Search Results (23)

Aspirin has been the default backbone of antiplatelet therapy after percutaneous coronary intervention (PCI) for over two decades, anchored by landmark trials that established 12-month dual antiplatelet therapy (DAPT) as the standard of care. Three developments have prompted reassessment of this paradigm: the markedly lower thrombotic risk of contemporary drug-eluting stents, the greater potency and consistency of potent P2Y₁₂ inhibitors (ticagrelor, prasugrel), and increasing recognition that major bleeding independently worsens outcomes after PCI. Recent randomised trials have systematically tested aspirin withdrawal at varying time points. Immediate aspirin-free strategies (NEO-MINDSET, STOPDAPT-3) demonstrated an early signal of excess ischaemic events in the ACS component of enrolled populations, suggesting that aspirin remains important during the earliest post-PCI period in ACS. One-month strategies (T-PASS, ULTIMATE-DAPT, TARGET-FIRST) and three-month strategies (TWILIGHT, TICO, DUAL-ACS) showed that transition to P2Y₁₂ monotherapy after an initial DAPT period significantly reduces bleeding without increasing ischaemic events in selected populations. Beyond one year, long-term randomised trials including the HOST-EXAM 10-year follow-up (Lancet 2026) and the STOPDAPT-2 5-year landmark analysis (Circ Cardiovasc Interv 2026), together with study-level meta-analyses (PANTHER) and recent individual patient data meta-analyses, provide converging evidence that clopidogrel monotherapy outperforms aspirin for chronic secondary prevention without excess bleeding. The choice of P2Y₁₂ agent is critical: clopidogrel monotherapy in ACS during the first post-procedural year carries excess thrombotic risk owing to CYP2C19 pharmacogenomic variability, whereas ticagrelor and prasugrel provide more reliable protection. This review synthesises the mechanistic rationale, trial evidence across all time points, special clinical contexts (oral anticoagulation, coronary artery bypass grafting, high bleeding risk), guideline evolution, and methodological considerations, providing a practical framework for individualising post-PCI antiplatelet therapy. Full article

The increase in population and demand for the various needs of citizens increases the interaction with the geo-environment. Thus, the rate of natural events affecting daily human life increases. Such an event occurred on a rock cliff in a densely populated area in İstanbul (Türkiye). More than four rock blocks (approximately 3–5 m³) belonging to the Paleozoic sequence of İstanbul, composed of nodular limestone with sandy-clay interlayers, detached and fell. The blocks traveled along a path of approximately 60 m and stopped by crushing a couple of buildings downslope. The path was rough and contained various surface conditions (e.g., bedrock, talus, and plants). This study was initiated by the examination of the dimensions of failed rock blocks, their paths, and topographic conditions. Unmanned vehicles (drones) facilitated the generation of 3D numerical models of topographic changes on the site. Quantifying discontinuity properties (such as persistence, spacing, roughness, etc.) and defining weathering properties comprises the second stage, along with sampling. Based on digital topographic data and field observations, cross-sections were defined by means of possible rockfall areas within the area of potentially unstable blocks. Numerical analysis and rockfall analysis were conducted along these critical sections. Interpretation of laboratory data and results obtained from numerical studies leads to an understanding of the mechanism of the recent rockfall event and demonstrates the most critical areas to be considered and reinforced. The research comprises proposing appropriate reinforcement techniques due to the strong Turkish regulations along the “Bosphorus Waterfront Protected Zone”. The study advises pre-cleaning of potentially unstable blocks after a fence production on paths where rocks could fall, and rock anchors in some localities with varying lengths. The latest part of the research covers the re-assessment of mitigation processes with numerical models, which shows that the factor of safety increased to the desired levels. The reinforcement applications at the site match well with the proposed prevention methods. Full article

