Search Results (296)

Large Language Models (LLMs) are capable of generating text that is similar to or surpasses human quality. However, it is unclear whether LLMs tend to exhibit distinctive linguistic styles akin to how human authors do. Through a comprehensive linguistic analysis, we compare the vocabulary, Part-of-Speech (POS) distribution, dependency distribution, and sentiment of texts generated by three of the most popular LLMS today (GPT-3.5, GPT-4, and Bard) to diverse inputs. The results point to significant linguistic variations which, in turn, enable us to attribute a given text to its LLM origin with a favorable 88% accuracy using a simple off-the-shelf classification model. Theoretical and practical implications of this intriguing finding are discussed. Full article

Background/Objectives: Chronic liver diseases, including metabolic dysfunction-associated steatohepatitis (MASH) and chronic viral hepatitis (CVH), are major global health concerns due to their potential progression to cirrhosis, liver failure, and hepatocellular carcinoma. Because liver biopsy, despite meeting the diagnostic gold standard, is invasive and associated with complications, non-invasive fibrosis assessment tools have been increasingly recommended in clinical practice. This study aimed to compare the diagnostic performance of several non-invasive fibrosis markers (ARR, APRI, FI, FIB-4, API, NFS, BARD) and transient elastography in detecting advanced liver fibrosis (F4) in patients with MASH and CVH. Methods: This retrospective study included 237 adult patients (77 MASH, 160 CVH) who underwent liver biopsy between 2017 and 2025 at the University Clinical Center of Serbia. CVH included chronic hepatitis B (CHB) and C (CHC). Patients were evaluated using serum fibrosis indices and TE, and results were compared to histological staging (F0–F4). ROC analysis assessed diagnostic performance. Results: Cirrhosis (F4) was more common in CVH than MASH (p < 0.001). In MASH, NFS (AUROC 0.931), FIB-4 (0.915), BARD (0.872), and APRI (0.878) showed high diagnostic accuracy for F4. In CHC, APRI (0.931), FIB-4 (0.863), and TE (0.938) had strong performance, while in CHB, TE (0.987) outperformed FIB-4 (0.821). Sensitivity and specificity varied by test and cohort, with TE consistently yielding the best results where available. Conclusions: Non-invasive methods, particularly NFS and FIB-4 for MASH and TE for CVH, effectively identify advanced fibrosis. Their application could significantly reduce the need for biopsy, especially in high-risk groups. TE demonstrated superior accuracy, but access limitations highlight the continued relevance of serum-based scores. Full article

This study investigates the development and optimization of a multi-component modifying additive based on industrial waste for improving the mechanical and durability properties of concrete. The additive consists of microsilica (Ms), phosphogypsum (PhG), soapstock (Sp), and post-alcohol bard (PaB), and its performance was evaluated using a staged experimental approach. The results showed that the optimal content of microsilica is 20% of the cement mass; the optimal content of phosphogypsum is 15% of the combined mass of the cement and microsilica; the optimal content of soapstock is 10% of the total mass of the cement, microsilica, and phosphogypsum; and the optimal post-alcohol bard is 5% of the water mass. At these concentrations, the compressive strength increased by up to 28.3% compared to the reference sample. Soapstock significantly reduced water absorption (up to 36.8%) and improved freeze–thaw resistance due to the hydrophobization of the cement matrix. However, excessive soapstock content led to a reduction in strength. The addition of post-alcohol bard provided a plasticizing effect and reduced water absorption, with the optimal concentration for strength being 2.5%, while the highest freeze–thaw resistance was observed at 5%. The combined effect of the components resulted in the formation of a denser microstructure and improved durability of concrete. These findings demonstrate the effectiveness of industrial waste-based additives in enhancing concrete performance and durability, contributing to sustainable material development. Full article

