Search Results (20,973)

Diagnosing wheat allergy remains challenging due to the use of oral wheat provocations, which implicate risks to patients and highlights the need for safer, non-invasive diagnostic methods. Here, we present the first direct comparison of a pediatric and adult cohort to study wheat allergy and wheat tolerance using an improved and validated basophil activation test (BAT). Blood samples from 24 children and 26 adults, clinically classified as facing oral food challenges, were analyzed using our bin-based BAT, enabling standardized data analysis and visualization. In children, the BAT showed significantly higher median basophil activation in wheat-allergic compared to wheat-tolerant individuals. Receiver operating characteristic analysis revealed that BAT responses to wheat, gluten, and gliadin extracts (area under the curve (AUC): 0.71–0.73) had greater diagnostic accuracies than extract-based wheat and gluten-specific immunoglobulin E (sIgE) measurements (AUC: 0.69, 0.70). However, Tri a 19-sIgE, showed the highest diagnostic performance (AUC: 0.97). In adults, BAT responses did not differ significantly between allergic and tolerant individuals. The bin-based BAT is a robust and reproducible diagnostic tool for wheat allergy diagnosis with automated data analysis capabilities. Significant differences were only evident in the pediatric cohort, indicating age-related immunological differences in basophil responsiveness or immune sensitization profiles. These differences could be linked to immune system maturation, variations in immunoglobulin E (IgE) avidity, or differential expression of the high-affinity IgE receptor (FcεRI) on basophils. While Tri a 19 sIgE was the best single predictor in children, its clinical utility remains controversial due to conflicting results in the scientific literature. Full article

Achieving successful primordial germ cell (PGC)-based genome editing requires a deep understanding of their molecular identity. For the first time, a comparative transcriptomic analysis of chicken PGCs and adult liver cells to define their specific gene expression signature was performed. PGCs were isolated from Rhode Island Red chicken embryos, cultured, and subjected to RNA sequencing alongside liver tissue. Differential expression analysis with Benjamini–Hochberg correction identified 1909 differentially expressed genes (DEGs). Functional annotation revealed that PGCs possess a unique transcriptional landscape, characterized not only by enhanced proliferation and metabolic activity but also by a profound molecular convergence with neural crest cells. This is evidenced by the upregulation of gene modules governing long-range migration, neuronal signaling, and specialized “neuro-lipid” metabolism (e.g., sphingolipid and plasmalogen pathways). Additionally, we identified unannotated transcripts linked to immune pathways and ciliary signaling. Our study expands the functional annotation of avian PGCs and reveals an unexpected evolutionary recruitment of conserved morphogenetic programs, providing a refined molecular foundation for advanced germline editing technologies. Full article

Background and Objectives: Glioblastoma (GBM) is the most aggressive form of primary brain tumor, characterised by high recurrence rates and poor patient prognosis. This study aimed to identify gene-expression signatures and molecular networks associated with primary and recurrent GBM to better understand the biological mechanisms underlying tumor progression. Materials and Methods: Gene expression analysis of TCGA data was conducted to identify differentially expressed genes across tumor, recurrent, and normal brain tissues. Analysis of overlapping differentially expressed gene sets revealed both common and specific gene-expression profiles across the groups, highlighting genes potentially involved in GBM recurrence. Gene network and canonical pathway analyses were performed using Ingenuity Pathway Analysis (IPA) to identify key pathways and cellular functions altered in GBM. Results: Our data identified distinct molecular signatures in tumor, recurrent, and normal brain samples, highlighting dysregulated genes associated with cellular growth, proliferation, and movement. Transcriptomic stratification revealed progressive tumor- and recurrence-adapted states, with composite Tumor Scores (TS) and Recurrence Scores (RS) classifying samples into four classes: normal-like, proliferative, transitional, and recurrence-adapted tumor states. Conclusions: These findings provide insights into the signaling networks and biological mechanisms underlying GBM recurrence and may guide the identification of potential therapeutic targets to improve the management of this malignancy. Full article

