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Cyclodextrin inclusion complexes enhance the solubility and anti-virulence activity of metronidazole against uropathogenic Proteus mirabilis
Proteus mirabilis is a major uropathogen implicated in catheter-associated urinary tract infections and infection-induced urolithiasis, often exhibiting multidrug resistance. Improving the solubility and bioactivity of existing drugs represents a promising pharmaceutical strategy to overcome these challenges. In this study, inclusion complexes of metronidazole with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD) were prepared using physical mixing and kneading methods. Complexes were characterized using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). In vitro release behaviour, minimum inhibitory concentration (MIC), and effects at sub-MIC levels on motility, urease-associated phenotype, and biofilm formation were evaluated. β-CD and HP-β-CD systems demonstrated improved release profiles compared to metronidazole alone. While MIC values remained within the mg/mL range, HP-β-CD complexes showed reduced MIC relative to aqueous metronidazole, achieving a four-fold reduction in MIC. At sub-MIC concentrations, β-CD and HP-β-CD formulations were associated with significant suppression of motility, reduced urease-associated phenotypes, and inhibition of biofilm formation. Molecular docking suggested spatial compatibility between metronidazole and cyclodextrins, though mechanistic conclusions remain predictive. These findings indicate that cyclodextrin-based complexation enhances physicochemical performance of metronidazole and may support adjunctive anti-virulence modulation in P. mirabilis. Further mechanistic and in-vivo studies are required to validate translational relevance.
Factors associated with psychological resilience, COVID-19-related anxiety, and COVID-19 vaccine hesitancy among academic professionals
Helminth-derived stefin-1 selectively reduces leukemic cell viability and promotes apoptosis in U937 cells
Leukemia remains a challenging hematological malignancy, particularly due to treatment resistance and the limited availability of therapies that selectively target cancer cells. Helminth-derived cysteine protease inhibitors (stefins) are mainly known for their roles in host–parasite interactions, but their effects on cancer cells have not been well explored. In this study, we investigated the biological activity of recombinant Fasciola gigantica Stefin-1 (rFgStefin-1) in the human U937 leukemic cell line. Treatment with rFgStefin-1 reduced cell viability in a dose- and time-dependent manner, with an IC₅₀ of approximately 11 µM at 48 h. In contrast, normal peripheral blood mononuclear cells (PBMCs) showed minimal changes under the same conditions. Flow cytometry analysis demonstrated increased apoptotic cell populations together with mitochondrial membrane depolarization following rFgStefin-1 treatment. At the molecular level, rFgStefin-1 treatment was associated with an increased BAX/BCL-2 ratio, increased cleaved caspase-3 expression, reduced AKT-associated signaling, and enhanced PARP cleavage. These findings were supported by both qRT-PCR and Western blot analyses. Overall, these results suggest that rFgStefin-1 promotes apoptosis in leukemic cells while exerting limited effects on normal cells under the tested conditions. Further studies are required to clarify the underlying molecular mechanisms and to evaluate the effects of rFgStefin-1 in additional leukemia models and in vivo systems.
