Search Results (446)

Background/Objectives: Idiopathic epilepsy is a lifelong neurologic disorder in dogs, but its genetic basis remains incompletely understood in many breeds. This study aimed to identify risk-associated markers in Siberian Huskies, quantify their effects, assess potential risk modifiers, and characterize the shared haplotype background of the associated signal. Methods: A genome-wide association study was conducted in 113 Siberian Huskies genotyped on the Illumina CanineHD array, integrating association, regression, and haplotype/IBD analyses. An independent follow-up cohort of 57 additional dogs was genotyped at the lead marker by Sanger sequencing. Sex and gonadectomy status/timing were also evaluated as potential modifiers of risk, using multivariable regression and time-to-event analyses. Results: A strong, localized association was identified on canine chromosome 3 (CFA3) within KCNIP4. The lead intronic marker was significantly enriched in cases, with all risk-allele homozygotes affected, most heterozygotes affected, and no control homozygotes observed. Risk-associated chromosomes shared extended haplotypes across the region, consistent with carriers inheriting a common risk haplotype from a relatively recent shared ancestor. Among carriers, male sex was associated with higher odds of epilepsy and earlier seizure onset, with more tentative evidence for a similar association with gonadectomy before 5 years of age. Conclusions: These findings prioritize a CFA3 region encompassing KCNIP4 as a major risk locus for idiopathic epilepsy in Siberian Huskies. Fine-mapping with high-coverage sequencing and functional follow-up will be required to pinpoint the causal variant(s) and support development of risk assessment tools. Until those studies are completed, this marker should be regarded as a research finding rather than a predictive test. Full article

Background: Polygenic risk scores for Alzheimer’s disease (AD), organized by gene networks shared between the blood and brain, may provide insights into underlying disease mechanisms common to both tissues. Methods: We derived a blood–brain network-based polygenic risk score (nbPRS) from AD-associated genetic variants for three blood-brain networks, selected by the preservation of blood and brain gene co-expression networks, and AD association. Participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI, n = 1109), Framingham Heart Study (FHS, n = 8310), the Religious Orders Study Memory Aging Project (ROSMAP, n = 1215), and Mount Sinai Brain Bank (MSBB, n = 323) were stratified into low- and high-nbPRS subgroups, then profiled using longitudinal and cross-sectional data. We compared the conversion from normal cognition to AD between nbPRS subgroups. Genes differentially expressed among low- and high-nbPRS individuals were profiled with classical neuropathological markers and we investigated potential biologically relevant pathways for the genes significantly expressed in high-risk individuals. Results: Individuals with high nbPRS in three AD-associated networks (M2, M6, M14) demonstrated significant impairment in executive function and memory performance, whereas high-risk individuals in networks M2 and M14 had significantly reduced hippocampal volume. We observed high-risk individuals in M2 and M14 developed AD at twice the rate of low-risk individuals in these networks. HLA genes were differentially expressed with transcriptome-wide significance among low- and high-nbPRS individuals in M14 and associated with neuroinflammatory and tau pathology. Conclusions: Polygenic risk scores derived from blood and brain networks can differentiate individuals with a high risk of AD conversion. Full article

Background/Objectives: Pediatric emergency nursing requires timely, accurate interventions, yet educational content is not always aligned with clinical priorities. Identifying and prioritizing educational gaps based on clinical relevance and nurses’ current performance is essential to improve pediatric emergency care. Methods: This descriptive cross-sectional study assessed clinical performance and educational needs among nurses working in emergency departments, general wards, and intensive care units. Data were collected using a structured questionnaire on 20 pediatric emergency conditions and related procedures. Priorities were identified using the Borich Needs Assessment and the Locus for Focus model, based on differences between required and present competence and the level of perceived importance. Results: Educational needs were consistently high across participant characteristics. In both the Borich needs assessment and the Locus for Focus model, the highest priorities were identified in pediatric emergency nursing competencies related to time-critical emergencies and core procedures, particularly resuscitation and high-risk medication administration. Conclusions: Educational priorities in pediatric emergency nursing span urgent conditions and skill-intensive procedures. Although performance varied by age and experience, educational needs were consistently high, supporting continuous, standardized training. Simulation-based and mobile-enabled, scenario-focused education should be considered to enhance preparedness and response capacity among nursing students and early-career nurses. Full article

