Search Results (11,683)

Congenital cataracts (CCs) are a leading cause of preventable childhood blindness, with genetic factors playing a crucial role in their etiology. Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder associated with CCs but is often underdiagnosed due to variable expressivity, particularly in female carriers. Objective: This study aimed to explore the genetic landscape of CCs in a Swiss cohort, focusing on two novel NHS and one novel GJA8 variants and their phenotypic presentation. Methods: Whole-exome sequencing (WES) was conducted on 20 unrelated Swiss families diagnosed with CCs. Variants were analyzed for pathogenicity using genetic databases, and segregation analysis was performed. Clinical data, including cataract phenotype and associated systemic anomalies, were assessed to establish genotype–phenotype correlations. Results: Potentially pathogenic DNA sequence variants were identified in 10 families, including three novel variants, one in GJA8 (c.584T>C) and two NHS variants (c.250_252insA and c.484del). Additional previously reported variants were detected in CRYBA1, CRYGC, CRYAA, MIP, EPHA2, and MAF, reflecting genetic heterogeneity in the cohort. Notably, NHS variants displayed significant phenotypic variability, suggesting dose-dependent effects and X-chromosome inactivation in female carriers. Conclusions: NHS remains underdiagnosed due to its variable expressivity and the late manifestation of systemic features, often leading to misclassification as isolated CC. This study highlights the importance of genetic testing in unexplained CC cases to improve early detection of syndromic forms. The identification of novel NHS and GJA8 variants provides new insights into the genetic complexity of CCs, emphasizing the need for further research on genotype–phenotype correlations. Full article

Leptospirosis is a globally significant zoonosis affecting animal health, productivity, and the environment. While typically associated with tropical climates, its persistence in semi-arid regions such as La Laguna, Mexico—characterized by low humidity, high temperatures, and limited water sources—remains poorly understood. Although these adverse environmental conditions theoretically limit the survival of Leptospira, high livestock density and synanthropic reservoirs (e.g., rodents) may compensate, facilitating transmission. In this cross-sectional study, blood sera from 445 dairy cows (28 herds: 12 intensive [MI], 16 semi-intensive [MSI] systems) were analyzed via microscopic agglutination testing (MAT) against 10 pathogenic serovars. Urine samples were cultured for active Leptospira detection. Risk factors were assessed through epidemiological surveys and multivariable analysis. This study revealed an overall apparent seroprevalence of 27.0% (95% CI: 22.8–31.1), with significantly higher rates in MSI (54.1%) versus MI (12.2%) herds (p < 0.001) and an estimated true seroprevalence of 56.3% (95% CI: 50.2–62.1) in MSI and 13.1% (95% CI: 8.5–18.7) in MI herds (p < 0.001). The Sejroe serogroup was isolated from urine in both systems, confirming active circulation. In MI herds, rodent presence (OR: 3.6; 95% CI: 1.6–7.9) was identified as a risk factor for Leptospira seropositivity, while first-trimester abortions (OR:10.1; 95% CI: 4.2–24.2) were significantly associated with infection. In MSI herds, risk factors associated with Leptospira seropositivity included co-occurrence with hens (OR: 2.8; 95% CI: 1.5–5.3) and natural breeding (OR: 2.0; 95% CI: 1.1–3.9), whereas mastitis/agalactiae (OR: 2.8; 95% CI: 1.5–5.2) represented a clinical outcome associated with seropositivity. Despite semi-arid conditions, Leptospira maintains transmission in La Laguna, particularly in semi-intensive systems. The coexistence of adapted (Sejroe) and incidental serogroups underscores the need for targeted interventions, such as rodent control in MI systems and poultry management in MSI systems, to mitigate both zoonotic and economic impacts. Full article

Rural roads are critical for connecting isolated communities to essential services such as education and health and administrative services, as well as production and market opportunities in low-income countries. More than 70% of movements of people and goods in Sub-Saharan Africa are heavily reliant on rural transport systems, using both motorised but mainly alternative means of transport. However, rural roads often suffer from poor construction due to the use of low-strength, in situ soils and limited financial resources, leading to premature failures and subsequent traffic disruptions with significant economic losses. This study investigates the use of rice husk ash (RHA), a waste byproduct from rice production, as a sustainable supplement to Ordinary Portland Cement (OPC) for soil stabilisation in order to increase durability and sustainability of rural roads, hence limit recurrent maintenance needs and associated transport costs and challenges. To conduct this study, soil samples collected from Mulungushi, Zambia, were treated with combinations of 6–10% OPC and 10–15% RHA by weight. Laboratory tests measured maximum dry density (MDD), optimum moisture content (OMC), and California Bearing Ratio (CBR) values; the main parameters assessed to ensure the quality of road construction soils. Results showed that while the MDD did not change significantly and varied between 1505 kg/m³ and 1519 kg/m³, the OMC increased hugely from 19.6% to as high as 26.2% after treatment with RHA. The CBR value improved significantly, with the 8% OPC + 10% RHA mixture achieving the highest resistance to deformation. These results suggest that RHA can enhance the durability and sustainability of rural roads and hence improve transport systems and subsequently improve socioeconomic factors in rural areas. Full article