Background: Survival among children and adolescents and young adults (AYA) with cancer has improved substantially over recent decades; however, dominant survivorship models remain reactive—activated post-treatment and anchored to static exposure- and organ-based screening. This design underuses the anticipatory window at diagnosis and overlooks environmental and social determinants that modulate outcomes across the life course. Methods: We narratively reviewed international frameworks including the Children’s Oncology Group (COG), the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG), the Pan-European Network for Care of Survivors after Childhood and Adolescent Cancer (PanCare) and the National Comprehensive Cancer Network (NCCN), and synthesized evidence on environmental determinants, exposomics, toxicogenomics, and implementation. Building on two decades of real-world practice, we describe the evolution from the Pediatric Environmental History (PEHis) to the Ambiomic Health Compass (AHC), integrating genomic, exposomic, geospatial, clinical, and biomonitoring layers into routine care. In this framework, survivorship is conceptualized as beginning at the time of cancer diagnosis (“day 0”). Results: PEHis operationalizes guideline-based care with structured environmental and social assessment, personalized plans, and community integration, contributing to improved survival, healthier behaviors, reduced treatment-related mortality and stronger oncology–primary-care coordination. AHC extends PEHis with dynamic risk recalibration, contextual alerts, targeted biomonitoring, and toxicogenomic interpretation, enabling anticipatory decisions from day 0. The manuscript summarizes the paradigm shift (current vs. Ambiomic models), the domain-specific expansion over existing guidelines, the core clinical/system tools, and time-bound metrics (12, 24, 60 months) to support implementation and evaluation. Conclusions: Survivorship should move upstream—from late surveillance to ambiomic, exposure-aware care beginning at diagnosis. Integrating advanced exposomics, mutational epidemiology, and explainable analytics can reduce preventable events and chronicity, enhance equity, and align pediatric oncology with planetary health. The PEHis–AHC continuum offers a scalable blueprint for next-generation survivorship programs in Europe and beyond. Ambiomic medicine does not replace precision medicine—it completes and extends it by integrating exposomics, social context, and anticipatory analytics from day 0. Full article

As a result of recent seismic events, it has been observed that earthquake-resistant design worldwide has evolved to the point where structures are generally able to respond adequately to such natural demands. Nevertheless, it has also become evident that nonstructural components and contents anchored to structures have not exhibited equally satisfactory performance. To study the effects of earthquakes on these elements and compare the results with current Chilean code provisions, the present study focuses on determining the maximum absolute floor accelerations in a shear wall building, the most common structural typology in Chilean residential construction. The structure was subjected to destructive seismic excitations representative of the earthquakes that struck Chile in 2010, 2015, and 2017. Based on the obtained accelerations, the demands on nonstructural elements were critically assessed using the current Chilean seismic design code. In this context, the nonlinear behavior of the supporting structure was considered with a damping ratio of 5%. Through time history simulations, floor acceleration records were generated, from which pseudo-accelerations were calculated. Finally, by applying an innovative procedure developed in this study, floor acceleration amplification factors were determined, as well as acceleration spectra intended to guide a more adequate design of nonstructural components. Full article

South Asia’s worsening air pollution crisis represents one of the most urgent public health and environmental challenges of the 21st century. Nearly two billion people—over one-quarter of the global population—reside in this region, where air quality levels routinely exceed World Health Organization (WHO) guidelines by factors of 10 to 15. This has translated into an unprecedented health burden, with approximately two million premature deaths annually, widespread chronic respiratory and cardiovascular disease, and rising economic losses. According to recent World Bank estimates, welfare losses amount to over 5% of regional GDP, a figure far exceeding the projected costs of coordinated mitigation. Despite this, South Asia continues to lack a binding regional framework capable of addressing its shared airshed. Existing cooperative efforts—such as the Malé Declaration on Control and Prevention of Air Pollution (1998)—have provided a useful platform for dialog and pilot monitoring, but they remain voluntary, under-resourced, and insufficient to manage the transboundary nature of the crisis. National-level programs, including India’s National Clean Air Programme (NCAP), Bangladesh’s National Air Quality Management Plan (NAQMP), and Nepal’s National Air Quality Management Action Plan (AQMAP), demonstrate domestic commitment but are constrained by fragmentation, limited financing, and lack of regional integration. This gap represents the central knowledge and governance challenge that prompted the present commentary. To address it, we propose a dual-track architecture designed to institutionalize binding regional cooperation. Track A would establish a United Nations-anchored South Asian Transboundary Air Pollution Protocol, under the auspices of the United Nations Environment Programme, the World Health Organization (WHO), and the United Nations Economic and Social Commission for Asia and the Pacific (UNESCAP). This protocol would codify legally enforceable emission standards, compliance committees, financial mechanisms, and harmonized monitoring. Track B would establish a South Asian Association for Regional Cooperation (SAARC) Prime Ministers’ Council on Air Quality (SPMCAQ) to provide political leadership, align domestic implementation, and authorize rapid responses to cross-border haze events. Lessons from the Indian Ocean Experiment, the ASEAN Agreement on Transboundary Haze Pollution, and Europe’s Convention on Long-Range Transboundary Air Pollution demonstrate that legally binding agreements combined with high-level political ownership can achieve durable reductions in pollution despite geopolitical tensions. By situating South Asia within these global precedents, the proposed framework provides a pragmatic, enforceable, and politically resilient pathway to protect health, reduce economic losses, and deliver cleaner air for nearly one-quarter of humanity. Full article