Astrocyte activation and gliosis contribute to brain-wide neuroinflammation following experimental subarachnoid hemorrhage
Outcomes of proximal humeral chondroblastoma treated with intralesional curettage, electrocauterization of the cavity and bone grafting: A retrospective study
Objectives This study aimed to evaluate the 7-year outcomes of proximal humeral chondroblastoma treated with intralesional curettage, electrocauterization of the cavity and bone grafting in pediatric patients. Methods A total of 17 patients diagnosed with proximal humeral chondroblastoma who underwent surgical treatment consisting of intralesional curettage, cavity electrocauterization, and bone grafting at our center between January 1, 2008, and January 1, 2018, were retrospectively enrolled. All patients received postoperative splint immobilization for four weeks and were followed up for a minimum of seven years. Tumor recurrence was evaluated based on clinical manifestations and radiographic X-ray examination. Clinical outcomes included functional performance assessed using the Musculoskeletal Tumor Society (MSTS) score and the Quick Disabilities of the Arm, Shoulder and Hand (Quick DASH) scale, as well as postoperative complications. Results In total, 17 patients with proximal humeral chondroblastoma were enrolled in our study, including 10 males and 7 females, with a mean age of 10.9 ± 1.8 years old (range from 8 to 14 years). Among these 17 cases, there were 6 cases with lesions extending through the epiphyseal plate, and 11 cases with lesions located inside the epiphysis. During follow-up, 1 patient suffered reoperation due to tumor recurrence. Shortening of the affected upper limb occurred in 9 patients (52.9%), which was significantly associated with a young age(P = 0.012). The mean shortening was 1.2 ± 0.9 cm compared with the contralateral limb. The overall mean postoperative MSTS was 27.5 ± 1.4 points, with no significant difference between observed the limb shortening group (27.3 ± 1.4) and the non-shortening group (27.8 ± 1.4,P = 0.550). The overall Quick DASH score averaged 4.8 ± 3.9 (0–15.9), and no statistically significant difference was detected between the shortening group (5.3 ± 4.5) and the non-shortening group (4.3 ± 2.8; P = 0.452). Conclusions Intralesional curettage, cavity electrocauterization and bone grafting is an optional treatment for children with proximal humeral chondroblastoma but still has a risk of recurrence. Shortening of the affected upper limb is a common complication, which is possibly associated with young age but has no impact on the final functional outcomes. Level of Evidence Level IV, retrospective case series.
A comprehensive benchmark of deep learning architectures for appearance-based gaze estimation
SPP1 promotes cisplatin resistance in cervical cancer by regulating KRAS expression
Background Chemotherapy resistance is a major treatment issue for cervical cancer (CC), contributing to high morbidity and mortality. This study identifies key molecular drivers of CC progression and cisplatin (DDP) resistance, focusing on secreted phosphoprotein 1 (SPP1). Methods Differentially expressed genes (DEGs) were identified from TCGA-CC and GSE46857 datasets. Protein-protein interaction network analysis and topological ranking determined candidate genes. SPP1 expression was evaluated in CC cell lines using qPCR and Western blotting. Cisplatin-resistant CC cells were used to examine SPP1’s role in drug resistance. Functional assays assessed cell proliferation, apoptosis, migration, and invasion. Results Bioinformatics analysis identified SPP1 as a hub gene upregulated in CC. SPP1 expression was higher in CC and DDP-resistant cells. Silencing SPP1 inhibited cell growth and enhanced apoptosis, while overexpression had the opposite effects. Silencing SPP1 enhanced DDP sensitivity, while overexpression reduced DDP cytotoxicity. Mechanistically, SPP1 positively correlated with KRAS expression, and KRAS modulation partially reversed SPP1’s effects on DDP resistance. Conclusion SPP1 is upregulated in CC and DDP-resistant cells, promoting tumor progression and chemoresistance via KRAS. Targeting the SPP1-KRAS axis may help overcome chemotherapy resistance in CC.
