Search Results (156)

Gastric cancer traditionally affects older adults, and its precursor lesions and risk factors are well-documented in this population. Helicobacter pylori (H. pylori) infection remains highly prevalent in Saudi Arabia and contributes to gastric pathology. However, early-onset gastric cancer (EOGC), diagnosed in individuals aged ≤ 45 years, presents unique challenges and remains poorly understood in young populations. Therefore, we conducted an observational cohort study using a prospective longitudinal design (2021–2024) involving 1823 Saudi nationals aged 18–45 years who underwent zoom high-definition chromoendoscopy to evaluate the prevalence of premalignant gastric lesions (PGLs) and EOGC. We found a high H. pylori prevalence (78.0%) with PGLs in 1.9% of participants and EOGC-adenocarcinoma in 0.7% of patients. All EOGC cases arose from dysplasia, with most PGLs being classified as OLGA/OLGIM stage II/III. Multiple risk factorswere significantly associated with PGLs and EOGC, including H. pylori infection (p = 0.022), increasing age (p < 0.001), a family history of gastric cancer (p < 0.001), poor dietary habits (p < 0.001), obesity (p < 0.001), and smoking (p < 0.001). Additional EOGC risk factors include dage of 36–45 years (p = 0.018), EBV infection (p = 0.016), and diabetes mellitus (p = 0.001). These findings demonstrate the notable presence of PGLs and EOGC in young Saudi adults and emphasize the importance of early detection and risk factor management in this vulnerable population. Full article

Acinetobacter baumannii has emerged as a major pathogen responsible for healthcare-associated infections, particularly in intensive care units, contributing to significant morbidity and mortality due to its multidrug resistance and ability to persist in clinical environments. This study aimed to investigate the phenotypic and genomic characteristics of all multidrug-resistant A. baumannii isolates collected between January and June 2022 from two tertiary care hospitals in Thessaloniki, Greece. A total of 40 isolates were included. All isolates exhibited resistance to colistin; however, none harbored the mcr-1 to mcr-9 genes, as confirmed by polymerase chain reaction (PCR). PCR-based screening for virulence-associated genes revealed high prevalence rates of basD (100%), pld (95%), csuE (87.5%), and bap (77.5%). In contrast, ompA and pglC were not detected. Twitching motility ranged from 2 to 50 mm, with 25% of the isolates classified as non-motile and 20% as highly motile. Swarming motility was observed in all strains. Additionally, all isolates demonstrated positive α-hemolysis, suggesting a potential virulence mechanism involving tissue damage and iron acquisition. Pulsed-field gel electrophoresis (PFGE) revealed significant genomic diversity among the isolates, indicating a low likelihood of patient-to-patient or clonal transmission within the hospital setting. These findings highlight the complex relationship between antimicrobial resistance and virulence in clinical A. baumannii isolates and emphasize the urgent need for robust infection control strategies and continued microbiological surveillance. Full article

Background/Objectives: The development of normal fetal cardiac function, a dynamic process that has not yet been precisely documented throughout the literature, is difficult to quantify by classic echocardiography. Our aim was to analyze the function of the fetal myocardium through speckle tracking and establish reference values for global and segmental longitudinal strain for both ventricles in fetuses with a gestational age (GA) between 22 and 39 weeks. Methods: We conducted a prospective study in which 170 fetuses underwent echocardiographic evaluation and those 150 that were eligible for the study underwent offline speckle tracking analysis. Results: A mixed-design ANOVA model with Greenhouse–Geisser correction showed no significant differences in regional strain measurements among GA groups (F [2, 147] = 1.25, p = 0.289) but showed significant differences in regional strain measurements among the right ventricle (RV), left ventricle (LV), and interventricular free wall (Greenhouse–Geisser F [1.3, 195.2] = 45.70, p < 0.001, GG ε = 0.66, original df = 2, 294). The wall-by-segment interaction term of the model was statistically significant for regional strain (Greenhouse–Geisser F [2.7, 394.2] = 27.00, p < 0.001, GG ε = 0.67, original df = 4, 588), while the segment-by-gestational age group term had a tendency toward statistical significance (Greenhouse–Geisser F [3.0, 221.4] = 2.21, p = 0.088, GG ε = 0.75, original df = 4, 294). The results of Welch’s ANOVA model showed no significant difference in right-ventricle peak global longitudinal strain (pGLS) between GA groups (F [2.0, 92.2] = 0.52, p = 0.5972) and global longitudinal strain measurements (F [2.0, 89.6] = 27.00, p = 0.3733). Conclusions: The reference values for longitudinal strain, represented by the pGLS for LV, ranged from −20.79 to −8.05 for fetuses with a GA between 22 and 27 weeks, from −20.14 to −8.99 for fetuses with a GA between 28 and 33 weeks, and from −20.19 to −8.88 for fetuses with a GA between 34 and 39 weeks. For RV pGLS, the reference values were between −18.99 and −6.35, also depending on GA. Reference ranges for the large gestational groups studied can help us to recognize subtle changes in fetal cardiac function. Full article

