Search Results (107,622)

Mitochondrial transcription factor A (TFAM) is essential for mitochondrial DNA (mtDNA) maintenance and function, but its role in glioblastoma (GBM) remains largely unexplored. Analysis of patient astrocytomas and TCGA datasets has revealed progressive TFAM downregulation with increasing malignancy, with the lowest expression in glycolytic/plurimetabolic (GPM) subtypes. Functional and transcriptomic profiling of mesenchymal GBM cell lines showed that TFAM silencing in GPM-type U87MG cells enhanced proliferation, S-phase entry, reactive oxygen species (ROS) production, and adhesion, while reducing motility. These changes were correlated with upregulation of LDHC and TRAF2 and downregulation of androgen receptor-linked motility genes and LOXL2. By contrast, TFAM loss in mitochondrial (MTC)-type A172 cells caused minimal phenotypic alterations, associated with elevated SOD1 expression and activation of antioxidant, mitochondrial membrane, and survival pathways, alongside suppression of oxidative phosphorylation and vesicle-trafficking genes. TFAM overexpression reduced proliferation in U87MG but had a limited impact on A172 cells. Taken together, these findings establish TFAM as a subtype-specific regulator of GBM cell proliferation, redox balance, and motility. TFAM loss drives a proliferative, ROS-sensitive phenotype in GPM-type cells, while eliciting adaptive, stress-resilient programs in MTC-type cells. This study identifies TFAM and downstream effectors, TRAF2 and LOXL2, as potential therapeutic targets, supporting the development of metabolic subtype-tailored strategies for GBM treatment. Full article

The MoonRay project is carrying out a concept study of a permanent lunar cosmic-ray (CR) and gamma-ray observatory, in view of the implementation of habitats on our satellite. The idea is to build a modular telescope that will be able to overcome the limitations, in available power and weight, of the present generation of CR instruments in Low Earth Orbit, while carrying out high-energy gamma-ray observations from a vantage point at the South Pole of the Moon. An array of fully independent modules (towers), with limited individual size and mass, can provide an acceptance more than one order of magnitude larger than instruments in flight at present. The modular telescope is designed to be deployed progressively, during a series of lunar missions, while collecting meaningful scientific data at the intermediate stages of its implementation. The operational power will be made available by the facilities maintaining the lunar habitats. With a geometric factor close to 15 m²sr and about 8 times larger sensitive area than FERMI-LAT, MoonRay will be able to carry out a very rich observational program over a time span of a few decades with an energy reach of 10 PeV allowing the exploration of the CR “knee” and the observation of the Southern Sky with gamma rays well into the TeV scale. Each tower (of approximate size 20 cm × 20 cm ×100 cm) is equipped with three instruments. A combined Charge and Time-of-Flight detector (CD-ToF) can identify individual cosmic elements, leveraging on an innovative two-layered array of pixelated Low-Gain Avalanche Diode (LGAD) sensors, with sub-ns time resolution. The latter can achieve an unprecedented rejection power against backscattered radiation from the calorimeter. It is followed by a tracker, providing also photon conversion, and by a thick crystal calorimeter (55 radiation lengths, 3 proton interaction lengths at normal incidence) with an energy resolution of 30–40% (1–2%) for protons (electrons) and a proton/electron rejection in excess of 10⁵. A time resolution close to 100 ps has been obtained, with prototypal arrays of 3 mm × 3 mm LGAD pixels, in a recent test campaign carried out at CERN with Pb beam fragments. Full article

Grid frequency is a critical factor for the stability of a power system. However, with the penetration of massive dynamic load requirements and information and communication infrastructure, grid frequency is vulnerable to cyberattacks on the load side. In this paper, we model dynamic load-altering attacks (LAAs) on grid frequency and propose a control-based mitigation strategy. First, the dynamic grid-frequency model for frequency-sensitive loads is constructed. Then, the vulnerability of grid frequency to dynamic LAAs is analyzed using eigenvalue sensitivity analysis. To design the mitigation strategy, a stability condition with the first-order dynamic model is derived. Further, a second-order dynamic model is constructed to illustrate the joint impact of dynamic LAAs and the control strategy on eigenvalues, thereby revealing insights into mitigating factors for maintaining grid frequency stability. Finally, we conduct extensive simulations to evaluate the vulnerability of grid frequency under dynamic LAAs and to validate the effectiveness of the mitigation strategy. Full article