Texture analysis on muscle T2 maps can reveal changes in upper trapezius muscles related to primary headache disorders
Abstract Migraine and tension-type headache (TTH) are highly prevalent primary headache disorders. Neck pain is common among patients with migraine or TTH, but objective biomarkers for the neck’s myofascial involvement within the trigemino-cervical complex (TCC) are lacking. This study aimed (1) to apply texture analysis (TA) to magnetic resonance imaging (MRI) covering the upper trapezius muscles with T2 maps, which are particularly sensitive to subtle edematous changes such as those following inflammation; and (2) to associate demographics, characteristics of sleep and sports, headache, and neck pain with muscle T2 values and derived texture features. Seventy-one participants (mean age 24.0 ± 3.0 years, 59 females; 22 healthy controls [HC], 21 migraine, 16 TTH, 12 migraine with TTH) underwent MRI of the upper trapezius muscles, followed by bilateral muscle segmentations and extraction of muscle T2 and first- and second-order texture features. Comparisons between HC and participants with primary headache disorders were performed following removal of outliers with the robust regression followed by outlier identification (ROUT) method (Mann-Whitney U tests, adjustment for multiple comparisons). Principal component analysis (PCA), linear, and logistic regression analyses (using bootstrapping with 5,000 permutations) were conducted based on image-derived parameters and headache and neck pain characteristics. Significant group differences were found between HC and participants with primary headache disorders for muscle T2 (30.14 ± 1.05 vs. 31.10 ± 0.92 ms, p < 0.001), sumaverage (0.007163 ± 0.0011 vs. 0.006366 ± 0.0012, p = 0.017), kurtosisglobal (1.15 ± 0.32 vs. 1.63 ± 0.81, p = 0.024), and energy (0.003514 ± 0.0006 vs. 0.004176 ± 0.0012, p = 0.043). According to PCA, a cluster including age, days with headache over the last three months, neck pain, muscle T2, kurtosisglobal, and skewnessglobal was identified, with a cluster close to the opposite direction including average hours of sports per week, average hours of sleep per week, sex, and varianceglobal. Muscle T2 ( p = 0.015) and sumaverage ( p = 0.022) were significantly associated with days with headache over the last three months. Furthermore, sumaverage was significantly associated with the presence of neck pain ( p = 0.024). T2 mapping with TA may provide objective and quantitative parameters for myofascial involvement and peripheral sensitization within the TCC, partially associated with clinical parameters such as the number of days with headache.
Socioeconomic disparities in children’s neurodevelopment before and during primary education: Evidence from Bagamoyo, Tanzania
Background Socioeconomic disparities in children’s neurodevelopment constitute a critical yet understudied developmental challenge in low- and middle-income countries (LMICs), yet longitudinal evidence from Sub-Saharan Africa (SSA) remains limited. This study aimed to evaluate the relationship between household wealth and neurocognitive trajectories in a cohort of Tanzanian children aged 6 months to 10 years. Methods We randomly selected 590 children aged 6 months to 10 years in Bagamoyo district, a low to moderate-malaria-endemic area in Tanzania. Participants completed comprehensive, age-appropriate neurodevelopmental assessments. The family’s socioeconomic status was derived from their household assets. Standardized, age-adjusted neurodevelopmental scores were regressed on socioeconomic status tertiles and by developmental periods: early childhood (6 months-3 years), preschool (4–5 years), and school age (6–10 years). Results While children from high- and low-Socioeconomic status (SES) families start with similar neurodevelopmental scores, a significant and sustained gap begins to emerge around age 2 years. This divergence results in a substantial disadvantage for children from the poorest households, with scores showing a difference of −0.36 Standard Deviation (SD) (95% CI: −0.64 to −0.08) during the preschool years and −0.41 SD (95% CI: −0.73 to −0.09) at school age. Conclusion Our results suggest that programs targeting the preschool period may be most effective in mitigating disparities in neurodevelopment.
Targeting NLRP3 with GDC-2394 ameliorates airway inflammation and smooth muscle hyperplasia in experimental asthma by suppressing the IL-6/JAK2/STAT3 axis
Police emergency dispatch model based on emergency level analysis and traffic planning
Emergency dispatching and rescue during emergencies have become a hot research topic in the field of transportation planning. Therefore, to address the low efficiency of cross-regional police emergency dispatch, the study carries out relevant exploration on the basis of emergency event level analysis and transportation planning. The emergency rescue demand evaluation system is constructed using the superior and inferior solution distance method to carry out the emergency hierarchy analysis. The police emergency dispatch model is constructed and solved using the improved particle swarm algorithm. The validation revealed that the improved solution algorithm improved the iteration efficiency by 54.33% on average and reduced the iteration time overhead by 56.10% on average over the particle swarm algorithm and the beetle antennae search algorithm. In the scheduling of emergency 1, the material demand satisfaction rate of all demand points was above 80%, among which the vegetable material demand satisfaction rate was 100%. In the scheduling of emergency 2, the demand for supplies at all demand points was above 91.3%, with the demand satisfaction rate for tent supplies as high as 100%. The above results indicate that the police emergency dispatch method can leverage the full advantages of transportation networks. By integrating intelligent optimization algorithms with artificial intelligence technology, the method achieves material dispatch for cross-regional emergency rescue incidents. This method is both feasible and practical.
