Search Results (20,556)

Background/Objectives: The COVID-19 (Coronavirus Disease, 2019) pandemic affected all countries in a variety of ways, and forced policymakers to adapt national health infrastructure. In this context, the strategic adaptation and policy evolution of small island states are understudied. Therefore, the objective of this study was to quantitatively analyse the relationship between confirmed COVID-19 cases and health policy decisions in Northern Cyprus. We also examined the shifting management strategies employed during the pandemic using a replicable statistical analysis framework. Methods: In this mixed-methods study, we used systematic thematic analysis to categorise official policy decisions from March 2020 to December 2022. Yearly linear regression models using SPSS and Python correlated the monthly number of decisions with the number of confirmed COVID-19 cases. The analyses included R² values, p-values, and visualisations with 95% confidence intervals. Results: The findings of this study highlight a three-phase strategic period. In 2020, the results (R² = 0.03, p = 0.63) showed no significant relationship, indicating initial uncertainty. The results (R² = 0.60, p = 0.003) indicate a strong negative correlation in 2021, which reflects the consistency of the proactive suppression strategies adopted. Conversely, for 2022, the results (R² = 0.79, p < 0.001) show a strong positive correlation representing the shift to a reactive mitigation strategy, in which the government responded based on case peaks. Conclusions: This study’s primary finding is that strategic agility was key to managing the pandemic. For small island states in particular, the effectiveness of geographic advantages like border control depends on a coherent strategy that transcends initial uncertainty. Our data-driven framework provides a tool for analysing this strategic evolution and guiding responses to future pandemics. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) alters maternal metabolism during pregnancy and may impact the biochemical composition of breast milk. Given the critical role of human milk in early-life metabolic programming, identifying metabolic alterations in GDM milk and understanding the effects of insulin therapy has important implications for neonatal health. This study aims to investigate the metabolomic profile of transitional breast milk in mothers with gestational diabetes mellitus compared with healthy controls and to evaluate the impact of insulin therapy on milk metabolite composition. Methods: Breast milk samples were collected between postpartum days 10 and 15 from 80 mothers with GDM and 80 matched controls. Metabolomic profiling was performed using gas chromatography–mass spectrometry (GC–MS), and data were analyzed using multivariate and univariate statistical techniques including PCA, PLS–DA, logistic regression, and ROC analysis. Conclusions: A total of 133 metabolites were identified, and GDM mothers exhibited a distinct metabolomic signature characterized by significant alterations in carbohydrate, amino acid, and microbial-derived metabolites. In particular, galactinol, arabitol, and pyrogallol were significantly decreased, while α-ketoglutaric acid and citric acid were elevated in the GDM group. Insulin-treated mothers showed unique metabolic changes involving glycolytic intermediates (glycerone phosphoric acid), purine metabolism (xanthine), and oxidative pathways (isocitric acid, gluconic acid lactone). Multivariate models based on the top metabolites achieved moderate discriminatory performance (AUC = 0.68). GDM is associated with substantial metabolic changes in transitional breast milk, and insulin therapy appears to modulate these alterations further. These findings suggest that maternal metabolic status and its treatment can shape the neonatal nutritional environment, potentially influencing early metabolic programming. Full article

By applying the Non-Perturbative Approach (NPA), the corresponding linear differential equation is obtained. Aimed at organizational investigation, the resulting linear equation is used. Strong agreement between numerical calculations and the precise frequency is demonstrated, and the reliability of the results acquired is established by the correlation with the numerical solution. Additionally, this study explores a new control process to affect the stability and behavior of dynamic motorcycle systems that vibrate nonlinearly. A multiple time-scale method (MTSM) is applied to examine the analytical solution of the nonlinear differential equations describing the aforementioned system. Every instance of resonance was taken out of the second-order approximations. The simultaneous primary and 1:1 internal resonance case ($\mathsf{\Omega }\approx {\omega }_{eq},$${\omega }_2\approx {\omega }_{eq}$) is recorded as the worst resonance case caused while working on the model. We investigated stability with frequency–response equations and bifurcation. Numerical solutions for the system are covered. The effects of the majority of the system parameters were examined. In order to mitigate harmful vibrations, the controller under investigation uses (PD) proportional derivatives with (PPF) positive position feedback as a new control technique. This creates a new active control technique called PDPPF. A comparison between the PD, PPF, and PDPPF controllers demonstrates the effectiveness of the PDPPF controller in reducing amplitude and suppressing vibrations. Unwanted consequences like chaotic dynamics, limit cycles, or loss of stability can result from bifurcation, which is the abrupt qualitative change in a system’s behavior as a parameter. The outcomes showed how effective the suggested controller is at reducing vibrations. According to the findings, bifurcation analysis and a control are crucial for designing vibrating dynamic motorcycle systems for a range of engineering applications. The MATLAB software is utilized to match the analytical and numerical solutions at time–history and frequency–response curves (FRCs) to confirm their comparability. Additionally, case studies and numerical simulations are presented to show how well these strategies work to control bifurcations and guarantee the desired system behaviors. An analytical and numerical solution comparison was prepared. Full article

