Search Results (4,147)

To characterize the distinct expression profiles of microRNAs (miRNAs) in serum and tissue and to delineate the heterogeneity of their regulatory mechanisms in early-stage ovarian cancer (EOC), thereby identifying candidate biomarkers for non-invasive early diagnosis. Differentially expressed miRNAs were identified by integrating publicly available datasets of EOC tissues and serum samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Core miRNAs were subsequently screened through integrated differential expression analysis, weighted gene co-expression network analysis (WGCNA), and feature importance ranking derived from optimized machine learning models. Protein–protein interaction (PPI) networks and functional enrichment analyses (GO and KEGG) were performed on predicted target genes to systematically compare the functional discrepancies between serum- and tissue-derived miRNAs. No overlapping core miRNAs were observed between the two compartments. Serum miRNAs exhibited an overall up-regulated trend, whereas tissue miRNAs were predominantly down-regulated. Although the regulatory pathways demonstrated significant heterogeneity, they ultimately converged on the cell cycle and the PI3K-Akt signaling pathway, indicating high functional homology. Furthermore, serum miRNAs are not merely passive leakage products from tissues; current evidence suggests they may be selectively packaged into exosomes to participate in tumor regulation. Despite divergent expression profiles, serum and tissue miRNAs share homologous regulatory functions in EOC. These findings suggest that serum miRNAs accurately reflect the core molecular status of tumor tissues, providing a robust molecular foundation for liquid biopsy-based early detection strategies. Full article

Background: Problematic pornography use (PPU) has emerged as a clinically significant phenomenon with severe repercussions for mental health and interpersonal relationships. Despite advances in prevalence studies, a gap remains in understanding the subjective processes of recovery and personal transformation. Objective: To describe the lived experience of individuals in recovery from PPU and compulsive sexual behavior and to analyze the perceived factors and dynamics of group support within their process of change. Methods: A qualitative study was conducted following Van Manen’s phenomenological-hermeneutical approach. In-depth semi-structured interviews were held with 27 individuals (26 men, 1 woman) engaged in structured recovery. Data analysis was performed through thematic analysis supported by ATLAS.ti Scientific Software Development GmbH, 2026. Results: A structured trajectory was identified across three phases: personal collapse, group engagement, and transformative mechanisms. Accountability emerged as a salient perceived mechanism of change, fostering sincerity (35.7%) and relapse prevention (19.1%). The "mirror effect" and "rational hope" within the support group facilitate a profound identity shift from a "spoiled identity” to a state of personal authenticity. Conclusions: For individuals engaged in structured support groups, recovery from PPU transcends mere abstinence, requiring a profound identity transformation facilitated by collective connection and honesty. These findings suggest the potential utility of integrating group-based accountability into therapeutic interventions for behavioral addictions tailored to the patient’s experiential profile. Full article

Immunotherapy has transformed cancer treatment; however, clinical benefit remains limited to a subset of patients, underscoring the need for robust biomarkers that capture tumor-immune interactions across cancer types. In this study, we performed a comprehensive pan-cancer, multi-omics characterization of the immune checkpoint–related molecules CD70, CD80, and TIGIT to evaluate their diagnostic, prognostic, and immunological relevance. Using integrative analyses of transcriptomic, epigenomic, genomic, pharmacogenomic, and single-cell RNA-sequencing data from The Cancer Genome Atlas and complementary resources, we assessed expression patterns, DNA methylation, somatic mutations, copy number alterations, immune infiltration, tumor stemness, and drug sensitivity. CD70, CD80, and TIGIT were broadly dysregulated across multiple malignancies, with coordinated overexpression particularly evident in kidney renal clear-cell carcinoma. Elevated expression of these immune checkpoints was associated with advanced tumor stage, aggressive molecular subtypes, and unfavorable survival outcomes in selected cancers, including uveal melanoma and renal malignancies. Functional analyses revealed significant associations between checkpoint expression and key oncogenic pathways, including epithelial–mesenchymal transition, apoptosis, and hormone receptor signaling, suggesting links with tumor progression and immune activation states. Immune deconvolution analyses indicated that TIGIT expression is associated with a T-cell–inflamed microenvironment and reduced neutrophil infiltration, while CD80 exhibited methylation-dependent associations with immune cell composition. Genomic and epigenetic alterations were found to correlate with checkpoint expression patterns and immune phenotypes across tumor types. Pharmacogenomic profiling identified associations between checkpoint expression and sensitivity to multiple anticancer agents; however, these findings are based on cell line datasets and should be considered predictive. Single-cell transcriptomic analyses further resolved cell-type–specific expression patterns, distinguishing tumor-intrinsic from immune-restricted expression profiles. Collectively, our findings establish CD70, CD80, and TIGIT as integrative biomarkers of tumor progression, immune contexture, and therapeutic response, providing a rationale for their clinical exploitation in precision immuno-oncology. Full article