We develop a symmetry-based variational theory that shows the coarse-grained balance of work inflow to heat outflow in a driven, dissipative system relaxed to the golden ratio. Two order-2 Möbius transformations—a self-dual flip and a self-similar shift—generate a discrete non-abelian subgroup of $\mathrm{PGL}(2,\mathbb{Q}\left(\sqrt{5}\right))$. Requiring any smooth, strictly convex Lyapunov functional to be invariant under both maps enforces a single non-equilibrium fixed point: the golden mean. We confirm this result by (i) a gradient-flow partial-differential equation, (ii) a birth–death Markov chain whose continuum limit is Fokker–Planck, (iii) a Martin–Siggia–Rose field theory, and (iv) exact Ward identities that protect the fixed point against noise. Microscopic kinetics merely set the approach rate; three parameter-free invariants emerge: a $62\%:38\%$ split between entropy production and useful power, an RG-invariant diffusion coefficient linking relaxation time and correlation length ${\mathcal{D}}_{\alpha }={\xi }^z/\tau$, and a $\vartheta ={45}^{\circ }$ eigen-angle that maps to the golden logarithmic spiral. The same dual symmetry underlies scaling laws in rotating turbulence, plant phyllotaxis, cortical avalanches, quantum critical metals, and even de-Sitter cosmology, providing a falsifiable, unifying principle for pattern formation far from equilibrium. Full article

Gray mold disease, caused by the fungus Botrytis cinerea, affects a wide variety of plants. In this study, we conducted several in vitro tests and genomic analyses on three strains of this fungus (BcPgIs-1, BcPgIs-3, MIC) previously isolated from diseased pomegranate fruits, collected at two geographic locations in Mexico. Our goal was to identify possible differences among these strains. The development of the three strains in distinct culture media, the production of extracellular enzymes, and their effect on the progression of infection in pomegranate fruits were evaluated. The genomes were sequenced using the Illumina platform and analyzed with various bioinformatics tools. All strains possess genetic determinants for virulence and cell wall polymer degradation, but MIC exhibited the highest pectinolytic activity in vitro. This strain also produced sclerotia in a shorter time (7 days) in PDA medium. BcPgls-3 demonstrated the highest conidia production across all the culture media used. Both BcPgls-3 and MIC damaged all the pomegranate fruits 8 days after inoculation, while the BcPgls-1 required up to 9 days. Sequencing of the three strains yielded high-quality sequences, resulting in a total of 17 scaffolds and genomes that exceed 41 million bp, with a GC content of approximately 42%. Phylogenomic analysis indicated that the MIC strain is situated in a group separate from BcPgIs-1 and BcPgIs-3. BcPgIs-3 possesses more coding sequences, but MIC has more genes for CAZymes and peptidases. The three strains share 10,174 genes, while BcPgIs-3 and MIC share 851. These findings highlight the differences among the strains studied, which may reflect their adaptive capacities to their environment. Results contribute to our understanding of the biology of gray mold in pomegranates and could assist in developing more effective control strategies. Full article

