Search Results (17,373)

Despite the great advances in basic research results, glioblastoma multiforme (GBM) still remains an incurable tumour. To date, a GBM diagnosis is a death sentence within 15–18 months, due to the high recurrence rate and resistance to conventional radio- and chemotherapy approaches. The effort the scientific community is lavishing on the never-ending battle against GBM is reflected by the huge number of clinical trials launched , about 2003 on 10 September 2024. However, we are still far from both an in-depth comprehension of the biological and molecular processes leading to GBM onset and progression and, importantly, a cure. GBM is provided with high intratumoral heterogeneity, immunosuppressive capacity, and infiltrative ability due to neoangiogenesis. These features impact both tumour aggressiveness and therapeutic vulnerability, which is further limited by the presence in the tumour core of niches of glioblastoma stem cells (GSCs) that are responsible for the relapse of this brain neoplasm. Epigenetic alterations may both drive and develop along GBM progression and also rely on changes in the expression of the genes encoding histone-modifying enzymes, including histone deacetylases (HDACs). Among them, HDAC6—a cytoplasmic HDAC—has recently gained attention because of its role in modulating several biological aspects of GBM, including DNA repair ability, massive growth, radio- and chemoresistance, and de-differentiation through primary cilia disruption. In this review article, the available information related to HDAC6 function in GBM will be presented, with the aim of proposing its inhibition as a valuable therapeutic route for this deadly brain tumour. Full article

Background: The early exposure of nutrients during pubertal mammary gland development may reduce the risk of developing breast cancer later in life. Anticancer n-3 polyunsaturated fatty acids (n-3 PUFA) are shown to modulate pubertal mammary gland development; however, the mechanisms of action remain unclear. Prior work focused on effects at the whole tissue level, and little is known at the cellular level, such as at the level of mammary epithelial cells (MECs), which are implicated in cancer development. Methods: This pilot study examined the effects of lifelong n-3 PUFA exposure on the transcriptome by RNA-Seq in the isolated MECs of pubertal (6–8-week-old) female fat-1 transgenic mice capable of de novo n-3 PUFA synthesis. edgeR and DESeq2 were used separately for the differential expression analysis of RNA sequencing data followed by the Benjamani–Hochberg procedure for multiple testing correction. Results: Nine genes were found concordant and significantly different (p ≤ 0.05) by both the DESeq2 and edgeR methods. These genes were associated with multiple pathways, suggesting that n-3 PUFA stimulates estrogen-related signaling (Mlltl0, Galr3, and Nrip1) and a glycolytic profile (Soga1, Pdpr, and Uso1) while offering protective effects for immune and DNA damage responses (Glpd1, Garre1, and Rpa1) in MECs during puberty. Conclusions: This pilot study highlights the utility of RNA-Seq to better understanding the mechanistic effects of specific nutrients such as n-3 PUFA in a cell-specific manner. Thus, further studies are warranted to investigate the cell-specific mechanisms by which n-3 PUFA influences pubertal mammary gland development and breast cancer risk later in life. Full article

Contemporary Management Accounting Practices (MAPs) were developed to address the weaknesses of traditional practices and to meet financial managers’ need for accurate and timely information. Consequently, they contribute to optimal decision-making that enhances firms’ efficiency and competitiveness, leading to improved organizational performance. Simultaneously, the success of Accounting Information Systems (AIS) is essential, as they improve the quality of information and reporting. In information- and competition-intensive environments such as the hotel industry, AIS user satisfaction, as an indicator of AIS success, can play a decisive role in the effective use of contemporary MAPs. The purpose of this paper is to explore the relationship between contemporary MAPs usage and hotel performance, and to investigate the moderating role of AIS user satisfaction. Using hierarchical multiple regression analysis, the findings indicate that the interaction of contemporary MAPs usage and AIS user satisfaction results in improved hotel performance. This study contributes to the current knowledge by developing a framework of the relationship of Management Accounting and Information Technology, through the lens of Contingency Theory and the Information Systems Success Model of DeLone and McLean. Additionally, the findings provide managerial implications for financial managers and IS developers. Full article