Endogenous gene tagging using CRISPR has changed the understanding of the role played by different proteins due to the ability to track and study proteins in their natural state. With CRISPR-based gene tagging, it is possible to insert fluorescent, luminescent, epitope, affinity, and proximity labels into the target protein at its endogenous genomic location without affecting its physiological expression and dynamics. Here, we discuss the DNA-repair mechanisms employed in endogenous gene tagging, including homology-dependent repair, NHEJ-based integration, and alternative approaches that can be used with challenging cell types. Key aspects of efficient CRISPR tagging experiments are also described. Additionally, we review recent advances in the increasing array of protein tag technologies, including fluorescent proteins, split-reporter technologies, NanoLuc/HiBiT, peptide epitopes, and proximity biotinylation enzymes. Lastly, we review the scalability of endogenous tagging approaches using multiplex editing, atlas-scale proteome tagging, iPSC-based disease modeling, and drug discovery platforms for assessing target engagement, protein degradation, phenotype screening, and mechanism of action of compounds. Although difficult in primary and pluripotent cells, new methods based on avoiding double-strand breaks, such as prime editing, PASTE, and CRISPR associated transposases, will drive the future expansion of endogenous tagging approaches. Such developments firmly set up CRISPR gene tagging as a fundamental technology in quantitative cell biology and translational pharmacology. Full article

Substantial advances have been made since the 1970s in reducing the environmental impacts of ammonia production. Renewable-driven electrochemical synthesis offers a promising pathway to decarbonize ammonia production. This review examines an integrated route in which hydrogen is generated photoelectrochemically under concentrated solar irradiation and subsequently used in electrochemical ammonia synthesis. Photoelectrochemical cells are fabricated by electrostatically depositing photosensitive particles onto cathodes to enhance light-driven hydrogen production. Hydrogen production rates and ammonia yield depend strongly on temperature and electrolyte composition. The synthesized hydrogen is fed into a molten salt electrochemical reactor that operates at atmospheric pressure and receives nitrogen from a dedicated supply. This combined solar–electrochemical approach can produce low-carbon ammonia with improved safety and reduced environmental impact, offering a scalable alternative to conventional processes. Full article