Common bean (Phaseolus vulgaris L.) is a critical protein-rich legume supporting food and nutritional security globally. However, Fusarium wilt, caused by Fusarium solani, remains a major constraint to production, with yield losses reaching up to 84%. While biocontrol strategies have been explored, most microbial agents are sourced from mesophilic environments and show limited effectiveness under abiotic stress. Here, we report the isolation and characterization of extremophilic Bacillus spp. from the hypersaline Lake Bogoria, Kenya, and their biocontrol potential against F. solani. From 30 isolates obtained via serial dilution, 9 exhibited antagonistic activity in vitro, with mycelial inhibition ranging from 1.07-1.93 cm 16S rRNA sequencing revealed taxonomic diversity within the Bacillus genus, including unique extremotolerant strains. Molecular screening identified genes associated with the biosynthesis of antifungal metabolites such as 2,4-diacetylphloroglucinol, pyrrolnitrin, and hydrogen cyanide. Enzyme assays confirmed substantial production of chitinase (1.33–3160 U/mL) and chitosanase (10.62–28.33 mm), supporting a cell wall-targeted antagonism mechanism. In planta assays with the lead isolate (B7) significantly reduced disease incidence (8–35%) and wilt severity (1–5 affected plants), while enhancing root colonization under pathogen pressure. These findings demonstrate that extremophile-derived Bacillus spp. possess robust antifungal traits and highlight their potential as climate-resilient biocontrol agents for sustainable bean production in arid and semi-arid agroecosystems. Full article

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical public health threat due to its rapid nosocomial dissemination, limited therapeutic options, and elevated mortality rates. This study aimed to characterize the epidemiology, carbapenemase profiles, and antimicrobial susceptibility patterns of CRKP isolates, as well as the clinical features and outcomes observed in infected or colonized patients. Materials and Methods: We conducted a retrospective analysis of clinical and microbiological data from patients with CRKP infections or colonization admitted between January 2023 and January 2024. Descriptive statistics were used to assess prevalence, resistance patterns, and patient outcomes. Two binary logistic regression models were applied to identify independent predictors of sepsis and in-hospital mortality. Results: Among 89 CRKP isolates, 45 underwent carbapenemase typing. More than half were metallo-β-lactamase (MBL) producers, with 44.4% co-harbouring NDM and OXA-48-like enzymes. Surgical intervention was associated with a significantly lower risk of sepsis (p < 0.01) and in-hospital mortality (p = 0.045), whereas intensive care unit (ICU) stay was a strong predictor of both outcomes. ICU admission conferred a 10-fold higher risk of sepsis (95%Cl 2.4–41.0) and a 40.8-fold higher risk of in-hospital death (95% Cl 3.5–473.3). Limitations: This single-center retrospective study included a limited number of isolates in certain groups. Additionally, cefiderocol (FDC) susceptibility was assessed by disk diffusion rather than by the broth microdilution method. Conclusions: Our study underscores the increasing prevalence of metallo-beta-lactamase-producing CRKP, particularly strains harbouring dual carbapenemases. Timely recognition of high-risk patients, combined with the implementation of targeted infection control measures and the integration of novel therapeutic options, is crucial to optimize clinical management and reduce mortality associated with CRKP. Full article

Chromosomal microarray analysis (CMA) was performed for 40 patients with B-ALL undergoing treatment according to the ALL-2016 protocol to investigate the copy number alterations (CNAs) and copy neutral loss of heterozygosity (cnLOH) associated with minimal residual disease (MRD)-positive remission. Aberrations involving over 20,000 genes were identified, and a random forest approach was applied to isolate a subset of genes whose CNAs and cnLOH are significantly associated with poor therapeutic response. We have assembled the triple matched healthy population data and used that data as a reference, but not as a matched control. We identified a recurrent cluster of cnLOH in the 19q13.2–19q13.31 region, significantly enriched in MRD-positive patients (70% vs. 47% in the reference group vs. 16% in MRD-negative patients). This region includes the pregnancy-specific glycoprotein (PSG) gene family and the oncogene ERF, suggesting a potential role in leukemic persistence and treatment resistance. Additionally, we observed significant deletions involving 7p22.3 and 16q13, often as part of large-scale losses affecting almost the entire chromosomes 7 and 16, indicative of global chromosomal instability. These findings highlight specific genomic regions potentially involved in therapy resistance and may contribute to improved risk stratification in B-ALL. Our findings emphasize the value of high-resolution CMA in diagnostics and risk stratification and suggest that PSG genes and other candidate genes could serve as biomarkers for predicting treatment outcomes. Full article