Endothelial hyperpermeability is a hallmark of diverse inflammatory and vascular pathologies, including sepsis, acute respiratory distress syndrome (ARDS), ischemia–reperfusion injury, and atherosclerosis. Traditionally considered a passive return to baseline following stimulus withdrawal, barrier recovery is now recognized as an active, endothelial-driven process. Earlier work identified individual components of this restorative phase, such as cyclic adenosine monophosphate (cAMP)/exchange protein directly activated by cAMP 1 (Epac1) signaling, Rap1/Rac1 activation, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, and targeted cytoskeletal remodeling, as well as kinase pathways involving PKA, PKG, and Src. However, these were often regarded as discrete events lacking a unifying framework. Recent integrative analyses, combining mechanistic insights from multiple groups, reveal that nitric oxide (NO) generated early during hyperpermeability can initiate a delayed cAMP/Epac1 cascade. This axis coordinates Rap1/Rac1-mediated cortical actin polymerization, VASP-driven junctional anchoring, retro-translocation of endothelial nitric oxide synthase (eNOS) to caveolar domains, PP2A-dependent suppression of actomyosin tension, and Krüppel-like factor 2 (KLF2)-driven transcriptional programs that sustain endothelial quiescence. Together, these pathways form a temporally orchestrated, multi-tiered “inactivation” program capable of restoring barrier integrity even in the continued presence of inflammatory stimuli. This conceptual shift reframes NO from solely a barrier-disruptive mediator to the initiating trigger of a coordinated, pro-resolution mechanism. The unified framework integrates cytoskeletal dynamics, junctional reassembly, focal adhesion turnover, and redox/transcriptional control, providing multiple potential intervention points. Therapeutically, Epac1 activation, Rap1/Rac1 enhancement, RhoA/ROCK inhibition, PP2A activation, and KLF2 induction represent strategies to accelerate endothelial sealing in acute microvascular syndromes. Moreover, applying these mechanisms to arterial endothelium could limit low-density lipoprotein (LDL) entry and foam cell formation, offering a novel adjunctive approach for atherosclerosis prevention. In this review, we will discuss both the current understanding of endothelial hyperpermeability mechanisms and the emerging pathways of its active inactivation, integrating molecular, structural, and translational perspectives. Full article

In recent decades, Chinese literary studies has shifted away from center–periphery models, favoring frameworks that emphasize multiplicity and decentralization. While this turn has opened space for new perspectives, it risks overlooking persistent hierarchies that continue to shape literary careers, where certain publishers remain more central to an author’s advancement than others. This essay reconsiders the center–periphery framework through an analysis of Huizu wenxue, a literary journal published in Changji, Xinjiang Uygur Autonomous Region. Despite its geographic distance from China’s dominant literary hubs, Huizu wenxue has long served as a key platform for Hui literature. Drawing on interviews, as well as textual and paratextual analysis, I demonstrate how the journal functions both as a launchpad for emerging Hui authors and as an institutional anchor for a nationwide Hui literary community. Through dedicated columns that showcase new Hui talent and events that foster professional networks, Huizu wenxue has, since its inception, continually played a central role in shaping Hui literary production and supporting authors’ careers. Because it operates from the margins of the People’s Republic of China’s yet wields significant influence within Hui literary circles, I argue that Huizu wenxue is best understood as a “peripheral center.” Full article

Financial support for environmental causes is more urgent than ever before. Thus, understanding consumer willingness to pay (WTP) for tourism is vital for policymakers, businesses, and researchers. This bibliometric study examined the trend of research on willingness to pay and tourism using 428 articles published in the Scopus indexed database between 1994 and 2023. The articles were extracted using the keywords “Willingness to pay tourism”. A Microsoft Excel sheet was used in the descriptive analysis, and a VOSviewer version 1.6.20 was used for the citation and co-occurrence analysis. The study found that willingness to pay is a complex aspect of environmental economics and tourism behaviour that is shaped by various aspects. Amongst other things, willingness to pay is shaped by aspects such as tourist biogeography, amongst others is the level of environmental awareness, environmental sensitivity, and education. In many respects, it is shaped by demographic factors such as age, gender, income bracket, and area of origin. Even though the major thrust of willingness to pay was anchored on sustainability and environmental protection, recent events in the mold of climate change, the COVID-19 pandemic, and technological innovation have played major roles in shaping tourists’ behaviour. Given the emerging thrust and focus, there is a need to respond to geographic knowledge gaps in tourism hotspots to understand how this will shape tourism sustainability from a Sustainable Development Goals (SDG) perspective going forward. In doing so, it will be critical to ensure continued fostering and understanding of how tourists’ willingness to pay for tourism destinations can lead to better design, marketing, and managed services to create memorable experiences that drive consumer loyalty. Full article