Objective: Preanalytical errors account for the vast majority of preanalytical incidents and remain a fundamental threat to the reliability of test results. Although the types and frequencies of these errors have been extensively studied in the literature, their time-dependent variability has received comparatively little attention. This study aimed to evaluate how preanalytical specimen rejection rates vary across intraday time intervals and to assess the independent influence of time on preanalytical quality. Methods: This retrospective observational study included a total of 579,845 specimens accepted by the central laboratory of Istanbul Atlas University Hospital between January 2024 and December 2025. Specimens were analyzed with respect to preanalytical rejection reasons, the distribution and rate of these reasons across clinical units, and time of day. Each day was divided into six equal four-hour intervals: Z1 (00:00–04:00), Z2 (04:00–08:00), Z3 (08:00–12:00), Z4 (12:00–16:00), Z5 (16:00–20:00), and Z6 (20:00–24:00). Statistical analyses were performed using the Pearson chi-square test, and effect sizes were quantified using Cramér’s V coefficient. Results: Of the 579,845 specimens examined, 4365 were rejected, yielding an overall rejection rate of 0.79%. Rejection rates were found to be non-uniformly distributed across the day (p < 0.001). The highest rejection rate was observed during the Z2 interval (04:00–08:00) at 1.98%, whereas the lowest was recorded during Z3 (08:00–12:00) at 0.45%. Negative binomial regression analysis identified the Z2 interval as the only time period independently associated with an increased rejection risk Incidence Rate Ratio (IRR) = 1.63; 95% Confidence Interval (CI): 1.22–2.19. Among clinical units, the highest rejection rate was recorded in the emergency department (1.92%). Analysis of error types revealed that the majority of rejections were attributable to hemolysis (47.5%) and clotted specimens (26.3%). Hemolysis rates peaked in the emergency department, while clotted specimens occurred more frequently within intensive care units. Analysis of time and error interactions revealed that clotted specimens peaked during Z1 and Z2, whereas hemolysis became the primary cause of rejection during Z3 and Z4. Conclusions: Preanalytical specimen rejection rates exhibited significant variation according to time of day, clinical unit, and error type, with time emerging as a factor independently associated with preanalytical quality. The coexistence of elevated rejection risk during Z2 (04:00–08:00) and markedly low rejection rates during Z3 (08:00–12:00) indicates that the relationship between workload and error frequency is not linear. Although hemolysis and clotted specimens constituted the dominant error types, their distribution followed distinct patterns depending on the clinical unit and time interval. These results underscore the necessity of time-based monitoring to pinpoint unit-specific risks, providing a clear roadmap for targeted quality improvement interventions. Full article

The proliferation of Unmanned Aerial Vehicles (UAVs) in various applications has created a pressing need for robust and efficient communication systems. Fifth-generation (5G) networks can support UAV connectivity through high bandwidth and low-latency communication; however, rapid three-dimensional UAV mobility creates handover-management challenges that can increase signalling overhead, service interruption, and Quality of Service (QoS) degradation. This paper presents an integrated framework that combines LSTM-based multi-UAV trajectory prediction with proactive handover optimization using an Advantage Actor–Critic (A2C) Deep Reinforcement Learning (DRL) agent. The LSTM predictor is evaluated on a real-world UAV trajectory dataset and reports a root mean square error (RMSE) of 4.37 m over a 5 s prediction horizon after conversion to a local East–North–Up coordinate frame. A lightweight simulation-level coordination mechanism is included to reduce simultaneous target-cell contention among multiple UAVs; it is not claimed as a new standardized 3GPP signalling procedure. Handover performance is evaluated by replaying 180 held-out flight trajectories in a controlled 5G simulation across ten independent random seeds. Under these stated assumptions, the proposed framework achieves a handover success rate of $94.2\pm 0.8$%, an average SINR of $15.8\pm 0.2$ dB, a handover delay of $45.2\pm 1.1$ ms, and a handover frequency of $0.85\pm 0.05$ HOs/min, outperforming the tuned 3GPP A3, reactive SINR, and CASH baselines in the reported simulation results (Wilcoxon signed-rank test, $p<0.01$, Bonferroni-corrected). The experimental setup is described in detail to support methodological transparency and facilitate future replication, but the handover results should be interpreted as simulation-based evidence rather than live-network validation. Full article