Background/Objectives: Human adenovirus 55 (HAdV55) is a notable pathogen causing community-acquired pneumonia; outbreaks occur frequently in military camps, hospitals, and schools, thereby posing a threat to public health security. This study aimed to develop a method for detecting HAdV55 nucleic acid by targeting the conserved region of the Hexon gene. The sequence was amplified using enzymatic recombination isothermal amplification (ERA) technology, in conjunction with CRISPR-Cas12a technology, to enhance the amplification signal. Methods: Optimized primer and crRNA sequences were selected through ERA isothermal amplification testing. The ERA-CRISPR/Cas12a detection method was completed within 30 min at a constant temperature of 42 °C. Results: Sensitivity was assessed by detecting standard plasmids and live strains at various dilution concentrations. The detection limits were determined to be 9 copies/reaction for standard plasmids and 2.5 copies/reaction for cultured HAdV55 strains. Specificity tests were conducted on positive samples for five common respiratory pathogens and five other adenovirus subtypes, all of which showed no cross-reactivity. Conclusions: A rapid ERA-CRISPR/Cas12a nucleic acid detection method for HAdV55 has been successfully developed, demonstrating high sensitivity and specificity without the need for expensive or complex instruments. This method holds promise for on-site pathogen screening and detection. Full article

A 70-year-old Japanese woman with longstanding hearing loss and asthma developed floating sensations, left finger numbness, and postural instability one day after influenza vaccination, leading to hospital admission. Neurological examinations showed hearing loss, hyperreflexia, left-predominant ataxia, bilateral mild bathyanesthesia, and inability to tandem gait. Cerebrospinal fluid (CSF) analysis showed no pleocytosis or malignant cells, but revealed positive oligoclonal bands and elevated myelin basic protein. Despite no contrast agent use due to asthma, brain magnetic resonance imaging (MRI) revealed pontine hyperintensities on diffusion-weighted imaging (DWI) and T2-fluid attenuated inversion recovery (T2-FLAIR) sequences, along with hyperperfusion on arterial spin labeling (ASL) imaging. Serum anti-aquaporin-4 antibodies (AQP4-Ab) were negative by ELISA. Given the temporal proximity to vaccination and elevated demyelination markers, brainstem-type acute disseminated encephalomyelitis (ADEM) was initially suspected. Symptoms nearly resolved after two cycles of methylprednisolone pulse therapy. Notably, hyperperfusion gradually improved on ASL imaging. Post-discharge, a cell-based assay confirmed the diagnosis of neuromyelitis optica spectrum disorder (NMOSD) by detecting positive anti-AQP4-Ab. She has been relapse-free for about a year without any immunosuppressants or biologics. Although contrast-enhanced MRI remains the gold standard modality for lesion evaluation due to its high sensitivity, hyperperfusion on ASL may provide a useful alternative in patients for whom contrast agents are contraindicated, such as those with asthma or impaired renal function. Full article

This study aimed to evaluate the effectiveness of a multimodal trust assessment approach that integrated electroencephalography (EEG) and self-report questionnaires compared with unimodal methods within the context of lower-limb rehabilitation training. Twenty-one mobility-impaired participants performed tasks using handrails, walkers, and stairs. Synchronized EEG, questionnaire, and behavioral data were collected. EEG trust scores were derived from the alpha-beta power ratio, while subjective trust was assessed via questionnaire. An adaptive neuro-fuzzy inference system was used to fuse these into a composite score. Analyses included variance, correlation, and classification consistency against behavioral ground. Results showed that EEG-based scores had higher dynamic sensitivity (Spearman’s ρ = 0.55) but greater dispersion (Kruskal–Wallis H-test: p = 0.001). Questionnaires were more stable but less temporally precise (ρ = 0.40). The fused method achieved stronger behavioral correlation (ρ = 0.59) and higher classification consistency (κ = 0.69). Cases with discordant unimodal results revealed complementary strengths: EEG captured real-time neural states despite motion artifacts, while questionnaires offered contextual insight prone to bias. Multimodal fusion through fuzzy logic mitigated the limitations of isolated assessment methods. These preliminary findings support integrated measures for adaptive rehabilitation monitoring, though further research with a larger cohort is needed due to the small sample size. Full article

