Search Results (1,477)

Endothelial dysfunction (ED) arises in multiple pathologies, and its severity correlates with disease progression. Common ED biomarkers could provide prognostic value for associated complications. This study aims to identify shared ED biomarkers and assess their prognostic significance. Endothelial cells in culture (human microvascular endothelial cells, HMEC-1) were exposed to sera from patients in five disease groups (n = 20 patients/group)—liver cirrhosis with portal hypertension, idiopathic pulmonary arterial hypertension, placental disorders such as intrauterine growth restriction, coronary artery disease with acute myocardial infarction, and chronic kidney disease—or matched controls, in the absence/presence of anti-inflammatory (apixaban) and antioxidant (EUK134) compounds. We explored changes in: VCAM-1, ICAM-1, eNOS, VWF, extracellular matrix thrombogenicity, and reactive oxygen species (ROS). In serum samples, proteomics and metabolomics analyses (including lipids, amino acids, and polar metabolites) were performed through an extraction protocol to identify common ED biomarkers. Expression of VCAM-1, ICAM-1, VWF, platelet adhesion, and ROS increased in most groups versus controls (p < 0.05). Both drugs decreased all biomarker levels except eNOS (n = 6 for in vitro experiments). For serum ED biomarkers, 18 metabolites and 24 proteins showed AUC-ROC and hit rates >77.5%, and six metabolites were associated with event-free survival. These diseases share ED driven by systemic inflammatory, oxidative, and metabolic stress, are partially reversible in vitro, and are linked to biomarkers associated with clinical outcomes. Overall, ED emerges as a modifiable pathological axis with potential prognostic value. Full article

The occurrence of marine heatwaves (MHWs) and phytoplankton blooms is accelerating under climate change, yet the frequency and drivers of their compound co-occurrence remain poorly understood. Using coastal-optimized satellite observations from 2003–2020, we mapped global compound MHW–phytoplankton bloom (MHW-PB) events across coastal large marine ecosystems and quantified their spatiotemporal trends and environmental predictors. Compound events are increasing at 4.8% yr⁻¹, driven primarily by a 6.5% yr⁻¹ rise in MHW frequency; a temporal shuffle test confirms this trend falls below random co-occurrence expectation, indicating biological suppression actively constrains compound event growth. The compound independence factor (CIF) reveals latitudinal heterogeneity: low-latitude upwelling systems show MHW–PB mutual exclusivity, while high-latitude and eutrophic coastal regions show positive co-occurrence tendency. Interpretable machine learning further shows that nutrient availability dominates bloom responses at low latitudes whereas light dominates at high latitudes, with MHW intensity exhibiting nutrient-dependent non-linear associations with bloom probability. Paradoxically, compound frequency accelerates nearly twice as fast in low latitudes (6.1% yr⁻¹) as in high latitudes (3.5% yr⁻¹), driven by rapid tropical MHW acceleration. These diverging regimes signal dual ecological risks: trophic mismatches in upwelling systems and escalating hypoxia and harmful algal bloom hazards in eutrophic coastal waters. Full article

The electrical system is a crucial infrastructure of modern society. It provides the energy needed for society to continue its development. However, this critical infrastructure is increasingly threatened by the extreme weather events driven by the escalating climate crisis, posing significant challenges to sustainable development and energy security. Therefore, it is important to conduct comprehensive risk analyses of the electrical system to prepare for future challenges. This paper presents an electrical risk assessment conducted within the European project ICARIA, aiming to evaluate the effects of global climate change on critical infrastructure resilience. The study improves on the first risk assessment conducted, evaluating the electrical system’s vulnerability to flooding events, such as heavy rains or rising sea levels, in the Metropolitan Area of Barcelona. A key contribution to this research is the integration of direct impact assessments and cascading effect analyses, which identify how localised failures in electrical assets can spread throughout the system, potentially leading to a blackout. The research focuses on modelling various flood projections, using extreme weather scenarios and return periods ranging from 1 to 100 years. These projections are employed to evaluate the risk assessment methodology and quantify potential impacts on the electrical grid, including Expected Annual Damage (EAD) and Energy Not Supplied Cost (ENSC). The results aim to provide policymakers and grid operators with valuable insights, enabling the development of data-driven adaptation strategies and climate-resilient infrastructure planning to mitigate the risks posed by extreme weather events. Full article