The anomalous magnetic moment of the tau lepton, $a_{\tau }$, represents a fundamental test of the Standard Model (SM) and a high-sensitivity probe for New Physics in the third generation of leptons. Due to the tau’s extremely short lifetime, traditional spin-precession measurements remain inaccessible, necessitating innovative experimental strategies at high-energy colliders. This review provides a comprehensive overview of the current experimental landscape, highlighting the recent paradigm shift from LEP-era constraints to the unprecedented precision reached at the LHC. We emphasize the importance of Ultra-Peripheral Heavy-Ion Collisions (UPCs), which act as a “photon-photon collider” of extreme intensity. By leveraging the $Z^4$ enhancement of the coherent photon flux in Lead–Lead ($PbPb$) interactions, these collisions provide a theoretically robust “quasi-static” environment. To interpret these developments, we first establish the general theoretical framework within the Standard Model Effective Field Theory (SMEFT). This allows us to critically compare the UPC results with the latest measurements from proton–proton collisions—including the recent CMS observation of the $\gamma \gamma \to \tau \tau$ process and the ATLAS constraints from the high-mass Drell–Yan tail—evaluating their complementarity and the challenges related to Effective Field Theory validity at the TeV scale. Finally, we outline the future prospects for $a_{\tau }$ at Belle II and the Future Circular Collider (FCC) stages. While FCC-hh in $PbPb$ mode provides a theoretically clean environment, its sensitivity remains limited to $\mathcal{O}\left({10}^{-2}\right)$. Conversely, the next generation of lepton facilities, specifically Belle II and FCC-ee, aims for the $\mathcal{O}\left({10}^{-5}\right)$ level, required to probe SM electroweak loop corrections. Long-term projections for a high-energy Muon Collider suggest a potential reach of $\mathcal{O}\left({10}^{-6}\right)$. Full article

The discovery of the Higgs boson in 2012 at the Large Hadron Collider marked a major milestone in our understanding of electroweak symmetry breaking. Since then, increasingly precise measurements by the ATLAS and CMS Collaborations, based primarily on proton–proton collision data at \(\sqrt{s}\) = 13 TeV corresponding to about 140 fb−1 per experiment, have confirmed its compatibility with Standard Model predictions within current uncertainties. The Higgs boson mass is now measured with a precision of about 0.08%, while its couplings to fermions and bosons are determined at the 7–20% level. The completion of the LHC programme and the High-Luminosity LHC, will probe Higgs boson couplings at the fewpercent level. However, sub-percent precision is required for stringent tests of the Standard Model, as any deviation would signal new physics beyond it. This strongly motivates future collider facilities, designed both as high-precision Higgs factories and, in many cases, as energy-frontier machines. Within the framework of the update of the European Strategy for Particle Physics, we discuss the physics case and main characteristics of the proposed particle collider options, highlighting their complementarity, technological challenges, and expected performance. The 2026 Strategy Update identifies the FCC-ee collider as the preferred next flagship project at CERN. Operating at the Z pole and at centre-of-mass energies between 240 and 365 GeV, it would enable model-independent, per-mille-level precision on Higgs boson couplings, while providing a pathway to a future high-energy hadron collider. The Higgs sector thus constitutes a central laboratory for precision tests of the Standard Model and for exploring the fundamental structure of our universe. Full article

Background and Aims: TDF is a first-line antiviral for CHB with pleiotropic effects including immunomodulation and fibrosis regression, but its virus-independent mechanisms are unclear. This study delineates TDF’s direct molecular and metabolic landscape in vivo using multi-omics. Methods: Wild-type mice received TDF or vehicle for 4 months. Liver tissues underwent RNA-seq and targeted metabolomics, followed by integrative systems biology. Results: TDF caused no hepatotoxicity but induced transcriptomic reprogramming: broad upregulation of immune/inflammatory pathways and suppression of metabolic pathways. Metabolomics confirmed perturbations in amino acid and fatty acid homeostasis. Multi-omics revealed coordinated downregulation of arginine/proline, alanine/aspartate/glutamate, and phenylalanine metabolism, restricting fibrogenic amino acids. TDF also suppressed the TCA cycle (downregulating Idh, Sdh, and Mdh), suggesting a metabolic bottleneck that was associated with paradoxically accumulated succinate and oxoglutarate—immunomodulatory danger signals. Conclusions: This first integrated atlas shows TDF actively remodels the hepatic microenvironment independent of viral infection, bridging metabolic suppression with immune activation. These findings provide an immunometabolic framework that offers new perspectives for understanding the clinical application of TDF and identifies potential biomarkers for CHB therapy. explaining TDF’s clinical superiority and identifying potential biomarkers for CHB therapy. Full article

