Search Results (723)

The Peace-Athabasca Delta (PAD) in northern Alberta, Canada, is one of the world’s largest inland freshwater deltas and is largely located within the Wood Buffalo National Park, a UNESCO World Heritage Site. Owing to its ecological and socioeconomic significance, the PAD has been designated a Ramsar wetland of international importance. A paucity of large-scale Peace River ice jam flooding and concurrent drying trend during the past five decades has motivated various studies on relevant processes and on possible remedial action. In turn, many of these studies are informed by a flood record that was compiled in 1995, based on Historical information and Traditional Knowledge (H-TK flood record). Later work has expressed occasional reservations regarding the accuracy of this record, while much more is now known about the physical and hydroclimatic controls of PAD ice jams. This paper examines the 20th century portion of the H-TK record in the light of recent scientific advances made since the 1990s and of a wealth of hydrometric and climatic indicators, along with eyewitness corroborations, that extend back to the early 1900s. Systematic observational data and monitoring reports that have become available since the 1990s have also provided valuable documentation of PAD flooding. It is concluded that the record of major ice-jam floods is reliable, while the possibility of “missed” events cannot be precluded. The record of minor ice jam floods, which is largely inferred from reversed tributary flows entering Lake Athabasca, may not be reliable because more than half of the reported events might not have occurred at all. The value of the H-TK record is primarily in the major events, which generate overland inundation and can amply recharge various ponds, lakes, and wetlands of the PAD. Implications of the results for pre- and post-regulation flood frequencies and for future park management are discussed. Full article

River ice is a common feature in most Canadian rivers and streams during the cold season. River channel hydraulics under ice conditions may cause higher water levels at a relatively lower discharge compared to the open-water flood events. Elevated water levels resulting from river ice processes throughout fall freeze-over, mid-winter, and spring break-up are important hydrologic events with diverse morphological, ecological, and socio-economic impacts. This study analyzes the timing of maximum water levels (occurring during freeze-over, spring break-up, and open-water periods) and the typology of maximum ice-related events (at freeze-over, mid-winter, and spring break-up) using data from the Canadian River Ice Database. The study also compares annual maximum water levels during the river ice and open-water periods at selected hydrometric stations from 1966 to 2015, divided into two 25-year windows: 1966–1990 and 1991–2015. A return period classification method was applied to define ice-influenced, open-water, and mixed-regime conditions. The results indicate that the majority of ice-influenced maximum water levels occurred during spring break-up (~79% in 1966–1990 and ~69% in 1991–2015), followed by fall freeze-up (~13% and ~23%) and mid-winter break-up (~8% and ~7%) for the two periods, respectively. Among 15 stations analyzed for 1966–1990 and 42 stations for 1991–2015, the proportion of annual maximum water levels dominated by open-water conditions increased from 47% to 55%, while ice-dominated events decreased from 13% to 12%, and mixed-regime events dropped from 40% to 33%. However, a focused comparison of eight common stations revealed minimal change in the distribution of water level-generating events between the two periods. The findings offer valuable insights into the spatial distribution of maximum water level-generating mechanisms across Canada. Full article

Background: Catheter ablation is an established first-line treatment for supraventricular tachycardia (SVT). Traditionally, these procedures have been performed under fluoroscopic guidance. The objective of this study was to demonstrate the feasibility and safety of a completely fluoroless approach, as well as to evaluate clinical outcomes. Methods: This retrospective, single-center analysis included two patient cohorts, comprising a total of 400 patients: 200 in the main (fluoroless) group and 200 in the control (fluoroscopy) group. In the main group, ablation was performed using a 3D mapping system and intracardiac echocardiography (ICE) without the use of fluoroscopy and lead aprons. In the control group, procedures were conducted under fluoroscopic guidance. The primary outcomes were feasibility and safety. Secondary outcomes included acute procedural success, defined as non-inducibility of tachycardia, and chronic success, measured as arrhythmia recurrence-free survival during a 6-month follow-up period. Results: Completely fluoroless ablation was successfully performed in all patients in the main group (100%). Procedures were shorter in the fluoroless group (59.0 ± 25.8 min vs. 72.7 ± 34.0 min, p < 0.001), with no difference in acute success rates (100% vs. 100%). No serious complications occurred in the main group, compared to one event in the control group (0 vs. 1.0, p = 0.313). Arrhythmia recurrence rates during follow-up were similar between groups (HR: 0.877, 95% CI: 0.367–2.097, p = 0.769). Conclusions: A completely fluoroless, “apron-less” approach to SVT ablation is feasible, with complication and success rates comparable to the traditional fluoroscopy-guided approach. Full article