Background/Objectives: Exposure of cells to ionizing radiation induces isolated DNA lesions, including single-strand breaks, apurinic/apyrimidinic sites, and oxidized bases, as well as clustered damages of different complexity. The latter types of damage are difficult to repair, and the failure to process them accurately and efficiently is related to the induction of mutagenesis, genomic instability, cancer, and aging. Since various types of clustered lesions may occur simultaneously after radiation exposure, leading to a complex architecture of DNA damage, the study of the concomitant formation and the removal kinetics of clustered DNA damage is important to determine the mutagenic and, consequently, the carcinogenic potential of ionizing radiation. Methods: With the aim of capturing real-time coexisting lesion types and assessing the repair kinetics of clustered damages, the simultaneous determination of double-strand breaks, apurinic/apyrimidinic site clusters, and oxypurine clusters induced by γ-irradiation of Saccharomyces cerevisiae yeast cells was performed immediately after exposure and at time intervals during incubation in Liquid Holding Recovery conditions. Results: Ionizing radiation induced lethal and mutagenic events, leading to a dose-dependent linear increase in double-strand breaks, apurinic/apyrimidinic site clusters, and oxypurine clusters. The kinetic study showed that double-strand break frequencies declined during Liquid Holding Recovery, although a transient increase was detected at early time points. At 160 Gy, apurinic/apyrimidinic site clusters repair was evident, whereas at 400 Gy the frequency of damage increased before returning to the initial value at 24 h. In contrast, oxypurine clusters showed no net increase in repaired lesions over 24 h. Conclusions: The complex nature and topological characteristics of ionizing radiation-induced clustered DNA damage may influence lesion processing. Also, ionizing radiation may disrupt redox cellular homeostasis, leading to DNA damage and delayed effects. Full article

Understanding the molecular mechanisms of carcinogenesis, including disruptions in the homologous recombination system, is fundamental to understanding malignant transformation. Dysfunction of homologous recombination genes, such as BRCA1 and BRCA2, contributes to genomic instability and the development of more aggressive tumor clones. The use of chemical carcinogens enables the modeling of tumor formation and the monitoring of changes in molecular genetic parameters. This approach is important for understanding how tumor cells adapt to genotoxic stress and for advancing the development of personalized cancer therapies. The objective of this study was to evaluate the expression of key homologous recombination system genes in a model of chemically induced carcinogenesis in mice. Materials and Methods: Male outbred ICR (CD-1) laboratory mice (n = 40) were used to study chemically induced carcinogenesis. The animals were divided into four groups: two control groups and two experimental groups, which received 3-methylcholanthrene (MC) or trichloroacetic acid (TCA). Tumor cells were identified by histological analysis of autopsy material using light microscopy after standard hematoxylin and eosin staining. RNA and DNA were extracted from cell suspensions using the RNeasy Plus Mini Kit and QIAamp DNA Mini Kit (Qiagen, Hilden, Germany), respectively. The expression levels of homologous recombination genes were assessed by RT-PCR and microarray analysis. Digital PCR was performed to assess chromosomal aberrations in the Brca1 gene. Results: Tumor formations were identified in laboratory animals two months after 3-methylcholanthrene. Histological analysis revealed morphological changes in a pleomorphic cell tumor, forming diverse, multidirectional fascicular and swirling structures, as well as large solid foci composed of markedly polymorphic spindle-shaped and epithelioid cells. Analysis of copy number aberrations in the examined samples showed that the frequency of Brca1 deletions was 60%, while 40% of animals had normal gene copy number. To further characterize the molecular changes, we assessed gene expression levels through expression microarray analysis. A total of 14 genes were hypoexpressed in the tumor compared to the normal tissue, with p < 0.05. A high level of differential expression was characteristic for Rad50, Rad51, Brca1, Brca2, and Pold4. Two genes, Rad52 and Bard1, exhibited increased expression levels. It was shown that as the tumor mass increased, so did the frequency of homologous recombination genes with hypoexpression. Conclusions: Our findings confirm that MC and TCA influence tumor formation and reveal that suppression of homologous recombination genes may contribute to this process. In addition, it has been established that as tumors progress, the expression of DNA repair genes declines and aberrant gene states accumulate. These data emphasize the importance of studying the state of DNA repair genes for the development of more effective strategies for cancer diagnosis and therapy. Full article