Fusarium verticillioides is a globally prevalent phytopathogenic fungus responsible for multiple diseases in maize and a major producer of the mycotoxin fumonisin B1 (FB1), a highly toxic fungal secondary metabolite (FSM). The histone code, which includes reversible modifications such as acetylation and methylation, plays a critical role in regulating chromatin structure and gene expression. In fungi, di- and tri-methylation of histone H3 at lysine 9 (H3K9me2/3) serves as a key epigenetic mark associated with heterochromatin formation and transcriptional repression. In this study, we identified and characterized a putative heterochromatin protein 1 (HP1) family member in F. verticillioides, designated FvHP1, based on conserved domain architecture and phylogenetic analyses. FvHP1 retains essential residues required for H3K9me2/3 recognition, supporting its functional conservation within the HP1 protein family. Phenotypic analysis of the ΔFvHP1 mutant revealed impaired vegetative growth, reduced conidiation and virulence, and altered FB1 mycotoxin production. Additionally, the accumulation of red pigment in the mutant was linked to the deregulation of secondary metabolism, specifically the overproduction of fusarubin-type naphthoquinones, such as 8-O-methylnectriafurone. These results support the role of FvHP1 in facultative heterochromatin-mediated repression of sub-telomeric biosynthetic gene clusters, including the pigment-associated PGL1 cluster. Our findings provide new insights into the epigenetic regulation of fungal pathogenicity and metabolite production, as well as the first evidence of a functional HP1 homolog in F. verticillioides. Full article

Background/Objectives: Leprosy remains a global public health challenge, especially in hyperendemic areas, where spatial, socioeconomic and serological factors influence its persistence. In this study, an integrative review was carried out to analyze the relationship between these factors and the prevalence of Mycobacterium leprae infection, as well as the risk of falling ill. Methods: The integrative search was conducted in the BVS (Medline and LILACS) and Scopus databases, including studies published between 2010 and 2024; PRISMA was followed. Results: The findings indicate that spatial analysis, using geographic information systems, is essential for identifying transmission clusters and targeting control strategies. Poor socioeconomic conditions, such as low income and inadequate sanitation, significantly increase the risk of infection. In addition, serology, especially the detection of Anti-PGL-1 antibodies, has proved to be a promising tool for tracking subclinical infections and improving epidemiological surveillance. However, the integration of spatial, social and serological factors is still limited in the literature. Conclusions: We conclude that multidisciplinary approaches, combining spatial, socioeconomic and serological factors, are fundamental to optimizing control strategies and reducing leprosy transmission in vulnerable populations. Full article

Oriented object detection in aerial imagery presents unique challenges due to the arbitrary orientations, diverse scales, and limited availability of labeled data. In response to these issues, we propose RASST—a lightweight Rotationally Aware Semi-Supervised Transformer framework designed to achieve high-precision detection under fully and semi-supervised conditions. RASST integrates a hybrid Vision Transformer architecture augmented with rotationally aware patch embeddings, adaptive rotational convolutions, and a multi-scale feature fusion (MSFF) module that employs cross-scale attention to enhance detection across object sizes. To address the scarcity of labeled data, we introduce a novel Pseudo-Label Guided Learning (PGL) framework, which refines pseudo-labels through Rotation-Aware Adaptive Weighting (RAW) and Global Consistency (GC) losses, thereby improving generalization and robustness against noisy supervision. Despite its lightweight design, RASST achieves superior performance on the DOTA-v1.5 benchmark, outperforming existing state-of-the-art methods in supervised and semi-supervised settings. The proposed framework demonstrates high scalability, precise orientation sensitivity, and effective utilization of unlabeled data, establishing a new benchmark for efficient oriented object detection in remote sensing imagery. Full article

