Search Results (10,370)

In this study, GH19 chitinase (Chi) gene family was systematically identified and characterized using genomic assemblies from four cotton species: Gossypium barbadense, G. hirsutum, G. arboreum, and G. raimondii. A suite of analyses was performed, including genome-wide gene identification, physicochemical property characterization of the encoded proteins, subcellular localization prediction, phylogenetic reconstruction, chromosomal mapping, promoter cis-element analysis, and comprehensive expression profiling using transcriptomic data and qRT-PCR (including tissue-specific expression, hormone treatments, and Fusarium oxysporum infection assays). A total of 107 GH19 genes were identified across the four species (35 in G. barbadense, 37 in G. hirsutum, 19 in G. arboreum, and 16 in G. raimondii). The molecular weights of GH19 proteins ranged from 9.9 to 97.3 kDa, and they were predominantly predicted to localize to the extracellular space. Phylogenetic analysis revealed three well-conserved clades within this family. In tetraploid cotton, GH19 genes were unevenly distributed across 12 chromosomes, often clustering in certain regions, whereas in diploid species, they were confined to five chromosomes. Promoter analysis indicated that GH19 gene promoters contain numerous stress- and hormone-responsive motifs, including those for abscisic acid (ABA), ethylene (ET), and gibberellin (GA), as well as abundant light-responsive elements. The expression patterns of GH19 genes were largely tissue-specific; for instance, GbChi23 was predominantly expressed in the calyx, whereas GbChi19/21/22 were primarily expressed in the roots and stems. Overall, this study provides the first comprehensive genomic and functional characterization of the GH19 family in G. barbadense, laying a foundation for understanding its role in disease resistance mechanisms and aiding in the identification of candidate genes to enhance plant defense against biotic stress. Full article

This study presents an approach based on machine learning (ML) techniques to analyze the relationship between emergency room (ER) admissions for cardiorespiratory diseases (CRDs) and environmental factors. The aim of this study is the development and verification of an interpretable machine learning framework applied to environmental and health data to assess the relationship between environmental factors and daily emergency room admissions for cardiorespiratory diseases. The model’s predictive accuracy was evaluated by comparing simulated values with observed historical data, thereby identifying the most influential environmental variables and critical exposure thresholds. This approach supports public health surveillance and healthcare resource management optimization. The health and environmental data, collected through meteorological sensors and air quality monitoring stations, cover eleven years (2013–2023), including meteorological conditions and atmospheric pollutants. Four ML models were compared, with XGBoost showing the best predictive performance (R² = 0.901; MAE = 0.047). A 10-fold cross-validation was applied to improve reliability. Global model interpretability was assessed using SHAP, which highlighted that high levels of carbon monoxide and relative humidity, low atmospheric pressure, and mild temperatures are associated with an increase in CRD cases. The local analysis was further refined using LIME, whose application—followed by experimental verification—allowed for the identification of the critical thresholds beyond which a significant increase in the risk of hospital admission (above the 95th percentile) was observed: CO > 0.84 mg/m³, P_atm ≤ 1006.81 hPa, Tavg ≤ 17.19 °C, and RH > 70.33%. The findings emphasize the potential of interpretable ML models as tools for both epidemiological analysis and prevention support, offering a valuable framework for integrating environmental surveillance with healthcare planning. Full article

Phospholipids (PLs) are a group of biomolecules found in the milk fat globule membranes (MFGMs). Recently, MFGM phospholipids have attracted increasing amounts of attention due to their unique composition, stability, and potential health benefits, including protective effects against Alzheimer’s disease, hypercholesterolemia, and certain types of cancer. Although buffalo milk is the second most commonly produced milk and has high nutritional value, few studies have focused on the properties of buffalo MFGM. This study investigates the PLs composition of buffalo milk and related dairy by-products (whey and buttermilk). Milk and whey were collected from two dairy farms (A—small and B—big) to produce mozzarella buffalo cheese (high-pasteurization milk for GDO production and low for local); while buttermilk was obtained from a butter-making farm. Phospholipids were purified by a solid-phase extraction method and then identified by high-performance liquid chromatography with an evaporative light-scattering detector (HPLC/ELSD). Five classes of phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM)] were identified. The thermal process of milk did not significantly affect the PLs milk. However, local whey showed a higher concentration of total PLs than GDO, which was mainly represented by PE followed by PC content. Farm A exhibited higher PL content than B, particularly with a greater concentration of SM. Buttermilk showed the lowest PLs content. These findings offer valuable insights for the dairy industry and related applications, contributing to the valorization of buffalo dairy products. Full article