This study presents the high-speed visualization of the detonation wave structure in a small-scale hydrogen–oxygen rotating detonation combustor. A 68 mm Rotating Detonation Combustor was modified with a quartz-glass ring, such that radial optical access into the annular detonation chamber was realized. The optical access window covers approximately the first 22 mm of the detonation chamber. The modified experiment was hot-fire tested with the propellant combination gaseous hydrogen–oxygen. Simultaneous high-speed imaging from the back-end of the chamber and normal to the chamber axis allows a thorough investigation of the detonation wave characteristics. Both high-speed cameras were operated at 180,000 frames per second in order to resolve and capture the detonation waves. The downstream camera was used in order to investigate the number of waves and the spinning direction. A stable regime of three co-rotating waves was observed. The wave speed achieved 71% of the theoretical CJ-velocity. The second camera recorded the passing detonation waves through a quartz ring via OH* emissions. From the post-processed OH* images, a better understanding of the detonation wave structure, including the filling height of the fresh gas mixture as well as the approximate angles of the detonation and the shock wave, could be gained. The obtained height of the detonation wave is about 11–12 mm or 6–7 detonation cell sizes for the given setup and experimental conditions. Full article

Objective: This study aimed to compare the accuracy of two large language models (LLMs)—ChatGPT (version 3.5) and Google Gemini (formerly Bard)—in answering dental caries-related multiple-choice questions (MCQs) using a simulated student examination framework across seven examination lengths. Materials and Methods: A total of 125 validated dental caries MCQs were extracted from Dental Decks and Oxford University Press question banks. Seven examination groups were constructed with varying question counts (25, 35, 45, 55, 65, 75, and 85 questions). For each group, 100 simulations were generated per LLM (ChatGPT and Gemini), resulting in 1400 simulated examinations. Each simulated student received a unique randomized subset of questions. MCQs were answered by each LLM using a standardized prompt to minimize ambiguity. Outcomes included mean score, passing rate (≥60%), and performance differences between LLMs. Statistical analyses included independent t-tests, one-way ANOVA within each LLM, and two-way ANOVA examining interactions between LLM type and question count. Results: Across all seven examination formats, Gemini significantly outperformed ChatGPT (p < 0.001). Gemini achieved higher passing rates and higher mean scores in every examination length. One-way ANOVA revealed significant score variation with increasing exam length for both LLMs (p < 0.05). Two-way ANOVA demonstrated significant main effects of LLM type and question count, with no significant interaction. Randomization had no measurable effect on Gemini performance but influenced ChatGPT scores. Conclusions: Gemini demonstrated superior accuracy and higher passing rates compared to ChatGPT in all simulated examination formats. While both LLMs struggled with complex caries-related content, Gemini provided more reliable performance across question quantities. Educators should exercise caution in relying on LLMs for automated assessment or self-study, and future research should evaluate human–AI hybrid models and LLM performance across broader dental domains. Full article

The article presents the current state of knowledge on genetic modifiers of ovarian cancer risk in women carrying pathogenic variants (PVs) in the BRCA1 and BRCA2 genes, which are major contributors to hereditary susceptibility to this malignancy. Although PV carriers have high disease penetrance (BRCA1: ~40% and BRCA2: 11–27%), substantial variability in individual risk is observed, suggesting the influence of additional genetic variants. Background: Ovarian cancer is characterized by late detection and high mortality, and a significant portion of risk among BRCA1/2 carriers is shaped by reproductive and environmental factors as well as genetic modifiers. The article emphasizes that carriers of the same BRCA PV can exhibit markedly different risk levels depending on additional variants that modulate key biological processes, such as DNA repair, cell cycle regulation, and apoptosis. Methods: A systematic literature search covering the years 1996–2025 was conducted in the PubMed database. Initially, 734 publications were identified; after removing duplicates, thematically irrelevant articles, non-full-text papers, and studies not meeting the inclusion criteria, 47 articles were included in the review. These studies covered candidate gene analyses, GWAS, and data from the CIMBA consortium, which enables the examination of large cohorts of PV carriers. Results: The review identified numerous variants associated with increased or decreased ovarian cancer risk in BRCA1 carriers, including the following: OGG1, DR4, MDM2, CYP2A7, CASP8, ITGB3, HRAS1, TRIM61, and MTHFR. The reviewed studies also identified both protective and risk-increasing variants among BRCA2 PV carriers: UNG, TDG, and PARP2, and haplotypes in ATM, BRIP1, BARD1, MRE11, RAD51, and 9p22.2. The analysis identified 11 variants affecting both BRCA1 and BRCA2 carriers, most of which increase risk, including the following: IRS1, RSPO1, SYNPO2, BABAM1, MRPL34, PLEKHM1, and TIPARP. Protective variants include BNC2 and LINC00824. The only SNP reaching genome-wide significance (p < 5 × 10⁻⁸) was in BNC2. Conclusions: The article summarizes the growing number of genetic modifiers of ovarian cancer risk among BRCA1/2 carriers and highlights their potential to improve individualized risk assessment, enhance patient stratification, support personalized prevention and surveillance strategies, deepen the understanding of disease biology, and identify potential therapeutic targets. Full article