Outdoor ice rinks have long been a staple for inexpensive exercise and entertainment in cold environments. However, the possible deterioration of or impact on outdoor ice rinks from a changing climate is poorly understood due to no or little monitoring of data of such facilities. To investigate long-term changes in ice rinks over recent decades, an energy-balance-based ice rink model (with three versions considering precipitation and melt) was applied to a simulated ice rink for two representative area—Dorset of south-central Ontario and the Experimental Lakes Area (ELA) of northwestern Ontario, Canada. The model was calibrated and tested using four-year ice rink data (since limited data are available) and applied to a 40-year period starting in 1978 to reproduce the dates of rink-on and rink-off, rink duration in a season, and ice water equivalent under daily climate inputs, and to illustrate any changing trend in these variables, i.e., the ice rink responses to changed climate. Results showed no clear trend in any ice rink features over four decades, attributed to winter temperature that did not increase substantially (a weak driver), no change in events of rain-on-ice and snowfall-on-rink, and reduced wind speed (possibly slowing ice melting). This is the first trial of a physically based rink model to evaluate outdoor ice rinks. More in situ monitoring and in-depth modelling are necessary, and this model can help guide the monitoring. Full article

Background/Objectives: Neuroblastoma (NB) is an aggressive pediatric malignancy that accounts for nearly 15% of all childhood cancer-related deaths, with high-risk cases showing a poor 20% prognosis and limited response to current therapies. Survivin, encoded by the BIRC5 gene, is an anti-apoptotic protein frequently overexpressed in NB and linked to treatment resistance and unfavorable clinical outcomes. Methods and Results: An analysis of 1235 NB patient datasets revealed a significant association between elevated BIRC5 expression and reduced overall and event-free survival, highlighting survivin as an important therapeutic target in NB. To explore this strategy, we evaluated the efficacy of YM-155, a small-molecule survivin inhibitor, across multiple NB cell lines. YM-155 displayed potent cytotoxic activity in six NB cell lines with IC₅₀ values ranging from 8 to 212 nM and significantly inhibited colony formation and 3D spheroid growth in a dose-dependent manner. Mechanistic analyses revealed that YM-155 downregulated survivin at both mRNA and protein levels, induced apoptosis by about 2–7-fold, and caused G0/G1 phase cell cycle arrest. Moreover, YM-155 treatment enhanced p53 expression, suggesting reactivation of tumor suppressor pathways. Notably, combining YM-155 and the chemotherapeutic agent etoposide resulted in synergistic inhibition of NB growth with ED75 values ranging from 0.17 to 1, compared to either agent alone. In the xenograft mouse model, YM-155 inhibited tumor burden in contrast to controls by about 3-fold, and without any notable toxic effects in vivo. Conclusion: Overall, our findings identify YM-155 as a promising therapeutic agent for high-risk NB by directly targeting survivin and enhancing chemosensitivity. These results support continued preclinical development of survivin inhibitors as part of rational combination strategies in pediatric cancer treatment. Full article

The first comprehensive mass balance estimation for the world’s largest tropical icefield is presented. Geodetical mass balance was calculated using photogrammetry from aerial and satellite images spanning from 1955 to 2024. The results meet expected quality standards using some new satellite sources, such as the Peruvian PeruSAT-1, although the quality of airborne imagery is consistently lower than that of satellite sources. The Nevado Coropuna icefield remained almost stable between 1955 and 1986 with −0.04 m dh yr⁻¹. Since then, it has undergone a sustained and accelerated negative mass balance, reaching a maximum annual dh yr⁻¹ of −0.73 ± 0.19 in the 2020–2023 timeframe. The glacier loss is not equal across the entire ice mass, but more acute in the northern and northeastern outlet tongues. Debris-covered ice and rock glaciers show a much weaker negative mass balance signal. The impact of ENSO events is not evident in the overall ice evolution, although their long-term relevance is acknowledged. Overall, the negative response of Nevado Coropuna to global warming (−0.36 ± 0.12 m.w.e. yr⁻¹ for the 2013 to 2024 period) is less pronounced than that of other Peruvian glaciers, but more severe than that reported for the nearby Dry Andes of Chile and Argentina. Full article

