Search Results (78)

Background/Objectives: In the last few decades, the dengue virus, a prevalent flavivirus, has demonstrated various epidemiological, economic, and health impacts around the world. Dengue virus serotype 2 (DENV2) plays a vital role in dengue-associated mortality. The RNA-dependent RNA polymerase (RdRp) of DENV2 is a charming druggable target owing to its crucial function in viral reproduction. In recent years, streptomycetes natural products (NPs) have attracted considerable attention as a potential source of antiviral drugs. Methods: Seeking prospective inhibitors that inhibit the DENV2 RdRp allosteric site, in silico mining of the Streptome database was executed. AutoDock4.2.6 software performance in predicting docking poses of the inspected inhibitors was initially conducted according to existing experimental data. Upon the assessed docking parameters, the Streptome database was virtually screened against DENV2 RdRp allosteric site. The streptomycetes NPs with docking scores less than the positive control (68T; calc. −35.6 kJ.mol⁻¹) were advanced for molecular dynamics simulations (MDS), and their binding affinities were computed by employing the MM/GBSA approach. Results: SDB9818 and SDB4806 unveiled superior inhibitor activities against DENV2 RdRp upon MM/GBSA//300 ns MDS than 68T with ΔG_binding values of −246.4, −242.3, and −150.6 kJ.mol⁻¹, respectively. A great consistency was found in both the energetic and structural analyses of the identified inhibitors within the DENV2 RdRp allosteric site. Furthermore, the physicochemical characteristics of the identified inhibitors demonstrated good oral bioavailability. Eventually, quantum mechanical computations were carried out to evaluate the chemical reactivity of the identified inhibitors. Conclusions: As determined by in silico computations, the identified streptomycetes NPs may act as DENV2 RdRp allosteric inhibitors and mandate further experimental assays. Full article

Microgrids are increasingly being adopted as alternatives to traditional power transmission networks, necessitating improved performance strategies. Various mathematical optimization techniques are used to determine optimal controller parameters for these systems. These optimization methods can generally be categorized into natural, biological, and engineering-based approaches. In this research, the authors evaluated and compared several optimization techniques to enhance the secondary controller of DC microgrids, focusing on reducing operating time and minimizing error rates. Optimization tools were utilized to identify the optimal gain control parameters, aiming to achieve the best possible system performance. The enhanced controller response enables quicker recovery to steady-state conditions during sudden disturbances. The root-mean-square error (RMSE) served as a performance metric, with the proposed approach achieving a 15% reduction in RMSE compared to previous models. This improvement contributes to faster response times and lower energy consumption in microgrid operation. Full article

Background: Identifying liquid biopsy biomarkers with high efficacy is crucial for cancer diagnosis. Exosomal cargo, including miRNAs and proteins, offers enhanced stability in biofluids compared with their free circulating forms, but direct comparisons of their diagnostic performance remain limited. This study evaluates and compares the diagnostic value of selected miRNAs and protein markers in exosomal versus non-exosomal fractions across stages of lung carcinogenesis in a rat model. Methods: Lung cancer was induced in rats, and blood and lung tissue samples were collected at consecutive stages of tumor induction. We investigated the expression patterns of key miRNAs (miR-19b, miR-21, and miR-145) in exosomes, serum, and tissue and quantified levels of tumor biomarkers CEA and CYFRA 21-1 in exosomal and serum fractions. Results: Our results revealed distinct expression patterns of the evaluated miRNAs across exosomes, serum, and tissue, throughout different stages of tumor induction. The expression of exosomal miRNAs dynamically changed in parallel with the tumor induction process, demonstrating high diagnostic efficacy. Specifically, exosomal miR-19b and miR-21 were significantly upregulated from an early induction stage, whereas their serum and tissue forms increased only during the late stages of induction. On the other hand, miR-145 was consistently downregulated across all fractions at every stage. Both exosomal and serum CEA levels increased significantly during tumor induction, while serum CYFRA 21-1 outperformed its exosomal counterpart. Strong positive correlations linked exosomal miR-19b and miR-145 with their non-exosomal counterparts, while moderate correlations were seen for miR-21 and the protein markers. Conclusions: Our findings underscore the value of integrating exosomal biomarkers in liquid biopsies, highlighting their potential to improve early detection and monitoring of lung cancer development. Full article

Understanding information extracted from receipts is a critical task for real-world applications such as financial tracking, auditing, and enterprise resource management. In this paper, we introduce ReceiptQA, a novel large-scale dataset designed for receipt understanding through question-answering (QA). ReceiptQA contains 171,000 question–answer pairs derived from 3500 receipt images, constructed via two complementary methodologies: (1) LLM-Generated Dataset: 70,000 synthetically generated QA pairs, where each receipt is paired with 20 unique, context-specific questions. These questions are produced using a state-of-the-art large language model (LLM) and validated through human annotation to ensure accuracy, relevance, and diversity. (2) Human-Created Dataset: 101,000 manually crafted questions spanning answerable and unanswerable queries. This subset includes carefully designed templates of varying difficulty (easy/hard) to comprehensively evaluate QA systems across diverse receipt domains. To benchmark performance, we evaluate leading vision–language models (VLMs) and language models (LMs), including GPT-4o, Phi-3B, Phi-3.5B, LLaVA-7B, InternVL2 (4B/8B), LLaMA-3.2, and Gemini. We further fine-tune a LLaMA-3.2 11B model on ReceiptQA, achieving significant improvements over baseline models on validation and test sets. Our analysis uncovers critical strengths and limitations of existing models in handling receipt-based QA tasks, establishing a robust benchmark for future research. Full article

