Search Results (10,196)

Optic neuritis (ON) has been recognized since antiquity, but its modern clinical identity emerged only in the late 19th century and was definitively shaped by the Optic Neuritis Treatment Trial (ONTT). The ONTT established the natural history, visual prognosis, association with multiple sclerosis (MS), and therapeutic response to corticosteroids, building the foundation for contemporary ON management. Subsequent discoveries—most notably aquaporin-4 IgG-associated ON (AQP4-ON), myelin oligodendrocyte glycoprotein antibody-associated ON (MOG-ON), and double-negative ON—have fundamentally transformed this paradigm, shifting ON from a seemingly uniform demyelinating syndrome to a group of biologically distinct disorders. These subtypes differ in immunopathology, clinical course, MRI features, retinal injury patterns, CSF profiles, and long-term outcomes, making early and accurate differentiation essential. MRI provides key distinctions in lesion length, orbital tissue inflammation, bilateral involvement, and chiasmal or optic tract extension. Optical coherence tomography (OCT) offers complementary structural biomarkers, including severe early ganglion cell loss in AQP4-ON, relative preservation in MOG-ON, and variable patterns in double-negative ON. CSF analysis further refines diagnosis, with oligoclonal bands strongly supporting MS-ON. Together, these modalities enable precise early stratification and timely initiation of targeted immunotherapy, which is critical for preventing irreversible visual disability. Despite major advances, significant unmet needs persist. Access to high-resolution MRI, OCT, cell-based antibody assays, and evidence-based treatments remains limited in many regions, contributing to global disparities in outcomes. The understanding of the pathogenesis of double-negative optic neuritis, the identification of reliable biomarkers of relapse and visual recovery, and the determination of standardized cut-off values for multimodal diagnostic tools—including MRI, OCT, CSF analysis, and serological assays—remain unresolved challenges. Future research must expand biomarker discovery, refine imaging criteria, and ensure equitable global access to cutting-edge diagnostic platforms and therapeutic innovations. Four decades after the ONTT, ON remains a dynamic field of investigation, with ongoing advances holding the potential to transform care for patients worldwide. Together, these advances expose a fundamental tension between historically MS-centered diagnostic frameworks and the emerging biological heterogeneity of ON, a tension that underpins the structure and critical perspective of the present review. Full article

Cancer is one of the leading causes of mortality worldwide, with breast and colon cancers being among the most common neoplasms in men and women, respectively. Despite significant advancements in treatment, there is a pressing need to enhance specificity and reduce systemic side effects. Importantly, a distinctive feature of cancer cells is their acidic extracellular environment, which profoundly influences cancer progression. In this study, we evaluated the anticancer activity of a pH-sensitive nanocomposite based on silver nanoparticles and pegylated carboxymethyl chitosan (AgNPs-CMC-PEG) in breast cancer (MCF-7) and colon cancer (HCT 116) cell lines. To achieve this, we synthesized and characterized the nanocomposite using UV-Vis spectroscopy, Dynamic Light Scattering (DLS), Fourier-Transform Infrared Spectroscopy (FT-IR), and Scanning Electron Microscopy (STEM-in-SEM). Furthermore, we assessed cytotoxic effects, apoptosis, and reactive oxygen species (ROS) generation using MTT, DAPI, and H2DCFDA assays. Additionally, we analyzed the expression of DNA methyltransferases (DNMT3a) and histone acetyltransferases (MYST4, GCN5) at the mRNA level using RT-qPCR, along with the acetylation and methylation of H3K9ac and H3K9me2 through Western blot analysis. The synthesized nanocomposite demonstrated an average hydrodynamic diameter of approximately 175.4 nm. In contrast, STEM-in-SEM analyses revealed well-dispersed nanoparticles with an average core size of about 14 nm. Additionally, Fourier-transform infrared (FTIR) spectroscopy verified the successful surface functionalization of the nanocomposite with polyethylene glycol (PEG), indicating effective conjugation and structural stability. The nanocomposite exhibited a pH and concentration dependent cytotoxic effect, with enhanced activity observed at an acidic pH 6.5 and at concentrations of 150 µg/ml, 75 µg/ml, and 37.5 µg/ml for both cell lines. Notably, the nanocomposite preferentially induced apoptosis accompanied by ROS generation. Moreover, expression analysis revealed a decrease in H3K9me2 and H3K9ac in both cell lines, with a more pronounced effect in MCF-7 at an acidic pH. Furthermore, the expression of DNMT3a at the mRNA level significantly decreased, particularly at acidic pH. Regarding histone acetyltransferases, GCN5 expression decreased in the HCT 116 line, while MYST4 expression increased in the MCF-7 line. These findings demonstrate that the AgNPs-CMC-PEG nanocomposite has therapeutic potential as a pH-responsive nanocomposite, capable of inducing significant cytotoxic effects and altering epigenetic markers, particularly under the acidic conditions of the tumor microenvironment. Overall, this study highlights the advantages of utilizing pH-sensitive materials in cancer therapy, paving the way for more effective and targeted treatment strategies. Full article