Background: Extra-intestinal pathogenic Escherichia coli (ExPEC) represents a major global public health challenge due to its ability to cause diverse clinical infections, including urinary tract infections, bacteremia, neonatal meningitis, and sepsis. The growing prevalence of multidrug-resistant (MDR) ExPEC strains, which rapidly erode antibiotic efficacy, underscores vaccine development as a critical priority. Bioconjugate vaccines have emerged as a promising approach to mitigate ExPEC-associated infections. Methods and Results: In this study, we utilized protein glycan coupling technology (PGCT) based on oligosaccharyltransferase (OST) PglL to engineer a tetravalent bioconjugate vaccine targeting four predominant ExPEC serotypes (O1, O2, O6, and O25). We conducted a series of experiments to demonstrate the efficacy of the conjugate vaccine in eliciting humoral immune responses and inducing the production of specific antibodies against Escherichia coli O1, O2, O6, or O25 serotypes. Conclusions: This work establishes the first application of the O-linked PGCT system for engineering bioconjugate vaccines against ExPEC infections. Full article

Various techniques have been used for the molecular identification of Mycobacterium leprae (M. leprae). The aim of this review was to identify the relationship between the molecular presence of M. leprae and the process of infection and/or illness of contact of leprosy cases. A systematic review was carried out by searching the Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane Library, Embase, Scopus, Web of Science and the Latin American and Caribbean Health Sciences Literature (LILACS) databases in January 2024. The studies were selected by two pairs of reviewers. Observational cross-sectional, case–control and cohort studies were included. A descriptive synthesis of the results by category was carried out. A total of 443 studies were identified, and 36 were included in the review. Twelve molecular targets were tested to identify the presence of the bacillus. A relationship was established between the identification of M. leprae DNA and factors related to the index case, housing characteristics, living conditions, epidemiology and anti-PGL-1 serology. None of the studies identified evaluated the molecular viability of M. leprae among contacts. The detection of M. leprae DNA alone does not necessarily predict the development of infection or clinical illness among contacts. Full article

Reportedly, the number of κ-casein (κ-CN) B alleles increases the proportion of κ-CN to total protein and the κ-CN content. This phenomenon is caused by single-nucleotide polymorphisms (SNPs) in the promoter region of CSN3, which encodes the B variant. Therefore, a series of 5′-deleted promoter plasmids were constructed to define the core promoter of CSN3. The promoter activity was analyzed by comparing the luciferase activity among the recombinant vectors with truncated promoters. No mutation occurred in the core promoter region (5′-ctatcgtcagatctttcctttctgtcatcttcctattggtg-3′) of CSN3 in 40 cows. A 2092 bp promoter region of CSN3 was re-sequenced for detection, and nine variants were found, of which only three variants had mutation frequencies > 40%, which were −1002T>−, −1654T>A, and −2039T>G. The CSN3 promoter polymorphisms did not correlate with the CSN3 A and B alleles according to the Pearson’s chi-square test (p > 0.05). Moreover, the luciferase activity analysis of the CSN3 promoter showed no difference among pGL3 recombinants with different polymorphic CSN3 promoters (p > 0.05). In the genetic selection of dairy cows, mutations in the CSN3 core promoter should be focused upon. These findings provide a reference for the regulatory mechanism of bovine milk proteins and offer guidance for the genetic selection and breeding of cows. Full article

Blueberry plants are among the most important fruit-bearing shrubs, but they have shallow, hairless roots that are not conducive to water and nutrient uptake, especially under drought conditions. Therefore, the mechanism underlying blueberry root drought tolerance should be clarified. Hence, we established a yeast expression library comprising blueberry genes associated with root responses to drought stress. High-throughput sequencing technology enabled the identification of 1475 genes potentially related to drought tolerance. A subsequent KEGG enrichment analysis revealed 77 key genes associated with six pathways: carbon and energy metabolism, biosynthesis of secondary metabolites, nucleotide and amino acid metabolism, genetic information processing, signal transduction, and material transport and catabolism. Metabolomic profiling of drought-tolerant yeast strains under drought conditions detected 1749 differentially abundant metabolites (DAMs), including several up-regulated metabolites (organic acids, amino acids and derivatives, alkaloids, and phenylpropanoids). An integrative analysis indicated that genes encoding several enzymes, including GALM, PK, PGLS, and PIP5K, modulate key carbon metabolism-related metabolites, including D-glucose 6-phosphate and β-D-fructose 6-phosphate. Additionally, genes encoding FDPS and CCR were implicated in terpenoid and phenylalanine biosynthesis, which affected metabolite contents (e.g., farnesylcysteine and tyrosine). Furthermore, genes for GST and GLT1, along with eight DAMs, including L-γ-glutamylcysteine and L-ornithine, contributed to amino acid metabolism, while genes encoding NDPK and APRT were linked to purine metabolism, thereby affecting certain metabolites (e.g., inosine and 3′,5′-cyclic GMP). Overall, the yeast functional screening system used in this study effectively identified genes and metabolites influencing blueberry root drought tolerance, offering new insights into the associated molecular mechanisms. Full article