Equine sarcoids are the most common dermatological neoplasm in horses worldwide, associated with bovine papillomavirus (BPV) infection and characterized by high recurrence rates after conventional therapies. Bacillus Calmette–Guérin (BCG) immunotherapy has historically been used for sarcoid treatment, yet its role in contemporary veterinary oncology remains debated. This narrative review critically examines the immunological mechanisms, clinical efficacy, and limitations of BCG in equine sarcoid therapy, while integrating insights from comparative oncology and One Health perspectives. A systematic search following PRISMA-based criteria identified 55 relevant studies published over the past four decades. Evidence indicates that BCG activates innate and adaptive immunity through TLR2/4 signaling, macrophage polarization, and enhanced CD8+ T-cell responses, leading to partial or complete sarcoid regression in select cases. However, therapeutic outcomes are highly variable due to heterogeneity in protocols (dose, strain, adjuvant use) and frequent adverse inflammatory reactions. Comparative analyses highlight that modern alternatives—such as cryotherapy, cisplatin-based protocols, and topical imiquimod—achieve higher efficacy and lower recurrence rates in many clinical settings. Although BCG is now rarely considered a first-line therapy, it remains relevant in resource-limited regions, such as the Amazon Biome, where cost-effectiveness and accessibility are critical. Future directions include randomized controlled trials, standardized protocols, and innovative approaches such as checkpoint inhibition, CRISPR-Cas9 targeting of viral oncogenes, and nanoparticle delivery systems. This review provides a balanced and data-driven synthesis of BCG immunotherapy, clarifying its historical contributions, current limitations, and translational opportunities for advancing equine and comparative oncology. Full article

This study investigates underground heat sources and develops effective strategies for mitigating heat hazards in coal mines, with a focus on the design and optimization of cooling systems. Using the 3107 fully mechanized mining face of Menkeqing Coal Mine as a case study, geological survey data and in situ measurements were combined to evaluate the severity of thermal hazards. Thermodynamic and heat transfer models were applied to quantify heat dissipation from multiple sources. Computational fluid dynamics (CFD) simulations, based on data-driven modeling and geometric reconstruction, tested different equipment layouts and spacing configurations to identify optimal cooling schemes. Field implementation of the designed cooling system confirmed its effectiveness, offering practical guidance for improving heat hazard control and cooling system optimization in deep coal mines. Full article

Objective: Vitamin D deficiency (VDD) is common in pregnancy and may affect lipid metabolism. The underlying mechanisms are multifactorial, but most evidence so far comes from non-pregnant populations. This study aims to identify metabolites and metabolic patterns associated with VDD in early pregnancy and to evaluate their relationships with maternal lipid profiles. Methods: A nested case–control research was carried out in the Zhoushan Pregnant Women Cohort (ZPWC). Cases were defined as women with VDD (25(OH)D < 20 ng/mL), and controls (≥20 ng/mL) were matched 1:1 using propensity scores based on age, pre-pregnancy BMI, gestational week, and calendar year at blood sampling. The untargeted metabolomics of first-trimester maternal plasma were measured. Metabolic profiles were analyzed using partial least squares-discriminant analysis (PLS-DA). Principal component analysis (PCA) was applied to visualize group separation, and metabolite set enrichment analysis (MSEA) was performed to reveal biologically relevant metabolic patterns. Associations between VDD-related metabolite components in early pregnancy and lipid levels in mid-pregnancy were assessed using linear regression models. Results: 44 cases and 44 controls were selected for the study. There were 60 metabolites identified as being connected to VDD. Among these, 26 metabolites, primarily glycerophospholipids and fatty acyls, exhibited decreased levels in the VDD group. In contrast, 34 metabolites showed increased levels, mainly comprising benzene derivatives, carboxylic acids, and organooxygen compounds. PCA based on these metabolites explained 52.8% of the total variance (R²X = 0.528) across the first six principal components (PC1: 16.4%, PC2: 10.6%, PC3: 9.2%, PC4: 6.3%, PC5: 5.7%, PC6: 4.6%). PC2, dominated by lineolic acids and derivatives, was negatively associated with total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) (all p < 0.01). PC3, dominated by glycerophosphocholines, was negatively associated with TC, TG, and high-density lipoprotein cholesterol (HDL-C) (all p < 0.05). MSEA revealed significant enrichment of the pantothenate and CoA biosynthesis pathway after multiple testing correction (FDR < 0.05). Conclusions: This study reveals distinct metabolic alterations linked to VDD and suggests potential mechanisms underlying its association with maternal lipid metabolism in early pregnancy. Full article

