Search Results (80,346)

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) exhibits pronounced racial disparities in incidence and outcomes, yet the molecular basis remains poorly understood. Here, we examined racial differences in gene rearrangements (MYC, BCL2, BCL6), fusions (IGH::MYC, IGH::BCL2), and their interactions among White, Black, Asian, and Other-race groups in patients with DLBCL to uncover genetic drivers of disparities. Methods: We analyzed 919 DLBCL cases (2006–2023) from Johns Hopkins Hospital using fluorescence in situ hybridization to detect gene abnormalities. We used logistic regression and proportional odds models, adjusted for age and sex, to evaluate racial differences in five gene abnormalities and 10 gene–gene interaction pairs. Pearson’s Chi-squared and Goodman–Kruskal’s gamma tests assessed prevalence and interaction severity across racial groups. Results: MYC rearrangements and the MYC*IGH::MYC interaction were marginally more frequent in the White group than in Black and Other groups (p = 0.092, p = 0.098, respectively). IGH::BCL2 fusions were more prevalent in the Asian group than in the White group (p = 0.095), and the BCL2*IGH::BCL2 interaction was significantly higher in the Asian group (p = 0.049) than in the White group. Although high-grade B-cell lymphoma (HGBCL) prevalence showed no significant racial differences (p = 0.16), the Asian group exhibited a higher proportion of aggressive HGBCL with concurrent IGH::MYC and IGH::BCL2 fusions compared with the White group (p = 0.076). Age significantly influenced all gene abnormalities and interactions (p < 0.001–0.052), except for MYC rearrangements and specific pairs. Sex and sex–race interactions showed no significant effects. Conclusions: This study highlights molecular contributions to the racial differences in DLBCL disease. Further research collecting ancestry-specific biomarkers, treatment regimens, and clinical variables and outcomes is needed to advance personalized treatment strategies. Full article

Advances in additive manufacturing have accelerated the development of 3D-printed dental resin composites. These materials contain a higher proportion of organic matrix and less filler than light-cured representatives, which may affect their behavior in the oral environment. This study aimed to evaluate the biological and chemical properties of 3D-printed dental resin composites before and after artificial aging, and to compare them with the light-cured representative. Specimens from a light-cured composite (Omnichroma—OMCR) and two 3D-printed composites (GT Temp PRINT—GTPR; SprintRay CROWN—SPRY) were subjected to aging treatments: unaged (T0) or thermocycled for 5000 (T1) and 10,000 cycles (T2). Biological evaluation was performed using MTT assay and Live/Dead cell fluorescence microscopy using human gingival fibroblasts, whereas Raman spectroscopy analysed materials’ structural changes. Materials exhibited good biocompatibility (>70% cell viability), with OMCR displaying greater variability. OMCR was more susceptible to chemical degradation under thermal stresses than both 3D-printed materials. Tested 3D-printed composites can provide comparable or even superior biological and chemical properties compared to light-cured representative, likely due to optimized resin formulations and post-curing protocols that improve polymer network organization and reduce residual monomer release. These findings support the potential of tested 3D-printed composites for manufacturing dental restorations. Full article

This study investigated the long-term trends in human parainfluenza virus (HPIV) types 1, 2, and 3 in Korea by year, age group, and season. A total of 23,284 nasopharyngeal swabs collected from patients with respiratory symptoms at a tertiary hospital in Korea between 2007 and 2024 were tested for HPIV using real-time reverse-transcription polymerase chain reaction. Of the 23,284 specimens tested, 481 were positive for HPIV-1, 164 for HPIV-2, and 1102 for HPIV-3. HPIV-3 showed the highest incidence between 2010 and 2016, a decline after 2018, a sharp decline during the 2020 COVID-19 pandemic, and a resurgence in 2021. HPIV-1 and HPIV-2 incidence fluctuated between 2007 and 2019, followed by a sharp decline in 2020. HPIV-3 activity peaked in spring and summer, whereas HPIV-1 and HPIV-2 peaked in autumn. For all three types, infection rates were generally highest among children aged 1–12 years, followed by those in infants, but infection rates varied significantly by type, year, season, and age group. These findings emphasize targeted pediatric prevention, predictive modeling of seasonal peaks, and continued molecular surveillance to clarify the genetic and antigenic diversity of HPIV types after the pandemic, supporting the Sustainable Development Goals (SDG 3 for Good Health and Well-Being). Full article