This study aimed to describe the gross and histological features of multiple endocrine and non-endocrine neoplasia, including multiple PGLs found in two Boxer dogs. Additionally, the identified PGLs were immunohistochemically evaluated, and the subunits 2, 3, and 4 of the SDHD gene were screened for possible mutations. The tumors identified include aortic and carotid body PGLs, thyroid follicular-compact carcinoma, and subcutaneous lipomas. One case also had a Leydig cell tumor and adrenal cortex hyperplasia, while the other had H-type pancreatic carcinoma. Three out of 4 PGLs appeared benign, but one aortic body tumor showed malignant features with neoplastic emboli at its edge. Immunohistochemical analysis confirmed the neuroendocrine origin of all PGLs, with positive staining for Chromogranin A, NSE, and variable positivity for S100. No somatic mutations were found in exons 2, 3, and 4 of the SDHD gene in any of the evaluated PGLs. The absence of mutations in the evaluated SDHD gene subunits suggests the involvement of other genetic factors or pathways in the development of these tumors, warranting further investigation in this field. Full article

Pheochromocytomas (PCCs) and paragangliomas (PGLs), denoted PPGLs, are rare neuroendocrine tumours and are highly heterogeneous. The phenotype–genotype correlation is poor; therefore, additional studies are needed to understand their pathogenesis. We describe the clinical characteristics of 63 patients with PPGLs and perform a genetic study. Genetic screening was performed via a targeted gene panel, and clinical variables were compared among patients with a positive molecular diagnosis and negative ones in both PCC and PGL cohorts. The mean age of patients with PCC was 50.0, and the mean age of those with PGL was 54.0. Disease-causing germline variants were identified in 16 individuals (25.4%), twelve and five patients with PCC and PGL, respectively. Genetically positive patients were younger at diagnosis in both cohorts. Variants in genes associated with either isolated PPGLs or syndromic forms of the disease were detected in a cohort of PPGLs. We have identified novel variants in known genes and set the importance of genetic screening to every patient with PPGLs, with a special focus on the young. A longer follow up of patients with variants in genes associated with syndromic forms is of clinical value. Full article

Certain species of Mucorales have been identified as causative agents of mucormycosis, a rare yet often lethal fungal infection. Notably, these fungi exhibit intrinsic resistance to common azole drugs, which target lipids. Given the pivotal role of lipids in drug resistance and their contribution to innate resistance to azoles, this study provides a comprehensive overview of key lipid classes, including sphingolipids (SLs), glycerophospholipids (GPLs), and sterols, in Rhizopus delemar 99-880, a well-characterized reference strain among Mucorales. Using shotgun lipidomics as well as liquid- and gas-chromatography-based mass spectrometric analyses, we identified the lipid intermediates and elucidated the biosynthetic pathways of SLs, PGLs, and sterols. The acidic SLs were not found, probably because the acidic branch of the SL biosynthesis pathway terminates at α-hydroxy phytoceramides, as evident by their high abundance. Intermediates in the neutral SL pathway incorporated higher levels of 16:0 fatty acid compared to other pathogenic fungi. A strikingly high phosphatidylethanolamine (PE)/phosphatdylcholine (PC) ratio was observed among GPLs. Ergosterol remains the major sterol, similar to other fungi, and our analysis confirms the existence of alternate ergosterol biosynthesis pathways. The total lipidomic profile of R. delemar 99-880 offers insights into its lipid metabolism and potential implications for studying pathogenesis and drug resistance mechanisms. Full article