The prevalence of squamous cell carcinoma is increasing, and efforts that aid in an early and accurate diagnosis are crucial to improve clinical outcomes for patients. Cornulin, a squamous epithelium-specific protein, has recently garnered attention due to its implications in the progression of squamous cell carcinoma developed in several tissues. As an epidermal differentiation marker, it is involved in skin anchoring, regulating cellular proliferation, and is a putative tumor suppressor. The physiologically healthy squamous epithelium displays a considerable level of Cornulin, whereas squamous cell carcinomas have marked downregulation, suggesting that Cornulin expression levels can be utilized for the early detection and follow-up on the progression of these types of cancer. Cornulin’s expression patterns in cervical cancer have been examined, and findings support the stepwise downregulation of Cornulin levels that accompanies the progression to neoplasia in the cervix. Additional studies documented a similar trend in expression in other types of cancer, such as cutaneous, esophageal, and oropharyngeal squamous cell carcinomas. The consistent and predictable pattern of Cornulin expression across several squamous cell carcinomas and its correlation with key clinicopathological parameters make it a reliable biomarker for assessing the transformation and progression events in the squamous epithelium, thus potentially contributing to the early detection, definitive diagnosis, and more favorable prognosis for these cancer patients. Full article

The specific binding of the ubiquitous ‘marker of self’ protein CD47 to the SIRP$\alpha$ protein anchored in the macrophage plasma membrane results in the inhibition of the engulfment of ‘self’ cells by macrophages and thus constitutes a key checkpoint of our innate immune system. Consequently, the CD47–SIRP$\alpha$ protein complex has been recognized as a potential therapeutic target in cancer and inflammation. Here, we introduce a lattice-based mesoscale model for the biomimetic system studied recently in fluorescence microscopy experiments where GFP-tagged CD47 proteins on giant plasma membrane vesicles bind to SIRP$\alpha$ proteins immobilized on a surface. Computer simulations of the lattice-based mesoscale model allow us to study the biomimetic system on multiple length scales, ranging from single nanometers to several micrometers and simultaneously keep track of single CD47–SIRP$\alpha$ binding and unbinding events. Our simulations not only reproduce data from the fluorescence microscopy experiments but also are consistent with results of several other experiments, which validates our numerical approach. In addition, our simulations yield quantitative predictions on the magnitude and range of effective, membrane-mediated attraction between CD47–SIRP$\alpha$ complexes. Such detailed information on CD47–SIRP$\alpha$ interactions cannot be obtained currently from experiments alone. Our simulation results thus extend the present understanding of cooperative effects in CD47–SIRP$\alpha$ interactions and may have an influence on the advancement of new cancer treatments. Full article

The landmark black hole images recently taken by the Event Horizon Telescope (EHT) have allowed the detailed study of the immediate surroundings of supermassive black holes (SMBHs) via direct imaging. These tantalizing early results motivate an expansion of the array, its instrumental capabilities, and dedicated long-term observations to resolve and track faint dynamical features in the black hole jet and accretion flow. The next-generation Event Horizon Telescope (ngEHT) is a project that plans to double the number of telescopes in the VLBI array and extend observations to dual-frequency 230 + 345 GHz, improving total and snapshot coverage, as well as observational agility. The Large Millimeter Telescope (LMT) is the largest sub-mm single dish telescope in the world at 50 m in diameter, and both its sensitivity and central location within the EHT array make it a key anchor station for the other telescopes. In this work, we detail current and planned future upgrades to the LMT that will directly impact its Very Large Baseline Interferometry (VLBI) performance for the EHT and ngEHT. These include the commissioning of a simultaneous 230 + 345 GHz dual-frequency, dual-polarization heterodyne receiver, improved real-time surface measurement and setting, and improvements to thermal stability, which should enable expanded daytime operation. We test and characterize the performance of an improved LMT joining future ngEHT observations through simulated observations of Sgr A* and M 87. Full article