Introduction: Studying the structure and dynamics of living communities is essential from both ecological and wildlife management perspectives. Objective: The main objective of this study was to analyze the fish community structure inhabiting different river sections across several basins in the Mediterranean area. The data collected here contributed to: (i) creating a regional and national reference inventory to assess ichthyological biodiversity; (ii) generating digital cartographic information on species distribution and potential habitats; and (iii) providing scientific data to update national legal protection for governments. Methodology: Fish assemblages were monitored using electrofishing, which ensures reproducible data and long-term comparability. The study period extended until autumn 2025, with intensive sampling at 30 sites across major water bodies in the Valencian Community and selected rivers in Mijares, Turia, Jucar and Palancia basins. Results: The results reveal notable ichthyological richness in the studied basins (Turia, Júcar, Palancia, Mijares), with 12 native species identified. Cyprinidae and Leuciscidae were the most representative families, both in species number and spatial distribution, consistent with their dominance in Mediterranean river systems. Areas with the highest species richness corresponded to the middle and lower river sections and to ecologically valuable coastal wetlands. However, the study also detected 10 invasive alien species, representing 45% of the total fish fauna recorded. This high proportion reflects the significant ecological alteration affecting rivers and wetlands in these basins and underscores the urgent need for management actions to limit the spread of invasive species and reduce their impact on native biodiversity. The most widespread IAS were the bleak (A. alburnus), mainly in the Júcar basin, and the mosquitofish (G. holbrooki), predominantly in coastal wetlands. Conclusions: This study contributes directly to updating the Atlas of Ichthyofauna of the Valencian Community, providing a robust and current information base to support environmental decision-making at regional and national levels. The findings highlight the importance of strengthening proactive conservation measures, particularly in areas where biodiversity is most vulnerable. Full article

The Iberian Peninsula hosts one of the world’s most endemic fish faunas. Its extensive evolutionary, palaeogeographic, and geological history has produced a distinctive freshwater fish fauna. Many of these species have very limited distributions, making them especially vulnerable to habitat disturbance. Past monitoring of this biodiversity has revealed alarming results, indicating that most native Spanish species are at risk. The causes of this serious situation are varied and reflect the ongoing deterioration of freshwater ecosystems. The main pressures faced by populations include pollution, loss of river connectivity caused by hydraulic infrastructure, regulation of watercourses, water extraction, fishing, and the presence of invasive species. Additionally, the effects of climate change worsen the risk of extinction for these populations, particularly through the increased frequency and intensity of droughts and heatwaves. It is evident that current planning models and investments are inadequate to conserve freshwater fish. To prevent the extinction of many populations in Spain, especially Iberian endemics, it is crucial to change the management of aquatic ecosystems and adopt integrated solutions that halt population declines and promote the sustainable use of aquatic resources. The IUCN Red Lists of Threatened Species are vital indicators of biodiversity health and are widely used to guide and structure conservation efforts. These lists, published in the Red Books, result from a thorough evaluation process that employs specific categories and criteria to assess the extinction risk of species, both globally and regionally. This report presents preliminary findings from a monitoring study on the current state of freshwater fish in Spain. The monitoring results reveal that, based on IUCN assessment criteria, two species are classified as extinct (EX), four as critically endangered (CR), eighteen as endangered (EN), and twenty-one as vulnerable (VU). Of fifty-seven species documented, 79% are considered threatened. The project’s final outcome is the development of the Atlas and Red Book of Freshwater Fish of Spain. This resource includes the main native and invasive freshwater and diadromous fish species, offers detailed information on their biological and ecological traits, and provides an up-to-date inventory of records along with an assessment of their conservation status. Full article