Parkinson’s disease (PD) is a progressive, multisystemic α-synucleinopathy, recognized as the second most prevalent neurodegenerative disorder globally. Its neuropathology is characterized by the degeneration of dopaminergic neurons, particularly in the substantia nigra pars compacta (SNpc), and the intraneuronal accumulation of α-synuclein-forming Lewy bodies. Oxidative stress is a key contributor to PD pathogenesis. Thioredoxin-interacting protein (TXNIP) is a crucial regulator of cellular redox balance, inhibiting the antioxidant function of thioredoxin. This pilot study aimed to investigate the protein expression and localization of TXNIP in the SNpc of PD patients compared to healthy controls. We performed immunohistochemical analyses on 12 post-mortem human brain sections (formalin-fixed, paraffin-embedded) from six subjects with PD and six healthy controls. The study was performed on PD subjects with Braak stage 6. Our findings revealed that in control samples, TXNIP protein was distinctly and closely associated with neuromelanin (NM) pigment within the cytoplasm of SNpc dopaminergic neurons. Conversely, in PD samples, there was a markedly weak cytoplasmic expression of TXNIP, and critically, this association with NM pigment was absent. Furthermore, PD samples exhibited a significant reduction in both dopaminergic neurons and NM content, consistent with advanced disease. These findings, which mirror previous transcriptomic data showing TXNIP gene under-expression in the same subjects, suggest that altered TXNIP expression and localization in SNpc dopaminergic neurons are features of late-stage PD, potentially reflecting neuronal dysfunction and loss. Full article

Background/Objectives: Ultrasound imaging is widely employed to assess kidney health and diagnose renal diseases. Accurate segmentation of renal structures in ultrasound images plays a critical role in the diagnosis and treatment of related kidney diseases. However, challenges such as speckle noise and low contrast still hinder precise segmentation. Methods: In this work, we propose an encoder–decoder architecture, named MAT-UNet, which incorporates two distinct attention mechanisms to enhance segmentation accuracy. Specifically, the multi-convolution pixel-wise attention module utilizes the pixel-wise attention to enable the network to focus more effectively on important features at each stage. Furthermore, the triple-branch multi-head self-attention mechanism leverages the different convolution layers to obtain diverse receptive fields, capture global contextual information, compensate for the local receptive field limitations of convolution operations, and boost the segmentation performance. We evaluate the segmentation performance of the proposed MAT-UNet using the Open Kidney US Data Set (OKUD). Results: For renal capsule segmentation, MAT-UNet achieves a Dice Similarity Coefficient (DSC) of 93.83%, a 95% Hausdorff Distance (HD95) of 32.02 mm, an Average Surface Distance (ASD) of 9.80 mm, and an Intersection over Union (IOU) of 88.74%. Additionally, MAT-UNet achieves a DSC of 84.34%, HD95 of 35.79 mm, ASD of 11.17 mm, and IOU of 74.26% for central echo complex segmentation; a DSC of 66.34%, HD95 of 82.54 mm, ASD of 19.52 mm, and IOU of 51.78% for renal medulla segmentation; and a DSC of 58.93%, HD95 of 107.02 mm, ASD of 21.69 mm, and IOU of 43.61% for renal cortex segmentation. Conclusions: The experimental results demonstrate that our proposed MAT-UNet achieves superior performance in multiple renal structure segmentation in ultrasound images. Full article

Since its first appearance as a human pathogen in 1976, Legionella pneumophila has been identified as a causative agent of community-acquired pneumonia (CAP). It survives in rivers, bays, lakes, and water reservoirs, and it is categorized as the fourth most common causative agent of CAP leading to hospitalization. We aimed to investigate patterns in which environmental, seasonal and regional factors may affect the prevalence of Legionnaires’ disease in Crete during the last two decades (2000–2022).The data used originated from the national surveillance database and included any person reported with travel-associated Legionnaires’ disease (TALD) between January 2000 and December 2022. Meteorological data were collected from the National Weather Service. The meteorological variables included (max) temperature (in °C), cloudiness (in octas), wind speed (in knots), and relative humidity (RH) (%). The statistical analysis was based on a case-crossover design with 1:1 matching characteristic. We revealed both seasonal and regional effects on the incidence of Legionnaires’ disease. Cases are significantly more frequent in autumn, in comparison to the other three seasons, while Rethymnon is the prefecture with fewer cases in comparison to Chania or Heraklion. In addition, our research showed that the majority of cases occurred during the years 2017–2018. TALD in Crete is significantly associated with temperature in °C and wind speed in knots. Our research suggests that temporal and spatial factors significantly influence disease cases. These results are in line with studies from foreign countries. The study results aspire to expand our knowledge regarding the epidemiological characteristics of Legionnaires’ disease in relation to local, geographical and meteorological factors on the island of Crete. Full article