Background: Chronic obstructive pulmonary disease (COPD) is a complex condition influenced by both environmental and genetic factors. Among the genetic determinants, polymorphisms in the CHRNA3/5 and EPHX1 genes have been implicated in nicotine dependence and susceptibility to COPD in several populations. However, evidence remains limited in admixed populations such as Brazilians. Methods: This cross-sectional study investigated the association between CHRNA3 (rs1051730, rs8034191) and EPHX1 (rs2234922) polymorphisms with tobacco nicotine dependence and COPD in a Brazilian cohort. Genotyping was performed using TaqMan^® SNP assays, and pulmonary function was assessed via spirometry according to ATS/ERS standards. Associations between genetic variants, tobacco intake, and COPD status were evaluated using χ² and Fisher’s exact tests, with odds ratios (ORs) and 95% confidence intervals (CIs). Post hoc power analyses were conducted to estimate detectable effect sizes. Results: A total of 123 active or former smokers were analyzed. The CHRNA3 variants (rs1051730 and rs8034191) showed a trend toward higher prevalence among individuals with heavy tobacco intake (>40 pack-years), though no significant allelic or genotypic differences were found between COPD and control groups (p > 0.05). The EPHX1 rs2234922 A allele was significantly more frequent in COPD patients, suggesting increased disease risk (p < 0.05), while the GG genotype appeared protective. Post hoc power analyses indicated moderate power (≈0.56–0.63) for the observed associations. Conclusions: In this Brazilian population, the CHRNA3/5 polymorphisms may influence nicotine dependence, while EPHX1 rs2234922 appears to be associated with COPD susceptibility. These findings support a potential genetic contribution to disease risk and tobacco nicotine dependence, warranting further large-scale studies to confirm these associations and explore their therapeutic implications. Full article

Background/Objectives: Due to the numerical dominance of environmental and commensal strains, understanding antimicrobial resistance (AMR) transmission in Escherichia coli requires consideration of non-clinical as well as pathogenic isolates. In this cross-sectional study, associations between the genetic context of non-clinical E. coli and AMR carriage are examined in isolates sampled from different niches within a One Health continuum. Methods: Two hundred eighty-eight E. coli isolates collected in Alberta, Canada (2018–2019) from wastewater, well water, feces of broiler chickens and feedlot cattle, and retail beef and chicken meat were selected from existing surveillance collections using a stratified random sampling structure. Using short-read whole genome assemblies, phylogenetic relationships were inferred from pan-genome multiple sequence alignments. Principal coordinate analysis and permutational analysis of variance (PERMANOVA) of a Jaccard dissimilarity matrix derived from gene presence/absence data were used to investigate contributions of source and AMR strata to observe genetic dissimilarity. Population clustering and gene under- or over-representation by source and cluster were also explored. Results: Minimal phylogenetic segregation of isolates was noted based on source or AMR strata, and both contributed significant but small proportions of observed genetic dissimilarity, with the largest proportion attributed to phylogroup. There was notable diversity of E. coli within and between sources; however, in some larger clusters, differential gene presence/absence was potentially linked to ecological niche rather than source of isolation. Conclusions: This study highlights the ecological complexity of AMR in E. coli in non-clinical contexts, offering a novel lens on how niche-specific factors can influence population structure and AMR carriage. It also provides insight into apparent discrepancies in the literature regarding clustering of E. coli by source. These findings support a more integrative One Health approach to AMR surveillance, emphasizing the need to account for microbial diversity and niche-specific adaptation across interconnected systems. Full article