Background/Objectives: The elongated egg is a morphological mutant of silkworm (Bombyx mori) eggs, yet the biochemical processes and molecular mechanisms underlying this trait remain unclear. Methods: In this study, we performed transcriptome sequencing on the ovaries of female pupae from the Nistari silkworm strain (comparing normal and elongated eggs) during the first three days post-pupation using high-throughput sequencing. Results: A total of 153.56 Gb of filtered data was obtained, identifying 23,366 genes and 35,798 mRNAs. Comparative analysis across three control groups revealed 374 differentially expressed genes (DEGs), with 131 upregulated and 243 downregulated genes in the elongated egg group. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were primarily associated with protein hydrolysis, DNA metabolic processes, and euchromatin/heterochromatin organization. Trend expression analysis revealed that transcriptional activity in elongated eggs was significantly higher than in normal eggs, particularly on day 3 of the pupal stage. Conclusions: Weighted gene co-expression network analysis (WGCNA) classified gene expression patterns into twelve modules, with two modules showing specificity. Thirteen hub genes were identified, which are functionally linked to translation initiation, protein density regulation, post-translational modification, and protein turnover. These findings provide foundational insights into the molecular mechanisms driving the formation of the elongated egg in silkworms. Full article

Background/Objectives: This study aimed to compare the biological effects of two amelogenin-derived peptides—the leucine-rich amelogenin peptide (LRAP) and a synthetic peptide (SP)—on human dental pulp stem cells (hDPSCs) and human bone marrow–derived mesenchymal stem cells (hBMSCs). The investigation focused on cell viability, osteogenic differentiation, mineralization, gene expression, and β-catenin expression. Methods: hDPSCs and hBMSCs were cultured in osteogenic medium and treated with LRAP and SP at 1, 5, 10, 50, and 100 ng/mL. Cytotoxicity was assessed by MTT assay, while osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity and Alizarin Red S staining. Gene expression of RUNX2, COL1A1, OCN, MEPE, and DMP1 was quantified by qPCR. β-catenin localization was analyzed by immunofluorescence. Statistical analysis was performed using one-way ANOVA with Tukey’s post hoc test (p < 0.05). Results: Both peptides exhibited good biocompatibility with hBMSCs, while high concentrations (≥50 ng/mL) reduced hDPSC viability. In both cell types, LRAP and SP increased ALP activity and mineral deposition in a concentration-dependent manner, with the greatest effects at 10 ng/mL. LRAP significantly upregulated osteogenic (RUNX2, COL1A1, OCN) and odontogenic (MEPE, DMP1) gene expression in hDPSCs. Immunofluorescence revealed nuclear β-catenin translocation in hDPSCs and membrane-associated accumulation in hBMSCs, indicating activation of canonical and non-canonical pathways, respectively. Conclusions: LRAP and SP promote osteogenic differentiation through distinct cell-type-specific signaling mechanisms, highlighting their potential as biomimetic agents for mineralized tissue regeneration. Full article

Background/Objectives: Lung cancer remains the leading cause of cancer-related deaths worldwide, with Non-Small Cell Lung Cancer (NSCLC) accounting for the majority of cases, primarily Squamous Cell Carcinoma (SCC) and Adenocarcinoma (ADC). The aim of this systematic review is to summarise and critically appraise the performance of machine learning (ML)-based radiomics models in the differential diagnosis and overall survival analysis for lung SCC and ADC. Methods: PRISMA standards were followed in conducting the review. The quality of the studies was assessed using the Radiomics quality score (RQS) tool. Results: A total of 11 studies were included, demonstrating that deep learning and radiomics-based machine learning models significantly improve the non-invasive classification of lung squamous cell carcinoma and adenocarcinoma. Deep learning systems achieved an accuracy of 67–97%, and machine learning models showed an accuracy of 75–87%. The integration of radiomic features further enhanced diagnostic precision, showing strong potential for reliable histologic subtype differentiation. Conclusions: Machine learning-based radiomics models and deep learning significantly enhance the non-invasive, accurate differentiation of lung squamous and adenocarcinoma cell carcinoma when combined with clinical and pathological data. Full article

Global warming has become one of the most serious threats to biodiversity. However, the responses of endangered tree species in subtropical regions to climate change and their potential distribution shifts remain elusive. In this study, we selected nine rare and endangered tree species in the subtropical forests of China encompassing both coniferous and broad-leaved groups, and conducted an assessment of their suitable distribution patterns and spatial shifts under current and future climate scenarios (SSP126, SSP370, and SSP585). For this we utilized an optimized MaxEnt model integrating multidimensional environmental variables including climate, soil, and topography. The results show that the model has high predictive accuracy after parameter optimization, with mean AUC values exceeding 0.98 for both broad-leaved and coniferous tree species. Our analysis of environmental factors indicates clear differences in distribution-limiting factors between the two functional groups. Broad-leaved species are primarily constrained by temperature-related variables, particularly the mean temperature of the coldest quarter (Bio11) and the mean diurnal range (Bio2), whereas coniferous species are more sensitive to moisture conditions, with the precipitation of the driest quarter (Bio17) as the key limiting factor for their potential distributions. Under current climatic conditions, highly suitable habitats for both functional groups are mainly concentrated in the middle and lower reaches of the Yangtze River. Under future climate scenarios, broad-leaved species are in general expected to expand in marginal areas, while coniferous species show pronounced scenario dependence, with significant contractions occurring under certain scenarios and time periods. Despite the evident changes at distribution margins, the overall shifts in the centroids of potential distributions for both functional groups will be limited, with core suitable areas remaining relatively stable. This study reveals differences in the spatial response patterns between conifers and broad-leaved trees, and provides a scientific basis for the development of differentiated conservation strategies and the identification of conservation priority areas under climate change. Full article