During the construction of deep underground soft rock strata, the adverse effects of high geostress, unfavorable geological conditions, and excavation disturbances are significant, easily triggering Material-Stress-Induced (MSI) large deformation disasters, leading to the failure of support structures or even collapse, thus posing great challenges to the safe construction of this type of underground engineering. Based on this, this study first classifies the large deformations, analyzes the instability mechanism of material-stress-induced large deformation in soft rock, and identifies the influencing factors of this type of large deformation from three aspects. Subsequently, a numerical investigation (FLAC3D 6.00) is utilized to examine the surrounding rock deformation characteristics under different material factors (uniaxial compressive strength and elastic modulus), stress factors (burial depth and lateral pressure coefficient), and construction factors (excavation method, support pattern, and timing of initial support installation). On this basis, a multi-factor sensitivity comparison analysis is conducted, which clarifies the differences and prioritization of parameter influences on large deformation, and reveals the dominant role of controlling factors such as elastic modulus. The analysis demonstrates a strong negative correlation between the examined material factors (uniaxial compressive strength and elastic modulus) and the magnitude of surrounding rock displacement, with both values eventually converging. A significant positive correlation between the examined stress factors and the magnitude of surrounding rock displacement was observed. A pronounced positive correlation was observed between stress factors and surrounding rock deformation. These factors distinctly have different effects on the peak displacement of different surrounding rock parts. Vault settlement demonstrates the most pronounced displacement, while arch bottom deformation is the least apparent. The three excavation methods exhibit relatively low sensitivity to surrounding rock displacement. Similarly, the support patterns demonstrate limited influence on surrounding rock deformation. The material factor of soft surrounding rock is the main controlling factor of the large deformation of soft surrounding rock in deep underground engineering. The elastic modulus has the strongest influence on the displacement of the surrounding rock. When the elastic modulus is less than 2 GPa, the sensitivity coefficient is much higher than the stress factors. The research results can provide some reference and guidance for similar underground projects. Full article

Background/Objectives: Lower respiratory tract infections (LRTIs) are frequent in the intensive care unit (ICU) and drive empiric broad-spectrum antibiotic use. Rapid multiplex PCR assays may improve pathogen detection and stewardship compared with conventional culture. We evaluated the real-world impact of the BioFire^® FilmArray^® Pneumonia Panel Plus (FA-PNEU^®) on antimicrobial management in suspected nosocomial LRTI. Methods: This was a single-centre, prospective observational cohort study conducted in a tertiary ICU (Madrid, Spain) between April 2021 and March 2025. Adult patients with suspected hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), or ventilator-associated tracheobronchitis (VAT) were included if paired respiratory samples underwent FA-PNEU^® and conventional culture (CC). Diagnostic accuracy and prescribing changes were analysed. Results: A total of 344 samples from 236 patients were included. FA-PNEU^® demonstrated high sensitivity (93.4%) and negative predictive value (97.9%) but moderate specificity (65.0%) and low positive predictive value (36.5%). False positives occurred in 85.8% of patients with prior antibiotic therapy targeting the detected organism. Antibiotic management was considered directly influenced by FA-PNEU^® when any prescribing decision (initiation, escalation, de-escalation, or discontinuation) explicitly followed the panel’s results rather than other clinical or microbiological information. Using this definition, FA-PNEU^® directly influenced antibiotic therapy in 57.6% of cases, while in 17.7%, prescribing was instead guided by a suspected alternative infection. In patients without prior antibiotics, treatment initiation or withholding was fully concordant with FA-PNEU^® results, while in those already receiving therapy, 60.8% underwent modification, two-thirds in agreement with the panel. Conclusions: In critically ill patients with suspected nosocomial LRTI, FA-PNEU^® provided rapid, high-sensitivity diagnostics that substantially influenced antimicrobial prescribing. Its greatest value lies in ruling out bacterial infection and guiding stewardship, though results must be interpreted within the full clinical and microbiological context. Full article

Fiber-reinforced polymer (FRP) composites have become a popular solution for upgrading reinforced concrete (RC) structures due to their corrosion resistance, high strength-to-weight ratio, and speed of implementation. However, their organic resin binder has issues, including temperature sensitivity, poor performance in moist conditions, a high cost, and potential health risks. Additionally, reversing FRP repair can be difficult and may damage the original structure, posing a significant reversibility issue. A promising alternative to FRP is the fiber-reinforced cementitious matrix (FRCM), which replaces the organic resin with an inorganic cementitious mortar. This new class of composite uses a breathable textile instead of the tightly packed fibers in FRP. The present article provides a comprehensive assessment of the two composites (FRP and FRCM) used for the retrofitting of RC compression members, with the purpose of identifying existing knowledge gaps and outlining future research objectives. The materials used in different strengthening approaches using both FRP and FRCM have been identified, and their stress–strain characteristics under tensile load have been outlined. The study also explores techniques of implementation using the two materials. This study presents available studies comparing the utilization of FRCM composites with FRP for the axial retrofitting of RC compression members in both ambient and high-temperature conditions. Full article