The integration of different sources of geological and hydrogeological information and the application of interdisciplinary methods have informed the origin of the thermal springs of Alhama de Aragón and Jaraba, as well as other associated semi thermal springs (1200 L/s of combined flow, 711 L/s at over 30 °C), which is the main objective of this article. These springs come mainly from the autogenous recharge that occurs in the Cretaceous calcareous outcrops that border the Almazán Basin to the north, both in the Ebro Basin (Jalón Valley) and in the Duero Basin. The aquifer, shaped by upper Cretaceous limestones under the Palaeogene and Neogene rocks of the Almazán Basin, has extensive depths of more than 4000 m in the NE sector. This hydrostratigraphic unit has been affected by a generalized pre-Paleogene karstification that provides the main porosity to the aquifer. The underground flow moves in a NW–SE direction, crossing the Duero–Ebro divide, favoured by the topographic difference in elevation between the two basins. The regional flow is coherent with the progressive increase in temperature, infiltrating recharge water age (about 20–25 years in the semi-thermal springs, and more than 60 years in the Alhama and Jaraba springs), mineralization, and flow of the springs through which the system discharges. This issue is key to being able to design any sustainable conservation strategy in terms of quantity and quality of resources within the recharge area of the most important thermal springs in Spain. The Jaraba and Alhama de Aragón hot springs share the same or similar temperature, chemical composition, and geological contact of the spring. Their tritium isotopic composition and its evolution over time are practically the same. Their isotopic composition in D and ¹⁸O is also very similar. Both springs share the same recharge zone of similar altitude and constitute the end of flow tubes of similar length and flow rate. Full article

In this paper, we investigate the vacuum bosonic current density induced by a carrying-magnetic-flux cosmic string in a $(D+1)$-de Sitter spacetime considering the presence of two flat boundaries perpendicular to it. In this setup, the Robin boundary conditions are imposed on the scalar charged quantum field on the boundaries. The particular cases of Dirichlet and Neumann boundary conditions are studied separately. Due to the coupling of the quantum scalar field with the classical gauge field, corresponding to a magnetic flux running along the string’s core, a nonzero vacuum expectation value for the current density operator along the azimuthal direction is induced. The two boundaries divide the space in three regions with different properties of the vacuum states. In this way, our main objective is to calculate the induced currents in these three regions. In order to develop this analysis we calculate, for both regions, the positive frequency Wightman functions. Because the vacuum bosonic current in dS space has been investigated before, in this paper we consider only the contributions induced by the boundaries. We show that for each region the azimuthal current densities are odd functions of the magnetic flux along the string. To probe the correctness of our results, we take the particular cases and analyze some asymptotic limits of the parameters of the model. Also some graphs are presented exhibiting the behavior of the current with relevant physical parameter of the system. Full article

Lithium–sulfur batteries (LSBs) exhibit high theoretical specific capacities, abundant resource reserves, and low costs, making them promising candidates for next-generation lithium-ion batteries (LIBs). However, significant challenges, such as the shuttle effect and volume expansion, hinder their practical applications. To address these issues, this study introduces a unique intermediate layer comprising N-doped carbon nanofiber/TiO₂/diatomite (NCNF/TiO₂/DE) from the perspective of membrane modification. The intermediate layer comprises nitrogen-doped titanium dioxide/carbon nanofiber (NCNF/TiO₂) materials, with diatomite filling the fiber gaps. This forms a three-dimensional (3D) conductive network that provides ample space for sulfur volume expansion and numerous adsorption active sites, thereby accelerating electrolyte penetration and lithium-ion diffusion. These features collectively contribute to the outstanding electrochemical performance of the battery. At 0.1 C, the NCNF/TiO₂/DE-800-coated separator battery achieved a first-cycle discharge specific capacity of 1311.1 mAh g⁻¹, significantly higher than the uncoated lithium–sulfur battery (919.6 mAh g⁻¹). Under varying current densities, the NCNF/TiO₂/DE-800 material demonstrates good electrochemical reversibility and exhibits high lithium-ion diffusion rates and low charge-transfer resistance. Therefore, this study provides an advanced intermediate layer material that enhances the electrochemical performance of lithium–sulfur batteries. Full article