Immature anophelines and their habitat characteristics in an urban setting of central Ethiopia
Phenotypic variations of naturally grown Iris persica L. accessions as revealed using multivariate analytical methods
Iris persica L. is a high-value ornamental species naturally distributed across montane regions of Iran, yet its intraspecific morphological variation remains underexplored. Understanding phenotypic diversity among wild accessions is critical for identifying superior genotypes suitable for conservation and horticultural breeding. This observational study was conducted on 78 naturally occurring I. persica accessions collected from seven ecogeographical regions of Markazi Province, Iran. Each accession represented a single independently growing individual plant, and 39 morphological and colorimetric traits were evaluated using multivariate statistical analyses. The results revealed considerable variation among accessions. Descriptive statistics showed that flower diameter ranged from 34.52 to 80.56 mm, fall length from 35.39 to 57.70 mm, and spathe length from 25.86 to 64.56 mm. Principal component analysis identified ten principal components explaining 82.46% of the total variation, with the first component (33.30%) driven primarily by flower size, fall length, and spathe length. The heatmap analysis clustered accessions into four distinct morphological groups, indicating clear phenotypic differentiation. Correlation analysis revealed significant positive associations between flower diameter and flower surface ( r = 0.87, p < 0.01), fall length and flower surface (r = 0.76, p < 0.01), and flower diameter and flower length ( r = 0.76, p < 0.01). Stepwise regression analysis indicated that fall length, flower diameter, and spathe length were key predictors of flower diameter. This study demonstrates extensive morphological diversity in I. persica , providing a strong basis for the selection of superior genotypes for ornamental breeding programs. Accessions such as ‘Alibolaghi-6’, ‘Sorkhe-4’, ‘Sorkhe-14’, ‘Shahbaz-11’, ‘Sorkhe-11’, ‘Sorkhe-12’, ‘Sorkhe-6’, ‘Palangdarreh-8’, ‘Sorkhe-5’, and ‘Bolagh-8’ exhibited outstanding floral characteristics and are recommended as potential candidates for future cultivar development and conservation strategies.
Quality of life and associated factors of adults with physical and visual disabilities residing in care-homes in the capital of a lower middle-income country: Sri Lanka
Bacterial profile and antimicrobial resistance patterns of bloodstream infections at Amhara Public Health Institute, Bahir Dar, Ethiopia
Background Managing bloodstream infections in resource-constrained regions like Ethiopia is challenging due to scarce blood culture surveillance data. To guide empirical therapy, this study determines the bacterial profiles and antimicrobial resistance patterns among patients with suspected bloodstream infections at the Amhara Public Health Institute. Methods This retrospective study analyzed blood culture records from the Amhara Public Health Institute spanning January 1, 2020, to December 30, 2023. Blood samples were processed using standardized manual culture techniques in accordance with World Health Organization (WHO) protocols. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute (CLSI) guidelines. Statistical analysis was conducted using SPSS version 20, employing descriptive statistics and regression models, with statistical significance defined as p < 0.05. Results True bacterial pathogens were isolated from 50.3% (N = 340) of the 676 patients, with Gram-negative bacteria predominating (61.2%, N = 208) over Gram-positive bacteria (38.8%, N = 132). Notably, ESKAPEE pathogens accounted for 96.5% (N = 328) of all isolates, led by Klebsiella spp. (25.9%, N = 88), Enterococcus spp. (20.9%, N = 71), and S. aureus (15.6%, N = 53). Among Gram-positive isolates, high resistance was observed against oxacillin (74.5%, N = 41), penicillin (72%, N = 36), and vancomycin (51.1%, N = 24). Gram-negative isolates exhibited critical resistance to national frontline therapeutics, including ampicillin (100%, N = 24), ceftriaxone (92.4%, N = 157), and trimethoprim-sulfamethoxazole (89.4%, N = 126). Overall, multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) profiles were detected in 43.8% (N = 149), 30.5% (N = 104) and 5.3% (N = 18) of isolates with similar distributions observed among ESKAPEE strains. Sex and age were the only independent predictors of culture positivity, with female sex reducing bloodstream infection odds by 44% (p = 0.002). Conversely, neonates (≤ 28 days) and young adults (15–24 years) had 4.7 times (p = 0.001) and 9.5-times (p = 0.001) higher odds compared to elderly patients. Conclusions This study reveals a severe 50.3% (N = 340) bloodstream infection rate dominated by highly resistant Gram-negative and ESKAPEE pathogens, disproportionately affecting males, neonates, and young adults. Combating this threat requires immediate antibiotic stewardship, updated guidelines, and advanced laboratory testing (anaerobic culture, minimum inhibitory concentration, and molecular sequencing) to track and manage resistance.