Snowfall and road surface freezing cause traffic disruptions and skidding accidents. When widespread extreme cold events or sudden heavy snowfalls occur, the continuous monitoring and management of extensive road networks until the restoration of traffic operations is constrained by the limited personnel and resources available to road authorities. Consequently, road surface condition prediction models have become increasingly necessary to enable timely and sustainable decision-making. This study proposes a road surface condition prediction model based on CCTV images collected from roadside cameras. Three databases were constructed based on different definitions of moisture-related surface classes, and models with the same architecture were trained and evaluated. The results showed that the best performance was achieved when ice and snow were combined into a single class rather than treated separately. The proposed model was designed with a simplified structure to ensure applicability in practical operations requiring computational efficiency. Compared with transfer learning using deeper and more complex pre-trained models, the proposed model achieved comparable prediction accuracy while requiring less training time and computational resources. These findings demonstrate the reliability and practical utility of the developed model, indicating that its application can support sustainable snow removal decision-making across extensive road networks. Full article

In recent decades, frequent cold waves and low-temperature events in mid-to-high latitude Eurasia have severely impacted socioeconomic activities in Northeast China. Accurately identifying anticyclones is essential due to their close relation to cold air activity. This study proposes a new anticyclone identification method using the Mask region-based convolutional neural network (Mask R-CNN) model to detect synoptic-scale anticyclones by capturing their two-dimensional structural features and investigating their relationship with snow-ice disasters in Northeast China. It is found that compared with traditional objective identification methods, the new method better captures the overall structural characteristics of anticyclones, significantly improving the description of large-scale, strong anticyclones. Specifically, it incorporates 7.3% of small-scale anticyclones into larger-scale systems. Anticyclones are closely correlated with local cooling and cold air mass changes over Northeast China, with 60% of anticyclones accompanying regional cold air mass accumulation and temperature drops. Two case studies of the rare rain-snow and cold wave events revealed that these events were preceded by the generation and eastward expansion of an upstream anticyclone identified by the new method. This demonstrates that the proposed method can effectively track anticyclones and the evolution of cold high-pressure systems, providing insights into extreme cold events. Full article

Introduction. Adverse drug events (ADEs) are between the third and sixth most common cause of death worldwide. Biosimulation studies performed using real-world data could generate relevant drug safety information without exposing patients to ADEs. Methods. Iclepertin (BI-425809) was virtually added to the actual drug regimens of n = 4,405,063 individuals. Changes in risk level were estimated for drug-induced long QT syndrome and CYP450 drug interactions. The properties used for iclepertin included: dose of 10 mg (oral) once daily; bioavailability (F) = 71%; Cmax of 222 nM; CYP3A4 weak affinity substrate (partial metabolic clearance of ~80%); IC₅₀ for hERG block of 30 μM. Results. A change in total medication risk score (MRS) was observed (6.3 ± 6.6 to 7.2 ± 6.6) following the addition of iclepertin in ~50% (n = 2,138,247) of the studied population. Among individuals with a change in MRS, ~65% had a 2-unit increase (max 11 units). The number of individuals classified in the High/Severe MRS category increased by 0.33%. The addition of iclepertin to individuals receiving CYP3A4 perpetrator drugs produced a greater change in MRS (+1.5) when compared to individuals not exposed to CYP3A4 perpetrators (+0.8). An additional 0.0032% of the population (n = 139) would be at risk of QT prolongation following the intake of iclepertin. Subset analyses performed in individuals with schizophrenia (targeted indication) demonstrated that these individuals had higher MRS values (13.0 ± 10.3) compared to those without schizophrenia (6.2 ± 6.9). However, the addition of iclepertin did not produce a greater increase in MRS in the schizophrenia population vs. the control population. Our pharmacoeconomic model did not account for any beneficial effects of the drug but the model based on MRS changes predicted a USD 91 yearly increase in medical expenditures (emergency department visits and hospitalizations) per individual (USD 3172 to USD 3263) following the addition of iclepertin. A similar increase was observed in the schizophrenia population following iclepertin addition. Conclusions. The increase in MRS associated with the addition of iclepertin to the drug regimen of a large population was minimal and mostly driven by CYP3A4 interactions. Using this model, interactions can be identified a priori, making risk mitigable and preventable without exposing patients to toxicity. Full article