A newly emerging disease affecting Schizolobium parahyba (commonly known as pachaco), termed “decline and dieback,” has been reported in association with the fungal pathogens Fusarium sp. and Botryodiplodia sp. This study assessed the antagonistic potential of two Trichoderma sp. isolates (CEP-01 and CEP-02) against these phytopathogens under controlled laboratory conditions. The effects of three temperature regimes (5 ± 2 °C, 24 ± 2 °C, and 30 ± 2 °C) on the growth and inhibitory activity of two Trichoderma spp. isolates were evaluated using a completely randomized design. The first experiment included six treatments with five replicates, while the second comprised twelve treatments, also with five replicates. All assays were conducted on PDA medium. No fungal growth was observed at 5 ± 2 °C. However, at 24 ± 2 °C and 30 ± 2 °C, both isolates reached maximum growth within 72 h. At 24 ± 2 °C, both Trichoderma spp. isolates exhibited inhibitory activity against Fusarium sp. FE07 and FE08, with radial growth inhibition percentages (RGIP) ranging from 37.6% to 44.4% and 52,8% to 54.6%, respectively. When combined, the isolates achieved up to 60% inhibition against Fusarium sp., while Botryodiplodia sp. was inhibited by 40%. At 30 ± 2 °C, the antagonistic activity of Trichoderma sp. CEP-01 declined (25.6–32.4% RGIP), whereas Trichoderma sp. CEP-02 showed increased inhibition (60.3%–67.2%). The combination of isolates exhibited the highest inhibitory effect against Fusarium sp. FE07 and FE08 (68.4%–69.3%). Nonetheless, the inhibitory effect on Botryodiplodia sp. BIOT was reduced under elevated temperatures across all treatments. These findings reinforce the potential of Trichoderma spp. isolates as a viable and eco-friendly alternative for the biological control of pathogens affecting S. parahyba, contributing to more sustainable disease management practices. The observed inhibitory capacity of Trichoderma sp., especially under optimal temperature conditions, highlights its potential for application in integrated disease management programs, contributing to forest health and reducing reliance on chemical products. Full article

Anti-Ku antibodies are rare autoantibodies associated with connective tissue diseases (CTDs), but their clinical significance remains poorly understood due to limited studies. Semi-quantitative immunodot assays yield positive, negative, or borderline results, with the clinical relevance of borderline findings remaining unclear. The purpose of this study is to characterize the clinical spectrum of anti-Ku-positive patients and evaluate the clinical significance of anti-Ku-borderline results in CTD management. A retrospective cohort study was conducted at Hôpital Erasme, including all patients with anti-Ku-positive or borderline results, over a 10-year period. Clinical and biological data were collected from medical records and analyzed for disease associations, organ involvement, and outcomes. Among 47 anti-Ku-positive patients, systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS) were the most common diagnoses. Interstitial lung disease (ILD) occurred in 23.4% and renal involvement in 12.8% of patients. Cytopenia was significantly associated with glomerulonephritis. Organ damage, particularly pulmonary and renal involvement, correlated with increased mortality. In the borderline group (n = 33), SLE and SS remained the predominant diagnoses. During follow-up, three patients died (all with isolated ILD without associated CTD), one required chronic dialysis, and one underwent lung transplantation. ILD was present in 7/22 (31.8%) borderline patients, and renal involvement in 7/32 (21.9%). This study demonstrates significant associations between anti-Ku antibodies and organ damage, with increased mortality risk. The high prevalence of pulmonary and renal involvement in anti-Ku-borderline patients suggests that these results carry substantial clinical significance and should prompt comprehensive CTD evaluation. These findings support treating borderline anti-Ku results with the same clinical vigilance as positive results, given their similar association with severe organ involvement and adverse outcomes. Full article