Background/Objectives: Allergic features of anisakiasis, caused by ingestion of third-stage larvae of Anisakis simplex via raw or undercooked fish, manifest clinically as acute gastroallergic anisakiasis (GAA) or chronic urticaria with Anisakis sensitization (CU+). Differentiating these clinical phenotypes remains challenging. This study aimed to evaluate the maturation and avidity of specific antibodies (IgE, IgG4, IgG, and IgA) as biomarkers for discriminating between acute and chronic forms of anisakiasis. Methods: A prospective cohort of 65 patients from Madrid, Spain, was classified into three groups: GAA (n = 22), CU+ (n = 22), and chronic urticaria without sensitization (CU−, n = 21). Serum samples were analyzed for antigen-specific immunoglobulins using ELISA and Western blot. Avidity indices (AIs) were quantified through urea dissociation assays. Statistical comparisons and correlation analyses were performed to associate antibody avidity with clinical phenotype and demographic variables. Results: GAA patients exhibited significantly lower IgE avidity indices compared to CU+ individuals (mean AI: 79.9% vs. 88.5%), indicating a less mature IgE response during acute infection. Conversely, IgG4 and IgG avidity were elevated in GAA relative to CU+, reflecting an active but transient immune response. IgA antibodies were detected in both groups, although avidity differences lacked discriminatory capacity. No sex- or age-related differences in antibody avidity were observed. Longitudinal follow-up of GAA patients demonstrated an increase in IgE avidity over time. Conclusions: Quantitative assessment of antibody avidity, particularly for IgE and IgG4, enhances understanding of A. simplex immunopathogenesis and serves as a valuable biomarker for distinguishing acute from chronic clinical presentations. These findings support the use of avidity indices in the diagnosis, staging, and clinical management of anisakiasis. Full article

In order to explore the main regulatory genes and related pathways of growth traits, transcriptome sequencing was performed on the hypothalamus, pituitary, and liver tissues of 12-month-old greater amberjack (Seriola dumerili) with different growth rates. In total, 504 (118 up- and 386 down-regulated), 556 (283 up- and 273 down-regulated), and 699 (224 up- and 475 down-regulated) differentially expressed genes (DEGs) were identified in the hypothalamus, pituitary, and liver tissues, respectively. GO and KEGG pathway analyses revealed significant differences in the expression of several genes involved in growth, metabolism, and immune-related pathways. The mRNA expression levels of genes related to growth (ghrh, ghra, igf1), cell proliferation (fgf19, fgfr4, mapk8b, map2k4b, and map4k3), and lipid metabolism (acsl5, dgat2, lipeb, cyp7a1, and fabp10a) were up-regulated in the fast-growing (FG) group, while the cartl and sst1.1 were down-regulated. Conversely, genes associated with glycolysis (fbp1a, pklr, pgm2), citrate cycle (aclya, idh1), and immune-related pathways (irf1b, cxcl10, tnfb, lysg, ifi44, mapk11, and mapk12b) were up-regulated in the slow-growing (SG) group. These findings indicate that the FG exhibited greater lipid metabolism capacity and cell proliferation ability, while the SG expended additional energy to cope with environmental stress, with hindered growth during immune response. This study enhances our understanding of the genetic mechanisms underlying differences in growth rates and provides essential gene resources for future growth-related molecular breeding programs in greater amberjack. Full article