Background/Objectives: Dyslipidemia is a prevalent metabolic disorder and a recognized risk factor for cancer mortality. However, it remains unclear whether systemic lipid profiles in the general population share epigenetic landscapes that drive cancer aggressiveness. Methods: We analyzed blood DNA methylation profiles alongside three key lipid variables (triglycerides [TGY], total cholesterol [TCH], and HDL cholesterol [HDL]) from 2749 individuals in the KoGES cohort. These were integrated with TCGA data across 32 cancer types using a novel ‘Hybrid Pi-score’ algorithm to capture robust epigenetic associations. Results: The global epigenetic landscape revealed that triglycerides (TGY) share a significantly broader and stronger epigenetic network with cancer prognosis compared to cholesterol markers, particularly in metabolic cancers like LIHC and KIRC. Directional consistency analysis confirmed that methylation alterations associated with hypertriglyceridemia in healthy individuals mirror those observed in high-mortality cancer groups. Network analysis identified CPT1A (carnitine palmitoyltransferase 1A) as a master epigenetic locus, acting as a central hub linking dyslipidemia to tumor progression. Conclusions: This study provides molecular evidence that systemic dyslipidemia, particularly elevated triglycerides, drives oncogenic epigenetic remodeling. The identification of CPT1A suggests that managing lipid profiles may be critical for mitigating the “metabolic fuel” that accelerates cancer progression. These findings advocate for integrating lipid biomarkers into cancer risk stratification. Full article

Background: The Garifunas are a distinctive Afro-indigenous community of Honduras, originating from the historical admixture of Island Carib, Arawak, and West African peoples in the seventeenth-century Caribbean. With an estimated 43,111 individuals residing primarily along the northern Atlantic coast. Their dual ancestral composition yields a genetic profile that differs meaningfully from those of other Honduran reference populations, consistent with pairwise FST comparisons with previously published Lenca and Tawahka datasets generated on the identical platform; yet no population-specific short tandem repeat (STR) reference dataset had previously been established. Methods: We genotyped 23 autosomal STR loci using the PowerPlex Fusion 6C System (Promega Corporation) in 100 unrelated Garifuna individuals (70 females, 30 males) sampled from three coastal settlements in the department of Atlántida: Triunfo de la Cruz, Ensenada, and Corozal. DNA was extracted from blood collected on FTA cards, and statistical parameters were computed using Genepop v4.2 and Arlequin v5.3.2.2. Results: A total of 217 distinct alleles were identified, with 5 to 19 alleles per locus (mean 9.43 ± 3.54). Expected heterozygosity (He) ranged from 0.6392 (D13S317) to 0.9010 (SE33), with a population mean of 0.7893. No locus deviated from Hardy–Weinberg equilibrium after Bonferroni correction (α = 0.0022). The combined random match probability was approximately 1.9 × 10⁻²⁶, and the combined chance of exclusion reached 99.99999993%. Conclusions: This study provides the first Honduran Garifuna population-specific autosomal STR reference database for precise forensic likelihood ratio estimates, kinship assessments, and population genetic studies. The Garifuna’s high diversity—consistent with their West African and Amerindian ancestry—indicates the risk of systematic bias when non-specific databases are used. Full article

The northeast monsoon prevailing over southeastern China in late seasons, generally from October to March, frequently generates water level anomalies upstream of the Taiwan Strait (TWS) that reach the coastal waters of Guangdong in South China, and, with compounding astronomical high tides, elevate coastal flood risk over the region. The risk of coastal flooding or sea inundation is further heightened when monsoon forcing co-occurs with storm surge brought by late-season tropical cyclones (TCs). This study integrates tide gauge observations from Hong Kong (HK) and its vicinity together with Delft3D Flexible Mesh simulations to diagnose a tide-modulated anomaly wave mechanism. Observations show that anomalies originating in or near TWS arrive in HK with station-dependent phasing. These water level anomalies exhibit a characteristic ~6 h periodicity west of the Taiwan Shoal, and display peaks that systematically align with the astronomical high tide. Time–frequency analysis reveals a wave period transformation from ~12 h north of Dongshandao over the coast of southeastern China to ~6 h west of the Taiwan Shoal. We test the hypothesis that wind-forced water anomalies generated in or near TWS undergo shoal-modulated nonlinear tide–wind interaction and tidal-current advection that transform their dominant period and phase-lock them to the tide, producing four anomaly peaks per day downstream and station-dependent phasing in HK. Hindcasts of the November 2024 monsoon episode reproduce the observed timing, periodicity, and spatial transition, while constituent experiments demonstrate that semi-diurnal forcing entering via the TWS is the primary driver of the ~6 h signal, with the Taiwan Shoal acting as the modulation locus. Accurate water level forecasts for the Guangdong coast, therefore, need to incorporate upstream wind forcing over the TWS and bathymetric controls around the Taiwan Shoal, with practical implications for compound flood risk during spring tides and co-occurring monsoon and/or TC events. Full article