Zinc oxide (ZnO) is the most efficient curing activator employed in the industrial rubber production. However, ZnO and Zn(II) ions are largely recognized as an environmental hazard being toxic to aquatic organisms, especially considering Zn(II) release during tire lifecycle. In this context, aiming at reducing the amount of microcrystalline ZnO, a novel activator was recently synthetized, constituted by ZnO nanoparticles (NPs) anchored to silica NPs (ZnO-NP@SiO₂-NP). The objective of this work is to define the possible hazards deriving from the use of ZnO-NP@SiO₂-NP compared to ZnO and SiO₂ NPs traditionally used in the tire industry. The safety of the novel activators was assessed by in vitro testing, using human lung epithelial (A549) and immune (THP-1) cells, and by the in vivo model zebrafish (Danio rerio). The novel manufactured nanomaterial was characterized morphologically and structurally, and its effects evaluated in vitro by the measurement of the cell viability and the release of inflammatory mediators, while in vivo by the Fish Embryo Acute Toxicity (FET) test. Resulting data demonstrated that ZnO-NP@SiO₂-NP, despite presenting some subtoxic events, exhibits the lack of acute effects both in vitro and in vivo, supporting the safe-by-design development of this novel material for the rubber industry. Full article

Therapeutic options for treating advanced melanoma have progressed rapidly in recent decades. Until 6 years ago, the regimen for treating advanced melanoma consisted mainly of cytotoxic agents such as dacarbazine and type I interferons. Since 2014, anti-programmed cell death 1 (PD1) antibodies have been recognized as anchor drugs for treating advanced melanoma, with or without additional combination drugs such as ipilimumab, but the efficacies of these immunotherapies are not fully satisfactory. In this review, we describe the development of the currently available anti-PD1 Abs-based immunotherapies for advanced melanoma, focusing on their efficacy and immune-related adverse events (AEs), as well as clinical trials still ongoing for the future treatment of advanced melanoma. Full article

Event detection is usually the primary purpose of wireless sensor networks (WSNs). Therefore, it is crucial to determine where and when an event occurs in order to map the event to its spatio-temporal domain. In WSN localization, a few anchor nodes are those aware of their locations via the Global Positioning System (GPS), which is energy-consuming. Non-anchor nodes self-localize by gathering information from anchor nodes to estimate their positions using a localization technique. Traditional algorithms use at least three static anchors for the localization process. Recently, researchers opted to replace multiple static anchors by a single mobile anchor during the localization process. This paper proposes a Kalman filter based on bounding box localization algorithm (KF-BBLA) in WSNs with mobile anchor node. We present a new mobile anchor localization strategy to minimize energy, hardware costs, and computation complexity, while improving accuracy and cost-effectiveness. Network connectivity measurement and the bounding box localization method are used in order to identify the bounded possible localization zone. The Kalman filter is then used to minimize the uncertainty produced by the connectivity process. We aim also to minimize the localization inaccuracies generated by the bounding box algorithm. Simulation results show that our proposed approach significantly reduces the localization error compared to other localization algorithms chosen from the recent literature by up to $20\%$. We use the cumulative distribution function (CDF) as an indicator to assess the accuracy of our proposed algorithm. Full article

Despite its low abundance, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂) is a key modulator of membrane-associated signaling events in eukaryotic cells. Temporal and spatial regulation of PI(4,5)P₂ concentration can achieve localized increases in the levels of this lipid, which are crucial for the activation or recruitment of peripheral proteins to the plasma membrane. The recent observation of the dramatic impact of physiological divalent cation concentrations on PI(4,5)P₂ clustering, suggests that protein anchoring to the plasma membrane through PI(4,5)P₂ is likely not defined solely by a simple (monomeric PI(4,5)P₂)/(protein bound PI(4,5)P₂) equilibrium, but instead depends on complex protein interactions with PI(4,5)P₂ clusters. The insertion of PI(4,5)P₂-binding proteins within these clusters can putatively modulate protein–protein interactions in the membrane, but the relevance of such effects is largely unknown. In this work, we characterized the impact of Ca²⁺ on the organization and protein–protein interactions of PI(4,5)P₂-binding proteins. We show that, in giant unilamellar vesicles presenting PI(4,5)P₂, the membrane diffusion properties of pleckstrin homology (PH) domains tagged with a yellow fluorescent protein (YFP) are affected by the presence of Ca²⁺, suggesting direct interactions between the protein and PI(4,5)P₂ clusters. Importantly, PH-YFP is found to dimerize in the membrane in the absence of Ca²⁺. This oligomerization is inhibited in the presence of physiological concentrations of the divalent cation. These results confirm that cation-dependent PI(4,5)P₂ clustering promotes interactions between PI(4,5)P₂-binding proteins and has the potential to dramatically influence the organization and downstream interactions of PI(4,5)P₂-binding proteins in the plasma membrane. Full article