Background: Anticoagulation is the cornerstone of thromboembolic event prevention. Adversely, anticoagulants (ACs) are linked to a variety of adverse events. We aimed to assess the link between vitamin K antagonists (VKA) and direct anticoagulant (DOACs) use and acute kidney injury (AKI) using the FDA Adverse Events Reporting System (FAERS) Database. Methods: We conducted a disproportionality analysis on the adverse events (AEs) of interest in the FAERS database using the reporting odds ratio (ROR), proportional reporting ratio (PPR) with the Yates correction (x²yates), and the information component (IC). Results: A total of 20,253 cases of AKI associated with use of ACs were analyzed. Edoxaban, dabigatran and warfarin showed greater association with AKI (ROR 2.63; ROR 1.46; ROR). In cases with manifest bleeding, edoxaban, dabigatran, warfarin and rivaroxaban had a stronger statistical association with AKI. Rivaroxaban showed greater association with AKI compared to other ACs when used concomitantly with Aspirin (ROR 2.25). Conclusion: We showed increased odds of reporting AKI with use of edoxaban, dabigatran and warfarin compared to other anticoagulants. In cases with reported bleeding, AKI was more commonly reported with all five analyzed anticoagulants, except for apixaban, highlighting its favorable side-effect profile. Caution and clinical awareness are needed when prescribing ACs to vulnerable populations. Full article

The Beaufort Sea has experienced significant sea ice retreat in recent decades, driven by both thermodynamic and dynamic processes. This study investigates the drivers and predictability of summer sea ice retreat in the Beaufort Sea by integrating an ocean–sea ice model with satellite-derived sea ice concentration data and atmospheric reanalysis products. Model diagnostics from 1994 to 2019 reveal that thermodynamic processes dominate annual sea ice loss (approximately 90%), with vertical heat flux accounting for roughly 85% of total oceanic heat input. The summer sea ice minimum area and the day of opening, derived from either model results and satellite observations, have a strong correlation with R² = 0.60 and R² = 0.77, respectively, enabling regression equations based solely on remote sensing data. Further multiple linear regression incorporating preceding winter (January to April) accumulated temperature and easterly wind yields moderately robust forecasts of minimum sea ice area (R² = 0.49) during 1998–2020. Additionally, analysis of reanalysis wind data shows that the timing of minimum sea ice area is significantly influenced by the frequency and intensity of sub-seasonal easterly wind events during melt season. These results demonstrate the critical importance of remote sensing in monitoring Arctic sea ice variability and enhancing seasonal prediction capability under a rapidly changing climate. Full article

Oxidative stress (OS) is known to cause severe liver injury in weaning piglets; however, the cellular and molecular mechanisms underlying this process remain poorly understood. In this study, we employed a diquat (DQ)-induced OS model in weanling piglets and performed single-cell transcriptome sequencing of liver tissue to elucidate the key molecular and cellular events involved in OS-induced hepatic damage. First, piglets were treated with 12 mg/kg DQ and the same amount of saline, and the histopathology, biochemical indicators, and single-cell RNA sequencing (scRNA-seq) of piglets were analyzed. Mouse hepatocytes were used to verify the mechanism of differentially expressed genes, including STAT3 knockdown/overexpression, reactive oxygen species (ROS) detection and apoptosis assay. DQ exposure caused significant oxidative damage in the liver of piglets, which was manifested as decreased superoxide dismutase (SOD) activity (p < 0.05), glutathione (GSH) consumption (p < 0.05) and increased malondialdehyde (MDA) (p < 0.05). Cell type-specific responses were revealed by scRNA-seq, with hepatocytes showing the most pronounced transcriptomic alterations (752 genes up-regulated and 918 genes down-regulated). The expression of STAT3 was up-regulated in hepatocytes (p < 0.05) and down-regulated in B cells. The functional enrichment of macrophages involved FOXO/MAPK signaling and OS pathways. In vitro experiments showed that DQ treatment (IC50 = 125.8 μmol/L) led to an increase in ROS content and apoptosis, STAT3 silencing aggravated ROS and apoptosis (p < 0.05), and STAT3 overexpression alleviated ROS and apoptosis (p < 0.05). STAT3 activation increases HO-1 and Bcl-2, while inhibiting Bax and shifting the Bax/Bcl-2 ratio toward cell survival. It has been shown that DQ induces OS and apoptosis in a cell type-dependent manner, in which STAT3 plays a key regulatory role in antioxidant defense and cell survival. Targeting STAT3 may be a therapeutic strategy for DQ-induced hepatotoxicity. Full article