Accurate measurement of sea-surface winds is critical for climate science, physical oceanography, and the rapidly expanding offshore wind energy sector. Buoy-based platforms—moored meteorological buoys, drifters, and floating LiDAR systems (FLS)—provide practical alternatives to fixed offshore structures, especially in deep water where bottom-founded installations are economically prohibitive. Yet these floating platforms are subject to continuous pitch, roll, heave, and yaw motions forced by wind, waves, and currents. Such six-degree-of-freedom dynamics introduce multiple error pathways into the measured wind signal. This paper synthesizes the current understanding of motion-induced measurement errors and the techniques developed to compensate for them. We identify four principal error mechanisms: (1) geometric biases caused by sensor tilt, which can underestimate horizontal wind speed by 0.4–3.4% depending on inclination angle; (2) contamination of the measured signal by platform translational and rotational velocities; (3) artificial inflation of turbulence intensity by 15–50% due to spectral overlap between wave-frequency buoy motions and atmospheric turbulence; and (4) beam misalignment and range-gate distortion specific to scanning LiDAR systems. Compensation strategies have progressed through four recognizable stages: fundamental coordinate-transformation and velocity-subtraction algorithms developed in the 1990s; Kalman-filter-based multi-sensor fusion emerging in the 2000s; Response Amplitude Operator modeling tailored to FLS platforms in the 2010s; and data-driven machine-learning approaches under active development today. Despite this progress, key challenges persist. Sensor reliability degrades under extreme sea states precisely when accurate data are most needed. The coupling between high-frequency platform vibrations and turbulence remains poorly characterized. No unified validation framework or benchmark dataset yet exists to compare methods across platforms and environments. We conclude by outlining research priorities: end-to-end deep-learning architectures for nonlinear error correction, adaptive algorithms capable of all-sea-state operation, standardized evaluation protocols with open datasets, and tighter integration of intelligent software with next-generation low-power sensors and actively stabilized platforms. Full article

Drought stress critically constrains plant development and morphogenesis, representing a substantial challenge to crop production systems. Dehydrins (DHNs), belonging to the late embryogenesis abundant (LEA) protein superfamily, play crucial roles in plant adaptation to environmental stress conditions. Nevertheless, the capacity of Suaeda salsa SsDHN protein to confer drought resistance has not been adequately investigated. In the present study, transgenic tobacco lines with constitutive SsDHN expression (SsDHN-OE) were employed to examine its influence on seedling development under water-limited conditions. Results indicated that constitutive SsDHN expression enhanced biomass accumulation, foliar expansion, root elongation, and root surface dimensions in water-stressed seedlings. Moreover, transformed lines demonstrated elevated proline (Pro) accumulation and abscisic acid (ABA) content, augmented antioxidant enzyme activity, and intensified stomatal regulation under stress conditions. Conversely, photoinhibition intensity, chloroplast structural degradation, malondialdehyde (MDA) accumulation, electrolyte leakage, hydrogen peroxide (H₂O₂), and superoxide radical (O₂⁻) concentrations were diminished. Furthermore, transcript abundance of stress-responsive genes—encompassing NtNCED3, NtSnRK2.2, NtRD26, NtLEA5, NtPOD, NtSOD, NtCAT, and NtAPX1—was markedly increased in SsDHN-OE lines experiencing drought stress. Taken together, these findings establish that SsDHN functions as a positive regulator of drought resilience in plants. Full article