Genome editing is widely used and conceptually simple, yet in practice, it is hindered by laborious workflows and high costs. These challenges stem from the difficulty of identifying and isolating cells that contain the desired user-defined modifications, a problem compounded by the wide variability in editing efficiencies across cell types. While homology-directed repair (HDR) provides a mechanism for precise genome modification following nuclease-induced double-strand breaks (DSBs), it is frequently outcompeted by the dominant mutagenic non-homologous end-joining (NHEJ) pathway in mammalian cells. Therefore, we developed a novel enrichment method, Essential HDRescue, to increase the frequency of HDR events at a target site by co-targeting an essential genomic locus. Using both intrinsic positive and negative selection at a common essential gene, we enabled enrichment of precise editing events at a second, unlinked target site. We demonstrated that co-targeting essential genes in cancer cell lines and iPSCs increased HDR rates without the need for an exogenous reporter or selective drug. Analysis of resulting clones revealed that Essential HDRescue produced up to a 6-fold increase in single-allele edits and an ~4-fold increase in homozygous edits relative to single-targeted controls. By harnessing the intrinsic cellular dependencies that arise from DSB repair at essential loci, Essential HDRescue offers a widely applicable method to improve precise genome editing outcomes in mammalian cells, leaving only a minimal, protein-silent scar at the essential gene. Full article

Bees are essential pollinators for agricultural systems, making accurate, automated monitoring of their behavior critical for assessing colony health and ecosystem stability. Recent advances in computer vision and artificial intelligence have enabled large-scale bee traffic monitoring at hive entrances; however, most existing event classification methods focus exclusively on simple entrance and exit events. This simplification overlooks compound movements—such as U-turns and guarding behaviors—that represent a substantial portion of bee activity and can lead to inaccurate trajectory reconstruction and misleading behavioral interpretations. In this work, we systematically analyze existing event classification strategies used in automatic bee traffic monitoring, evaluating their performance on both simple and compound movements. We then propose extended classification methods that explicitly model compound events by incorporating bidirectional movement patterns derived from positional and angular cues. Using a manually annotated dataset of computer-vision-based hive entrance recordings, we compare threshold-based, displacement-based, and angle-based approaches under simple and mixed-event conditions. Our results demonstrate that compound events account for over one-third of all detected movements and that classification methods explicitly designed to handle bidirectional behavior substantially outperform traditional approaches in both accuracy and robustness. In particular, threshold-based bidirectional classification achieves near-perfect performance when full trajectories are available, while displacement-based methods provide a reliable alternative under partial observations. These findings highlight the importance of modeling compound behaviors in automated bee monitoring systems and contribute to more accurate flight reconstruction, behavioral analysis, and AI-driven decision support for precision agriculture and pollinator management. Full article

Landmark epidemiological studies and clinical trials, such as the Seven Countries Study, the Lyon Diet Heart Study, the PREDIMED Study and the CORDIOPREV Study, have shown significant reductions in cardiovascular events in those following the Mediterranean diet (MD). The aim of the present work is to summarize the most robust available evidence and the major biological pathways underlying the protective effects of the MD, with particular emphasis on the role of PAF inhibitors. Mechanistically, MD functions through a complex synergy of antioxidant, anti-inflammatory, and antithrombotic effects that collectively improve lipid profiles, enhance endothelial function, optimize postprandial metabolism and cell membrane signaling, making it a functional model for human longevity. The PAF-Implicated Atherosclerosis Theory has emerged as a key unifying framework, proposing that Platelet-Activating Factor (PAF)—a highly potent lipid inflammatory mediator—plays a central role in the initiation and progression of atherosclerosis. Oxidized LDL promotes the production of PAF and PAF-like lipids, leading to endothelial dysfunction, vascular inflammation, and atherosclerotic plaque formation. Traditional Mediterranean foods are rich in natural PAF inhibitors, particularly the polar lipid fractions of extra virgin olive oil, as well as wine, fish, vegetables, onions, and garlic. Animal studies demonstrate that these compounds can reduce or even regress atherosclerotic lesions, independently of serum cholesterol levels. Human dietary interventions have further shown that MD-based meals and functional foods enriched with PAF inhibitors reduce PAF activity and improve thrombosis-related biomarkers. This mechanistic framework helps explain phenomena such as the “French Paradox” and the cardio-protective effects associated with fish consumption. Moreover, the extraction of PAF inhibitors from Mediterranean food by-products, such as olive pomace, offers promising ecological and economic advantages. Collectively, targeting PAF and increasing dietary intake of PAF inhibitors represent promising strategies for the prevention and management of atherosclerosis and other inflammatory diseases, supporting the view that PAF may function as a major, modifiable risk factor in these conditions. Full article