Deep eutectic solvents (DESs) have attracted much attention as sustainable electrolytes for redox flow batteries. Despite the tremendous advantages of DES-based electrolytes, their high viscosity property has a negative effect on their mass transfer, limiting current density and power density. The ultrasonic effect has been demonstrated as an efficient strategy to improve mass transfer characteristics. Incorporating ultrasonic waves into a deep eutectic solvent (DES) electrolyte enhances the mobility of redox-active ions, thereby accelerating the reaction dynamics of the Fe(III)/Fe(II) redox pair. This enhancement makes it suitable for use in non-aqueous electrolyte-based redox flow batteries. However, it is necessary to consider the loss of ultrasonic on the internal structure of the battery, as well as the loss of battery component materials and ultrasonic energy consumption in practical applications. Moreover, the continuous extension of the duration of ultrasonic action not only hardly leads to a more significant improvement of the battery performance, but is also detrimental to the energy and economic savings. Herein, intermittent ultrasound is used to overcome the quality transfer problem and reduce the operating cost. Good electrochemical performance enhancement is maintained with a roughly 50% reduction in energy consumption values. The mechanism as well as the visualization of the pulsed ultrasonic field on each half cell has been envisaged through fundamental characterization. Finally, the feasibility of interrupted ultrasonic activation applied to Fe/V RFB using DES electrolytes has been demonstrated, demonstrating similar behavior with continuous ultrasonic operation. Therefore, the interrupted ultrasonic field has been found to be a more effective operation mode in terms of energy cost, avoiding alternative undesirable effects like overheating or corrosion of materials. Full article

Variants in the RB1 gene are associated with retinoblastoma (RB) development, and their presence in germline cells considerably increases the risk of subsequent malignant neoplasms (SMNs) in RB survivors. We report a female patient with bilateral RB who developed two SMNs in less than ten years, with a de novo pathogenic nonsense variant in RB1 [NM_000321.3:c.306T>A, p.(Cys102*)] in heterozygosity. The updated literature review of similar cases of SMN in patients with a previous diagnosis of RB reveals a wide range in both the type of subsequent malignancy and the age at which these SMNs develop. In addition, we identified only three cases with two SMNs following RB diagnosis, with at least one of these being an EWS. This case broadens the clinical and genetic landscape of RB, demonstrates the importance of a multidisciplinary approach in these patients, and highlights genetic diagnosis as a mandatory feature for management. Full article

In Para-judo, the technical actions and tactical situations suitable for scoring in a combat have not been studied. The aim of this research was to determine the technical–tactical patterns of scoring actions in Para-judo, focusing on weight categories. An observational methodology was employed to conduct this study. The sample consisted of all male judokas with visual impairment (n = 172) in the senior category who participated in the World Championships held in Odivelas in 2018. A total of 232 combats and 313 scoring actions were analyzed. To obtain the results, we used different analytical techniques with SPSS: descriptive analysis, chi-square test, and T-pattern analysis. The significance level used was p < 0.05. Key findings show that the majority of scoring actions occurred in the first two minutes of combat, highlighting the importance of early initiative. Techniques such as ashi-waza, te-waza, and sutemi-waza demonstrated particular effectiveness across categories, with a focus on movements like sumi-otoshi, ouchi-gari, and ko-soto-gake. Moreover, the most common grip—lapel-sleeve—proved advantageous, aiding judokas in controlling the bout and achieving scores, especially when coupled with effective transition techniques. The study’s weight-specific analysis further revealed distinct patterns, emphasizing the importance of tailored training approaches. For instance, lighter judokas benefited from countering leg attacks with arm or sacrifice techniques to score waza-ari, while heavier judokas favored leg-to-leg counterattacks, often achieving ippon. The results suggest that judokas and coaches could benefit from a more systematic focus on grip stability, strategic positional work, and transition efficiency, particularly from standing to ground. This research contributes valuable insights into optimal techniques and strategies for visually impaired judokas, providing clear guidelines for training and competition. Full article