Background: In biosimilar studies, assessing the switchability and interchangeability of biosimilars with their reference products is essential for ensuring reliable clinical evaluation. This study explores optimal trial design strategies incorporating balanced and uniform structures to enhance statistical efficiency in treatment effect under a carryover setting. Methods: Using a linear mixed-effect model for log-transformed responses, we conducted a theoretical variance-based evaluation of all possible two-treatment switching designs in three-period and four-period crossover trials, considering settings with and without carryover effects. A total of 247 distinct three-period designs and 65,519 distinct four-period designs were enumerated and classified according to structural properties, with particular attention to those incorporating a non-switching arm (NSA). Results: SBUwP-NSA (Strongly Balanced Uniform-within-Period designs with a Non-Switching Arm) consistently achieved the minimum variance for treatment effect estimation in both carryover and no-carryover settings. In the absence of carryover effects, UwP-NSA (Uniform-within-Period designs with a Non-Switching Arm) attained equivalent efficiency. In contrast, commonly used dedicated switching designs exhibited substantially lower relative efficiency, achieving as little as 50–55% of the efficiency of the optimal designs, depending on carryover assumptions. Conclusions: This comprehensive theoretical evaluation demonstrates that incorporating strong balance and uniformity properties can yield substantial efficiency gains in switching studies. The results provide quantitative guidance for selecting efficient crossover designs, enabling improved estimation precision while maintaining practical relevance for interchangeability and switching assessments in biosimilar research. Full article

Understanding how birds adjust their flight in response to biomechanical characteristics and environmental conditions can be useful for interpreting homing behavior. This study investigates homing pigeons’ (Columba livia) flight behavior using multi-sensor biologgers, integrating GPS, tri-axial accelerometer, pressure, and temperature sensors. Flight biomechanics were assessed by extracting: wingbeat frequency from the Short-Time Fourier Transform of the total acceleration signal and peak-to-peak acceleration from the dorso-ventral component. Landscape characteristics were provided by classifying land cover along the route using a geographic atlas and by computing flight altitude above ground level through the combination of pressure-derived altitude and a digital elevation model. The results reveal a progressive decrease in wingbeat frequency along the homing route, showing a linear relationship with traveled distance. To assess whether this pattern can be interpreted in terms of flight regulation, flight altitude was modeled as a function of biomechanical and environmental variables using a linear mixed-effect approach. The analysis indicates that flight altitude is significantly affected by wingbeat frequency as well as by temperature, ground speed, and land cover, with wingbeat frequency and temperature showing the strongest negative association. Full article

This study examines the social, economic and cultural impacts that Latin American women face due to climate-induced displacement, considering these impacts as arenas of conflict and negotiation. Using an intersectional framework, the study analyses how climate disasters exacerbate structural inequalities rooted in patriarchal systems, thereby constraining women’s adaptive capacity while simultaneously catalysing resistance strategies. Through a comparative analysis of Bangladesh and the Dry Corridor in Central America using a Gender Vulnerability Index (GVI), the study reveals that displaced women navigate contested spaces, disputing access to resources, legal recognition and territorial belonging, while constructing transnational solidarity networks and cooperative economies. The emergence of women climate refugees challenges international legal frameworks, exposing critical gaps in protection regimes. The findings emphasise the need for gender-responsive policies that recognise women as transformative agents who negotiate power asymmetries in contexts of environmental crisis, not merely as vulnerable populations. This research contributes to our understanding of the nexus between climate change, gender and migration by foregrounding the dialectic of domination and agency in Latin American displacement processes. Full article

Nonsense mutations, responsible for ~11% of gene lesions causing human monogenic diseases, introduce premature termination codons (PTCs) that lead to truncated proteins and nonsense-mediated mRNA decay (NMD). In the central nervous system (CNS), these mutations drive severe, progressive neurological conditions such as spinal muscular atrophy, Rett syndrome, and Duchenne muscular dystrophy. Readthrough therapies—strategies to override PTCs and restore full-length protein expression—have evolved from early aminoglycosides to modern precision tools including suppressor tRNAs, RNA editing, and CRISPR-based platforms. Yet clinical translation remains hampered by inefficient CNS delivery, variable efficacy, and the absence of personalized stratification. In this review, we propose a translational framework—the 4 Ds of Readthrough Therapy—to systematically address these barriers. The framework dissects the pipeline into Detection (precision patient identification and biomarker profiling), Delivery (engineered vectors for CNS targeting), Decoding (context-aware molecular correction), and Durability (long-term safety and efficacy). By integrating advances in machine learning, nanocarriers, base editing, and adaptive trial designs, this roadmap provides a structured strategy to bridge the translational gap. We advocate that a synergistic, modality-tailored approach will transform nonsense suppression from palliative care to durable, precision-based cures for once-untreatable neurological disorders. Full article