To combat climate change, farmers want to develop sustainable agriculture that enhances food production while strengthening their capacity to cope with extreme weather events and pest and disease pressures. Promoting agroecological farming practices is a promising approach in enhancing sustainability and strengthening the climate-resilient farming systems. Recent research often overlooks to what extent the agroecological farming practices (AFP) provide a measurable advantage over non-AFP methods under increasing environmental challenges. In this regard, this study compares the extent of climate resilience between AFP mango-based farming systems and non-AFP mango-based farming systems in southern Ethiopia. AFP adopters applied ecological principles like intercropping, integrated pest management, agroforestry, canopy management, varietal diversity, and water and soil preservation to enhance biodiversity and soil health, and boost productivity and ecosystem services. The study employed a mixed-method design, drawing on the data from 395 selected households. The resilience of AFP and non-AFP farming systems was assessed by computing the 13 agroecosystem indicators of climate resilience using the Self-evaluation and Holistic Assessment of Climate Resilience of Farmers and Pastoralists (SHARP+) tool. Households in AFP mango-based farming system demonstrated greater diversification in agricultural production system compared to those in non-AFP mango farming system. The analysis of climate resilience indicators showed that the mango production systems under the AFP were more climate-robust than their conventional systems. Both the compound resilience score and the household resilience index showed that the mango farming systems under AFP substantially enhanced climate resilience. Hence, coordinated supports from the extension services, NGOs, and researchers are needed to scale up these benefits of AFP. Strengthening the AFP mango farming requires addressing the key barriers such as market access, input availability, and crop diversification strategies. This paper identifies important avenues for further AFP research in Sub-Saharan African countries. Full article

The growing complexity of human systems and the increasing frequency of climate-driven hazards have transformed some disasters from isolated events into cascading phenomena which propagate through critical infrastructure networks, disrupting essential services and amplifying systemic risk. This work examines the impacts of extreme storms and subsequent flooding on critical entities as defined under the new EU Directive (Critical Entities Resilience, CER). This study introduces a structured Critical Entities Disruption Database—Greece (CEDD-GR), as a methodological framework for systematically recording and analysing disruptions to critical entities, and applies it to the case of Storm Daniel (2023), one of the most severe flood events recorded in Greece. The analysis identified direct impacts across eight of the eleven sectors defined in the CER Directive, namely, energy, transport, health, drinking water, wastewater, public administration, digital infrastructure and food production, processing and distribution. A total of 21 different types of critical entities were documented, revealing the mechanisms through which failures affected different subsectors. The results underscore the systemic fragility of critical entities when exposed to extreme storms, compound flooding, and mass wasting processes (landslides, ground subsidence) and highlight the need for integrated resilience planning in line with the CER framework. Full article

The Sichuan Basin is a high-incidence area for China’s drought–flood abrupt alternation (DFAA) events. To reveal the spatiotemporal evolution characteristics and driving factors of drought–flood abrupt alternation (DFAA) compound disasters in the Sichuan Basin, this study identified drought-to-flood (DF) and flood-to-drought (FD) events using the Standardized Precipitation Evapotranspiration Index based on meteorological data and circulation factors from 1963 to 2022. By constructing a standardized drought–flood abrupt alternation magnitude index to classify event grades, combined with methods such as trend analysis, Morlet wavelet and Random Forest, the study explored the trend variation laws, spatial distribution patterns, and core driving factors of DFAA events in the basin. The results showed that on the interannual scale, the upward trend of FD events was more obvious than that of DF events, with a significant increase in the proportion of moderate and severe events; both the frequency and intensity of summer FD events increased significantly, and the intensity of winter FD events also exhibited a marked upward trend. Spatially, DF events occurred frequently in Guang’an and Chongqing, while FD events were concentrated in the western edge of the basin, as well as Yibin and Luzhou. Moderate and severe events were more prominent in the edge areas of the basin. The occurrence of DFAA events was generally jointly driven by the meteorological factors and regulation of large-scale sea surface temperature-circulation factors: the triggering factors of DF events showed a diversified and decentralized characteristic, while FD events were mainly driven by the subtropical high, and tropical sea surface temperature anomalies were the common precursor signal for both types of events. This study provides a scientific basis and technical support for the formulation of disaster prevention and mitigation strategies and the optimal management of water resources for compound extreme meteorological disasters in the Sichuan Basin. Full article