This study compares immersive VR-based control systems with conventional keyboard-based control to examine the efficacy of VR interfaces for controlling robotic arms in Internet of Things (IoT) education. A 5-DOF robotic arm with MG996R servomotors and controlled by an Arduino microcontroller and Raspberry Pi wireless communication was operated by 31 third-year engineering students in hands-on experiments using both control modalities. To determine student preferences across in-person, online, and hybrid learning contexts, the study applied a mixed-methods approach that combined qualitative evaluation using open-ended questionnaires and quantitative analysis through Likert-scale surveys. First, it should be mentioned that most of the reported papers either use a robotic arm or a VR system in education. However, we are among the first to report a combination of the two. Secondly, in most cases, there are either technical papers or educational quantitative/qualitative research papers on existing technologies reported in the literature. We combine an innovative education context (robotic arm and VR), completed with a quantitative and qualitative study, making it a complete experiment. Lastly, combining qualitative with quantitative research that complement each other is an innovative aspect in itself in this field. Full article

Transportation, environmental changes, and overcrowding can induce short-term stress in livestock, leading to physiological imbalances even within a short period. Cortisol is a stress-response hormone and its concentration in the blood can rapidly fluctuate depending on the individual and situation. This study evaluated the short-term effects of cortisol by applying blood cortisol concentrations that mimicked the normal and stress-induced levels observed in Korean native cattle (Hanwoo) to the culture medium of Hanwoo muscle stem cells (HWSC). Treatments were designed with five cortisol concentrations (0, 5, 10, 30, and 70 ng/mL) and four treatment times (0.5, 1, 2, and 3 h), based on the CCK-8 and viable cell count results. The expression levels of cortisol receptor-related genes (NR3C1, HSP70, and HSP90AA1) increased and reached a peak at 30 min post-treatment. After 30 min, the expression of these genes gradually decreased. However, in the case of HSP70, expression tended to increase again after 3 h of treatment. This could be seen as the regulation of cortisol inflow into the HWSC. Upon examining the oxidative effects of cortisol on superoxide dismutase 1 (SOD1), glutathione peroxidase (GPX), catalase (CAT), and oxygen consumption rate (OCR), the expression of antioxidant factors increased and peaked at 30 min of treatment. Following this peak, their levels generally began to decrease. However, in the 70 ng/mL group, the expression of these factors remained at a high level compared to the control group even after 30 min. In addition, the cellular respiration index and ATP production increased as the treatment prolonged, regardless of the concentration, as shown by the OCR analysis. These results can be considered a phenomenon corresponding to the accumulation of oxidative by products, such as Reactive Oxygen Species (ROS), caused by cortisol. The gene expression of apoptosis factors (p53, BAX, Caspase-3) temporarily increased at 30 min but then decreased. Caspase-3 protein activity was elevated at 30 min in the 70 ng/mL group, which later reduced. These results suggested that short-term cortisol administration had no effect on apoptosis in muscle cell culture. Therefore, the study findings elucidating the effects of short-term cortisol treatment on HWSC suggest that short-term stress may not have a significant negative effect on Hanwoo muscle. However, as this study was limited to muscle stem cells derived from Hanwoo, further investigation is required to determine whether the observed responses are consistent across different species and in vivo environments. Full article

