Search Results (4,602)

Telomere maintenance enables unlimited cell proliferation by counteracting telomere erosion. While the majority of tumors activate telomerase, a significant subset—approximately 10–15%—utilizes alternative lengthening of telomeres (ALT), a recombination-based mechanism. ALT-positive cancers are classically associated with genomic instability, anaphase bridges, chromosomal rearrangements, and resistance to DNA-damaging therapies. This process is closely associated with genetic instability, which contributes to chromosomal rearrangements and tumor evolution. Consequently, ALT has traditionally been considered an adverse prognostic marker in aggressive malignancies such as osteosarcoma, pancreatic neuroendocrine tumors, and high-grade sarcomas. Paradoxically, recent evidence demonstrates that ALT positivity correlates with improved survival in glioblastoma (GBM) and chondrosarcoma, two tumor types that have historically been regarded as immune-cold and therapeutically intractable. This favorable outcome likely reflects a convergence of factors, including replication stress and DNA damage that impose a fitness cost in slow-growing or metabolically constrained tumors. Loss of ATRX/DAXX, while enabling ALT, further amplifies chromatin fragility, and ALT-mediated instability may paradoxically enhance immunogenicity within immune-quiescent microenvironments. Moreover, ALT-positive cells exhibit unique therapeutic vulnerabilities, particularly to ATR and PARP inhibitors. Together, these observations support a context-dependent model in which ALT functions as a double-edged sword, acting as a driver of malignant aggressiveness in rapidly proliferating cancers while serving as a relative liability in slower-growing, immune-cold tumors. Understanding this duality not only refines prognostic stratification but also opens opportunities for precision oncology. By integrating ALT-specific biomarkers into clinical workflows and exploiting ALT-related DNA repair dependencies, clinicians may transform a once uniformly negative prognostic factor into an actionable therapeutic target. Full article

Fragile X syndrome (FXS, OMIM#300624) is the most common inherited cause of X-linked intellectual disability and behavior difficulties. In 99% of cases, it is caused by the pathological expansion (>200 repeats, full mutation -FM) of the CGG trinucleotide located at the 5′ UTR of the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene, leading to the lack of production of the FMRP. Clinical manifestations are well known in boys but are sometimes overlooked in girls, who may remain underdiagnosed. Premutation (PM) populations (55–200 repeats) may present other medical issues, such as FXPOI or FXTAS. Mosaic conditions, such as a combination of PM and FM lines in the same patient, may lead to milder phenotypes. With the improvement of genetic testing, information regarding the exact number of CGG triplet repeats and methylation status could help explain milder phenotypes in patients who may produce some FMRP. Chromosome X preferential inactivation (XCI) in FXS women can also play a role in clinical severity. We present four non-related families who were followed up in our FXS clinic. Some of their members showed FM on Southern blot, but had milder symptoms than expected. To rule out size mosaicism, a RT-PCR was performed, giving a different and more consistent molecular diagnosis. When mosaicism was not present, methylation status was performed, excluding full methylation. For females, XCI showed preferential inactivation in one case. Revisiting old molecular diagnoses should be considered in clinical practice, especially for patients with a milder phenotype than expected from their molecular reports. This personalized follow up may change their former diagnosis, prognosis, and expectations. Full article