Background: Sortilin (SORT1), linked to the 1p13.3 coronary risk locus, is implicated in lipid trafficking and atherogenesis; however, clinical studies of circulating SORT1 have produced inconsistent results. We evaluated whether circulating SORT1 is associated with angiographic burden and lesion localization in patients with premature or early clinical debut coronary atherosclerosis. Methods: This single-center, cross-sectional study analyzed a dataset collected from January to May 2023. Participants were classified as coronary atherosclerosis cases if the dataset contained an age of clinical debut of clinically significant atherosclerosis (n = 101). Controls had no recorded debut age and 0% stenosis in all assessed coronary segments (n = 27). Blood was collected in clot activator tubes; serum was stored at −40 °C until analysis. SORT1 (ng/mL) was measured using an Aviscera Bioscience ELISA. Coronary stenoses were recorded as percent diameter stenosis for left main (LM), proximal/mid/distal LAD, proximal/mid/distal LCx, and proximal/mid/distal RCA. Burden metrics included the number of segments with any stenosis (>0%), the number of obstructive segments (≥50%), the number of diseased vessels, and maximum stenosis. The prespecified primary endpoint was obstructive proximal LAD stenosis (≥50%). Nonparametric tests and Spearman correlations were used. Logistic regression evaluated the association between log2-transformed SORT1 and proximal LAD obstruction, adjusted for age, sex, LDL-C, statin use, and smoking/diabetes/hypertension durations. Results: SORT1 was higher in cases than controls (8.60 [2.60–17.10] vs. 2.30 [1.25–10.65] ng/mL; p = 0.0058). Within cases, SORT1 did not correlate with global angiographic burden (any-stenosis segments: ρ = −0.066, p = 0.513; obstructive segments: ρ = −0.060, p = 0.552; diseased vessels: ρ = −0.045, p = 0.652; maximum stenosis: ρ = −0.084, p = 0.403). Obstructive proximal LAD stenosis occurred in 44/101 (43.6%) and was associated with higher SORT1 (12.25 [4.18–17.45] vs. 4.10 [2.20–11.60] ng/mL; p = 0.0093). Each doubling of SORT1 was independently associated with proximal LAD obstruction (adjusted OR 1.48, 95% CI 1.12–1.95; p = 0.005). Conclusions: In this cross-sectional cohort, circulating SORT1 was associated with obstructive proximal LAD stenosis but not with global angiographic burden metrics. These findings are hypothesis-generating and warrant validation in independent cohorts with standardized preanalytics and prospective designs to assess temporal relationships and clinical utility. Full article

