEX. It quantifies population-specific risks, highlights children’s heightened vulnerability. The findings fill critical gaps in ACs exposure and provide a scientific basis for improved air quality management and pollution mitigation strategies in urban rail transit systems. Full article

Background/Objectives: Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia exhibiting 90% mortality without prompt treatment. The aim of this study was to investigate the association of therapeutic plasma exchange (TPE)-treated TTP in end-stage renal disease (ESRD) patients with mortality, demographics, and clinical comorbidities. We queried the United States Renal Data System for ESRD patients starting dialysis between 1 January 2005 and 31 December 2018, using International Classification of Diseases (ICD)-9 and ICD-10 codes for thrombotic microangiopathy, with a TPE procedure code entered within 7 days. Methods: Cox proportional hazards models were used to assess mortality, adjusting for demographic and clinical factors. Results: Among 1,155,136 patients, increased age [adjusted odds ratio (OR) = 0.96, 95% confidence interval (CI): 0.94–0.96]; black race (OR = 0.67, CI: 0.51–0.89); and Hispanic ethnicity (OR = 0.43, CI: 0.28–0.66) were associated with a lower risk of TPE-treated TTP diagnosis, whereas female sex (OR = 1.59, CI: 1.25–2.02) and tobacco use (OR = 2.08, CI: 1.58–2.75) had a higher risk. A claim for TPE-treated TTP carried a lower risk of death (adjusted hazard ratio = 0.024, CI: 0.021–0.028). Female sex, black race, Hispanic ethnicity, and hypothyroidism were also associated with decreased all-cause mortality. Conclusions: These findings suggest that ESRD patients with TPE-treated TTP are significantly protected from mortality compared with ESRD patients without this diagnosis. Full article

The coastal sandy land in northeast Hainan Province is typical for this land type, also exhibiting strong sand activity. This study is based on wind speed, wind direction, and sediment transport data obtained at a field meteorological station using an omnidirectional sand accumulation instrument from 2020 to 2024, studying the coastal aeolian environment and sediment transport distribution characteristics in the region. Its findings provide a theoretical basis for comprehensively analyzing the evolution of coastal aeolian landforms and the evaluation and control of coastal aeolian hazards. The research results show the following: (1) The annual average threshold wind velocity for sand movement in the study area is 6.84 m/s, and the wind speed frequency (frequency of occurrence) is 51.54%, dominated by easterly (NE, ENE) and southerly (S, SSE) winds. (2) The drift potential (DP) refers to the potential amount of sediment transported within a certain time and spatial range, and the annual drift potential (DP) and resultant drift potential (RDP) of Mulan Bay from 2020 to 2024 were 550.82 VU and 326.88 VU, respectively, indicating a high-energy wind environment. The yearly directional wind variability index (RDP/DP) was 0.59, classified as a medium ratio and indicating blunt bimodal wind conditions. The yearly resultant drift direction (RDD) was 249.45°, corresponding to a WSW direction, indicating that the sand in Mulan Bay is generally transported in the southwest direction. (3) When the measured data extracted from the sand accumulation instrument in the study area from 2020 to 2024 were used for statistical analysis, the results showed that the total sediment transport rate (the annual sediment transport of the observation section) in the study area was 110.87 kg/m·a, with the maximum sediment transport rate in the NE direction being 29.26 kg/m·a. These results suggest that when sand fixation systems are constructed for relevant infrastructure in the region, the construction direction of protective forests and other engineering measures should be perpendicular to the net direction of sand transport. Full article

