Search Results (2,161)

Let $G=(V,E)$ be a finite simple graph with $p=\left|V\right|$ vertices and $q=\left|E\right|$ edges, without isolated vertices or isolated edges. A vertex magic total labeling is a bijection f from $V\cup E$ to the consecutive integers$1,2,\dots ,p+q,$ with the property that, for every vertex $u\in V$, one has $f\left(u\right)+{\sum }_{uv\in E}f\left(uv\right)=k$ for some magic constant k. The vertex magic total labeling is called E-super if furthermore $f\left(E\right)=\{1,2,\dots ,q\}$. A graph is called (E-super) vertex magic if it admits an (E-super) vertex magic total labeling. In this paper, we verify the existence of E-super vertex magic total labeling for a class of 3-regular graphs with a perfect matching, and we confirm the existence of such a labeling for general regular graphs of odd degree containing particular classes of 3-factors, which provides us with known and new examples. Note that Harary graphs are among the popular models used in communication networks. In 2012, G. Marimuthu and M. Balakrishnan raised a conjecture that if $n>4$, $n\equiv 0\left(mod4\right)$ and m is odd, then the Harary graph $H_{m,n}$ admits an E-super vertex magic labeling. Among others, we are able to verify this conjecture except for one case while $m=3$ and $n\equiv 4\left(mod8\right)$. Full article

Emerging evidence indicates a high rate (>10%) of drug resistance (DR) associated with integrase strand transfer inhibitors (INSTIs) in developed countries, although there is limited information on DR during INSTI treatment in Uganda. With the increased use of INSTIs as standard first-line treatment, monitoring for DR using next-generation sequencing (NGS) has become essential. NGS can detect the lower-frequency variants that may be missed by traditional Sanger sequencing (SS). This study evaluates the diagnostic accuracy of next-generation sequencing (NGS) compared to Sanger sequencing for detecting HIV-1 INSTI resistance mutations and estimates the prevalence and factors associated with drug resistance among adults with virologic failure on INSTI-based regimens in Uganda. Utilizing the Illumina MiSeq platform for NGS, data was analyzed using STATA V.18 and a logistic regression model at 5% level of significance. This study demonstrates that NGS achieved 100% sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in detecting major mutations. NGS identified INSTI DRMs in 4% of adults at a ≥20% threshold and was able to detect both high- and low-abundance variants, which could have important implications for clinical outcomes. This study emphasizes the need for HIVDR testing before antiretroviral therapy (ART) initiation, given the increasing use of INSTIs. We recommend that healthcare providers adopt more sensitive diagnostics such as NGS and use detailed resistance profiles to tailor antiretroviral therapies. This approach is critical for effectively managing and preventing drug-resistant HIV strains. Full article

The four serotypes of dengue virus (DENV), types 1 to 4 (DENV-1 to DENV-4), exhibit approximately 60% identity in the encoded amino acid residues of viral proteins. Reverse transcription of RNA extracted from patient serum specimens followed by PCR amplification with serotype-specific probes is the current standard technique for DENV serotyping. However, this method is time- and cost-consuming, and rapid detection systems with low cost are desirable. Previously, we developed a prototype serotype-specific immunochromatography system. That system was composed of four strips with four corresponding distinct sample buffers, each specifically detecting a single DENV serotype. In the present study, we improved this system by combining pairs of strips into one lateral-flow cassette each, providing DENV-1 and DENV-2 detection in one device and DENV-3 and DENV-4 detection in a second device; this strategy successfully reduced the required sample volume. Furthermore, we were able to adjust the composition of the sample buffers such that a single sample buffer sufficed for all four DENV serotype detection reactions, allowing much easier handling of the devices. Evaluation of this new device against laboratory and clinical DENV isolates and clinical specimens from DENV-infected individuals showed sensitivity that was comparable to that of our previous version, yielding serotype specificity of 100%. These new devices are expected to be of use in the clinical setting, accelerating both prospective and retrospective epidemiological studies. Full article