The quality and flavor of chicken meat are fundamentally determined by muscle metabolite composition, which reflects the regulatory effects of genetic background on metabolic pathways and muscle development. In this study, we profiled the meat quality of breast muscle across 3 crossbreeding combinations (D×HD, HD×D, and D×LD) between the Yunong D line and Houdan chickens to elucidate the metabolic mechanisms underlying flavor variation. Eighteen representative breast muscle samples were analyzed using common physicochemical indexes, untargeted metabolomics based on Gas Chromatography-Time-of-Flight Mass Spectrometry (GC-TOF-MS) and Ultra-High-Performance Liquid Chromatography coupled with Quadrupole Exactive Mass Spectrometry (UHPLC-QE-MS). Differential metabolites were identified through Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). Multivariate analysis revealed distinct metabolic signatures among crossbreeding combinations, with HD×D exhibiting the most favorable tenderness, color, and water-holding capacity. A total of nine differential metabolites (5 upregulated and 4 downregulated) were identified between D×HD and HD×D, and thirty-eight metabolites (18 upregulated and 27 downregulated) between D×HD and D×LD. The identified metabolites were predominantly associated with amino acid metabolism, lipid biosynthesis, nucleotide turnover, and energy metabolism. Among these, arachidonic acid, taurine, L-alanine, and citric acid exhibited marked intergroup differences. Enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated significant involvement of pathways such as amino acid biosynthesis, taurine and hypotaurine metabolism, and ABC transporters in flavor formation. Hierarchical clustering and Pearson correlation analyses further delineated synergistic or antagonistic interactions among key metabolites, suggesting the existence of intricate regulatory mechanisms. These findings reveal critical metabolites and metabolic pathways associated with flavor attributes, offering both a theoretical framework and potential molecular targets for enhancing poultry meat quality through breeding strategies. Full article

Objective: Existing studies on short-chain fatty acids (SCFAs) and colorectal cancer (CRC) yield contradictory conclusions and are limited to single ethnic groups or sample types. This study aimed to (1) quantify associations between total SCFAs/subtypes (acetate, propionate, butyrate) and CRC/advanced colorectal adenoma (A-CRA) risks; (2) identify modifiers (ethnicity, sample type, intervention); and (3) clarify SCFA–gut microbiota interaction mechanisms via integrative Bayesian meta-analysis and multi-ancestry data integration. Methods: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science (inception to September 2025) using keywords: “Short-chain fatty acids”, “SCFAs”, “Colorectal cancer”, “CRC”, “Gut microbiota”, “Dietary fiber”, and “High-amylose maize starch butyrate”. Eligible studies included 14 peer-reviewed original studies (7 observational, cohort/case–control/cross-sectional; 7 RCTs) covering Europeans, Asians, and African Americans. Inclusion criteria: Quantitative SCFA data (total/≥3 subtypes), clear ethnic grouping, reported CRC/A-CRA risks or intervention outcomes. Exclusion criteria: Reviews, animal/in vitro studies, incomplete data, low-quality studies (Newcastle–Ottawa Scale [NOS] <6 for observational; high Cochrane risk for RCTs), or limited populations (single gender/rare genetics). A Bayesian hierarchical random-effects model quantified effect sizes (Odds Ratio [OR]/Mean Difference [MD], 95% credible intervals [CrI]), with heterogeneity analyzed via multi-ancestry stratification, intervention efficacy, and microbiota interaction analyses (Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] 2020; International Prospective Register of Systematic Reviews [PROSPERO]: CRD420251157250). Results: Total SCFAs were negatively associated with CRC (OR = 0.78, 95% CrI: 0.65–0.92) and A-CRA (OR = 0.72, 95% CrI: 0.59–0.87), with butyrate showing the strongest protective effect (CRC: OR = 0.63, 95% CrI: 0.51–0.77). Ethnic heterogeneity was significant: Europeans had the strongest protection (OR = 0.71), Asians had weaker protection (OR = 0.86), and African Americans had the lowest fecal SCFA levels and the highest CRC risk. Fecal SCFAs showed a stronger CRC association than serum/plasma SCFAs (OR = 0.73 vs. 0.85). High-Amylose Maize Starch Butyrate (HAMSB) outperformed traditional fiber in increasing fecal butyrate (MD = 4.2 mmol/L vs. 2.8 mmol/L), and high butyrate-producing bacteria (Clostridium, Roseburia) enhanced SCFA protection (OR = 0.52 in high-abundance groups). Conclusions: SCFAs (especially butyrate) protect against CRC and precancerous lesions, with effects modulated by ethnicity, sample type, and gut microbiota. High-Amylose Maize Starch Butyrate is a priority intervention for high-risk populations (e.g., familial adenomatous polyposis, FAP), and differentiated strategies are needed: 25–30 g/d dietary fiber for Europeans, 20–25 g/d for Asians, and probiotics (Clostridium) for African Americans. Future Perspectives: Expand data on underrepresented groups (African Americans, Latinos), unify SCFA detection methods, and conduct long-term RCTs to validate intervention efficacy and “genetics-microbiota-metabolism” crosstalk—critical for CRC precision prevention. Full article