Alzheimer’s disease (AD) and cancer are both age-related conditions, yet numerous large-scale epidemiological studies have consistently documented an inverse association, with individuals diagnosed with cancer exhibiting a reduced risk of AD and vice versa. Although this relationship has been replicated across diverse populations, its biological basis remains poorly understood. To address this gap, the present study applies a framework that integrates locus-level genetic correlation (rg) with genetically regulated gene expression to clarify the molecular factors contributing to the inverse epidemiological patterns observed between the two diseases. We used the largest available genome-wide association studies (GWAS) (Nmax = 448,150) to quantify local genetic correlations between AD and several age-associated cancers, including breast, prostate, lung, colorectal, melanoma, basal cell carcinoma, bladder, and endometrial cancer. Eight genomic regions showed significant negative local rg, at the 19q13.31–19q13.32 locus demonstrating strong negative correlations across multiple cancers, including breast, prostate, lung, melanoma, and endometrial cancer. To evaluate the contribution of genetically regulated gene expression, we conducted transcriptome-wide association studies (TWAS) using precomputed gene expression weights from cancer tissues (The Cancer Genome Atlas-TCGA), disease-agnostic tissues (Genotype-Tissue Expression-GTEx), and brain tissue (dorsolateral prefrontal cortex-DLPFC). For each AD–cancer pair, we prioritized genes that were nominally significant in both traits (p < 0.05) and exhibited inverse TWAS Z scores. This analysis identified 24 genes with opposite effect directions between AD and at least three cancer types. TWAS signals also aligned with local rg findings at the 19q13.31–19q13.32 region, suggesting that regulatory variation near this locus contributes to shared but opposing genetic effects beyond the canonical APOE signal. Across cancer types, genes inversely associated with AD converged on pathways involved in cell cycle regulation, apoptosis, DNA-damage response, and metabolic processes. These results support the hypothesis that biological mechanisms promoting proliferation and survival in cancer may oppose those contributing to neurodegeneration in AD. Full article

Background and Objectives: Judo is an Olympic contact sport with a high risk of injury owing to its physical, technical, and competitive demands. The role of psychological factors in recovery and Return to Sport (RTS), such as kinesiophobia and self-perception, is key in the injury process. These factors influence both the success and timing of return and are affected by variables such as locus of control, previous experience, and contextual factors. This study sought to analyse the relationship between sociodemographic, clinical, sports, and psychological variables with kinesiophobia and self-perception of RTS to identify psychological profiles. Materials and Methods: A cross-sectional observational study was conducted at the Centro de Alto Rendimiento de Judo (CEAR) in Valencia, Spain; involving 51 high-performance judokas (mean age 23.0 ± 3.8 years) competing at national or international level who were injured, out of competition or in the process of returning to training or competition. Data were collected using a self-administered questionnaire. Psychological variables were assessed using the Tampa Scale for Kinesiophobia (TSK-11) and the Psychological Readiness of Injured Athlete to Return to Sport (PRIA-RS) questionnaire. Results: No significant associations were found between sociodemographic, clinical–sports, and psychological variables (p > 0.05). The mean TSK-11 and PRIA-RS scores were 25.02 ± 5.79 and 36.49 ± 5.29, respectively. Cluster analysis identified three differentiated psychological profiles: one with high kinesiophobia, longer injury and time away from competition, and lower self-perceived readiness to RTS (n = 16); a second with lower fear, the lowest readiness, younger age, and shorter recovery time (n = 17); and a third with the lowest kinesiophobia, highest readiness, older age, and intermediate injury-related time (n = 18). Conclusions: Three psychological profiles were identified: young judokas with low self-perceived readiness to Return to Sport (RTS) and low kinesiophobia; older judokas with high readiness and minimal kinesiophobia; and a more vulnerable group with longer recovery times, high kinesiophobia, and low self-perceived readiness to RTS. Further studies with additional specific variables and biopsychosocial approaches are needed. Full article

Garlic (Allium sativum L.) cultivars in Korea, particularly the widely adaptable ‘Hongsan’, are challenging to identify in processed forms or seedlings due to the plasticity of phenotypic traits such as clove tip greening. This uncertainty increases the risk of mislabeling and the infringement of breeders’ rights under the UPOV framework. This study aimed to develop a stable SCAR marker for ‘Hongsan’-specific identification using a RAPD-based DNA pooling method. Sixty Operon primers (>60% GC) were screened against ‘Hongsan’ gDNA versus a multi-cultivar DNA pool (‘Daeseo’, ‘Uiseong’, ‘Danyang’, and ‘Namdo’); OPE-01 consistently amplified a unique 1.3 kb band, which was cloned and sequenced, revealing a 1272 bp sequence with a translocation junction (878 + 394 bp), a 18 bp insertion, and an EcoRI site on chromosome 2 (NCBI reference sequence: GCA_030737875.1). SCAR primers SaH191R/SaH513F produced a specific 545 bp amplicon in Hongsan, clearly distinguishing it from other cultivars and parental lines, indicating that the marker locus is related to the paternal line ‘9209’. This RAPD-to-SCAR marker overcomes reproducibility limitations and enables reliable authentication of Hongsan in processing powders and black garlic irrespective of environmental factors. This cost-effective and rapid assay ensures industry transparency, quality control, and IP protection for Korean garlic production. Full article