Background: This study aimed to evaluate prognostic factors of early filtering blebs using anterior segment swept-source optical coherence tomography (AS SS-OCT) in patients with uveitic and neovascular glaucoma. Methods: This retrospective cohort study included 22 eyes from 22 patients who underwent trabeculectomy (11 eyes each with uveitic or neovascular glaucoma). Intrableb characteristics were assessed using AS SS-OCT at 1 month, postoperatively. Surgical success was defined as intraocular pressure (IOP) ≤ 18 mmHg and ≥30% IOP reduction without medication at 12 months. Logistic regression was used to identify the prognostic factors associated with IOP control. Results: Sixteen eyes (72.7%) achieved surgical success, while six (27.3%) were unsuccessful. Eyes with successful IOP control at 12 months showed thicker and less reflective bleb walls with microcysts compared with unsuccessful cases of IOP control, in the early postoperative phase (all p < 0.033). However, IOP at the time of OCT did not significantly differ between the groups (p = 0.083). Multivariate logistic regression analysis revealed that higher bleb wall reflectivity at 1-month post-trabeculectomy was significantly associated with a higher surgical failure rate at 12 months after trabeculectomy (hazard ratio = 1.072, p = 0.032). Conclusions: Early intrableb assessment using AS SS-OCT may be beneficial for managing filtering blebs after trabeculectomy in uveitic and neovascular glaucoma. Higher bleb wall reflectivity in the early post-trabeculectomy phase may indicate poor features of the filtering bleb, suggesting the need for timely interventions for refractory cases. Full article

Wildfires have become increasingly frequent and destructive environmental hazards, especially in boreal ecosystems facing prolonged droughts and temperature extremes. This study presents an integrated spatio-temporal framework that combines Spatio-Temporal Density-Based Spatial Clustering of Applications with Noise (ST-DBSCAN), Fire Radiative Power (FRP), and the differenced Normalized Burn Ratio (ΔNBR) to characterize the dynamics and ecological impacts of large-scale wildfires, using the extreme 2023 Quebec fire season as a case study. The analysis of 80,228 VIIRS fire detections resulted in 19 distinct clusters across four fire zones. Validation against the National Burned Area Composite (NBAC) showed high spatial agreement in densely burned areas, with Intersection over Union (IoU) scores reaching 62.6%. Gaussian Process Regression (GPR) revealed significant non-linear relationships between FRP and key fire behavior metrics. Higher mean FRP was associated with both longer durations and greater burn severity. While FRP was also linked to faster spread rates, this relationship varied by zone. Notably, Fire Zone 2 exhibited the most severe ecological impact, with 83.8% of the area classified as high-severity burn. These findings demonstrate the value of integrating spatial clustering, radiative intensity, and post-fire vegetation damage into a unified analytical framework. Unlike traditional methods, this approach enables scalable, hypothesis-driven assessment of fire behavior, supporting improved fire management, ecosystem recovery planning, and climate resilience efforts in fire-prone regions. Full article

Background: Prostate cancer (PC) is the second leading cause of cancer-related death in men in the United States. A subset of patients develops non-metastatic, castration-resistant PC (nmCRPC), for which management requires a personalized consideration for appropriate treatment. However, there is no consensus regarding when to switch from androgen deprivation therapy (ADT) to more aggressive treatments like abiraterone or enzalutamide. Methods: We analyzed 5037 nmCRPC patients and employed a Weibull Time to Event Recurrent Neural Network to identify patients who would benefit from switching from ADT to abiraterone/enzalutamide. We evaluated this model using differential treatment benefits measured by the Kaplan–Meier estimation and milestone probabilities. Results: The model achieved an area under the curve of 0.738 (standard deviation (SD): 0.057) for patients treated with abiraterone/enzalutamide and 0.693 (SD: 0.02) for patients exclusively treated with ADT at the 2-year milestone. The model recommended 14% of ADT patients switch to abiraterone/enzalutamide. Analysis showed a statistically significant absolute improvement using model-recommended treatments in progression-free survival (PFS) of 0.24 (95% confidence interval (CI): 0.23–0.24) at the 2-year milestone (PFS rate increasing from 0.50 to 0.74) with a hazard ratio of 0.44 (95% CI: 0.39–0.50). Conclusions: Our model successfully identified nmCRPC patients who would benefit from switching to abiraterone/enzalutamide, demonstrating potential outcome improvements. Full article