A new species of Encotyllabe Diesing, 1850 (Monopisthocotylea: Capsalidae), Encotyllabe tantaliani n. sp., is described from the pharyngeal plates of the Lorna drum, Sciaena deliciosa (Tschudi, 1846) (Eupercaria: Sciaenidae), collected from two localities along the Peruvian coast. This new species was originally proposed as E. callaoensis Tantaleán, 1974, in an unpublished doctoral thesis, and is herein recognized as a nomen nudum under the International Code of Zoological Nomenclature (ICZN). Encotyllabe tantaliani n. sp. is distinguished from all known congeners by the following combination of morphological features: (1) an anteriorly tapering body proper, (2) slightly lobed testes markedly larger than the ovary, (3) vitelline follicles beginning at the level of the male copulatory organ (MCO) and absent from the regions of the reproductive organs, (4) a genital pore positioned posterolateral to the pharynx, and (5) an oblong-shaped MCO. Phylogenetic analysis based on cox1 sequence places E. tantaliani n. sp. in a clade with Encotyllabe percussa Morales-Ávila, Jufaili & Ogawa, 2024, a parasite of Lethrinus nebulosus (Forsskål, 1775) (Eupercaria: Lethrinidae) from the Arabian Gulf. Pairwise genetic distances support the distinctiveness of the new species from its closest congeners. Encotyllabe tantaliani n. sp. represents the first species of the genus described from a host belonging to the Sciaenidae host. Full article

Breeding value estimations of Warmblood horses in Poland are based on field performance, but the amount of stallions’ data is still insufficient (334 horses). The first study’s aim is to compare stallions’ results in different stages and evaluate the overall ability using both stages. The effects on preselection (first stage free movement) and performance tests (second stage under rider) were analyzed separately and together as the overall ability. Spearman correlations were evaluated. The second aim was to evaluate the training period on the results. Due to the pandemic and lack of tests, horses had different training periods during the six years studied. The combined year-place effect, horse specialization group, and birth country had effects on four of twelve traits. The regression on age influenced only the preselection jumping trait (p = 0.04), while the training period influenced canter (p = 0.04) and “success” (passed/or not) in the performance test (p = 0.04). It seems that the training period and horse age are more significant for young horses’ performance. The correlations between stages for the same traits are moderate for gaits (<0.53) and low for jumping (<0.3). Thus, at least on a basic phenotypical level, results do not correspond strongly with each other. Full article