Pseudostellaria heterophylla, an important traditional medicinal plant in China, has suffered increasing yield and quality loss due to leaf spot disease in recent years. In this study, the causal agent was conclusively identified as Sclerotiophoma versabilis through detailed morphological characteristics and multi-locus phylogenetic analyses based on the internal transcribed spacer regions (ITS), the 28S large subunit of the nrDNA (LSU), RNA polymerase II (rpb2), and ß-tubulin (tub2) sequences. Pathogenicity tests fulfilled Koch’s postulates, thereby resolving previous taxonomic inconsistencies regarding this disease. The effects of environmental and nutritional factors on mycelial growth, conidial germination, and infection were systematically evaluated. Optimal mycelial growth occurred at 20–25 °C, pH 6–8, under continuous light. Optimal mycelial growth occurred at 20–25 °C, pH 6–8, under continuous light, while conidial germination was maximized at 20–25 °C and pH 6–7 under continuous light. Starch and glycine were identified as the most favorable carbon and nitrogen sources for the fungal mycelial growth, respectively. Infection assays indicated an incubation period of approximately 3 d and maximal disease development at moderate temperatures under low-light conditions, with 6 d-old cultures exhibiting the greatest infectivity. Microscopic observations revealed that S. versabilis penetrated host tissues directly or via stomata without forming specialized infection structures. These findings integrate taxonomic resolution with ecological and infection biology analyses, providing mechanistic insight into the environmental drivers of leaf spot epidemics and a scientific basis for disease-risk assessment and management in P. heterophylla production systems. Full article

Enterocytozoon bieneusi is a microsporidian species found ubiquitously in both invertebrate and vertebrate hosts including domestic and wild animals and humans. Enterocytozoon bieneusi typically causes severe or chronic diarrhea, malabsorption and emaciation. This study aimed to investigate the prevalence and genotypic distribution of E. bieneusi in dogs in Fujian province, China. A total of 506 fecal samples from dogs were randomly collected from eight districts in Fujian province, China. The presence of E. bieneusi was confirmed through nested PCR targeting ITS gene. Further multilocus sequence typing (MLST) focused on the three microsatellite loci (MS1, MS3, and MS7) and minisatellite locus (MS4) loci. As a result, the infection rates of E. bieneusi in dogs were found to be 5.93% (30/506). A highly significant difference in the prevalence of E. bieneusi was observed across different urban areas (p < 0.01), with Longyan city exhibiting the highest infection rate (24.62%, 16/65), Zhangzhou and Xiamen the lowest (0.00%). Prevalence also varied significantly by source (p < 0.01), age (p < 0.01), gender (p < 0.05), symptom status (p < 0.01), and season (p < 0.01). Three known genotypes of E. bieneusi were identified in 30 dogs’ positive samples, including EbpC, PigEBITS5 and PtEb IX, whereas FJLYD1, FJLYD2 and FJSMD have been identified as new genotypes. EbpC, PigEBITS5, FJLYD1, FJLYD2, and FJSMD all belong to Group 1, while PtEb IX is assigned to Group 11. Genotypes belonging to Group 1, the first major phylogenetic clade, are considered to possess potential zoonotic risks. None of the positive samples amplified at all four loci, forming a single multilocus genotype (MLG). This study contributes to a deeper understanding of E. bieneusi in dogs, which provides critical data for the development of targeted control strategies in Fujian province. Full article