Local site conditions can significantly influence the amplitude, duration, and frequency content of seismic recordings, making the characterization of subsoil properties a critical component in seismic hazard assessment. However, despite extensive research, standardized methodologies for assessing site effects are still lacking. This study presents preliminary steps in the site characterization of a small area of Campi Flegrei caldera (Italy), with the aim of enhancing understanding of local lithology and seismic wave propagation. The analysis focuses on the broad-band seismic station CSTH, installed in 2021, and incorporates data from a temporary 2D array of five short-period sensors deployed around the station. These sensors recorded both ambient noise and seismic events associated with caldera dynamics. To improve the robustness of the characterization, data from two additional permanent broad-band stations (CPIS and CSOB) of the Istituto Nazionale di Geofisica e Vulcanologia—Osservatorio Vesuviano’s monitoring network, also located nearby a hydrothermal field, were included. Spectral analyses such as Power Spectral Density (PSD), Horizontal-to-Vertical (H/V) spectral ratios, and f-k array technique were performed to evaluate the frequency-dependent response of the site and to support the development of a comprehensive seismic site model. Full article

Background/Objectives: This study evaluated the real-world effectiveness of prophylactic Human Papillomavirus (HPV) vaccination in Korean women aged over 26 years, focusing on its impact on persistent HPV infection and disease progression. Methods: This multicenter prospective study analyzed data from the Korea HPV Cohort (2010–2021). After applying exclusion criteria, the final analytical cohort included 1,231 women aged ≥ 27 years with cytologic findings of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions and HPV infection. Propensity score matching was used to compare vaccinated (n = 340) and unvaccinated (n = 891) participants. After matching, 273 vaccinated and 273 unvaccinated individuals were included in the final analysis. The primary outcomes were persistent HPV infection and progression to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Logistic and Cox regression models were employed, with additional age-stratified analyses. Results: Among women aged 27–39 years, vaccination was significantly associated with a 54% reduction in the odds of persistent HPV infection (odds ratio = 0.46; 95% CI: 0.22–0.96; p = 0.040). In the full cohort, vaccinated participants had a 62% lower risk of progression to CIN2+ compared with unvaccinated participants (hazard ratio = 0.38; 95% CI: 0.18–0.81; p = 0.011). Body mass index had a notable impact on HPV persistence in HPV 16/18 genotype groups. Conclusions: HPV vaccination effectively reduced persistent infection and progression to CIN2+ in Korean women, particularly those vaccinated before age 40. These findings support the age-extended HPV vaccination policies in South Korea. Full article

Background: Despite therapeutic advances, morbidity and mortality remain high in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), primarily due to increased cardiovascular risk. Objectives: Our study aimed to evaluate the cardiovascular risk profile and biomarker dynamics in patients with RA and PsA treated with Janus kinase inhibitors (JAKis). To our knowledge, this is the first study assessing Lp(a) levels in this context. Methods: This prospective, observational study assessed 48 adult patients. The follow-up period was 12 months. Traditional cardiovascular risk factors and biological markers, including lipid profile, lipoprotein(a) [Lp(a)], and uric acid (UA), were assessed at baseline and follow-up. Correlations between JAKi therapy, lipid profile changes, and cardiovascular risk factors were investigated. Cox regression analysis was used to identify predictors of non-major cardiovascular events. Results: A strong positive correlation was observed between baseline and 12-month Lp(a) levels (r = 0.926), despite minor statistical shifts. No major cardiovascular events occurred during follow-up; however, 47.9% of patients experienced non-major cardiovascular events (e.g., uncontrolled arterial hypertension, exertional angina, and new-onset arrhythmias). Active smoking [hazard ratio (HR) 9.853, p = 0.005], obesity (HR 3.7460, p = 0.050), and arterial hypertension (HR 1.219, p = 0.021) were independent predictors of these events. UA (HR 1.515, p = 0.040) and total cholesterol (TC) (HR 1.019, p = 0.034) were significant biochemical predictors as well. Elevated baseline Lp(a) combined with these factors was associated with an increased event rate, particularly after age 60. Conclusions: Traditional cardiovascular risk factors remain highly prevalent and predictive, underscoring the need for comprehensive cardiovascular risk management. Lp(a) remained stable and may serve as a complementary biomarker for risk stratification in JAKi-treated patients. Full article