Mitochondria, pivotal organelles in cellular metabolism and energy production, have emerged as critical players in the pathogenesis of cancer. This review outlines the progress in mitochondrial profiling through mass spectrometry-based metabolomics and its applications in cancer research. We provide unprecedented insights into the mitochondrial metabolic rewiring that fuels tumorigenesis, metastasis, and therapeutic resistance. The purpose of this review is to provide a comprehensive guide for the implementation of mitochondrial metabolomics, integrating advanced methodologies—including isolation, detection, and data integration—with insights into cancer-specific metabolic rewiring. We first summarize current methodologies for mitochondrial sample collection and pretreatment. Furthermore, we then discuss the recent advancements in mass spectrometry-based methodologies that facilitate the detailed profiling of mitochondrial metabolites, unveiling significant metabolic reprogramming associated with tumorigenesis. We emphasize how recent technological advancements have addressed longstanding challenges in the field and explore the role of mitochondrial metabolism-driven cancer development and progression for novel drug discovery and translational research applications in cancer. Collectively, this review delineates emerging opportunities for therapeutic discovery and aims to establish a foundation for future investigations into the therapeutic modulation of mitochondrial pathways in cancer, thereby paving the way for innovative diagnostic and therapeutic approaches targeting mitochondrial pathways. Full article

During the course of genome mining initiatives, we identified a marine-derived Micromonospora, assigned here as strain WMMD956; the genome of WMMD956 appeared to contain a number of features associated with everninomicins, well-known antimicrobial orthosomycins. In addition, LCMS-based hierarchical clustering analysis and principal component analysis (hcapca) revealed that WMMD956 displayed an extreme degree of metabolomic and genomic novelty. Dereplication of high-resolution tandem mass spectrometry (HRMS/MS) and Global Natural Product Social molecular networking platform (GNPS) analysis of WMMD956 resulted in the identification of several analogs of the previously known everninomicin. Chemical structures were unambiguously confirmed by HR-ESI-MS, 1D and 2D NMR experiments, and the use of MS/MS data. The isolated metabolites, 1–3, were evaluated for their antibacterial activity against methicillin-resistant Staphalococcus aureus (MRSA). Full article

Fibrocapsa japonica (Raphidophyceae) is a cosmopolitan species frequently associated with harmful algal blooms (HABs) and fish mortality events, representing a potential threat to aquaculture and coastal ecosystems. This study provides the first comprehensive morphological, phylogenetic, pigmentary, and toxicological characterization of F. japonica strains isolated from Argentina. Light and transmission electron microscopy confirmed key diagnostic features of the species, including anterior flagella and the conspicuous group of mucocyst in the posterior region. Phylogenetic analysis based on the LSU rDNA D1–D2 region revealed monophyletic relationships with strains from geographically distant regions. Pigment analysis by HPLC identified chlorophyll-a (62.3 pg cell⁻¹) and fucoxanthin (38.4 pg cell⁻¹) as the main dominant pigments. Cytotoxicity assays using RTgill-W1 cells exposed for 2 h to culture supernatants and intracellular extracts showed strain-specific effects. The most toxic strain (LPCc049) reduced gill cell viability down to 53% in the supernatant exposure, while LC₅₀ values ranged from 1.6 × 10⁴ to 4.7 × 10⁵ cells mL⁻¹, depending directly on the strain and treatment type. No brevetoxins (PbTx-1, -2, -3, -6, -7, -8, -9, -10, BTX-B1 and BTX-B2) were detected by LC–MS/MS, suggesting that the cytotoxicity may be linked to the production of reactive oxygen species (ROS), polyunsaturated fatty acids (PUFAs), or hemolytic compounds, as previously hypothesized in the literature. These findings offer novel insights into the toxic potential of F. japonica in South America and underscore the need for further research to elucidate the mechanisms underlying its ichthyotoxic effect. Full article

The demand for wild animal meat, popularly called “bushmeat”, serves as a driving force behind the emergence of infectious diseases, potentially transmitting a variety of pathogenic bacteria to humans through handling and consumption. This study investigated the microbial load and bacterial diversity in bushmeat sourced from a prominent bushmeat market in Kumasi, Ghana. Carcasses of 61 wild animals, including rodents (44), antelopes (14), and African civets (3), were sampled for microbiological analysis. These samples encompassed meat, intestines, and anal and oral swabs. The total aerobic bacteria plate count (TPC), Enterobacteriaceae count (EBC), and fungal counts were determined. Bacterial identification was conducted using MALDI-TOF biotyping. Fungal counts were the highest across all animal groups, with African civets having 11.8 ± 0.3 log₁₀ CFU/g and 11.9 ± 0.2 log₁₀ CFU/g in intestinal and meat samples, respectively. The highest total plate count (TPC) was observed in rodents, both in their intestines (10.9 ± 1.0 log₁₀ CFU/g) and meat (10.9 ± 1.9 log₁₀ CFU/g). In contrast, antelopes exhibited the lowest counts across all categories, particularly in EBC from intestinal samples (6.1 ± 1.5 log₁₀ CFU/g) and meat samples (5.6 ± 1.2 log₁₀ CFU/g). A comprehensive analysis yielded 524 bacterial isolates belonging to 20 genera, with Escherichia coli (18.1%) and Klebsiella spp. (15.5%) representing the most prevalent species. Notably, the detection of substantial microbial contamination in bushmeat underscores the imperative for a holistic One Health approach to enhance product quality and mitigate risks associated with its handling and consumption. Full article