To address limitations such as cleaning difficulties or secondary contamination/damage of cultural relics caused by the uncontrollable diffusion of water/cleaning agent/dirty liquids during the cleaning process in traditional cleaning methods, this study, using cotton textiles as an example, systematically investigated the cleaning efficacy of four in situ methods (blank gel, cleaning gel, ultrasonic emulsification, and gel + ultrasonic emulsification synergistic cleaning) on eight types of stains, including sand, clay, rust, blood, ink, oil, and mixed solid/liquid stains. Building upon this, this study proposed an efficient, targeted, in situ, and controllable cleaning strategy tailored for fragile, stained textile relics. Results demonstrated that, regardless of the stain type, the synergistic cleaning method of G+U (gel poultice + ultrasonic emulsification) consistently outperformed the cleaning methods of blank gel poultice, cleaning gel poultice, and ultrasonic emulsification. Furthermore, the gel loaded with cleaning agents was always more effective than the blank gel (unloaded cleaning agents). The poultice methods of blank gel and cleaning gel were better suited for solid stains, while the ultrasonic emulsification cleaning method was more effective for liquid stains. Meanwhile, it was also found that the optimal cleaning method proposed in this study (the G+U synergistic cleaning method) was a cleaning method that restricted the cleaning agent within the gel network/emulsion system, and utilized the porous network physical structure of gel, the chemical action of emulsion’s wetting/dissolving dirt, and the cavitation synergistic effect of ultrasound to achieve the targeted removal of contaminants from relics’ surfaces. Crucially, the cleaning process of G+U also had the characteristics of controlling the cleaning area at the designated position and effectively regulating the diffusion rate of the cleaning solution within the treatment zone, as well as the reaction intensity. Therefore, the proposed optimal (the synergistic cleaning method of G+U) cleaning method conforms to the significant implementation of the “minimal intervention and maximal preservation” principle in modern cultural heritage conservation. Consequently, the synergistic cleaning method of G+U holds promise for practical application in artifact cleaning work. Full article

Mediterranean cities are increasingly exposed to climate hazards, water scarcity, and social vulnerabilities, demanding integrative approaches for sustainable regeneration. This study examines how participatory governance and co-design processes can shape nature-based solutions (NbS) for climate resilience in Barrios Altos, a socially and environmentally fragile district of Lorca, Spain. Within the framework of the NATUR-W project, the interventions reimagine a degraded hillside and adjacent public spaces into a multifunctional urban forest, complemented by green retrofits of social housing and the adaptive reuse of a historic prison. Methods combined baseline community assessments, stakeholder mapping, co-design workshops, and the establishment of a multi-stakeholder governance board, ensuring inclusive participation from residents, civil society, and municipal authorities. Results demonstrate that the co-created design addressed key community priorities—such as shade provision, safe accessibility, cultural venues, and child-friendly spaces—while integrating sustainable water management systems for irrigation and stormwater control. The participatory process enhanced local ownership, balanced technical feasibility with community aspirations, and fostered governance structures that increase transparency and accountability. Overall, the study illustrates how NbS, when embedded in collaborative governance frameworks, can deliver climate, social, and cultural co-benefits while advancing resilient, inclusive, and human-scale urban environments. Full article

Financial fragility among non-financial corporations (NFCs) has become a critical concern in developing economies, where both firm-specific and macroeconomic conditions shape corporate financial stability. Understanding these dynamics is essential to enhancing corporate resilience and informing effective regulatory interventions. This study is motivated by Minsky’s Financial Instability Hypothesis (FIH), to empirically investigate the determinants of financial fragility in Jordanian non-financial firms (NFCs) using panel data from 71 companies listed on the Amman Stock Exchange (ASE) between 2015 and 2021. By employing a panel logistic regression analysis, results reveal that Return on Assets (ROA) significantly supports financial stability, while inflation negatively impacts it, underlining the detrimental impact of increasing inflation rates on corporate financial health. The beneficial effects of GDP growth and institutional quality also emphasize how important governance and economic conditions are in promoting financial stability. The study offers an original insight on the dynamics of financial fragility in a developing market, with important ramifications for regulators, business managers, and policymakers looking to boost institutional quality, control inflation, and increase corporate profitability. The findings extend Minsky’s hypothesis to a developing-market context and provide implications for policymakers seeking to strengthen institutional frameworks, contain inflationary pressures, and promote corporate financial stability. Full article