The crude ethyl acetate extract of the culture of a marine sponge-associated fungus, Aspergillus unguis KUFA 0098, was tested for its capacity to inhibit the growth of ten phytopathogenic fungi, viz. Alternaria brassicicola, Bipolaris oryzae, Colletotrichum capsici, Curvularia oryzae, Fusarium semitectum, Lasiodiplodia theobromae, Phytophthora palmivora, Pyricularia oryzae, Rhizoctonia oryzae, and Sclerotium roflsii. At a concentration of 1 g/L, the crude extract was most active against P. palmivora, causing the highest growth inhibition (55.32%) of this fungus but inactive against R. oryzae and S. roflsii. At a concentration of 10 g/L, the crude extract completely inhibited the growth of most of the fungi, except for L. theobromae, R. oryzae, and S. roflsii, with 94.50%, 74.12%, and 67.80% of inhibition, respectively. The crude extract of A. unguis KUFA 0098 exhibited growth-inhibitory effects against B. oryzae and P. oryzae, causative agents of brown leaf spot disease and leaf blast disease, respectively, on rice plant var. KDML105, under greenhouse conditions. Chromatographic fractionation and purification of the extract led to the isolation of four previously described depsidones, viz. unguinol (1), 2-chlorounguinol (2), 2,4-dichlorounguinol (3), and folipastatin (4), as well as one polyphenol, aspergillusphenol A (5). The major compounds, i.e., 1, 2, and 4, were tested against the ten phytopathogenic fungi. Compounds 1 and 4 were able to inhibit growth of most of the fungi, except L. theobromae, R. oryzae, and S. roflsii. Compound 1 showed the same minimum inhibitory concentration (MIC) values as that of carbendazim against A. brassicicola, C. capsici, C. oryzae, and P. oryzae, while compound 4 showed the same MIC values as that of carbendazim against only C. capsici and P. oryzae. Compound 2 was not active against all of the ten phytopathogenic fungi tested. Full article

Background/Objectives: Changes in glucose metabolism impact central nervous system (CNS) homeostasis and, consequently, can lead to cognitive impairment and an increased risk for neurodegenerative and neuropsychiatric disorders. Astrocytes are glial cells that act as key regulators of brain glucose metabolism, thus representing important cellular targets for studies of different pathophysiological conditions, including hyperglycemia. Resveratrol, a natural polyphenol, has emerged as a potential protective strategy against diabetes and its complications; however, its glioprotective effects remain unclear. Based on these observations, we evaluated whether resveratrol could modify the inflammatory response in astroglial cells exposed to experimental hyperglycemic conditions. Methods: After reaching confluence, C6 astroglial cells were pre-incubated with 10 µM resveratrol in serum-free DMEM with 6 mM glucose for 24 h. The medium was then replaced with serum-free DMEM containing 12 mM glucose and 10 µM resveratrol for another 24 h. Controls were maintained in 6 mM glucose. Analyses included cell viability, metabolic activity, glucose and glutamate uptake, cytokine quantification by ELISA, and gene expression by RT-qPCR. Results: We show that high glucose levels modulate glucose and glutamate metabolism, and increase neuroinflammation, through the modulation of inflammatory mediators. In addition, high glucose upregulated the gene expressions of inducible nitric oxide synthase (iNOS), nuclear factor κB (NFκB), cyclooxygenase 2 (COX2), and Toll-like receptor 4 (TLR4) while decreasing mRNA levels of NLR family pyrin domain containing 3 (NLRP3) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). However, resveratrol was able to prevent most of these effects, particularly the high glucose-triggered inflammatory response. Resveratrol also modulated heme oxygenase 1 (HO-1) and nuclear factor erythroid-derived 2-like 2 (Nrf2), important targets associated with cellular protection. Conclusions: Our findings reinforce resveratrol as a potential glioprotective strategy against diabetes-related brain toxicity. Full article