Background: Most of the currently approved TB diagnostics are sputum-based. However, due to unusual clinical presentations of TB among HIV patients, they may not have TB symptoms and be able to produce sputum. Hence, these diagnostics may not be able to detect as many TB cases as possible among these patients. Therefore, this study assessed the performance of C-reactive protein (CRP) and interferon-gamma-inducible protein 10 (IP-10) as a screening tool for TB. Methods: This prospective study was conducted by consecutively recruiting patients with TB symptoms, collecting their sputum and blood samples, using sputum culture as the reference standard, and determining the best cut-off point of serum levels of CRP and IP-10 (separately and in combination) for TB diagnosis. Findings: CRP and IP-10 were measured in 408 patients with TB symptoms, of which 21% had culture-confirmed TB. CRP’s sensitivity and specificity were (91.4% and 33.2%), (95.3% and 42.6%) and (84.8% and 22.1%) for the whole study population, HIV-negative and HIV-positive patients, respectively. The sensitivity and specificity of IP-10 were (87.3% and 40.9%), (87.5% and 50.3%) and (79.4% and 47.2%) for the patients’ categories, respectively. Combination of CRP and IP-10 slightly improved the performance of the biomarkers among HIV-negative patients, with sensitivity of 97.5% and specificity of 43.3%. Interpretation: Though CRP and IP-10 performed better in HIV-negative patients than among people living with HIV (PLHIV), the performance of the biomarkers is lower than what is recommended by the WHO (sensitivity ≥ 90% and specificity ≥ 70%) for a TB screening tool. Hence, there is a need for better non-sputum-based TB diagnostics. Full article

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has emerged as a pivotal vulnerability in oral squamous cell carcinoma (OSCC). This review provides an overview of ferroptosis mechanisms and their implications for OSCC pathobiology and therapy. OSCC cells exhibit heightened reliance on anti-ferroptotic defenses such as GPX4, SLC7A11, FSP1, and Nrf2, and disrupting these pathways suppresses tumor growth and restores sensitivity to chemotherapy, radiotherapy, and immunotherapy. Genetic and epigenetic regulators, including p53, PER1, circ_0000140, and STARD4-AS1, critically modulate ferroptotic sensitivity, while metabolic enzymes such as ACSL4, LPCAT3, and TPI1 link ferroptosis to cellular plasticity and resistance. Preclinical studies highlight the promise of small-molecule inhibitors, repurposed agents (e.g., sorafenib, artesunate, trifluoperazine), natural compounds (e.g., piperlongumine, Evodia lepta, quercetin), and nanomedicine platforms for targeted ferroptosis induction. We further address ferroptosis within the tumor microenvironment, highlighting its immunogenic and context-dependent dual roles, and summarize genomic and transcriptomic evidence linking ferroptosis-related genes to patient prognosis. Beyond cancer, ferroptosis also contributes to non-malignant oral diseases, including pulpitis, periodontitis, and infection-associated inflammation, where inhibitors may protect tissues. Despite these advances, clinical translation is constrained by the lack of safe ferroptosis inducers and validated biomarkers. Future research should focus on developing pharmacologically viable GPX4 inhibitors, refining biomarker-driven patient stratification, and designing multimodal regimens that combine ferroptosis induction with standard therapies while preserving immune and tissue integrity. Ferroptosis therefore represents both a mechanistic framework and a translational opportunity to reshape oral oncology and broader oral disease management. Full article

Row crops are regarded as a transitional type between continuous and discrete vegetation. Previous studies idealized row crops as periodic hedgerows with rectangular cross-sections. However, these models relied on oversimplified assumptions, failing to capture the intrinsic heterogeneity of canopy or its dynamic evolution over the life cycle. In 2020, we proposed a row crop model with a gradual decrease in leaf area volume density (LAVD) from the center of the row to the edge, partially overcoming these limitations. Building on this previous model, this paper introduces the leaf shape factor proposed by Mõttus et al. into the model. Three control parameters, a leaf width control parameter (β), leaf length control parameter (ψ), and leaf azimuth control parameter (e), are proposed to regulate the spatial distribution of LAVD. Additionally, an empirical exponential function from Watanabe et al. is adopted to describe the leaf zenith angle distribution, enabling the realistic calculation of the G-function and Γ-function in conjunction with leaf azimuth distribution. The LAVD is formulated at three hierarchical scales: individual scale, row scale, and scene scale. The model delivers two key advancements: enabling pronounced spatial heterogeneity and high tunability of the LAVD, and accurately simulating row crops throughout the life cycle, which bridges the row structure and continuous stages of row crops. Radiative transfer simulations are conducted to derive the bidirectional reflectance distribution function (BRDF), which is validated against the discrete anisotropic radiative transfer (DART) model. Comparisons across three growth stages demonstrated good consistency. Furthermore, this paper investigates the sensitivity of the BRDF to three control parameters (β, ψ, and e). The results indicate that changes in three parameters significantly affect the reflectance in the darkspot direction, leading to a maximum error of 22.6%. In carrying out remote sensing applications such as parameter inversion and yield estimation for row crops, the new model is recommended for more accurate BRDF simulations. Full article