Industrial building renovation is a sustainable strategy to preserve urban heritage while meeting modern needs. However, how interior material scenes affect users’ emotions, thermal perception, and functional preferences remains underexplored in adaptive reuse contexts. This study used virtual reality (VR) to examine four common material scenes—wood, concrete, red brick, and white-painted surfaces—within industrial renovation settings. A total of 159 participants experienced four Lumion-rendered VR environments and rated them on thermal perception (visual warmth, thermal sensation, comfort), emotional response (arousal, pleasure, restoration), and functional preference. Data were analyzed using repeated measures ANOVA and Pearson correlation. Wood and red brick scenes were associated with warm visuals; wood scenes received the highest ratings for thermal comfort and pleasure, white-painted scenes for restoration and arousal, and concrete scenes, the lowest scores overall. Functional preferences varied by space: white-painted and concrete scenes were most preferred in study/work settings, wood in social spaces, wood and red brick in rest areas, and concrete in exhibition spaces. By isolating material variables in VR, this study offers a novel empirical approach and practical guidance for material selection in adaptive reuse to enhance user comfort, emotional well-being, and spatial functionality in industrial heritage renovations. Full article

Background: The development of brain metastases (BM) is a relatively uncommon but significantly adverse event in the spread of colorectal cancer (CRC). Although management of CRC BM has improved with advances in imaging and systemic therapies, clinical outcomes remain poor. Methods: This retrospective cohort study used the U.S. National Cancer Database to evaluate survival outcomes, treatment patterns, and prognostic factors in CRC patients diagnosed with BM between 2010 and 2020. Patients with isolated brain-only metastases formed the primary analytic cohort, while those with additional extracranial metastases were included for descriptive comparison. Multivariable Cox proportional hazards and logistic regression models were used to assess factors associated with of survival. Proportional hazards assumptions were tested using Schoenfeld residuals. Accelerated failure time models were also employed. Results: From a cohort of 1,040,877 individuals with CRC, 795 had metastatic disease present along with relevant data, of which 296 had isolated BM. Median overall survival (mOS) in BM-only metastatic disease group was 7.82 months (95% CI: 5.82–9.66). The longest survival was observed among patients treated with stereotactic radiosurgery combined with systemic therapy (SRS+Sys), with a median OS of 23.26 months (95% CI: 17.51–41.95) and a 3-year survival rate of 35.8%. In adjusted Cox models, SRS, systemic therapy, and definitive surgery of the primary site were each independently associated with reduced hazard of death. Rectal cancer patients had longer survival than those with colon primaries (mOS: 10.35 vs. 6.08 months). Age, comorbidity burden, and insurance status were not associated with survival in adjusted analyses. Conclusions: SRS+Sys was associated with longer survival compared to other treatment strategies. However, treatment selection is highly dependent on individual clinical factors such as performance status, comorbidities, and disease extent; therefore, these findings must be interpreted with caution Future prospective studies incorporating molecular and biomarker data are warranted to better guide care in this rare and high-risk group. Full article

Neocosmospora (Nectriaceae) is a globally distributed fungal genus, traditionally recognized as a group of plant pathogens, with most members known to cause severe plant diseases. However, recent studies have demonstrated that many of these fungi can also colonize plants endophytically, with certain strains capable of promoting plant growth and stimulating the production of secondary metabolites. In this study, 13 strains of Neocosmospora were isolated from the stems and leaves of Dracaena cambodiana and D. lourei in Yunnan Province, China. To clarify the taxonomic placement of these strains, morphological examination and multi-gene (ITS, nrLSU, tef1, rpb1, and rpb2) phylogenetic analyses were performed. Based on morphological and phylogenetic evidence, four new species are introduced and described here: N. hypertrophia, N. kunmingense, N. rugosa, and N. simplicillium. This study expands our understanding of the fungal diversity associated with Dracaena, provides essential data for the taxonomy of Neocosmospora, and serves as a resource for the future development and utilization of Neocosmospora endophytes. Full article