Background: Fragile X Syndrome (FXS) is the most common monogenic cause of autism spectrum disorders, and is characterized by the excessive immature excitatory synapses in cortical neurons, leading to excitatory/inhibitory imbalance and core autistic behaviors. This synaptic pathology has been attributed to dysregulated levels of synaptic proteins, including CYFIP2: a key regulator of synaptic structure and plasticity. However, the mechanism underlying the increased CYFIP2 protein level in FXS neurons remains unclear. Neurons abundantly secrete extracellular vesicles (EVs) enriched with bioactive cargos (proteins and miRNAs). Objectives: the goal of this research is to identify whether EV-dependent secretion plays important roles in regulating the intracellular CYFIP2 protein level in WT and FXS neurons. Methods and Results: our proteomic analysis reveals that CYFIP2 protein is packaged in EVs released by mouse cortical neurons. Pharmacological and genetic blockades of neuronal EV release significantly elevated intracellular CYFIP2 levels by 78 ± 14% and 168 ± 39%, respectively. Glutamate-evoked EV release significantly reduced the CYFIP2 level by 24 ± 2%. Neurons from Fmr1 KO mice, an FXS model, secreted significantly less EVs (46 ± 5%) than the wild type, and showed significantly elevated CYFIP2 (by 155 ± 31%). Evoking EV release in FXS neurons significantly lowered the intracellular CYFIP2 (by 53 ± 6%). Conclusions: these findings identify an EV-secretion-dependent mechanism that controls neuronal CYFIP2 level, implicating EV-mediated export in the regulation of synaptic protein homeostasis, synaptic remodeling, and FXS-associated synaptic deficits. Full article

Machining hard metals presents various challenges, especially with materials like WC-Co, known for their exceptional hardness and wear resistance, making them ideal for cutting tools. Among machining methods, Electrical Discharge Machining (EDM) stands out for its ability to machine hard materials with no mechanical damage, which is critical for machining fragile components. For form shape machining symmetrical parts like WC-Co bars, electrical discharge turning (EDT) could be applied. Despite its potential, limited research exists on deep form turning of hard metals like WC-Co using EDT. This study addresses that gap by comparing the final geometrical outcomes of two EDT setups: vertical and horizontal tool electrode configurations. Additionally, the impact of workpiece rotational speed on surface quality was examined. Results showed that the vertical tool electrode setup produced more accurate geometries and smoother surfaces. Furthermore, increasing the workpiece’s rotational speed improved flushing efficiency, resulting in reduced surface roughness and a cleaner machined surface. Full article

Coastal lagoons are fragile and dynamic ecosystems that are particularly vulnerable to climate change and anthropogenic pressures such as urbanization and eutrophication. These vulnerabilities highlight the need for frequent and spatially extensive monitoring of water quality (WQ). While satellite remote sensing offers a valuable tool to support this effort, the optical complexity and shallow depths of lagoons pose major challenges for retrieving water column biogeochemical parameters such as chlorophyll-a ([chl-a]) and suspended particulate matter ([SPM]) concentrations. In this study, we develop and evaluate a robust satellite-based processing chain using Sentinel-2 MSI imagery over two French Mediterranean lagoon systems (Berre and Thau), supported by extensive in situ radiometric and biogeochemical datasets. Our approach includes the following: (i) a comparative assessment of six atmospheric correction (AC) processors, (ii) the development of an Optically Shallow Water Probability Algorithm (OSWPA), a new semi-empirical algorithm to estimate the probability of bottom contamination (BC), and (iii) the evaluation of several [chl-a] and [SPM] inversion algorithms. Results show that the Sen2Cor AC processor combined with a near-infrared similarity correction (NIR-SC) yields relative errors below 30% across all bands for retrieving remote-sensing reflectance R_rs(λ). OSWPA provides a spatially continuous and physically consistent alternative to binary BC masks. A new [chl-a] algorithm based on a near-infrared/blue R_rs ratio improves the retrieval accuracy while the 705 nm band appears to be the most suitable for retrieving [SPM] in optically shallow lagoons. This processing chain enables high-resolution WQ monitoring of two coastal lagoon systems and supports future large-scale assessments of ecological trends under increasing climate and anthropogenic stress. Full article