Background/objectives. Emerging viral diseases represent an increasing threat to global health security, driven by environmental change, globalization, and intensified human–animal–environment interactions. The COVID-19 pandemic exposed critical weaknesses in preparedness systems but also demonstrated the transformative potential of recombinant vaccine technologies, which enable rapid, scalable, and safe responses to novel pathogens. We aim to examine the role of recombinant vaccine platforms in the management of emerging viral diseases, emphasizing their contribution to health system preparedness and exploring strategies for their integration into preparedness frameworks. Methods. We synthesized the current evidence on recombinant vaccine platforms (viral vector, protein subunit, DNA, and mRNA) through a targeted review of the scientific literature, regulatory documents, and global health policy reports. Drawing from experiences like COVID-19 (mRNA vaccines) and Ebola (rVSV-ZEBOV), we analyzed the advantages, challenges, and lessons from initiatives such as the CEPI, BARDA, HERA, and WHO frameworks. Results. Recombinant vaccine platforms offer significant advantages for epidemic preparedness through rapid adaptability, standardized production, and strong safety profiles. Nonetheless, challenges remain in manufacturing scalability, cold-chain logistics, regulatory harmonization, and equitable global access. Global initiatives such as the CEPI, WHO-led programs, BARDA, and regional manufacturing networks exemplify this collaborative approach, while regulatory mechanisms have proven to be essential to timely vaccine deployment. Conclusions. Recombinant vaccines have redefined preparedness by coupling scientific innovation with operational agility. Strengthening global coordination, regional production capacity, and public trust is essential to ensure that technological progress translates into equitable and effective public health impacts. Full article

Background: Cutaneous squamous cell carcinoma (cSCC) represents the second most common form of non-melanoma skin malignancy, and, when not amenable to curative surgery or radiotherapy, it is a life-threatening disease. The anti-PD-1 monoclonal antibody cemiplimab has transformed the outcome of advanced or metastatic cSCC, with response rates approaching 50% and sustained benefit beyond three years in clinical trials. Cemiplimab is now the first-line standard of care treatment for advanced disease. Methods: This retrospective observational study included consecutive adult patients with locally advanced (lac) or metastatic (m) cSCC who received cemiplimab (350 mg every three weeks) at the Center for Immuno-Oncology, University Hospital of Siena, Italy, either through an Expanded Access Program or routine clinical practice. Clinical outcome and treatment related adverse events (TRAEs) are reported. Results: Between December 2019 and December 2023, 27 patients (24 male; median age 82 years [range 41–90]) diagnosed with lacSCC (n = 20 [74.0%]) or mcSCC (n = 7 [25.9%]) were treated with cemiplimab as first line therapy and were followed until June 2024. Head and neck were the primary tumor location for 88.8% of patients, followed by trunk (7.4%) and lower extremities (3.7%). All patients had comorbidities, including six patients (22.2%) with hematologic malignancies. With a median follow-up of 31 months (data cut-off June 2024), the ORR was 66.6% (complete response 22.2%) and the disease control rate (DCR) 77.7%. Median progression-free survival (mPFS) and overall survival (mOS) were not reached, while 2-year PFS and OS rates were 65.2% and 71%, respectively. Treatment was well-tolerated, with three (11.1%) patients experiencing grade ≥3 TRAEs, and three patients discontinuing treatment due to TRAEs. Conclusions: Our real-world experience confirms the high rate of durable objective responses, good tolerability and long treatment duration of cemiplimab in elderly and frail cSCC patients as well. Full article

This study used soybean meal as the substrate and systematically optimized its enzymatic hydrolysis through single-factor experiments and response surface methodology. A predictive model based on a Box–Behnken design was developed to improve protein hydrolysis efficiency and increase the yield of functional products. The optimal conditions were 1.45% enzyme addition, a reaction time of 62 h, a temperature of 36.5 °C, and a moisture content of 35%. Under these conditions, the small-peptide content increased 16.33-fold. Structural analyses showed that enzymatic treatment markedly disrupted the compact surface of soybean meal, converting it into a loose, porous matrix. In addition, enzymolysis altered the protein secondary structure from ordered α-helices and folded conformations to more disordered, flexible forms, thereby improving the molecular-weight distribution. Composition analyses showed an 114.2% increase in total free amino acids, including essential amino acids. Moreover, DPPH radical-scavenging activity increased from 18.37% to 57.99%. Overall, this study optimized the enzymatic hydrolysis conditions for soybean meal and provides valuable insights for the development of high-value protein-peptide products. Full article