Investigation on the effect of waved struts on the energy absorption of BCC base mechanical metamaterials
Temporal trends in children pertussis burden in China and worldwide from 1990 to 2023: An analysis of the Global Burden of Disease Study 2023
Objective To evaluate the burden trends of children pertussis worldwide and in China from 1990 to 2023, and predict the disease burden for the next 10 years using a secondary analysis of Global Burden of Disease (GBD) 2023 data. Methods The primary metrics were mortality, disability-adjusted life - years (DALYs), prevalence, and incidence. A join – point regression model was used to estimate the average annual percentage change (AAPC). The autoregressive integrated moving average (ARIMA) model was used to predict the disease burden of pertussis from 2024 to 2033, and its adequacy was confirmed by the Ljung‑Box test. Results From 1990 to 2023, childhood pertussis mortality, DALYs, prevalence, and incidence declined sharply worldwide and in China. The global mortality rate in infants aged 1–5 months decreased by 57.7%, from 108.09 per 100,000 in 1990 to 45.73 per 100,000 population in 2023. Global age-standardized rates for both sexes, as well as those in all SDI regions, also showed steady downward trends. The rates of all four metrics peaked among infants aged 1–5 months in China and declined steadily with increasing age. For this infant group, the APC of pertussis prevalence and incidence in China decreased significantly during three different periods (1995–2004, 2009–2018, 2018–2021), but rose in two intervals (2004–2009, 2021–2023). ARIMA model projections revealed that age-standardized mortality and DALY rates will rise over the next decade, while prevalence and incidence will continue to decline. Notably, prevalence and incidence among infants aged 1–5 months are expected to increase slightly, rising from 277.59 and 2,026.43 per 100,000 in 2024 to 284.04 and 2,073.46 per 100,000 in 2033, respectively. Conclusion These findings underscore the disproportionate and persistent burden of pertussis in infants, indicating that prevention and treatment strategies should be adjusted to prevent further increase.
Bottom layer internal wave dynamics in the deep sea from decade-separated long-term observations
Leveraging free-text clinical records for heart disease classification through structured feature mapping
Hypertension and diabetes are major risk factors for heart disease, which remains among the leading causes of morbidity and mortality worldwide. Heart disease includes heart failure, myocardial infarction, stroke, and atherosclerosis. The identification and monitoring of these risk factors are crucial for early intervention and effective management. Machine learning techniques have the potential to improve the management and prevention of heart disease by enabling the automatic detection of risk factors, which in turn can help doctors personalize treatment and facilitate preventive interventions. In this study, heart disease risk factors were automatically extracted using a combination of multimodal data: both unstructured clinical narratives (e.g., the PrevComp corpus) and structured datasets (e.g., the UCI heart disease dataset) were used to predict the presence or absence of heart disease. The classification model is based on the Light Gradient Boosting Machine (LightGBM), a state-of-the-art implementation of the gradient boosting framework that employs tree-based learning algorithms. The developed classification model demonstrated a robust predictive accuracy of 83% for the presence/absence of heart disease, supporting its potential to accurately identify high-risk patients and improve clinical outcomes.