Alkali-activated aluminosilicate matrices are increasingly studied for their ability to stabilize hazardous metal contaminants via alkali activation at room temperature. In this study, metakaolin-based geopolymers were used to immobilize chromium and nickel salts, with systematic variation of key synthesis parameters, Na/Al molar ratio, metal concentration, anion type, and alkaline solution aging time, which have not been previously studied. A Design of Experiments approach was employed to study the effect of factors on metal leaching behavior and to better understand the underlying immobilization mechanisms. The analysis revealed that higher Na/Al ratios significantly enhance geopolymerization and reduce metal release, as supported by FTIR spectral shifts and decreased shoulder intensity. Notably, aging time had an influence on chromium behavior due to its effect on early silicate network formation, which can hinder the incorporation of chromium species. All tested formulations achieved metal immobilization rates of 98.8% or higher for both chromium and nickel. Overall, this study advances our understanding of geopolymer-based heavy metal immobilization. Full article

Landslides are among the most hazardous natural phenomena affecting Greater Abidjan, causing significant economic and social damage. Strategic planning supported by geographic information systems (GIS) can help mitigate potential losses and enhance disaster resilience. This study evaluates landslide susceptibility using logistic regression and frequency ratio models. The analysis is based on a dataset comprising 54 mapped landslide scarps collected from June 2015 to July 2023, along with 16 thematic predictor variables, including altitude, slope, aspect, profile curvature, plan curvature, drainage area, distance to the drainage network, normalized difference vegetation index (NDVI), and an urban-related layer. A high-resolution (5-m) digital elevation model (DEM), derived from multiple data sources, supports the spatial analysis. The landslide inventory was randomly divided into two subsets: 80% for model calibration and 20% for validation. After optimization and statistical testing, the selected thematic layers were integrated to produce a susceptibility map. The results indicate that 6.3% (0.7 km²) of the study area is classified as very highly susceptible. The proportion of the sample (61.2%) in this class had a frequency ratio estimated to be 20.2. Among the predictive indicators, altitude, slope, SE, S, NW, and NDVI were found to have a positive impact on landslide occurrence. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), demonstrating strong predictive capability. These findings can support informed land-use planning and risk reduction strategies in urban areas. Furthermore, the prediction model should be communicated to and understood by local authorities to facilitate disaster management. The cost function was adopted as a novel approach to delineate hazardous zones. Considering the landslide inventory period, the increasing hazard due to climate change, and the intensification of human activities, a reasoned choice of sample size was made. This informed decision enabled the production of an updated prediction map. Optimal thresholds were then derived to classify areas into high- and low-susceptibility categories. The prediction map will be useful to planners in helping them make decisions and implement protective measures. Full article

Background: Immune checkpoint inhibitors (ICIs) have limited efficacy in proficient mismatch repair (pMMR) and microsatellite stability (MSS) metastatic colorectal cancer (mCRC). Inhibition of vascular endothelial growth factor (VEGF) or cytotoxic chemotherapy can boost immunogenicity and has the potential to upregulate ICI efficacy. Methods: A comprehensive electronic literature search was conducted up to April 2025 to identify randomized controlled trials comparing cytotoxic chemotherapy plus bevacizumab with or without ICI. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), objective response rate (ORR), and severe adverse events (AEs: grade 3 or more). A meta-analysis was performed using random-effects models to calculate hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Results: Four studies involving 986 patients (With-ICI group, n = 651; Without-ICI group, n = 335) were included. The meta-analysis demonstrated a significant improvement in PFS in the With-ICI group compared with the Without-ICI group, with an HR of 0.82 (95% CI: 0.70–0.96, p = 0.01) without statistical heterogeneity. No significant improvements were observed between the With- and Without-ICI groups in OS and ORR meta-analyses, but the With-ICI group had a favorable trend in OS. A significant increase in serious AEs was not observed in the With-ICI group. Conclusions: This meta-analysis suggests a potential benefit of adding ICIs to chemotherapy plus bevacizumab in pMMR mCRC; however, the evidence remains preliminary and hypothesis-generating, warranting further investigation in biomarker-driven trials and clarification of long-term outcomes. Full article