We present the results of applications of ATLAS2.0 to experimental data in this final part of our series of publications. ATLAS2.0 retrieves particle microphysical parameters from multiwavelength Raman and high-spectral-resolution lidar measurements of backscatter (β) coefficients at three wavelengths, i.e., λ = 355, 532, and 1064 nm, extinction (α) coefficients at two wavelengths, i.e., 355 and 532 nm, and particle linear depolarization ratios (PLDR, δ) at three wavelengths, i.e., 355, 532, and 1064 nm, so-called 3β + 2α + 3δ datasets. The explicit use of PLDRs is a novel feature compared to all previously developed lidar data retrieval algorithms. For the tests of ATLAS2.0, we use data that were taken with NASA Langley Research Center’s airborne high-spectral-resolution lidar 2 (HSRL-2). We show the results of two case studies. We compare the particle microphysical parameters and single-scattering albedo (SSA) retrieved with ATLAS2.0 to results obtained with the first version of ATLAS, our Tikhonov regularization algorithm (TiARA), and in situ observations carried out aboard an aircraft that followed the airborne HSRL-2 instrument. The solutions converge within the retrieval uncertainties of these techniques. The discrepancy between the measured and backcalculated, i.e., retrieved 3β + 2α + 3δ data on average stays below 10%. The difference between the retrieved and measured PLDRs is, on average, even less. This comparably good convergence of the optical datasets (experimental versus backcalculated) of both measurement cases can only be achieved if the investigated aerosol particles are analyzed on the basis of a sphere-spheroid mixture. Full article

Methyl methacrylate (MMA)-based materials are widely used in temporary and permanent prosthetic dentistry; the prolonged presence of these materials in the oral cavity and potential residual monomer release can affect local biological responses. This study aimed to evaluate the biocompatibility and toxicity profiles of MMA, the monomeric unit of polymethyl methacrylate (PMMA), a key component of dental materials used in temporary prosthetic restorations. Molecular docking simulations were performed using CB-Dock2 and Autodock vina, while protein–protein interaction (PPI) analysis was performed using STRING and Cytoscape. In addition, Swiss ADME Target Prediction, toxicity prediction, and enrichment analyses were used to characterize the biological significance of selected targets in more detail. Molecular docking studies revealed promising interactions of MMA with valuable biomolecular targets relevant to biocompatibility. The toxicity profile revealed aspects of MMA that could be improved. Pharmacophore modeling, highlighting the importance of carbonyl and hydroxyl groups as pharmacophoric properties, revealed compounds with suitable biocompatibility profiles. Consequently, it emphasizes the interactions of MMA with biomolecules and safety considerations. It can guide the design and optimization of biocompatible materials as an exploratory avenue for future developments in dental biomaterials. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer. Human ccRCCs have increased glycolytic metabolism and decreased mitochondrial oxidative metabolism relative to normal kidneys. Our research using human RCC4 ccRCC cells and a murine model of ccRCC, TRACK (TRAnsgenic model/Cancer/Kidney), in which a triple-mutant (P402A, P564A, N803A) human HIF1α is selectively expressed in proximal tubule cells (PTCs), revealed highly induced ATF4, a stress-responsive transcription factor. We then investigated the role of ATF4 in the metabolic changes in ccRCC. Methods: We performed comprehensive analysis of the ccRCC Cancer Genomics Atlas (TCGA) data. We deleted ATF4 in PTCs of TRACK mice and human RCC4 cells. We conducted genome-wide transcriptomic and untargeted metabolomic studies of cortices of WT and CGERA∆T (TRACK mice with PTC-specific ATF4-knockout (KO)) mice and performed glucose isotopologue tracing in parental and ATF4 KO RCC4 cells. Results: Analysis of TCGA data showed increased mRNAs of enzymes in glycolysis and reduced mRNAs of enzymes in the TCA cycle. Transcriptomic and metabolomic studies demonstrated that ATF4 deletion suppressed glycolysis and enhanced TCA cycle metabolism in CGERA∆T versus WT cortices. Glucose isotopologue tracing showed that ATF4 deletion altered glycolysis pathway metabolite levels and shifted glucose metabolism towards the TCA cycle, evidenced by increased intracellular [¹³C₂]citrate in RCC4-ATF4 KO cells. Using the Seahorse XFe96 analyzer we also showed reduced glycolytic capacity and reserve in RCC4-ATF4 KO cells. Conclusions: Collectively, our results demonstrate that ATF4 regulates glycolysis in ccRCC, supporting ATF4 as a therapeutic target. Full article