This article will bring together and explore the relations between four aspects of Wittgenstein’s remarks on, and his relation to, religious language. The first is his sense of the special role that religious language can play in the lives of people. The focus is not on traditional issues in the philosophy of religion—not the Ontological Proof of the existence of God; not any of Aquinas’ Five Ways; not the argument from Design or the Cosmological Argument; and not any other philosophico-religious matter concerning arguments for the existence or non-existence of any deity. His interests lie elsewhere. Second, we see that what Wittgenstein is centrally concerned with is the life-structuring power that religious language can possess and exert; it concerns both the sense-making power of pattern-lives in religious narratives and the metaphorical content of religious ways of thinking and perceiving. The third aspect is the distinctive, and in its way transcendental, way of seeing the world and existence sub specie aeternitatis, that is, under the aspect of eternity. Or, I will suggest, under the aspect of timelessness, or of having the sense of being above and outside of time. Wittgenstein said that he was not a religious person, but that he could not help but to see every problem from a religious point of view. In this third theme of the article, I will attempt to explicate what that remark can mean—how it reveals what Wittgenstein elsewhere in his work calls “a way of seeing.” And then fourth, this article will connect these three aspects to the special, non-pragmatic (and often in the above sense, transcendental) way that we view works of art. In his Notebooks of 1914-16, Wittgenstein wrote, “The work of art is the object seen sub specie aeternitatis; and the good life is the world seen sub specie aeternitatis. This is the connection between art and ethics.” At the close, I suggest that the way we learn to see the world through and within religious language (again, apart from any theological claim concerning divine existence or not) is parallel to one important way of seeing art—where the parallel is one that casts light from each side to the other. Along with some other works, my most central example in art will be the paintings of Morandi: in conveying an unmistakable sense of timelessness, they both convey, and in viewing them invite us to enact, the special way of seeing objects sub specie aeternitatis. Full article

Introduction: The prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is rapidly increasing, possibly becoming the leading cause of chronic liver disease (CLD) in the coming years. Samaglutide (a long-acting glucagon-like peptide receptor agonist 1—GLP-1RA) therapy might be connected with an improved liver function. The aim of the presented study was to assess the impact of semaglutide administered at submaximal doses on biopsy-free scoring systems in patients with obesity and MASLD. Methods: We performed an observational, prospective, post-marketing study. The research included 30 patients (21 being women, mean age 47 ± 14 years) with obesity (Body mass index/BMI/39.7 ± 5.78 kg/m²) and known MASLD. All patients received semaglutide dosed initially 0.25 mg s.c. weekly, which was uptitrated (to a maximal dose of 1.5 mg) over 6 months. MASLD biopsy-free scoring systems (BFSS: SAFE, Fib-4, BARD, NAFLD Fibrosis Score, Fatty Liver Index—FLI, and Hepatic Steatosis Index—HSI) were assessed before and after 6 months of therapy. Results: In this study, a significant change (decrease) in FLI (92.4 ± 9.85 vs. 75.3 ± 21.0, p <  0.001), HSI (50.7 ± 6.78 vs. 45.0 ± 6.42, p < 0.001) and SAFE score (30.8 ± 80.7 vs. 11.2 ± 81.6, p < 0.033) was observed. The changes in the remaining BFSS (BARD, Fib-4 and NAFLD Fibrosis Score) were nonsignificant (p = 0.501; p = 0.303; p = 0.503). Conclusions: In our study, administration of sub-maximally dosed semaglutide was connected with improved FLI, HIS, and SAFE BFSS, suggesting the efficacy of submaximal semaglutide for improvement in MASLD. Full article