Wetlands are the largest natural source of atmospheric methane (CH₄), and their emissions are projected to increase during the 21st century in response to climate change. However, how extreme climate events such as extreme heat, extreme precipitation, and their compound occurrences modulate future wetland methane emissions, remains poorly constrained. Here, we quantify the impacts of extreme temperature, precipitation, and compound hot–wet events on global wetland methane emissions (eCH₄) using simulations from the dynamic global vegetation model LPJ-wsl driven by four CMIP5 climate models under a high-emission scenario (RCP8.5) for the period 2006–2099. Our results show that extreme heat events intensify and become substantially more frequent, with global occurrence increasing by more than 303% by the end of the century. Correspondingly, their contribution to global wetland methane emissions rises from ~26–28% in 2006 to ~73–83% by 2099, making extreme heat the dominant driver of future eCH₄ increases. Extreme precipitation events exhibit relatively modest changes in frequency and mixed intensity. In contrast, compound hot–wet events, despite their low baseline frequency, increase by more than 600% and are associated with disproportionately strong methane responses, driven by the combined effects of elevated temperatures and enhanced anaerobic conditions. Across all event types, tropical wetlands account for 75–90% of global methane emissions, while contributions from mid-latitudes increase modestly and high-latitude contributions remain comparatively small. These findings highlight the emerging importance of climate extremes—particularly extreme heat and compound hot–wet events—in shaping future wetland methane emissions. Explicit consideration of extreme-event dynamics is therefore essential for improving projections of methane–climate feedback under continued global warming. Full article

This article examines the geopolitical transformation of the European Union within the context of polycrisis and intensified strategic rivalry following the events of 2022. It addresses the question of whether the EU’s response to contemporary crises represents a mere temporary adjustment triggered by an emergency, or rather a more permanent reconfiguration of European integration. Methodologically, the paper employs a qualitative research design combining conceptual analysis, interdisciplinary theoretical synthesis, and document-based comparative process-tracing of selected post-2022 policy responses, including sanctions policy, energy governance, and geoeconomic industrial policy. The analysis demonstrates that the EU has not evolved into a coherent, sovereign geopolitical actor, but rather into a more strategically adaptive and selectively integrated compound polity. This transformation is characterised by differentiated institutional deepening, expanded executive coordination, and growing tensions between efficiency, legitimacy, and democratic accountability. The article contributes to debates on European integration by conceptualising its current trajectory as a hybrid adaptation to a fragmented global order. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by an exceptionally high global prevalence that is projected to continue rising in the near future. MASLD is strongly associated with a spectrum of cardiometabolic risk factors, and may itself, in turn, contribute to cardiovascular morbidity and mortality. This interconnection warrants the development of integrated treatment strategies targeting shared pathophysiological processes and addressing both hepatic, metabolic, and cardiovascular outcomes. In this work, we review the modern MASLD clinical development pipeline and highlight the most prominent drug candidates with known or purported cardiovascular benefits, discussing mechanistic links and supporting evidence ranging from preclinical experiments to real-world data. Although the drug development pipeline is extensive and diverse, evidence supporting cardiovascular benefits for most candidate molecules remains limited. Both of the FDA-approved therapies, resmetirom and semaglutide, have been found to significantly reduce the risk of major adverse cardiovascular events as well as cardiovascular and all-cause mortality in patients with MASH. In addition, significant improvements were observed in patients with heart failure with preserved ejection fraction treated with semaglutide, highlighting incretin mimetics as a promising class for managing cardiovascular disease concomitant with MASLD/MASH. Other investigational compounds, targeting the farnesoid X receptor, peroxisome proliferator-activated receptors, de novo lipogenesis enzymes, and fibroblast growth factors, have demonstrated improvements in blood lipid spectrum and glycemic control; however, their clinical effectiveness in patients at cardiovascular risk has yet to be established. Full article