Background/Objectives: The clinical presentation of homozygous familial hypercholesterolemia (HoFH) and severe heterozygous familial hypercholesterolemia (sHeFH) often demonstrates substantial overlap, as low-density lipoprotein cholesterol (LDL-C) levels may fall within similar ranges in both conditions. Methods: In this single-center 10-year retrospective study at the University of Debrecen, Hungary, we present the clinical characteristics of patients with 6 HoFH and 6 sHeFH diagnosed by genetic testing, discuss the diagnostic limitations encountered in clinical practice, and outline the key components of therapeutic management. Results: The mean age at diagnosis was lower in the HoFH group (31.83 ± 19.5 vs. 41.83 ± 15.9 years). The differences in total cholesterol (13.48 ± 7.4 vs. 11.02 ± 3.5 mmol/L) and LDL-C levels (10.89 ± 6.6 vs. 8.58 ± 3.26 mmol/L) between the groups were not statistically significant. Interestingly, vascular complications were more frequent in sHeFH group as well (4 vs. 1 patients). In neither the HoFH nor the sHeFH group were we able to achieve the target LDL-C levels, due in part to the specific features of the reimbursement system, patient and parental preferences, the extremely high baseline LDL-C levels, and certain genetic characteristics. Conclusions: Our findings highlight the importance of genetic testing-based personalized therapy in these specific patient subpopulations. We emphasize that serum LDL-C alone is insufficient to distinguish between HoFH and sHeFH patients, and that therapeutic challenges should be anticipated in both groups arising partly from limited patient adherence as well as from financial constraints. Full article

Killer-cell immunoglobulin-like receptors (KIRs) play a crucial role in the cytotoxic activity of natural killer (NK) cells, encompassing both inhibitory and activating types. A higher ratio of cytotoxic to inhibitory receptors may harm successful pregnancies by disrupting the uterine environment. Ongoing debates surround the impact of KIR gene variations on recurrent pregnancy loss (RPL) and infertility across populations. This study aimed to explore KIR gene polymorphisms in RPL and infertility among the Venezuelan admixed population. The Venezuelan population exhibits a genetic mix of Caucasian, African, and local Amerindian ancestry, distinguishing it from other Latin American admixed populations. This study included 100 controls and 86 patients: 73 women with idiopathic RPL (53 primary and 20 secondary) and 13 infertile patients (4 primary and 9 secondary). The frequency of activating receptors KIR2DS2 and KIR2DS3 was significantly lower (p < 0.05) in the whole patient group compared to controls. However, when analyzing the haplotypes and genotypes, the significance between patients and controls was lost. When comparing RPL and infertile patients, KIR2DS2, KIR2DL3, 2DL5, and 3DL1 were significantly less frequent in infertile women. In infertile women, KIR2DS3 frequency was increased compared to controls and RPL. The results suggest that the frequency of inhibitory receptors may differentiate patients with RPL and infertility. Further studies should ascertain the expression and function of KIRs in uterine NK cells in patients with RPL and infertility. Full article

Enterocytozoon bieneusi is the most frequently diagnosed microsporidian parasite in humans and a recognized cause of diarrheal disease, particularly in immunocompromised individuals. Its broad host range, which includes livestock, companion animals, and wildlife, highlights its zoonotic potential and warrants careful epidemiological assessment. This narrative review synthesizes available data on the occurrence and genetic diversity of E. bieneusi in European domestic ungulates (cattle, pigs, sheep, goats, horses, and water buffaloes) and pets (dogs and cats), aiming to provide an integrated perspective on animal reservoirs and their relevance for public health. Publications retrieved from the Web of Science Core Collection database were systematically screened, and country-specific results were extracted, emphasizing prevalence rates, genotype distributions, and zoonotic implications. Across Europe, cattle and pigs emerged as the most studied hosts, frequently harboring zoonotic group 1 genotypes such as I, J, BEB4, BEB6, and EbpA, while small ruminants, horses, and buffaloes remain comparatively undocumented. In pets, the dog-adapted genotype PtEb IX was predominant, but several zoonotic genotypes were also identified. Overall, the current evidence confirms the wide host range of E. bieneusi in Europe but also reveals significant data gaps compared to regions such as China, underlining the need for broader surveillance and harmonized molecular approaches within a One Health framework. Full article