Epidermolysis Bullosa (EB) comprises a group of inherited blistering disorders caused by pathogenic variants in genes essential for skin and mucosal integrity. Nonsense mutations, which generate premature termination codons (PTCs), result in reduced or absent protein expression and contribute to severe disease phenotypes in EB. Readthrough therapies, which may continue translation past PTCs to restore full-length functional proteins, have emerged as promising approaches. This review summarizes findings from preclinical studies investigating readthrough therapies in EB models, clinical studies demonstrating efficacy in EB patients, and emerging readthrough agents with potential application to EB. Preclinical and clinical studies with gentamicin have demonstrated restored type VII collagen and laminin-332 expression, leading to measurable clinical improvements. Parallel development of novel compounds—including aminoglycoside analogs (e.g., ELX-02), translation termination factor degraders (e.g., CC-90009, SRI-41315, SJ6986), tRNA post-transcriptional inhibitors (e.g., 2,6-diaminopurine, NV848), and nucleoside analogs (e.g., clitocine)—has expanded the therapeutic pipeline. Although challenges remain regarding toxicity, codon specificity, and variable protein restoration thresholds, continued advances in molecular targeting and combination therapies offer the potential to establish readthrough therapies as localized or systemic treatments addressing both cutaneous and extracutaneous disease manifestations in EB. Full article

Trace metal pollution in tropical freshwater ecosystems poses growing public health concerns, particularly in regions where fisheries are central to food security; however, little is known about metal exposure risks in the Western Amazon. This study presents the first assessment of trace metal concentrations in fish sold at the main market in El Coca, a rapidly growing city in the Ecuadorian Amazon. We analyzed 11 trace metals in 17 commercially important species and estimated seven health risk indices based on two fish consumption scenarios and international reference dose standards. Our results show that all species exceeded recommended thresholds for arsenic, mercury, and lead, while one species surpassed guidelines for aluminum. Metal concentrations varied by species and river of origin: small catfish from the Payamino River had elevated cadmium, chromium, copper, and manganese levels, potentially linked to upstream gold mining, whereas larger catfish showed higher mercury and arsenic accumulation. Monte Carlo simulations of risk indices suggested overall low disease risk, but the lack of local demographic data limits accurate assessments for vulnerable groups. Despite sampling limitations, our findings offer the first baseline for monitoring trace metal exposure in the northern Ecuadorian Amazon and underscore the need for targeted public health strategies in this understudied region. Full article

Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article

Retinal vessel segmentation in fundus images is critical for diagnosing microvascular and ophthalmologic diseases. However, the task remains challenging due to significant vessel width variation and low vessel-to-background contrast. To address these limitations, we propose WDM-UNet, a novel spatial-wavelet dual-domain fusion architecture that integrates spatial and wavelet-domain representations to simultaneously enhance the local detail and global context. The encoder combines a Deformable Convolution Encoder (DCE), which adaptively models complex vascular structures through dynamic receptive fields, and a Wavelet Convolution Encoder (WCE), which captures the semantic and structural contexts through low-frequency components and hierarchical wavelet convolution. These features are further refined by a Gated Fusion Transformer (GFT), which employs gated attention to enhance multi-scale feature integration. In the decoder, depthwise separable convolutions are used to reduce the computational overhead without compromising the representational capacity. To preserve fine structural details and facilitate contextual information flow across layers, the model incorporates skip connections with a hierarchical fusion strategy, enabling the effective integration of shallow and deep features. We evaluated WDM-UNet in three public datasets: DRIVE, STARE, and CHASE_DB1. The quantitative evaluations demonstrate that WDM-UNet consistently outperforms state-of-the-art methods, achieving 96.92% accuracy, 83.61% sensitivity, and an 82.87% F1-score in the DRIVE dataset, with superior performance across all the benchmark datasets in both segmentation accuracy and robustness, particularly in complex vascular scenarios. Full article

Background: Pulmonary fibrosis (PF), the end-stage manifestation of interstitial lung disease, is defined by excessive extracellular matrix deposition and alveolar destruction. Activated fibroblasts, the primary matrix producers, rely heavily on dysregulated glucose metabolism for their activation. While Salt Inducible Kinase 2 (SIK2) regulates glycolytic pathways in oncogenesis, its specific contributions to fibroblast activation and therapeutic potential in PF pathogenesis remain undefined. This study elucidates the functional role of SIK2 in PF and assesses its viability as a therapeutic target. Methods: SIK2 expression/localization in fibrosis was assessed by Western blot and immunofluorescence. Fibroblast-specific Sik2 KO mice evaluated effects on bleomycin-induced fibrosis. SIK2’s role in fibroblast activation and glucose metabolism impact (enzyme expression, metabolism assays, metabolites) were tested. SIK2 inhibitors were screened and evaluated therapeutically in fibrosis models. Results: It demonstrated significant SIK2 upregulation, specifically within activated fibroblasts of fibrotic lungs from both PF patients and murine models. Functional assays demonstrated that SIK2 is crucial for fibroblast activation, proliferation, and migration. Mechanistically, SIK2 enhances fibroblast glucose metabolism by increasing the expression of glycolysis-related enzymes. Additionally, this study demonstrated that the SIK2 inhibitor YKL06-061 effectively inhibited PF in both bleomycin and FITC-induced PF mouse models with the preliminary safety profile. Furthermore, we identified a novel therapeutic application for the clinically approved drug fostamatinib, demonstrating it inhibits fibroblast activation via SIK2 targeting and alleviates PF in mice. Conclusions: Our findings highlight SIK2 as a promising therapeutic target and provide compelling preclinical evidence for two distinct anti-fibrotic strategies with significant potential for future PF treatment. Full article

Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice. Full article

Background: Pancreatic adenocarcinoma (PDAC) with liver oligometastases (LOM) presents a therapeutic challenge, with optimal management strategies remaining uncertain. This study evaluates the long-term outcomes, patterns of disease progression, and potential factors influencing prognosis in this patient subset. Methods: Patients diagnosed with PDAC and LOM were retrospectively analyzed. Disease progression patterns, causes of death, and predictors of long-term outcomes were assessed. Results: Among 1442 patients diagnosed with metastatic PDAC between November 2009 and July 2024, 129 (9%) presented with LOM, defined as ≤3 liver lesions each measuring <2 cm. Patients with LOM had significantly improved overall survival (OS) compared to those with high-burden disease (p = 0.026). The cause of death (local regional disease vs. systemic disease) could be determined in 74 patients (57%), among whom age at diagnosis, history of smoking, and white blood cell (WBC) count differed significantly between groups. However, no significant difference in OS was observed between the two groups (p = 0.64). Sixteen patients (22%) died from local complications of the primary tumor, including 6 patients (7%) who showed no evidence of new or progressive metastases. In competing risk and multivariable analysis, a history of smoking remained the only factor significantly associated with death due to local complications. Conclusions: Approximately one in five patients with PDAC-LOM died from local tumor-related complications—some without metastatic progression—highlighting a potential role for surgical intervention. Further multicenter studies are warranted to refine diagnostic criteria and better identify patients who may benefit from surgery. Full article

Scrofuloderma, a cutaneous manifestation of tuberculosis, is a rare but clinically significant form of mycobacterial infection. It typically results from the local spread of Mycobacterium tuberculosis from an infected lymph node or bone area to the overlying skin. This disease is mainly characterized by chronic granulomatous inflammation, leading to skin ulcers and abscesses. Due to its nonspecific clinical presentation, scrofuloderma can mimic various dermatological conditions, making its diagnosis particularly challenging. This case report presents the clinical course of a patient who was positive for the Human Immunodeficiency Virus (HIV) with a diagnosis of scrofuloderma, managed at a tertiary healthcare center, with follow-up before and after treatment. A literature review was also made, highlighting the importance of maintaining a high index of clinical suspicion and utilizing appropriate diagnostic methods to ensure timely diagnosis. Full article

Pimelea is one of the highly toxic plants in Australia, particularly affecting cattle. It contains simplexin, a potent toxin that can cause Pimelea poisoning (St. George Disease) in livestock. A survey was conducted to assess the current impact of Pimelea on livestock production, pasture systems, and financial losses among agricultural producers. In addition, information was also sought about the environmental conditions that facilitate its growth and the effectiveness of existing management strategies. The survey responses were obtained from producers affected by Pimelea across nine different Local Government Areas, through three States, viz., Queensland, New South Wales, and South Australia. Pimelea was reported to significantly affect animal production, with 97% of producers surveyed acknowledging its detrimental effects. Among livestock, cattle were the most severely affected (94%), when compared to sheep (13%), goats (3%), and horses (3%). The presence of Pimelea was mostly observed in spring (65%) and winter (48%), although 29% of respondents indicated that it could be present all year-round under favorable rainfall conditions. Germination was associated with light to moderate rainfall (52%), while only 24% linked it to heavy rainfall. Pimelea simplex F. Muell. was the most frequently encountered species (71%), followed by Pimelea trichostachya Lindl. (26%). Infestations were reported to occur annually by 47% of producers, with 41% noting occurrences every 2 to 5 years. Financially, producers estimated average annual losses of AUD 67,000, with 50% reporting an average of 26 cattle deaths per year, reaching up to 105 deaths in severe years. Some producers were spending up to AUD 2100 per annum to manage Pimelea. While chemical and physical controls were commonly employed, integrating competitive pastures and alternative livestock, such as sheep and goats, was considered as a potential management strategy. This study reiterates the need for further research on sustainable pasture management practices to reduce Pimelea-related risks to livestock and agricultural production systems. Full article