Background/Objectives: Targeted gene sequencing (TGS) for Comprehensive Genomic Profiling (CGP) use in sarcomas has recently increased in clinical practice. We report on TGS real-world data over a period of 3 years (2022–2025) at the IRCCS Istituto Ortopedico Rizzoli, with the aim of identifying potential actionable targets and providing therapeutic indications for advanced sarcoma patients. Methods: We analyzed 22 advanced sarcoma patients by using the VariantPlex Pan Solid Tumor kit panel, including 185 genes. In nine cases, saliva samples for germinal DNA analysis were available. Sequencing was performed on the NextSeq-500 Platform and analyzed with Archer Analysis software. The Cancer Genome Interpreter and OncoKB Database tools were used to find potential actionable targets. Results: We found the most frequent genetic variants, including missense, deletion, duplication, and delins, in the NOTCH4, AR, BARD1, MUC16, and ROS1 genes. Copy Number alterations affected the CDKN2A, CDKN2B, TP53, RHOA, MYC, CCND3, and DDR2 genes mainly in osteosarcoma samples. In four patients, longitudinal analyses of subsequent lesions showed the maintenance of most genomic alterations and enrichment in missense or splice variants in PMS2, SMARCA4, ARID1A, AKT1, BMPR1A, and PTEN, indicating the occurrence of tumor evolution. Germline variants subtraction identified the specific somatic tumor mutations. Advantages and disadvantages of our approach were considered in order to refine the analysis setting and better select possible actionable targets. Conclusions: Early access to genomic analyses, routine germline assessment, and broad gene panels would help in identifying possible targeted drugs with sufficient evidence of activity beneficial to each patient. In the clinical management of advanced sarcoma patients, when analyzing cost-effectiveness and sustainability, the role of the Molecular Tumor Board in the governance of the complexity introduced by mutational oncology should be considered. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition shaped by metabolic dysfunction, adipose tissue distribution, inflammatory activation, and body composition. Understanding how these factors interact across distinct clinical phenotypes is essential for improving diagnostic accuracy and risk stratification. This study aimed to compare metabolic, inflammatory, and elastographic profiles between MASLD subgroups defined by adipose tissue dysfunction (ATD) and obesity, and to identify pathways linking metabolic dysregulation to hepatic fibrosis. Methods: We conducted a cross-sectional observational study including 178 adult participants evaluated clinically, biochemically, and by bioimpedance and shear wave elastography. Participants ranged in age from 19 to 82 years. Patients were stratified into a non-MASLD control group and two MASLD subgroups: MASLD with ATD (G1) and MASLD with obesity (G2). Anthropometric data, lipid profile, glycemic markers, cytokines (IL-6, IL-10, TNF-α), liver stiffness, and non-invasive fibrosis indices were compared across groups using standard statistical testing. Results: Patients with MASLD showed higher liver stiffness, triglycerides, and IL-6/IL-10 levels than controls. Between MASLD phenotypes, the ATD group (G1) exhibited a more inflammatory and dysmetabolic profile, with significantly higher triglycerides, IL-6 levels, neutrophil counts, and creatinine, alongside trends suggesting early sarcopenic changes. In contrast, the obese phenotype (G2) demonstrated greater hepatic structural involvement, including higher liver stiffness and BMI, AST/ALT ratio and Diabetes (BARD) scores, despite more favorable inflammatory parameters. Several associations between liver stiffness, IL-6, and glycemic control approached but did not reach statistical significance. Conclusions: MASLD progression appears to follow two complementary but distinct mechanisms: an inflammatory, adipose dysfunction pathway dominated by IL-6 activation and early anabolic decline, and a metabolic-overload pathway driven by obesity. Phenotype-specific evaluation integrating inflammatory markers, metabolic indices, and elastographic parameters may improve risk stratification and inform personalized therapeutic strategies. Full article