A sense of school belonging predicts NEET outcomes for adolescents. However, young people from marginalized groups often have a lower sense of school belonging than their majority peers. Emerging understandings of belonging as a complex, agentic process shaped by multiple relational, contextual, cultural and structural factors have posed problems for real-world applications of belonging. NEET young people tend to be viewed through a lens of risk factors, with a lack of research accounting for their experiences and feelings. While recent research recognizes the intersectional effects of disadvantage, or ‘compound disadvantage’, on NEET outcomes for young people from certain social groups, there is a lack of viable alternatives for educators and policymakers to account for these differential experiences of belonging in order to be able to respond to them. Connected Belonging is a relational and identity-building approach to enhancing young people’s wellbeing through supporting their connectedness and sense of self across the eight social domains of their lives. This paper outlines the development and validation of a young people’s survey, which enables education professionals to attend to and respond to the differing belonging experiences of diverse groups, operationalizing an intersectional lens on school belonging. After introducing the views of young people about systemic priorities to better support their engagement in education, training or work (EET), gathered through a youth voice event as part of a parallel research project, the paper outlines the process of developing, piloting and validating the tool. We argue that this survey tool has the potential to support improved attention to the views and experiences of diverse young people in a systematic, regular fashion. Furthermore, it offers potential for the evaluation of supportive actions grounded in youth voice. Full article

Background and Clinical Significance: Isolated prolongation of activated partial thromboplastin time (aPTT) without a bleeding tendency presents a frequent diagnostic challenge and often leads to prolonged, inconclusive evaluations. Case Presentation: We report the case of a pregnant woman with long-standing isolated aPTT prolongation in whom clinical exome sequencing enabled a definitive diagnosis. Two compound heterozygous variants in F12 were identified: NM_000505.4:c.1561G>A, p.(Glu521Lys), previously reported in Factor XII deficiency, and a novel in-frame insertion, NM_000505.4:c.1423_1425dup, p.(Cys475dup), absent from population databases and the prior literature. Familial genetic testing confirmed a trans configuration. Factor XII activity was markedly reduced to 1%, and mixing studies showed complete correction, consistent with coagulation factor deficiency without inhibitors. Variant interpretation using ClinGen specifications within a Bayesian framework classified both variants as likely pathogenic. Despite significant laboratory abnormalities, the patient experienced no bleeding or thrombotic complications and underwent cesarean delivery without adverse events. Conclusions: This case highlights that early integration of next-generation sequencing and quantitative variant interpretation frameworks can facilitate timely diagnosis, clarify clinical significance, and support appropriate management in patients with unexplained isolated aPTT prolongation. Full article

Due to ongoing global warming, the frequency and intensity of extreme weather events have increased substantially. Compared to individual extremes, compound drought and high temperature (CDHT) events represent a major climate risk in China. However, their spatiotemporal characteristics remain insufficiently understood, particularly at fine temporal scales. To address this gap, this study systematically investigated CDHT events across China from 1982 to 2023. Methodologically, CDHT events were identified at the raster level by combining an improved daily Standardized Precipitation Evapotranspiration Index (SPEI) with daily maximum temperature using a quantile relative dynamic threshold. The results show strong spatial heterogeneity: the longest event durations are primarily observed in Xizang, while higher event severity is concentrated in regions south of 30° N. Trend analysis reveals a widespread increase in the duration, frequency, and severity of CDHT events across most of China, with the most pronounced intensification detected in Xinjiang, Inner Mongolia, and Yunnan. Overall, these findings highlight a clear climate-driven intensification of CDHT events, offering new insights into their spatiotemporal dynamics. The results offer a robust scientific basis for improving risk assessment and developing targeted adaptation strategies to mitigate the impacts of compound climate extremes in China. Full article