Purpose: To evaluate the potential clinical role and reliability of Sonazoid-enhanced ultrasound (SEUS) as a diagnostic tool for liver metastatic lesions. Methods: An extensive literature search was conducted across five electronic databases, PubMed, Scopus, Embase, Cochrane Library, and Web of Science, from their inception up to January 2024 to identify all studies evaluating the use of Sonazoid-enhanced ultrasonography for detecting hepatic metastases. A meta-analysis was performed to assess diagnostic accuracy using the Meta-DiSc 2.0 software. Results: A total of 31 studies were included, 16 of which were eligible for meta-analysis and diagnostic test accuracy evaluation. A total of 13 studies in the meta-analysis evaluated the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) for 1347 metastatic and 1565 non-metastatic liver lesions. The pooled sensitivity and specificity for CEUS were 0.88 (95% CI: 0.82–0.92) and 0.92 (95% CI: 0.84–0.96), respectively. The combined positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 11.89 (95% CI: 5.42–26.09), 0.12 (95% CI:0.08–0.19), and 91.99 (95% CI: 32.15–263.17), respectively. Additionally, four studies of the meta-analysis assessed the diagnostic performance of contrast-enhanced intraoperative sonography (CE-IOUS) in detecting 664 metastatic and 246 non-metastatic liver lesions. The pooled sensitivity and specificity for CE-IOUS were 0.93 (95% CI: 0.82–0.97) and 0.84 (95% CI: 0.65–0.93), respectively. The aggregated positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated as 5.95 (95% CI: 2.32–15.25), 0.07 (95% CI: 0.02–0.24), and 77.68 (95% CI: 10.33–583.86), respectively. Conclusions: CE-IOUS and CEUS are reliable approaches for diagnosing liver metastatic lesions. CE-IOUS, in particular, exhibits higher accuracy in identifying liver metastatic lesions, indicating its potential effectiveness in clinical practice. Full article

Background: Recent randomized clinical trials (RCTs) of STEMI patients with multi-vessel disease (MVD) reported potential superiority of immediate (ICR) vs. staged complete revascularization (SCR). Inherently, the risk of procedural MI is less likely to be detected in ICR patients, and this may have influenced the results. Recently published meta-analyses encompassed observational studies without including STEMI data from the BioVasc trial. The aim of this meta-analysis was to perform an updated comparison of the two strategies in STEMI patients with MVD. Methods: Electronic databases were searched from their inception till August 2024 to identify RCTs assessing CR timing in STEMI patients with MVD. Only studies with an endpoint involving major adverse cardiovascular events (MACE) were included. Results: Six RCTs totaling 2023 patients were included in the analysis. The median time to staged PCI was 19 days. The incidence of MACE (as defined by each study’s protocol) was comparable between the two strategies [RR 0.86, 95% CI (0.58 to 1.27)]. There was also no difference in the risk of non-procedural MI [RR 0.91, 95% CI (0.49–1.67)], death [RR 1.47, 95% CI (0.89–2.44)] and cardiovascular death [RR 1.53, 95% CI (0.79–2.98)]. There was a significant 40% reduction in unplanned revascularization in patients undergoing ICR versus SCR [RR 0.60 (0.40 to 0.89), p = 0.01]. Conclusions: ICR reduced the risk of unplanned revascularization compared to SCR but had a comparable effect on MACE, death, cardiovascular death and non-procedural MI. Both strategies are safe in managing patients with acute MI and MVD. Full article

Objectives: Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than those of pancreatic ductal adenocarcinoma. Methods: We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022 and two cases from 2023–2024 who underwent RNA and TME analysis by Boston Gene. Patient information was extracted from our institutional database with the approval of the Institutional Review Board. Results: We identified 16 patients with available molecular testing results. Fourteen patients had metastatic disease, one had borderline resectable disease, and one had localized resectable disease at diagnosis. Fifteen patients were wild type for KRAS (one patient had unknown KRAS status). Somatic/germline mutations of DNA damage repair genes (BRCA1/2, PALB2, and ATM) were present in 5 of 12 patients tested for these genes. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. The median overall survival (OS) was 24 months for patients with metastatic disease. One of the additional two cases who underwent BostonGene testing was found to have NTRK1 fusion. RNA and TME analysis by Boston Gene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74, and MMP1 and higher RNA levels of CDH6 compared with PDAC. Full article