Global change represents one of the most pressing threats to ecosystems, profoundly influencing habitats and redefining management and conservation priorities. Rising temperatures, altered precipitation regimes, invasive species and the increasing frequency of extreme events, such as prolonged droughts and wildfires, are modifying the composition, structure, and resilience of forests. Often, these changes result in habitat fragmentation, which isolates populations and diminishes their ability to adapt. This situation calls for an urgent reassessment of traditional protected area management practices. In response to climate change, it is essential to prioritize conservation strategies that focus on adaptation and maintaining biodiversity, while combating the spread of invasive species. For this reason, this study aims to analyze the impact of global changes on forest vegetation within protected areas, using Aspromonte National Park, a highly biodiverse region, as a case study. It evaluates the transformations in habitat cover and fragmentation over twenty years by comparing the 2001 vegetation map of Aspromonte National Park with the Map of Nature of the Calabria region, to quantify spatial and temporal habitat variations using QGIS 3.42.3 software. Morphological Spatial Pattern Analysis (MSPA) and FRAGSTATS v4.2 were employed to evaluate habitat fragmentation. The results indicate that most forest habitats have experienced a slight increase in area over the past 20 years. However, the area occupied by Pinus nigra subsp. laricio forests (Habitat 42.65) has decreased significantly, most likely due to repeated fires in previous years. In conclusion, this study establishes a scientific foundation for guiding conservation policies in the protected area and promoting the resilience of native plant communities against global change. This is essential for ensuring their survival for future generations while mitigating both habitat fragmentation and the introduction and spread of non-native species. Full article

The development of urban underground spaces has led to an increasing number of projects involving super-large-diameter shield tunnels, making research on their impact on existing structures particularly significant. This paper investigated the numerical simulation on deformation and damage mechanism of existing underground structures induced by adjacent construction of super-large-diameter tunnels. A 3D finite element model using ABAQUS (version 2022) software incorporating the Concrete Damaged Plasticity (CDP) constitutive model was established, and this paper was used to systematically analyze the deformation, internal force response, and damage evolution of existing tunnels. The results showed the following: (1) The double-line tunnel excavation intensified settlement superposition, increasing the maximum settlement from −19.70 mm (single-line) to −24.51 mm (double-line) and transforming the settlement trough from a V shape to a W shape. (2) The vertical bending moment evolved from a single peak to double peaks being the dominant loading mode, with the maximum horizontal moment only about 1/8 of the vertical value. (3) During the construction, the peak tensile stress at the tunnel bottom reached 2.655 MPa, exceeding the C50 concrete tensile strength, but later decreased to 2.097 MPa. Damage was primarily caused by bending-induced tension. (4) Tunnel damage was triggered by the historical peak stress and accumulated irreversibly, resulting in a final state of low-stress and high-damage, with a maximum tensile damage of 92.4%. This research can provide a theoretical basis for safety control in similar adjacent engineering projects. Full article

This paper proposes an emergency power supply restoration strategy for a distribution network that considers the operational risk of an islanded microgrid in response to the issues of voltage exceeding limits and power imbalance faced during their operation. Firstly, a distribution network emergency power supply restoration model supported by a generalized dynamic islanded microgrid is constructed. By equating the alternate tie line with a virtual distributed generator (DG), the integrated power supply restoration problem of distribution network is transformed into a generalized island power distribution network division problem based on DGs. Then, the risk of islanded microgrid operation is considered and restricted by chance constraints. Finally, simulation results based on the improved IEEE-33 node distribution network show that, compared to the generalized island partitioning strategy which ignores operational risks, the proposed strategy increases the power supply restoration rate from 83.4% to 97.8% while successfully ensuring the stability of all islanded microgrids under the specified confidence level for operational risk. Full article

Smart campuses employ advanced digital technologies and intelligent communication systems to enhance educational, operational, and living environments. This study investigates stakeholder perceptions of smart campus priorities in Saudi Arabia through a structured questionnaire administered to students and faculty. The study considered King Fahd University of Petroleum and Minerals (KFUPM) in Dhahran as a case study in this regard. The survey examined 22 smart campus aspects grouped into six domains: smart education, smart mobility, smart energy and waste management, smart buildings and work environment, smart safety and security, and smart open spaces. The results indicated strong consensus regarding the importance of all domains, with an overall mean rating of 4.3 out of 5.0 and Relative Importance Index (RII) values ranging from 0.77 to 0.91. The highest-ranked aspects included IoT-enabled cooling energy optimization, smart public transportation, smart lighting systems, smart workflow management, e-libraries, and fire prevention and detection systems, reflecting a pronounced emphasis on infrastructure quality, energy efficiency, and operational effectiveness. The findings suggest that smart campus development in Saudi Arabia should prioritize high-impact, user-valued initiatives that align with Vision 2030 objectives including digital transformation. Strategic early investments in smart buildings, energy management, and mobility systems can deliver measurable benefits in this regard. Further research is recommended to consider additional case studies in the Saudi context to ensure that smart campuses remain contextualized and responsive to user needs. Full article