Background and Objectives: Gestational diabetes mellitus (GDM) is one of the most common medical conditions in pregnancy, with adverse effects on maternal and neonatal outcomes. Evidence suggests a beneficial effect of plant-based dietary patterns, rich in foods derived from plant sources and low in animal foods, on type 2 diabetes; however, their effects on GDM remain unclear. We aimed to investigate the association between pre-pregnancy provegetarian food patterns and the incidence of GDM in a Spanish cohort. Materials and Methods: This subsample of the Seguimiento Universidad de Navarra (SUN) cohort analyzed 3,589 Spanish university graduate pregnant women with a mean (standard deviation) age of 28 (±4.3) who were initially free of pre-existing diabetes at baseline. Dietary food consumption was evaluated through a validated, 136-item semi-quantitative food frequency questionnaire. The pre-pregnancy provegetarian food pattern was obtained by assigning positive scores to plant-based food groups and reverse scores to animal food groups. Energy-adjusted quintiles were applied to allocate points to construct the provegetarian food pattern, ranging from 12 to 60 points. Logistic regression models were performed to estimate the odds ratios (OR) of GDM across quintiles of a pre-pregnancy provegetarian food pattern, using the lowest quintile as the reference category. Results: We identified 178 incidence cases of GDM. Women in the highest quintile (Q5) of provegetarian food pattern before pregnancy exhibited a 42% relative reduction in the odds of GDM [adjusted OR (95% CI) Q5 vs. Q1: 0.58 (0.35, 0.97); p-trend = 0.109]. Higher consumption of meat and dairy before pregnancy was associated with a significantly increased risk of GDM [adjusted OR (95% CI) Q5 vs. Q1: 1.94 (1.19, 3.16); p-trend = 0.005] and [adjusted OR (95% CI) Q5 vs. Q1: 1.77 (1.07, 2.94); p-trend = 0.082], respectively. Conclusions: Higher pre-pregnancy consumption of a provegetarian food pattern was associated with a lower risk of developing GDM in Spanish women. Further studies are needed to confirm these findings. Full article

It is imperative to comprehend the mechanisms that underlie drug toxicity in order to enhance the efficacy and safety of novel therapeutic agents. The capacity to identify molecular pathways that contribute to drug-induced toxicity has been significantly enhanced by recent developments in omics technologies, such as transcriptomics, proteomics, and metabolomics. This has enabled the early identification of potential adverse effects. These insights are further enhanced by computational tools, including quantitative structure–activity relationship (QSAR) analyses and machine learning models, which accurately predict toxicity endpoints. Additionally, technologies such as physiologically based pharmacokinetic (PBPK) modeling and micro-physiological systems (MPS) provide more precise preclinical-to-clinical translation, thereby improving drug safety assessments. This review emphasizes the synergy between sophisticated screening technologies, in silico modeling, and omics data, emphasizing their roles in reducing late-stage drug development failures. Challenges persist in the integration of a variety of data types and the interpretation of intricate biological interactions, despite the progress that has been made. The development of standardized methodologies that further enhance predictive toxicology is contingent upon the ongoing collaboration between researchers, clinicians, and regulatory bodies. This collaboration ensures the development of therapeutic pharmaceuticals that are more effective and safer. Full article

Background/Objectives: Despite the discovery of antibiotics, bacterial infections persist globally, exacerbated by rising antimicrobial resistance that results in millions of cases, increased healthcare costs, and more extended hospital stays. The urgent need for new antibacterial drugs continues as resistance evolves. Fluoroquinolones and tetracyclines are versatile antibiotics that are effective against various bacterial infections. A hybrid antibiotic combines two or more molecules to enhance antimicrobial effectiveness and combat resistance better than monotherapy. Fluoroquinolones are ideal candidates for hybridization due to their potent bactericidal effects, ease of synthesis, and ability to form combinations with other molecules. Methods: This study explored the mechanisms of action for 40 hypothetical fluoroquinolone–tetracycline hybrids, all of which could be obtained using a simple, eco-friendly synthesis method. Their interaction with Escherichia coli DNA Gyrase and similarity to albicidin were evaluated using the FORECASTER platform. Results: Hybrids such as Do-Ba, Mi-Fi, and Te-Ba closely resembled albicidin in physicochemical properties and FITTED Scores, while Te-De surpassed it with a better score. Similar to fluoroquinolones, these hybrids likely inhibit DNA synthesis by binding to enzyme–DNA complexes. Conclusions: These hybrids could offer broad-spectrum activity and help mitigate bacterial resistance, though further in vitro and in vivo studies are needed to validate their potential. Full article