Background/Objectives: The clinical presentation of homozygous familial hypercholesterolemia (HoFH) and severe heterozygous familial hypercholesterolemia (sHeFH) often demonstrates substantial overlap, as low-density lipoprotein cholesterol (LDL-C) levels may fall within similar ranges in both conditions. Methods: In this single-center 10-year retrospective study at the University of Debrecen, Hungary, we present the clinical characteristics of patients with 6 HoFH and 6 sHeFH diagnosed by genetic testing, discuss the diagnostic limitations encountered in clinical practice, and outline the key components of therapeutic management. Results: The mean age at diagnosis was lower in the HoFH group (31.83 ± 19.5 vs. 41.83 ± 15.9 years). The differences in total cholesterol (13.48 ± 7.4 vs. 11.02 ± 3.5 mmol/L) and LDL-C levels (10.89 ± 6.6 vs. 8.58 ± 3.26 mmol/L) between the groups were not statistically significant. Interestingly, vascular complications were more frequent in sHeFH group as well (4 vs. 1 patients). In neither the HoFH nor the sHeFH group were we able to achieve the target LDL-C levels, due in part to the specific features of the reimbursement system, patient and parental preferences, the extremely high baseline LDL-C levels, and certain genetic characteristics. Conclusions: Our findings highlight the importance of genetic testing-based personalized therapy in these specific patient subpopulations. We emphasize that serum LDL-C alone is insufficient to distinguish between HoFH and sHeFH patients, and that therapeutic challenges should be anticipated in both groups arising partly from limited patient adherence as well as from financial constraints. Full article

Currently, an active debate is underway among the academic community, urban planners, and policymakers regarding optimal models of urban development, given that the majority of the population now resides in cities. One concept under discussion is the 15 min city, which posits that all urban residents should be able to reach key, frequently used services within a 15 min walk or cycle. Although the literature suggests numerous potential benefits, debate persists about whether such cities would be optimal from the standpoint of sustainable development objectives and residents’ quality of life. The ongoing discussion also concerns the extent to which existing cities are capable of aligning with this concept. This is directly linked to the actual spatial distribution of individual services within the city. The literature indicates a research gap arising from a shortage of robust case studies that would enable a credible assessment of the practical implementation of this idea across diverse cities, countries, and regions. This issue pertains to Poland as well as to other countries. A desirable future scenario would involve comprehensive mapping of all cities, with respect to both the spatial distribution of specific services and related domains such as the quality and coherence of linear infrastructure. This article presents an analysis of the spatial accessibility of basic urban services in the context of implementing the 15 min city concept, using the city of Koszalin (Poland) as a case study. This city was selected due to its representative character as a medium-sized urban centre, both in terms of population and area, as well as its subregional functions within Poland’s settlement structure. Koszalin also exhibits a typical spatial and functional layout characteristic of many Polish cities. In light of growing challenges related to urbanisation, climate change, and the need to promote sustainable mobility, this study focuses on evaluating access to services such as education, healthcare, retail, public transport, and green spaces. The use of Geographic Information System (GIS) tools enabled the identification of spatial variations in service accessibility across the city. The results indicate that only 11% of Koszalin’s area fully meets the assumptions of the 15 min city concept, providing pedestrians with convenient access to all key services. At the same time, 92% of the city’s area offers access to at least one essential service within a 15 min walk. Excluding forested areas not intended for development increases these values to 14% and 100%, respectively. This highlights the extent to which methodological choices in assessing pedestrian accessibility can shape analytical outcomes and the interpretations drawn from them. Moreover, given this article’s objective and the adopted analytical procedure, the assumed pedestrian walking speed is the key parameter. Accordingly, a sensitivity analysis was conducted, comparing the reference scenario (4 km/h) with alternative variants (3 and 5 km/h). This approach demonstrates the extent to which a change in a single parameter affects estimates of urban-area coverage by access to individual services reachable on foot within 15 min. The analysis reveals limited integration of urban functions at the local scale, highlighting areas in need of planning intervention. This article proposes directions for action to improve pedestrian accessibility within the city. Full article