Low-thrust orbit transfer problems are central to reducing mission costs and enabling cleaner, more efficient space travel. However, they remain difficult to solve using mathematically superior indirect methods of optimization. This is mainly due to the sensitivity to initial guesses and ill-conditioned matrices generated using traditional indirect methods. This paper applies the Uniform Trigonometrization Method (UTM), a cutting-edge indirect optimization technique, to four cases of low-thrust low Earth orbit (LEO)-to-geostationary Earth orbit (GEO) transfer problems. Using the UTM framework, including efficient numerical continuation and problem scaling strategies, smoother optimal control solutions were obtained. The convergence of standard boundary value problem solvers, like MATLAB’s bvp4c, significantly increases while using the simplicity and efficiency of the UTM. The UTM was able to solve Case 1 in a simpler manner compared to the traditional indirect method presented in the literature. In Case 2, the UTM found results for a constant thrust value of 1 N, while a direct pseudospectral method failed to converge. The results obtained using the UTM for Case 2 have 20 times longer flight duration and revolutions of spacecraft around the Earth. The UTM efficiently performs trade studies using a continuation approach that generates additional insights into all cases of this problem. In Case 4, the UTM was able to easily generate a bang–bang control structure, which traditionally requires solving a complex multi-point boundary value problem. The results generated using the UTM are very high-resolution, as it relies on the necessary conditions of optimality and guarantees locally optimal solutions. These findings position the UTM as a promising indirect approach for solving real-world long-duration orbit transfers. Full article

Degraded DNA is frequently encountered in biological samples due to mechanisms that favor the decomposition process and thus the fragmentation of DNA due to (extreme) environmental conditions. The reduced size of the DNA fragments may hamper the performance of genetic tests. This is why developmental evaluation and validation experiments of new markers and new technologies also involve the analysis of artificially degraded DNA. This study presents a method to reproducibly generate degraded DNA in only five minutes. Different concentrations and volumes of DNA extracted from blood were irradiated by UV-C light. This led to a gradual decrease in DNA fragment size that is typically targeted in genetic applications. An increase in DNA extract volume showed only little effect on the degradation performance; the starting DNA amount slightly shifted the observed degradation pattern. The process was assessed using degradation-sensitive quantitative real-time PCR and Short Tandem Repeat analysis. Repeated experiments resulted in comparable degradation patterns that were suitable for mimicking degradation states in biological samples and for evaluating genotyping applications. Full article

Background: Acute lymphoblastic leukemia (ALL) is a genetically heterogeneous malignancy driven by structural variants (SVs) that impact diagnosis, prognosis, and treatment. Traditional methods such as karyotyping, FISH, and PCR often fail to detect cryptic or complex rearrangements, which are critical for accurate risk stratification. Methods: Optical Genome Mapping (OGM) is a technology that directly analyzes ultra-high-molecular-weight DNA, enabling the identification of balanced and unbalanced SVs, copy number variations (CNVs), and gene fusions with high resolution. This review compares the advantages and limitations of OGM versus standard techniques in ALL. Results: OGM improves ALL diagnosis by detecting clinically relevant alterations such as IKZF1 deletions, cryptic KMT2A rearrangements, and kinase fusions, especially in cases with normal or uninformative karyotypes. It reduces artifacts by eliminating cell culture and shortens reporting times. OGM resolves complex events like intrachromosomal amplifications and chromothripsis, enhancing classification and therapy decisions. Limitations include reduced sensitivity in repetitive regions, challenges in detecting Robertsonian translocations, difficulties with complex ploidies, and lower sensitivity for low-frequency subclones. Conclusions: Integrating OGM with next-generation sequencing (NGS) allows comprehensive genomic profiling, improving diagnosis, prognosis, and personalized treatment in ALL. Future advancements promise to further enhance the clinical utility of OGM. Full article