Homologous recombination deficiency (HRD) is a clinically relevant biomarker that predicts sensitivity to PARP inhibitors and enables personalized cancer therapy. Validated local HRD testing solutions are essential to ensure timely and equitable access, ultimately improving treatment outcomes. We evaluated a shallow whole-genome sequencing (sWGS) approach for genomic instability (GI) assessment combined with a 52-gene targeted panel in ovarian cancer. Validation used reference materials and 24 archival samples with prior HRD characterization, comparing performance with the Myriad myChoice^® HRD test. A prospective cohort of 124 newly diagnosed ovarian cancer patients was then analyzed. sWGS-derived GI status showed strong concordance with the reference test (95.8% overall agreement; κ = 0.913; NPV 100%, PPV 93.3%). Pathogenic BRCA1/2 variants were detected in 30 patients (24.19%). An additional 22.76% were BRCA1/2-negative but GI-positive, giving an overall HRD prevalence of 47.15%. Platinum sensitivity occurred in 90.0% (18/20) of HRD-positive patients with follow-up. Among 12 patients assessed for PARP-inhibitor response, the overall response rate was 66.7% (95% CI 39.1–86.2) and disease control rate 83.3% (95% CI 55.2–95.3). TP53 alterations were most frequent (62.90%), followed by BRCA1 (19.35%) and BRCA2 (4.83%). Pathogenic variants in other HR-pathway genes (ATM, CHEK2, BRIP1, RAD51C, BARD1) appeared in 9.57% of BRCA-wild-type cases, with heterogeneous GI impact. Two cases showed concurrent BRCA2 variants and microsatellite instability, indicating possible eligibility for anti-PD-1/PD-L1 therapy in addition to PARPi. This first comprehensive analysis of Romanian ovarian cancer patients suggests that integrating sWGS-based genomic instability assessment with BRCA testing can improve HRD detection and reflects the heterogeneity of HR-pathway variants. Preliminary clinical observations were consistent with known HRD-associated treatment responses, although larger studies are needed to confirm these findings. Full article

Hereditary breast and ovarian cancer (HBOC) syndrome accounts for 5–10% of all breast and ovarian cancers, with BRCA1 and BRCA2 pathogenic variants being the most common genetic alterations. However, additional genes such as BARD1, whose protein product interacts with BRCA1 via its N-terminal RING domain, have been implicated as low-penetrance contributors to cancer risk. This study aimed to investigate the frequency and distribution of the BARD1 variant c.1518_1519delinsCA (p.Val507Met) in a cohort of 920 patients undergoing genetic testing for hereditary cancer predisposition. Next Generation Sequencing (NGS) was performed using a 28-gene panel, and allelic frequencies of BARD1 were analyzed. Among 920 patients, 159 (17.28%) were pure heterozygous for the c.1518_1519delinsCA variant. Notably, c.1519G>A was never observed without c.1518T>C, suggesting a strong linkage between the two variants. The allele frequencies observed (34.51% for A at c.1519 and 77.88% for C at c.1518) challenge current reference genome expectations. Data from the ALFA database confirmed that these frequencies are consistent with population-level variation, not sample bias. Our findings raise the hypothesis that the reference allele at position c.1518 may not reflect the true wild-type sequence. While both c.1518T>C and c.1519G>A are individually classified as benign, their combined occurrence as a dinucleotide substitution (c.1518_1519delinsCA) warrants further investigation. These results underscore the importance of accurate variant annotation and population-specific frequency data for clinical interpretation of NGS findings. Although BARD1 remains a low-frequency contributor to HBOC compared to BRCA1/2, its inclusion in multigene panels is supported by the potential relevance of such complex variants. Full article

This study investigates the efficacy of large language models (LLMs) in supporting responsible and optimized geographic site selection for large-scale solar energy farms. Using Microsoft Bing (predecessor to Copilot), Google Bard (predecessor to Gemini), and ChatGPT, we evaluated their capability to address complex technical and social considerations fundamental to solar farm development. Employing a series of guided queries, we explored the LLMs’ “understanding” of social impact, geographic suitability, and other critical factors. We tested varied prompts, incorporating context from existing research, to assess the models’ ability to use external knowledge sources. Our findings demonstrate that LLMs, when meticulously guided through increasingly detailed and contextualized inquiries, can yield valuable insights. We discovered that (1) structured questioning is key; (2) characterization outperforms suggestion; and (3) harnessing expert knowledge requires specific effort. However, limitations remain. We encountered dead ends due to prompt restrictions and limited access to research for some models. Additionally, none could independently suggest the “best” site. Overall, this study reveals the potential of LLMs for geographic solar farm site selection, and our results can inform future adaptation of geospatial AI queries for similarly complex geographic problems. Full article