β-blockers are among the most widely prescribed cardiovascular drugs and are increasingly recognised as emerging pollutants due to their persistence, continuous release into aquatic environments, and potential toxicological effects on aquatic organisms. Their removal in conventional wastewater treatment plants is often inefficient, highlighting the need for biological remediation strategies. This study aimed to identify bacterial strains with the highest potential for the biotransformation of β-blockers. Therefore, we isolated and characterised bacterial strains capable of transforming two commonly used β-blockers—propranolol and metoprolol. The strains BB2 and BB3, which were able to transform propranolol and metoprolol, respectively, were identified as Raoultella terrigena and Stenotrophomonas terrae, respectively. BB2 showed broad metabolic versatility, utilising a wide range of carbon sources, whereas BB3 exhibited limited substrate utilisation. Antibiotic resistance profiling further distinguished the strains, with BB2 resistant across multiple antibiotic classes and BB3 largely sensitive. Co-metabolic assays demonstrated that supplementation with specific carbon and nitrogen sources markedly enhanced β-blocker removal, increasing propranolol biotransformation from 5% to 50% and metoprolol from 4% to 36%. These findings demonstrate the bioremediation potential of newly isolated strains and emphasise the importance of aligning microbial metabolic traits with nutrient conditions to improve pharmaceutical removal in wastewater treatment systems. Full article

Protein misfolding diseases are characterized by structurally abnormal proteins that lose their functionality, resulting in cellular and tissue dysfunction. Neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and Huntington’s disease, share a common etiopathogenesis characterize by the accumulation of misfolded proteins. These proteins autonomously aggregate within neuronal cells, triggering inflammation and cell death. The accumulation of misfolded proteins triggers endoplasmic reticulum (ER) stress, leading to alter Ca²⁺ homeostasis. This prolonged stress condition induces the cleavage of procaspase 4 which is resident in ER and activates NF-kB pathway activation, leading to inflammatory responses and cell death. In this study, the efficacy of the drug Vx-445 (Elexacaftor), used in the pharmacological treatment of cystic fibrosis, was assessed in human adenocarcinomic basal alveolar epithelial (A549) and neuronal (SH-SY5Y) cell lines, where ER stress was induced by Thapsigargin. The aim was to assess whether the corrector was able to reduce ER stress by restoring cellular homeostasis and, probably, the proper folding of misfolded proteins and reducing the inflammatory response triggered by these events. Therefore, protein levels of IkBα, p-STAT 3 and COXII were analyzed by flow cytofluorimetry, while Ca²⁺ content was measured by spectrofluorimetry. The results obtained suggest a significant effect of Vx-445 in restoring cellular homeostasis, leading to reduced expression of inflammation-related proteins, such as IL-6, tested by ELISA. Although preliminary, these results encourage further studies to explore the potential repurpose of Vx-445 as a therapeutic candidate for conditions involving ER stress and chronic inflammatory diseases associated with protein misfolding, beyond its current use in cystic fibrosis. Full article

This paper presents the implementation of the Grid-Forming (GFM) control technique in renewable energy source inverters to synchronize with the grid and provide frequency support. Specifically, the GFM Droop Control technique, based on the Power–Frequency relationship, is employed. The proposed model was developed and validated in the Matlab-Simulink environment. By using electromagnetic transient (EMT) simulations, we were able to precisely monitor and analyze voltage and current waveforms, thereby confirming the approach’s effectiveness in enhancing grid stability and power quality. The implementation of the GFM control technique in islanded mode demonstrated high system frequency stability. In response to sudden load changes up to 5 MW (equivalent to over 30% of the total load), a maximum frequency deviation of 0.04 Hz and a maximum Rate of Change of Frequency (RoCoF) of 4 Hz/s were observed. The system ensured the frequency’s return to its nominal value of 60 Hz, thanks to the virtual inertia and frequency regulation provided by the GFM. The total harmonic distortion (THD) of current and voltage in steady-state operation consistently remained below 1%, thus complying with IEEE 1547 standards. In tests with the GFM interconnected to the grid, the droop+LPF control provided dynamic support to the external system, effectively mitigating both frequency deviations and RoCoF. The GFM contributes to the grid’s frequency stability by providing virtual inertia. The power quality at the point of common coupling (PCC) was excellent, as the voltage distortion was maintained below 0.5%, confirming that the injection of harmonic currents does not violate established limits. Full article