Ex vivo human tooth culture models preserve the native dentine–pulp complex and offer a translational platform to study pulp-capping biomaterials. This systematic review aimed to synthesize the evidence on histological pulp tissue responses to calcium silicate-based cement (CSCs) used for direct pulp capping in human tooth culture models. The review followed PRISMA 2020 guidance. Eligible studies were ex vivo whole human tooth culture models with direct pulp exposure treated with commercial or experimental CSCs and reporting histological outcomes. Risk of bias was assessed using the QUIN tool. Thirteen studies were included. Most used immature human third molars (from 15- to 19-year-old patients) and culture periods up to 28 days, with a minority extending observation to 45–90 days. Across hydraulic CSCs, Biodentine was the most frequently evaluated material, followed by ProRoot MTA and several experimental hydraulic and resin-modified formulations. Overall, hydraulic CSCs were consistently associated with biocompatible pulp responses and a pro-mineralization pattern characterized by periexposure mineralized foci/osteodentin-like tissue; where assessed, immunohistochemistry supported odontoblast-like differentiation. In contrast, the resin-modified CSC TheraCal LC and other experimental resin-modified CSCs showed more heterogeneous findings, with reports of absent, delayed, or less prominent mineralization compared with reference hydraulic CSCs. In intact human tooth culture models, hydraulic CSCs show reproducible biocompatibility and early mineralization features consistent with reparative dentinogenesis, whereas resin-modified CSCs demonstrate more variable histological performance. Full article

Historically, methods to detect subclinical mastitis have been used to aid treatment decisions. The limitations of these tests have led to the exploration of the use of differential somatic cell count (DSCC). The objective of this study was to evaluate the relationship between DSCC and antibiotic success in subclinically infected cows. Cows were pre-screened to confirm an SCC ≥ 200,000 cells/mL and a positive bacterial culture. At enrollment, aseptic quarter milk samples were collected for culturing and evaluated using SCC, DSCC, the California Mastitis Test (CMT), and electrical conductivity. Enrolled quarters were treated with an intramammary antibiotic and resampled 7-, 14-, 28-, and 35-days post-treatment and retrospectively classified as “Cured” or failed to cure (Failed) based on a bacteriological cure. The overall cure rate was 51.5%. Pre-treatment SCC, total leukocyte count (TLC), neutrophils, and CMT were lower in Cured quarters compared to Failed. Meanwhile, macrophage percentage was greater in Cured quarters compared to Failed. No difference was found between lymphocyte percentage and conductivity. When evaluating the use of multiple threshold optimizations to predict cure outcome, TLC tended to have the highest ranking for the metric of interest; however, SCC tended to numerically perform as well in sensitivity and specificity outside of the optimized parameter. Full article

Background/Objectives: Spinal excitability may undergo adaptive modulation in response to training load, sport-specific demands, and fatigue. While high-impact sports are known to influence reflex responsiveness, the extent to which these changes differ from athletes in lower-impact disciplines remains unclear. This study aimed to investigate post-exercise changes in Hmax/Mmax ratio among trained runners with varied sport backgrounds, and to identify emergent physiological profiles that may reflect differential spinal adaptation to fatigue. Methods: Twenty-two trained athletes underwent unilateral H-reflex testing before and after treadmill running performed to voluntary exhaustion. Amplitudes of the H-reflex and M-wave were recorded, and Hmax/Mmax ratios were analyzed. Based on a physiologically relevant threshold commonly used to distinguish normal from suppressed reflex amplitudes, participants were post hoc classified into three groups: Group A (pre- and post-test ratios above threshold), Group B (pre above, post below), and Group C (both below). A two-way repeated-measures ANOVA was used to assess between-group effects. Results: Significant differences were found across groups and conditions (p < 0.001). Group A maintained reflex ratios above the threshold, indicating stable excitability. Group B showed the greatest suppression (approximately 66%), transitioning from normal to subthreshold values. Group C remained consistently below-threshold. A significant interaction (p < 0.0001) confirmed that reflex modulation varied by physiological profile. A small but statistically significant reduction in H-reflex latency was also observed; however, this change remained within normal physiological variability. Conclusions: Postexercise H-reflex modulation revealed heterogeneous neuromuscular responses among athletes. These findings may contribute to understanding how sport-specific demands and fatigue shape spinal excitability and may help identify individuals with adaptive or potentially pathological profiles relevant to sports diagnostics. Full article

Background: Comparing biological properties among related proteins has traditionally benefited research in areas such as biomedicine, phylogeny and evolution. Moreover, these kinds of properties have significantly increased as a result of the development of open-access resources and databases. In this context, the multiple sequence alignment (MSA) methods continue to be extensively applied to compare protein sequences and to identify evolutionarily conserved regions. Methods: In this work, we present INPROF, a novel web server designed to centralize and automate the computation of a large collection of features derived from protein sequences. This tool allows us to deeply analyze protein relationships and their conserved information by comparing them through their MSA. Specifically, this platform computes up to 46 different metrics including information at several proteomic levels (categories) like sequences, structures, domains or ontological terms. INPROF was designed to enable bioinformaticians and researchers to create a complete catalogue of features for subsequent prediction and artificial intelligence modeling based on proteins. The INPROF web server and source code are freely available. Results: INPROF were validated by predicting disease’s severity in several RNA-Seq datasets from COVID-19 patients. Specifically, INPROF were extracted from canonical proteins related to differentially expressed genes. Classification performance proved that INPROF were able to accurately classify COVID-19 severity, even outperforming classical classification with expression data. Conclusions: INPROF web server is a flexible platform designed to compute 46 quantitative metrics describing protein interactions which provide biologically meaningful characteristics applicable to downstream classification and prediction algorithms. Full article