The objective of the present study was to evaluate the association between liver cirrhosis (LC) and subsequent Heart failure (HF). This retrospective cohort study utilized data from the Disease Analyzer database (IQVIA) and included adults with a first-time diagnosis of LC in 1293 general practices in Germany between January 2005 and December 2023. A comparison cohort without liver diseases was matched to the cirrhosis group using 5:1 propensity score matching. Univariable Cox proportional hazards models were used to assess the association between alcoholic vs. non-alcoholic LC and HF. The final study cohort included 5530 patients with alcoholic LC and 27,650 matched patients without liver disease, as well as 7063 patients with non-alcoholic LC and 35,315 matched patients without liver disease. After up to 10 years of follow-up, HF was diagnosed in 20.9% of patients with alcoholic LC compared to 10.3% of matched cohort, and in 23.0% of patients with non-alcoholic LC, compared to 14.2% in matched cohort. Alcoholic LC (Hazard Ratio (HR): 2.07 (95% CI: 1.85–2.31) and non-alcoholic LC (HR: 1.70; 95% CI: 1.56–1.82) were associated with an increased risk of HF. The association was also stronger in men than in women. LC, both alcoholic and non-alcoholic, is significantly associated with an increased long-term risk of HF. The association is particularly pronounced in patients with alcoholic cirrhosis and in men. To the best of the authors’ knowledge, this is the first real-world evidence for the positive association between LC and subsequent HF from Europe. Full article

Background and Objectives: Emerging evidence indicates that individuals exposed to adverse childhood experiences (ACEs) face elevated risks for various chronic illnesses. However, the association between ACEs and osteoporosis risk remains underexplored, particularly regarding potential modifications by genetic susceptibility. This prospective cohort study aims to examine the relationship of ACEs with incident osteoporosis and investigate interactions with polygenic risk score (PRS). Materials and Methods: This study analyzed 124,789 UK Biobank participants initially free of osteoporosis. Cumulative ACE burden (emotional neglect, emotional abuse, physical neglect, physical abuse, sexual abuse) was ascertained through validated questionnaires. Multivariable-adjusted Cox proportional hazards models assessed osteoporosis risk during a median follow-up of 12.8 years. Moderation analysis examined genetic susceptibility interactions using a standardized PRS incorporating osteoporosis-related SNPs. Results: Among 2474 incident osteoporosis cases, cumulative ACEs showed dose–response associations with osteoporosis risk (adjusted hazard ratio [HR]_{per one-unit increase} = 1.07, 95% confidence interval [CI] 1.04–1.11; high ACEs [≥3 types] vs. none: HR = 1.26, 1.10–1.43). Specifically, emotional neglect (HR = 1.14, 1.04–1.25), emotional abuse (HR = 1.14, 1.03–1.27), physical abuse (HR = 1.17, 1.05–1.30), and sexual abuse (HR = 1.15, 1.01–1.31) demonstrated comparable effect sizes. Sex-stratified analysis revealed stronger associations in women. Joint exposure to high ACEs/high PRS tripled osteoporosis risk (HR = 3.04, 2.46–3.76 vs. low ACEs/low PRS) although G × E interaction was nonsignificant (P-interaction = 0.10). Conclusions: These results suggest that ACEs conferred incremental osteoporosis risk independent of genetic predisposition. These findings support the inclusion of ACE screening in osteoporosis prevention strategies and highlight the need for targeted bone health interventions for youth exposed to ACEs. Full article