Background/Objectives: Cutaneous angiosarcoma (CAS) is a rare and aggressive endothelial malignancy with a high rate of local recurrence and distant metastasis. In advanced cases, where surgical resection is not feasible, systemic therapy remains the cornerstone of treatment. This review aims to summarize the current landscape of systemic therapies for unresectable or metastatic CAS and discuss emerging strategies, particularly focusing on immune checkpoint inhibitors (ICIs). Methods: A comprehensive review of the literature was conducted, including clinical trials, retrospective studies, and case series focusing on systemic treatments for advanced CAS. Therapeutic approaches covered include cytotoxic chemotherapy, molecular targeted therapies, and ICIs, as well as combination strategies. Special attention was given to biomarker studies and ongoing clinical trials. Results: Taxane-based chemotherapy, particularly paclitaxel, has demonstrated clinical activity and remains a standard option. Molecular targeted agents such as pazopanib have yielded modest efficacy. Recent trials of ICIs, including the SWOG S1609 DART and AngioCheck studies, have shown encouraging results in select subgroups, especially tumors from sun-exposed regions associated with high tumor mutational burden (TMB). Although AngioCheck did not meet its predefined response criteria, a subset of patients achieved disease control. Biomarkers such as TMB, PD-L1 expression, and tumor-infiltrating lymphocytes are under investigation to guide patient selection. Combination therapies with ICIs and tyrosine kinase inhibitors (TKIs) are being actively explored. Conclusions: While systemic therapies for CAS remain limited in efficacy, ICIs—particularly in combination with TKIs—represent a promising avenue. Future trials should emphasize biomarker-driven, CAS-specific strategies to improve clinical outcomes in this challenging malignancy. Full article

Fibroblast growth factor 21 (FGF21), a pleiotropic hormone, is a significant modulator of energy homeostasis. We evaluated serum FGF21 levels in patients with a deficiency of mitochondrial aminoacyl-tRNA synthetase (mt-aARSs). Six patients with mitochondrial aminoacyl tRNA synthetase deficiency and twelve healthy volunteers were included in this study. Whole-exome sequencing was used for molecular diagnosis. Serum FGF21 levels in the case group and healthy volunteers were analyzed using the enzyme-linked immunosorbent assay. Exome sequencing test revealed nine different pathogenic variants in the AARS2, EARS2, DARS2, SARS2, and WARS2 genes. A statistically significant difference was found between the serum FGF21 levels of the case and control groups: case group (n = 6), 882.49 ± 923.60 pg/mL; control group (n = 12), 20.89 ± 2.63 pg/mL (p < 0.001). The area under the ROC curve for FGF21 in the differential diagnosis of mitochondrial aminoacyl-tRNA synthetase deficiency was 1.000 (0.813–1.000). Sensitivity and specificity were 100%, and positive and negative predictive values were also 100% for an FGF21 cut-off value > 27.4 pg/mL. Assessment of FGF 21 levels as an indicator of mitochondrial damage in mt-aARSs deficiency may provide insight into the level of damage. Investigation of the biochemical mechanisms underlying the different levels of damage caused by different aminoacyl tRNA synthetases will be important in terms of elucidating clinical heterogeneity. Full article

Wellbore stability is a crucial factor affecting the safe exploitation of offshore natural gas hydrates. As a sustainable energy source, natural gas hydrate has significant reserves, high energy density, and low environmental impact, making it an important candidate for alternative energy. Although research on the stability of screen pipes during horizontal-well hydrate production is currently limited, its importance in sustainable energy extraction is growing. This study therefore considers the effects of hydrate phase change, gas–water seepage, energy and mass exchange, reservoir deformation, and screen pipe influence and develops a coupled thermal–fluid–solid–chemical field model for horizontal-well natural gas hydrate production. The model results were validated using experimental data and standard test cases from the literature. The results obtained by applying this model in COMSOL Multiphysics 6.1 showed that the errors in all simulations were less than 2%, with errors of 12% and 6% observed at effective stresses of 0.5 MPa and 3 MPa, respectively. The simulation results indicate that the presence of the screen pipe in the hydrate reservoir exerts little effect on the decomposition of gas hydrates, but it effectively mitigates stress concentration in the near-wellbore region, redistributing the effective stress and significantly reducing the instability risk of the hydrate reservoir. Furthermore, the distribution of mechanical parameters around the screen pipe is uneven, with maximum values of equivalent Mises stress, volumetric strain, and displacement generally occurring on the inner side of the screen pipe in the horizontal crustal stress direction, making plastic instability most likely to occur in this area. With other basic parameters held constant, the maximum equivalent Mises stress and the instability area within the screen increase with the rise in the production pressure drop and wellbore size, and the decrease in screen pipe thickness. The results of this study lay the foundation for wellbore instability control in the production of offshore natural gas hydrates via depressurization. The study provides new insights into sustainable energy extraction, as improving wellbore stability during the extraction process can enhance resource utilization, reduce environmental impact, and promote sustainable development in energy exploitation. Full article