Background: Brain metastases (BMs) are a common and challenging complication of non-small cell lung cancer (NSCLC), historically associated with a poor prognosis. The development of targeted therapies, specifically tyrosine kinase inhibitors (TKIs) for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene alterations, has significantly improved treatment outcomes. Methods: This article reports and evaluates the efficacy of different generations of TKIs for NSCLC with BMs. The primary endpoints assessed are intracranial objective response rates (IC-ORR), progression-free survival (PFS), and overall survival (OS). The analysis considers TKIs as monotherapy and in combination with radiotherapy. It also examines the impact of newer generation TKIs with enhanced blood–brain barrier (BBB) penetration on intracranial control. The report further discusses the integration of systemic therapy with local modalities like stereotactic radiosurgery (SRS) and the safety profiles of these agents, including central nervous system (CNS) and metabolic adverse events. Results: Newer generation TKIs demonstrate significantly enhanced BBB penetration, resulting in superior intracranial control compared to older generations. These agents show remarkable intracranial activity, contributing to improved IC-ORR, PFS, and OS. The optimal integration of systemic therapy with local modalities, such as SRS, is still under investigation. Treatment with these TKIs is associated with distinct safety profiles, including novel CNS and metabolic adverse events, which require careful management due to prolonged treatment durations. Conclusions: The management of CNS metastases in NSCLC is evolving towards more proactive and personalized therapeutic strategies. Newer generation TKIs have profoundly reshaped the treatment landscape by offering superior intracranial control. Further research is needed to determine the optimal integration of these systemic therapies with local modalities and to effectively manage the associated adverse events. Full article

Urban historic districts play a vital role in shaping the cultural identity and heritage of cities. However, many of these areas face challenges such as aging buildings and deteriorating infrastructure. At the same time, the increasing frequency of extreme rainfall has led to a rise in flood events, placing these vulnerable districts at greater risk. Therefore, it is essential to carry out a comprehensive and objective assessment of their resilience to flood disasters. This study establishes a G-IC model for evaluating the resilience of urban historic districts to flood disasters based on the game combination empowerment-improved cloud model method. The proposed method has been demonstrated in the Soviet-style building complex of the Daye Steel Plant in Huangshi and reveals that the driving force layer exhibits weak resilience; the pressure and state layers show general resilience; the impact and response layers demonstrate weak resilience; and the overall resilience of the district is categorized as weak. The consistency of the results was verified by calculating the cloud similarity, which shows that the constructed new model has certain rationality and feasibility, and the evaluation results are relatively accurate. The findings offer valuable insights for policy-making and support for decision-makers in local government departments. Full article

Cirrus clouds cover 25% of the Earth at any given time. However, significant uncertainties remain in our understanding of cirrus cloud formation, in particular, how it is impacted by aerosols. This study investigates the formation and properties of dust-induced cirrus clouds using long-term observational datasets, focusing on Central Asia’s Aral Sea region and the Iberian Peninsula. We identify cirrus events influenced by mineral dust using an algorithm that uses CALIPSO satellite data through spatial and temporal proximity analysis. Results indicate significant seasonal and regional variations in the prevalence of dust-induced cirrus clouds, with spring emerging as the peak season for the Aral Sea and high-altitude Saharan dust transport influencing the Iberian Peninsula. With the help of DARDAR-Nice data, we characterize dust-induced cirrus clouds as being thicker, forming at higher altitudes, and exhibiting distinct microphysical properties, including reduced ice crystal concentrations and smaller frozen water content. Furthermore, a statistical test using a non-parametric Mann–Whitney U test is employed and confirms the robustness of the study. These findings enhance our understanding of the interactions between mineral dust and cloud microphysics, with implications for global climate modeling and weather forecasting. This study provides methodological advancements for dust-induced cloud detection and highlights the need for integrating a dust–cloud feedback mechanism in weather and climate models. Full article