Background: Haemoglobinopathies are among the most common monogenic disorders worldwide. Early identification of asymptomatic carriers through reliable screening and molecular diagnostics is crucial for prevention programmes, especially in high-prevalence regions such as Southern Italy. Methods: A total of 5243 individuals were analysed between 2013 and 2024 using both biochemical and genetic parameters. First-level screening included full blood count, iron status, and high-performance liquid chromatography (HPLC) for haemoglobin variant quantification. Molecular analyses were performed using next-generation sequencing (NGS) for the HBA1, HBA2, and HBB genes. Results: We identified 267 individuals (11.2%) as carriers of α-thalassaemia and 473 individuals (16.7%) as carriers of β-thalassaemia. Among them, 5 were compound heterozygotes and 3 homozygous for the α-3.7 deletion. A rare case of HbG Philadelphia in association with a triplicated α-gene was also observed. The most common β-globin mutations included c.118C>T (β⁰39, 44%), IVS-I-110 (17.7%), IVS-I-6 (12.7%), and IVS-I-1 (12.3%). Among α-globin mutations, the most prevalent were -α^3.7 (48%), α2 IVS1 -5nt (15.4%), -20.5 Kb (14.2%), and triplicated α (11%). In total, 18.7% of individuals were found to carry either α- or β-thalassaemia traits. Conclusion: Our findings highlight the limitations of traditional diagnostic methods—such as the osmotic fragility test—and the importance of integrating haematological, biochemical, and molecular data to accurately identify thalassaemia carriers. The variability of genotype–phenotype correlations, especially in the context of immigration and genetic diversity, underscores the need for comprehensive molecular analysis. We propose a three-step diagnostic algorithm combining first-level screening, iron status assessment, and NGS-based sequencing for inconclusive cases. Full article

Early warning of structural damage from induced seismic events requires rapid and reliable ground motion forecasting. This study presents a novel real-time framework that couples a deep learning approach with structural fragility assessment to generate immediate damage alerts following the onset of seismic shaking. Long Short-Term Memory (LSTM) neural networks are employed to predict full S-wave accelerograms from initial P-wave inputs, trained and tested on accelerometric records from induced seismicity scenarios. The predicted S-wave motion is then used as input for a suite of fragility curves in real time to estimate the probability of structural damage for masonry buildings typical in rural areas of geothermal platforms. The proposed method captures both the temporal evolution of shaking and the structural response potential, offering critical seconds of lead time for automated decision-making systems. Results demonstrate high predictive accuracy of the LSTM model and effective early classification of structural risk. This integrated system provides a practical tool for early warning or rapid response in regions experiencing anthropogenic seismicity, such as those affected by geothermal operations. Full article

Urban drone operations are exposed to unpredictable risks, including engine failure and deliberate signal interference. A recent and ongoing disruption in Jeddah, Saudi Arabia, has seen widespread GPS spoofing that misleads devices by hundreds of kilometers, illustrating how fragile unmanned aerial vehicle (UAV) operations can become when over-reliant on GNSS-based navigation. Such disruptions highlight the urgent need for contingency planning in drone traffic management systems. This study introduces a safety-aware pre-flight path planning framework that proactively integrates emergency landing and GPS fallback options into UAV trajectory pre-flight planning. The planner considers proximity to predesignated emergency landing zones, communication coverage, and airspace restrictions, enabling UAVs to safely complete their operations. The approach is evaluated across realistic mission profiles such as delivery, inspection, and surveillance. Results show that the planner successfully maintains mission feasibility while embedding emergency readiness throughout each flight. This work contributes toward safer, failure-resilient drone integration in urban airspace, ensuring that contingency plans are proactively incorporated into path planning before the failure even occurs. Full article

This article reflects on the fading of personal and familial histories in the context of migration, trauma, and cultural transformation. While modern tools such as ancestry kits and digitized records promise clarity about our roots, they often fail to capture the emotional and narrative legacies that define us. Drawing on scholars such as Jan Mason, Gayatri Chakravorty Spivak, and Saidiya Hartman, this piece explores the silence that surrounds intergenerational memory. Whether caused by disruption, grief, or survival, silence is shown to be both an absence and a form of protection. The editorial calls for greater intentionality in preserving stories through conversation, documentation, and creative expression as a way to resist erasure and affirm identity in the face of historical neglect. In a world where wars, migration, and climate disasters are uprooting millions, we risk losing not just homes but the stories, languages, and rituals that carry who we are. This piece is a call to hold on to those fragile histories beyond the facts and dates, so that what is most human in our past is not silenced by the speed and forgetting of the present. Full article