Escherichia coli is a significant cause of Neonatal Calf Diarrhoea (NCD). Its extensive antigenic diversity, coupled with the ability to acquire antimicrobial resistance determinants, hampers treatment effectiveness and compromises the control measures. This study investigated the link between the presence of multidrug-resistant (MDR) E. coli and virulence factors (VFs) in NCD from central France (Departments of Cantal, Haute-Loire, Loire, and Puy-de-Dôme), between 2016 and 2022. E. coli was identified at TERANA Laboratories, France, using API 20E (BioMérieux^®) and MALDI-TOF Mass Spectrometry. Virulence factors, namely adhesins, were assessed with the slide agglutination method, and antimicrobial susceptibility testing was conducted across various antimicrobial classes. Out of 2367 E. coli strains isolated from cases of NCD, a high percentage were resistant to aminopenicillins (88.8%), aminoglycosides (89.1%), tetracyclines (79.7%), quinolones (48.4%), and sulphonamides (42.4%). More than half (58.6%) carried VFs, and 84.9% exhibited MDR profile, of which 61.34% (1233/2010) also harboured VFs. The adhesin CS31A-producing E. coli was the most prevalent, followed by the fimbrial adhesins F5 and F17 (60.8%, 20.0%, and 8.3%, respectively), all of which were associated with a high prevalence of MDR strains (79.1–93.9%). The highest occurrence of MDR profiles was observed in E. coli strains carrying CS31A and in those lacking VFs, both groups showing co-resistance to aminopenicillins, aminoglycosides, and tetracyclines or sulphonamides. The calf production sector may act as a reservoir for MDR E. coli strains, regardless of the presence of VFs, posing a major threat to public health and safety. Full article

Background/Objective: US military personnel deployed to the Middle East were potentially subjected to harmful exposures, such as carcinogens from burn pits, which may increase the risk of lymphoid malignancies. Our objective was to determine the association between deployment and the risk of developing lymphoid malignancies. Methods: This was a retrospective nested matched case-control study from a cohort of 3.5 million veterans who enlisted in the military after September 2001 and were followed until death or last follow up through September 2024. Cases of lymphoid malignancies were identified by the VA Central Cancer Registry and controls were randomly selected from the same base cohort, matched by year of birth, year of enlistment, sex, race, and ethnicity. Exposure was defined as deployment to the Middle East as determined by identification on the VA Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) roster with confirmed dates of deployment or paystubs. Results: There were 1037 cases of lymphoid malignancies and 3572 matched controls. Deployment was not associated with a higher risk of developing lymphoid malignancies compared to non-deployment. Exposure to OEF/OIF was not associated with a higher risk of developing certain types of lymphoid malignancies. Conclusions: In this large, matched case-control study of US veterans, deployment to the Middle East was not associated with increased risk of developing lymphoid malignancies. While these findings do not support an increased lymphoid malignancy risk, important limitations remain, including the absence of detailed exposure and potential confounding variables. Prospective monitoring of specific types and doses of exposures during military deployment, development of lymphoid and other malignancies, and their underlying pathophysiology is indicated. Full article

Background/Objectives: Medroxyprogesterone acetate (MPA) is a synthetic contraceptive that can be used orally or as a once-every-three-month injection (i.e., depot MPA [dMPA]). Prior research has reported an increased association between dMPA and cerebral meningioma but has been limited in generalizability to meningioma cases treated with surgery or cases derived from an administrative database of commercial insurance enrollees. The current study builds upon prior research by examining the association among public insurance enrollees utilizing both a non-active and active comparator. Methods: Utilizing Alabama Medicaid data, cases of cerebral meningioma were matched to up to ten controls based on age and year of Medicaid enrollment. A conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the association between MPA and dMPA exposure and cerebral meningioma were compared to both an active and non-active comparator. Results: Among 469 cases and 4690 matched controls, there was no association between oral MPA and cerebral meningioma. Associations for dMPA exposure were similar when using a non-active (OR 1.87, 95% CI 1.16–3.00) or active comparator (OR 1.93, 95% CI 01.01–3.69). These associations were strongest for prolonged exposure compared to a non-active (OR 3.80, 95% CI 1.88–7.68) and active comparator (OR 3.67, 95% CI 1.09–12.29). Conclusion: The current results are consistent with the prior literature that dMPA exposure is associated with an increased likelihood of meningioma for prolonged use. More research is needed to examine whether the association is limited to a certain histology or grade of meningioma. Clinicians should consider discussing with patients these reported associations prior to using dMPA. Full article