Background: Germline genetic variants impacting splicing are a frequent cause of disease. The clinical interpretation of such variants is challenging for many reasons including the immense complexity of splicing mechanisms. While recent advances in splicing algorithms have improved the accuracy of splice prediction, predicting the nature and abundance of aberrant splicing remains challenging. As RNA testing becomes more mainstream in the clinical diagnostic setting, the complexities of interpretation are coming to light. Methods: Data from patients undergoing concurrent DNA and RNA testing were retrospectively reviewed for unusual splicing impacts to underscore some of these complexities and serve as exemplars in how to avoid pitfalls in the interpretation of sequence variants. Results: Seven rare variants with unusual splicing impacts are presented: a variant at a consensus donor nucleotide position lacking a splice impact (NF1 c.888+2T>C); a mid-exonic missense variant creating a novel donor site and a cryptic acceptor site resulting in pseudo-intronization (BRIP1 c.727A<G p.Ile243Val); one variant creating a spliceosome switch from U12 to U2 (LZTR1 c.2232G>A p.Ala744Ala); two variants that would be expected to result in nonsense-mediated-mRNA-decay triggering splicing impacts that obviated nonsense-mediated-decay (APC c.1042C>T p.Arg348Ter and BRCA2 c.6762del; c.6816_6841+1534del); and two variants causing splicing impacts through pyrimidine tract optimization (NF1 c.5750-184_5750-178dup and ATM c.3480G>T p.Val1160Val). Conclusions: Paired DNA and RNA testing revealed unexpected splice events altering variant interpretation, expanding our knowledge of clinically important splicing mechanisms and highlighting the benefit of RNA testing. Full article

Ambiguity Resolution (AR) is regarded as an effective technique for enhancing positioning accuracy and reducing convergence time in Precise Point Positioning (PPP). However, the Wide-Lane Fractional Cycle Bias (WL FCB) and Narrow-Lane Fractional Cycle Bias (NL FCB) needed for AR are generated from network solutions based on numerous globally distributed stations, leading to considerable computational load and processing time. A prediction model for FCB is proposed using the Genetic Algorithm Optimized Backpropagation Neural Network (GA-BPNN), and high-precision predictions of WL and NL FCB for Day of Year (DOY) 321 in 2023 are successfully achieved. Comparisons with iGMAS products show that predicted WL FCB deviations are within 0.01 cycles, and predicted NL FCB over 12 h deviates within 0.1 cycles (excluding satellite C20). The performance of three PPP schemes, Float, Fixed (based on FCB from iGMAS), and BP-Fixed (based on FCB predicted by GA-BPNN), is compared through experiments. For GPS + BDS-3, the accuracies of the BP-Fixed scheme are 0.0034 m, 0.0039 m, and 0.0100 m in the east, north, and up directions, respectively. The ambiguity fixed rates reach 98.62% for BP-Fixed. These outcomes confirm that the positioning performance using the predicted FCB of GA-BPNN is highly consistent with that using FCB products. Full article

To address the low efficiency and high subjectivity of manual interpretation in fluorescence in situ hybridization (FISH) tissue and cell images, this study proposes an intelligent FISH image classification model based on an improved ResNet50 architecture. By analyzing the characteristics of multi-channel fluorescence signals and the bottlenecks of clinical interpretation, a Convolutional Block Attention Module (CBAM) is introduced to enhance the representation of salient fluorescence features through dual channel–spatial attention mechanisms. A Pyramid Pooling Module (PPM) is integrated to fuse multi-scale contextual information, improving the detection accuracy of small targets such as microdeletions. Furthermore, the shortcut connections in residual blocks are optimized to reduce feature loss. To mitigate the limitation of insufficient annotated samples, transfer learning is employed, combined with a focal loss function to enhance classification performance under class-imbalanced conditions. Experiments conducted on a clinical dataset of 12,000 FISH images demonstrate that the proposed model achieves an overall classification accuracy of 92.4%, representing a 9.9% improvement over the original ResNet50. The recall rate for complex categories (e.g., translocation and fusion) exceeds 90.7%, with an inference time of 22.3 ms per sample, meeting the real-time requirements of clinical diagnosis. These results provide an efficient and practical solution for the automated intelligent interpretation of FISH images, offering significant potential for precision-assisted diagnosis of tumors and genetic disorders. Full article