We present a case of a patient in their 80s initially presenting with myelodysplastic syndromes (MDS). Chromosomal analysis showed an abnormal female karyotype with a complex karyotype. Metaphase FISH confirmed four copies of KMT2A (MLL) in 24.5% [49/200] and amplification of KMT2A (MLL) with more than four copies in 22% [44/200]. FISH also revealed the presence of MYC (8q24) on the long arm of chromosome 2 at 2q33 locus, two copies of BCR on each homolog 22, and two additional copies of BCR on a derivative chromosome 22. Flow cytometric analysis revealed a population of aberrant myeloid blasts (15–17%). Bone marrow analysis showed hypercellular marrow with a significant increase in myeloid blasts (~50%) and trilineage dysplasia. Eventually, these findings were consistent with a final diagnosis of acute myeloid leukemia non-M3 and a complex karyotype, correlating with cytogenetics, flow cytometry, molecular, and clinical findings. The patient’s clinical course was marked by a rapid deterioration, including recurrent arrhythmias, hypoxic respiratory failure, and septic shock. Given their poor clinical status and adverse-risk molecular profile, care was transported to hospice. The presence of KMT2A amplification is a rare event in AML and is present in ~1% of AML and MDS cases. MYC translocation, KMT2A (MLL) amplification, and 5q/20q losses suggest secondary therapy-related AML and categorize this case in the adverse risk prognosis under the ELN 2022 guidelines. Full article

Background: Neuropsychiatric disorders such as Alzheimer’s disease (AD), bipolar disorder (BD), and depression exhibit shared glutamatergic abnormalities, although their upstream molecular mechanisms remain poorly defined. Magnesium (Mg²⁺) serves as a key regulator of N-methyl-D-aspartate (NMDA) receptor function; however, the role of Mg²⁺ transporters, particularly SLC41A1, has not been systematically investigated. As NMDA receptor dysregulation contributes to emotional and cognitive impairments, elucidating Mg²⁺-NMDA signaling may enable the development of novel therapeutic strategies. Methods: We integrated Mendelian randomization, locus colocalization, human brain transcriptomics, functional enrichment, and co-expression analyses to determine whether SLC41A1 functions as a cross-disorder molecular driver. In addition, in vitro electrophysiological experiments using field potential recordings in hippocampal Schaffer-CA1 synapses were conducted to validate its functional role in NMDA receptor-mediated synaptic transmission. Results: Genetically elevated SLC41A1 expression increased the risk of AD, BD, depression, and alcohol dependence, with strong colocalization analyses supporting shared causal variants. Transcriptomic profiling revealed SLC41A1 upregulation in AD and BD, with enrichment in magnesium transport, mitochondrial function, and synaptic signaling pathways. Co-expression networks across GTEx brain regions demonstrated strong correlations with NMDA-related genes (e.g., GRINA, CAMK2G, GRIN2C). Under NMDAR-selective recording conditions, both imipramine treatment and SLC41A1 knockdown significantly reduced NMDAR-mediated fEPSP amplitudes, supporting a role for SLC41A1 in regulating NMDA receptor-dependent synaptic responses. Conclusions: This study identifies SLC41A1 as a magnesium-centered, transdiagnostic therapeutic target that links Mg²⁺ homeostasis to NMDA-dependent synaptic dysfunction. These findings provide a mechanistic foundation for developing SLC41A1-modulating or magnesium-based therapeutic approaches for mood and cognitive disorders. Full article

Burkholderia pseudomallei is a saprophytic environmental bacterium and the causative agent of melioidosis, a serious opportunistic infection in tropical regions, including northern Australia. Infection occurs following environmental exposure via percutaneous inoculation, ingestion, or inhalation; however, the environmental reservoirs and transmission pathways responsible for human disease remain poorly defined. Groundwater has been implicated as a potential source of infection, but the factors influencing the persistence and mobility of B. pseudomallei in surface waters in North Queensland are not well understood. Water samples were collected from a groundwater-connected seasonal creek in Townsville, North Queensland, over a 12-month period encompassing wet and dry seasons. Samples were cultured on Ashdown agar and confirmed as B. pseudomallei by qPCR. Multi-locus sequence typing (MLST) was performed using targeted allele sequencing on the Oxford Nanopore MinION platform. Eighteen of 59 water samples were culture-positive for B. pseudomallei. Detection occurred exclusively in turbid, flowing water following ≥30 mm of rainfall and was observed in both wet and dry seasons. MLST of 48 isolates identified 18 sequence types, including 12 novel types. Six sequence types matched previously reported Townsville clinical isolates. These findings indicate that groundwater from a connected urban creek may function as a mobile reservoir for clinically relevant B. pseudomallei strains under specific hydrological and climatic conditions, highlighting rainfall-driven processes as key drivers of environmental exposure risk. Full article