Background: Pediatric bronchoscopy and bronchoalveolar lavage (BAL) are valuable procedures, used by pediatric pulmonologists in a wide variety of clinical scenarios. Reports of indications for BAL include investigations of infectious processes, for unusual or poorly responsive pneumonia, and non-infections reasons, including interstitial lung disease and aspiration syndromes. BAL in pediatric asthma is occasionally done in severe and uncontrolled asthma, to rule out co-morbid conditions or to investigate asthma phenotypes. We report here the results of BAL in young children with global pre-BAL diagnoses, with comprehensive analysis of the BAL cellularity and culture results, and with a post hoc review by an allergist. The results of BAL in children with enigmatic pulmonary processes were compared to the expected BAL cellularity in normal children, obtained by an expanded historical mini review. Methods: The initial objective was to perform a mini review of the collective published data for normal/control children with BAL differential cell counts with the purpose of using the results to compare normals to the information obtained on the symptomatic children with BAL results from pulmonologists in our combined allergy–pulmonary division. The exploratory study group was children 0–6 years of age who underwent a BAL from 2000 to 2024 at an academic pulmonary-allergy division. The children had presumptive diagnoses requiring investigation, including the most common diagnoses of asthma, chronic cough, aspiration, or refractory bronchitis, and in this post hoc protocol only the diagnoses provided on the pre- and/or post-operative summary by the divisional pulmonologist(s) performing the BAL were used in the post hoc analysis. Secondarily, the operative day pre- and/or post-lavage diagnoses were used to divide the children into groups (based on operative day diagnoses) to stratify their lavage results, based on eosinophils, neutrophils, culture positivity and lipid-laden macrophages. Normative data collected from the literature was used as the historically expected results for the BAL group(s) analysis. Results: A mini review of BAL cellularity across 25+ years of literature was performed to establish normative data for our subsequent analysis. Both eosinophils and neutrophils are low or absent in normal children based on the comprehensive literature review. As a part of a larger cohort of 500 children ages 0–20 years, 317 children ages 0–6 were selected for review. The protocol was approved by the University Institutional Review Board. Using the mini review as reference, we found that eosinophil counts of one or more were recovered in over 20% of all children, regardless of bronchoscopy indication. Neutrophilia > 50% of cells and/or bacteria colony counts > 100,000 organisms were also frequent findings (>50 percent of the children). As a separate observation, lipid-laden macrophages did not isolate to aspiration indications for the bronchoscopy and lavage. Conclusions: An updated mini review of the cellularity expected in control children provided a context to the findings in our studied exploratory sample population. There was a high recovery of neutrophils coupled with culture positivity found across all children undergoing BAL. Eosinophils > 1 were present in up to 25% with a pre-lavage asthmatic symptom indication, but almost an equal percentage in other children with non-asthma-like conditions was surprising. Lipid-laden macrophage data was unhelpful. Full article

This study evaluates how solution treatment and aging influence the deformation mechanisms, phase transformations and functional performance of NiTi alloys produced by laser powder bed fusion (LPBF). Tensile tests performed at room temperature (RT) and −20 °C (LT) were combined with Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) analyses to correlate mechanical response with transformation thermodynamics and microstructural evolution. In the as-fabricated (AF) condition, deformation is governed by twinning and martensitic plasticity due to suppressed stress-induced martensite (SIM). Solution treatment (ST) restores reversible SIM at RT and preserves partial recoverability at LT as a result of microstructural homogenization and internal stress relief. Aging at 500 °C (A1h, A20h) promotes Ni₄Ti₃ precipitation, increasing transformation temperatures and stabilizing martensite, which leads to entirely irreversible deformation at both temperatures. These findings establish a clear functional continuum—ranging from recoverable (ST) to dissipative (AF) and fully irreversible (A20h) behavior—and provide a mechanistic framework for tailoring LPBF NiTi components for actuators, energy-storage and energy-dissipation applications. Full article