Artificial neural networks have been evaluated and compared for modeling extreme wave forces exerted on coastal bridges during hurricanes. Long Short-Term Memory (LSTM) is selected for deep learning neural networks. A feedforward neural network (FFNN) is employed to represent the shallow learning network for comparison purposes. The two case studies consist of an emerged bridge deck destroyed by Hurricane Ivan and a submerged bridge deck impaired in Hurricane Katrina. Datasets for model training and verifications consist of wave elevation and force time series resulting from previous validated numerical wave load modeling studies. Results indicate that both deep LSTM and shallow FFNNs are able to provide very good predictions of wave forces with correlation coefficients above 0.98 by comparing model simulations and data. Effects of training algorithms on network performance have been investigated. Among several training algorithms, the adaptive moment estimation (Adam) training optimizer leads to the best LSTM performance, while Levenberg–Marquardt (LM) optimized backpropagation is among the most effective training algorithms for FFNNs. In general, a shallow FFNN-LM network results in slightly higher correlation coefficients and lower error than those from an LSTM-Adam network. For sharp variation in nonlinear wave forces in the emerged bridge case study during Hurricane Ivan, FFNN-LM predictions of wave forces show better matching with the quick variations in nonlinear wave forces. FFNN-LM’s speed is approximately 4 times faster in model training but is about twice as slow in model verification and application than the LSTM-Adam network. Neural network simulations have shown substantially faster than CFD wave load modeling in our case studies. Full article

Bluetongue virus (BTV) is the causative agent of the significant livestock disease Bluetongue (BT), which causes severe economic losses associated with its considerable impact on the health and trade of ruminants. Background/Objectives: BTV infection and vaccination against the virus typically result in the induction of antibodies with the capacity to neutralize viral infection. Classic neutralization approaches resemble the methodology applied for neutralizing antibodies (NAbs) quantification. To improve long-standing and new-generation methodologies for the quantification of NAbs or evaluation of antivirals, we offer here the development of a new luciferase-based microneutralization approach as a proof-of-concept. Methods: Central to this innovative approach is the recently generated set of replication-competent reporter-expressing recombinant BTV, where the NanoLuc luciferase protein expression serves as a quantifiable readout for viral replication. After evaluating a set of heat-inactivated serum samples with neutralizing activity (measured via SNTs), these were incubated with 100 PFU of NLuc-expressing rBTV of serotype 1, 4 or 8 and Vero cells were infected with the serum–virus mixture. Then, the luminescent signal was measured at 48 h post-infection. Results: Using the proposed NLuc-based assay and the luminescent signal in the supernatant, we could detect neutralizing activity as soon as 48 h post-infection. Importantly, we were able to observe a strong correlation between NAbs titers measured by classic microneutralization assay and by our bioluminescent approach (BTV-1 Spearman r = 0.932901; p-value < 0.0001; BTV-4 Spearman r = 0.8070192; p-value < 0.0001; BTV-8 Spearman r = 0.9983; p-value < 0.0001). In addition, the NLuc-based assay displayed a serotype-specific character potentially equivalent to classic SNT methods. Conclusions: In summary, our reporter-based microneutralization assay provides a rapid and suitable method to quantify BTV-neutralizing antibodies in serum samples of natural hosts after vaccination or infection, with a serotype-specificity equivalent to classic SNT methods. Full article