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the epigenetic de-repression of the double homeobox 4 (DUX4) gene, leading to asymmetric muscle weakness and atrophy that begins in the facial and scapular muscles and progresses to the lower limbs. This incurable condition can severely impair muscle function, ultimately resulting in a loss of ambulation. A thorough analysis of molecular factors associated with the varying degrees of muscle impairment in FSHD is still lacking. This study investigates the molecular mechanisms and biomarkers in the biceps brachii of FSHD patients, classified according to the FSHD clinical score, the A-B-C-D classification scheme, and global proteomic variation. Our findings reveal distinct metabolic signatures and compensatory responses in patients. In severe cases, we observe pronounced metabolic dysfunction, marked by dysregulated glycolysis, activation of the reductive pentose phosphate pathway (PPP), a shift toward a reductive TCA cycle, suppression of oxidative phosphorylation, and an overproduction of antioxidants that is not matched by an increase in the redox cofactors needed for their function. This imbalance culminates in reductive stress, exacerbating muscle wasting and inflammation. In contrast, mild cases show metabolic adaptations that mitigate stress by activating polyols and the oxidative PPP, preserving partial energy flow through the oxidative TCA cycle, which supports mitochondrial function and energy balance. Furthermore, activation of the hexosamine biosynthetic pathway promotes autophagy, protecting muscle cells from apoptosis. In conclusion, our proteomic data indicate that specific metabolic alterations characterize both mild and severe FSHD patients. Molecules identified in mild cases may represent potential diagnostic and therapeutic targets for FSHD. Full article

Deep eutectic solvents (DES) represent an innovative and environmentally friendly approach for chitin isolation. Chitin is a natural nitrogenous polysaccharide, characterized by its abundance of amino and hydroxyl groups. The hydrogen bond network in DES can disrupt the crystalline structure of chitin, facilitating its isolation from bioresources by dissolving or degrading other components. DES are known for their low cost, natural chemical constituents, and recyclability. Natural deep eutectic solvents (NADES), a subclass of DES made from natural compounds, offer higher biocompatibility, biodegradability, and the lowest biotoxicity, making them highly promising for the production of eco-friendly chitin products. This review summarized studies on chitin isolation by DES, including reviews of biomass resources, isolation conditions (raw materials, DES compositions, solid–liquid ratios, temperature, and time), and the physicochemical properties of chitin products. Consequently, we have concluded that tailoring an appropriate DES-based process on the specific composition of the raw material can notably improve isolation efficiency. Acidic DES are particularly effective for extracting chitin from materials with high mineral content, such as crustacean bio-waste; for instance, the choline chloride-lactic acid DES achieved purity levels comparable to those of commercial chemical methods. By contrast, alkaline DES are better suited for chitin isolation from protein-rich sources, such as squid pens. DES facilitate calcium carbonate removal through H⁺ ion release and leverage unique hydrogen bonding interactions for efficient deproteination. Among these, potassium carbonate-glycerol DES have demonstrated optimal efficacy. Nonetheless, further comprehensive research is essential to evaluate the environmental impact, economic feasibility, and safety of DES application in chitin production. Full article

In recent years, metal chip powders obtained from solid-state processes have shown great potential as a sustainable raw material for powder technologies. The material and fragmentation process of the chips has a significant role in the final characteristics of the powder particles, such as size and particle size distribution, shape, surface, and structure, which are essential parameters to consider when converting chips to powder for applications. However, tool steel chips as a powder raw material have not yet been significantly studied. In this study, the steel chips were from machining AISI H13 steel and the milling process used a ball mill, and the challenge was to obtain powder particle sizes of around 20 µm with suitable properties from the application of envisaged material extrusion (MEX). A comparison study with the commercial raw material for MEX, such as powder metal filament extrusion, was performed. This study highlights the behaviors of chip powders during all steps of MEX, namely, feedstock and filament production, 3D object shaping, thermal de-binding, and sintering. A comparison of the mixture based on powder from chips and commercial powders for MEX was performed after evaluating the mixing torque of the powder and the system of binders and additives suitable for the rheological characteristics required for an extrusion mixture, and optimizing the binder removal and the sintering conditions. The 3D objects resulting from chip powders had a refined microstructure, showing an increase of 15% in the microhardness when compared with the those resulting from commercial powders. Full article