The Yellow River Delta is one of China’s most ecologically fragile regions, experiencing prolonged pressures from rapid urbanization and ecological degradation. Existing research, however, has predominantly focused on constructing ecological security patterns under single scenarios, with limited systematic multi-scenario comparisons and insufficient statistical support. To address this gap, this study proposes an integrated framework of “land use simulation—multi-scenario ecological security pattern construction—statistical comparative analysis.” Using the PLUS model, three scenarios were constructed—Business-as-Usual (BAU), Priority Urban Development (PUD), and Priority Ecological Protection (PEP)—to simulate land use changes by 2040. Habitat quality assessment, Multi-Scale Pattern Analysis (MSPA), landscape connectivity, and circuit theory were integrated to identify ecological source areas, corridors, and nodes, incorporating a novel hexagonal grid partitioning method. Statistical significance was evaluated using parametric tests (ANOVA, t-test) and non-parametric tests (permutation test, PERMANOVA). Analysis indicated significant differences in ecological security patterns across scenarios. Under the PEP scenario, ecological source areas reached 3580.42 km² (12.39% of the total Yellow River Delta), corresponding to a 14.85% increase relative to the BAU scenario and a 32.79% increase relative to the PUD scenario. These gains are primarily attributable to stringent wetland and forestland protection policies, which successfully limited the encroachment of construction land into ecological space. Habitat quality and connectivity markedly improved, resulting in the highest ecosystem stability. By contrast, the PUD scenario experienced an 851.46 km² expansion of construction land, resulting in the shrinkage of ecological source areas and intensified fragmentation, consequently increasing ecological security risks. The BAU scenario demonstrated moderate outcomes, with a moderately balanced spatial configuration. In conclusion, this study introduces an ecological restoration strategy of “five zones, one belt, one center, and multiple corridors” based on multi-scenario ecological security patterns. This provides a scientific foundation for ecological restoration and territorial spatial planning in the Yellow River Delta, while the proposed multi-scenario statistical comparison method provides a replicable methodological framework for ecological security pattern research in other delta regions. Full article

Windborne debris generated during tornadoes and hurricanes plays a critical role in building damage. This damage occurs either through direct impact on structural and nonstructural components or indirectly by increasing internal pressure when debris penetrates openings (e.g., windows and doors) or creates new ones. These breaches can significantly raise internal pressure, even at lower wind speeds compared to debris-free conditions. Current provisions in ASCE 7, the nationally adopted standard for wind load calculations in the United States, account for factors such as building geometry, location, and exposure category. However, they do not consider the effects of windborne debris on internal pressure coefficients. This study proposes an enhancement to ASCE 7 by incorporating debris effects through the use of a more conservative enclosure classification. Real-world damage observations from three tornado-impacted residential buildings are presented, followed by a failure mechanism analysis, supporting analytical fragility data, and numerical simulations of debris effects on building damage. The findings suggest that treating buildings as Partially Enclosed under ASCE 7 can more accurately reflect debris-induced internal pressures and improve building resilience under extreme wind events. Full article

This study examines the complex relations between corruption, income inequality, and sustainable economic development within the European Union (EU) for the 2003–2023 period. Employing panel data for all 27 EU member states, as well as for the subgroups of Old (OMS) and New Member States (NMS), the analysis applies pooled OLS, random- and fixed-effects models, and panel-corrected standard errors (PCSE) estimations. The results indicate that higher perceived corruption is robustly associated with greater income inequality, while higher tertiary education attainment, greater social protection expenditures, and increased urbanization apparently reduce inequality. Subsample evidence reveals that institutional context conditions the strength of these relationships, with NMS exhibiting a more significant corruption–inequality nexus. These findings highlight that achieving sustainable and inclusive economic growth in the EU depends on institutional integrity and good governance. Strengthening anti-corruption frameworks, investing in human capital, and enhancing social protection are essential policy instruments for supporting the EU’s sustainable development objectives. Full article