Background/Objectives: Aseptic loosening (AL) is among the most common causes of late failure following total hip arthroplasty (THA), often necessitating complex revision surgery. Current diagnostic tools, mainly based on clinical and radiological findings, are primarily able to identify advanced changes of periprosthetic osteolysis (PPOL). Therefore, early detection of AL remains a challenge. Circulating microRNAs (miRNAs) have emerged as promising, minimally invasive biomarkers in musculoskeletal disorders. This study investigates the expression of inflammation-related miRNAs let-7i-5p, let-7e-5p, miR-15a-5p, miR-30a-3p and miR-130a-3p in patients with confirmed AL after THA to evaluate their potential role in AL. Methods: AL patients undergoing revision were compared with asymptomatic post-THA individuals and controls with degenerative osteoarthritis. Preoperative, peripheral blood samples were collected; total RNA was extracted; and quantitative real-time PCR (qRT-PCR) was performed to quantify miRNA expression. The relative expression of miRNAs was calculated using the 2–ΔΔCt method after proper normalization of Ct values. Statistical analysis assessed differences between groups. Results: The under investigation miRNAs exhibited distinct expression patterns. Several targets demonstrated significant downregulation in AL patients, suggesting a potential link to inflammatory and osteolytic pathways like Toll-like receptor 4 (TLR4)–Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, NLRP3 inflammasome activation and macrophage polarization. Conclusions: The observed alterations in circulating miRNAs support their capability as biomarkers for early detection of AL following THA. Larger cohorts could facilitate translation into routine clinical diagnostics. Full article

Low-thrust orbit transfer problems are central to reducing mission costs and enabling cleaner, more efficient space travel. However, they remain difficult to solve using mathematically superior indirect methods of optimization. This is mainly due to the sensitivity to initial guesses and ill-conditioned matrices generated using traditional indirect methods. This paper applies the Uniform Trigonometrization Method (UTM), a cutting-edge indirect optimization technique, to four cases of low-thrust low Earth orbit (LEO)-to-geostationary Earth orbit (GEO) transfer problems. Using the UTM framework, including efficient numerical continuation and problem scaling strategies, smoother optimal control solutions were obtained. The convergence of standard boundary value problem solvers, like MATLAB’s bvp4c, significantly increases while using the simplicity and efficiency of the UTM. The UTM was able to solve Case 1 in a simpler manner compared to the traditional indirect method presented in the literature. In Case 2, the UTM found results for a constant thrust value of 1 N, while a direct pseudospectral method failed to converge. The results obtained using the UTM for Case 2 have 20 times longer flight duration and revolutions of spacecraft around the Earth. The UTM efficiently performs trade studies using a continuation approach that generates additional insights into all cases of this problem. In Case 4, the UTM was able to easily generate a bang–bang control structure, which traditionally requires solving a complex multi-point boundary value problem. The results generated using the UTM are very high-resolution, as it relies on the necessary conditions of optimality and guarantees locally optimal solutions. These findings position the UTM as a promising indirect approach for solving real-world long-duration orbit transfers. Full article

In order to reach and maintain hepatitis C virus (HCV) elimination goals, it is imperative to reach marginalized people who do not engage with traditional testing and treatment. Peer-led interventions are effective in engaging such individuals. Studies have demonstrated community pharmacy as a low-threshold setting for HCV testing, but pharmacy teams’ competing demands are a barrier to maximizing potential. This pilot project aimed to assess whether a pharmacy-based peer-led model of HCV testing was implementable, deliverable, able to engage marginalized people, and overcome pharmacy staff constraints. We implemented a peer-led HCV testing service in one community pharmacy in the Midlands, England, providing four focused phases of testing, totalling 198 h, over two years. In total, 591 tests for antibodies or RNA were undertaken, identifying 24 active infections. Subsequent phases retested 20%, 16%, and 11% of those tested in combined preceding phases. In response to feedback, phases 3 and 4 included health screening (blood pressure, cholesterol, diabetes, and nurse-performed Fibroscans^®). We demonstrate engagement and the ability to identify and refer those with abnormal results to appropriate healthcare. This pilot shows that peer-led testing in the pharmacy setting can be implemented and warrants further scale up and evaluation. Full article