The global reliance on electric vehicles (EVs) has been rapidly increasing due to the excessive use of fossil fuels and the resultant CO₂ emissions. Moreover, EVs facilitate using alternative energy sources, such as energy storage systems (ESSs) and renewable energy sources (RESs), promoting mobility while reducing dependence on fossil fuels. However, this trend is accompanied by multiple challenges related to EVs’ traction systems, storage capacity, chemistry, charging infrastructure, and techniques. Additionally, the requisite energy management technologies and the standards and regulations needed to facilitate the expansion of the EV market present further complexities. This paper provides a comprehensive and up-to-date review of the state of the art concerning EV-related components, including energy storage systems, electric motors, charging topologies, and control techniques. Furthermore, the paper explores each sector’s commonly used standards and codes. Through this extensive review, the paper aims to advance knowledge in the field and support the ongoing development and implementation of EV technologies. Full article

Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis—including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio—and MetS. In this descriptive cross-sectional study, 209 participants aged 24–70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment—Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively (p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 (p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 (p = 0.015), and for men, it had an AUC of 0.792 (p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS. Full article

Microgrids (MGs) are the new paradigm of decentralized networks of renewable energy sources, loads, and storage devices that can operate independently or in coordination with the primary grid, incorporating significant flexibility and supply reliability. To increase reliability, traditional individual MGs can be replaced by networked microgrids (NMGs), which are more dependable. However, when it comes to operation and control, they also pose challenges for cyber security and communication reliability. Denial of service (DoS) is a common danger to DC microgrids with advanced controllers that rely on active information exchanges and has been recorded as the most frequent cause of cyber incidents. It can disrupt data transmission, leading to ineffective control and system instability. This paper proposes digital twin (DT) technology as an integrated solution, with new, advanced analytics technology using machine learning and artificial intelligence to provide simulation capabilities to predict and estimate future states. By twinning the cyber-physical dynamics of NMGs using data-driven models, DoS attacks targeting cyber-layer agents will be detected and mitigated. A long short-term memory (LSTM) model data-driven digital twin approach for DoS attack detection and mitigation is implemented, tested, and evaluated. Full article

Drug-induced liver injury (DILI) represents a significant clinical challenge characterized by hepatic dysfunction following exposure to diverse medications. Methotrexate (MTX) is a cornerstone in treating various cancers and autoimmune disorders. However, the clinical utility of MTX is overshadowed by its ability to induce hepatotoxicity. The current study aims to elucidate the hepatoprotective effect of the alcoholic extract of Egyptian Araucaria heterophylla resin (AHR) on MTX-induced liver injury in rats. AHR (100 and 200 mg/kg) significantly decreased hepatic markers (AST, ALT, and ALP), accompanied by an elevation in the antioxidant’s markers (SOD, HO-1, and NQO1). AHR extract also significantly inhibited the TGF-β/NF-κB signaling pathway as well as the downstream cascade (IL-6, JAK, STAT-3, and cyclin D). The extract significantly reduced the expression of VEGF and p38 with an elevation in the BCL2 levels, in addition to a significant decrease in the IL-1β and TNF-α levels, with a prominent effect at a high dose (200 mg/kg). Using LC-HRMS/MS analysis, a total of 43 metabolites were tentatively identified, and diterpenes were the major class. This study presents AHR as a promising hepatoprotective agent through inhibition of the TGF-β/NF-κB and JAK/STAT3 pathways, besides its antioxidant and anti-inflammatory effects. Full article

The Wadi Ranga sulfidic jasperoids in the Southern Eastern Desert (SED) of Egypt are hosted within the Neoproterozoic Shadli metavolcanics as an important juvenile crustal section of the Arabian Nubian Shield (ANS). This study deals with remote sensing and geochemical data to understand the mechanism and source of pyritization, silicification, and hematization in the host metavolcanics and to shed light on the genesis of their jasperoids. The host rocks are mainly dacitic to rhyolitic metatuffs, which are proximal to volcanic vents. They show peraluminous calc-alkaline affinity. These felsic metatuffs also exhibit a nearly flat REE pattern with slight LREE enrichment (La/Yb = 1.19–1.25) that has a nearly negative Eu anomaly (Eu/Eu* = 0.708–0.776), while their spider patterns display enrichment in Ba, K, and Pb and depletion in Nb, Ta, P, and Ti, reflecting the role of slab-derived fluid metasomatism during their formation in the island arc setting. The ratios of La/Yb (1.19–1.25) and La/Gd (1.0–1.17) of the studied felsic metatuffs are similar to those of the primitive mantle, suggesting their generation from fractionated melts that were derived from a depleted mantle source. Their Nb and Ti negative anomalies, along with the positive anomalies at Pb, K, Rb, and Ba, are attributed to the influence of fluids/melt derived from the subducted slab. The Wadi Ranga jasperoids are mainly composed of SiO₂ (89.73–90.35 wt.%) and show wide ranges of Fe₂O₃t (2.73–6.63 wt.%) attributed to the significant amount of pyrite (up to 10 vol.%), hematite, goethite, and magnetite. They are also rich in some base metals (Cu + Pb + Zn = 58.32–240.68 ppm), leading to sulfidic jasperoids. Pyrite crystals with a minor concentration of Ag (up to 0.32 wt.%) are partially to completely converted to secondary hematite and goethite, giving the red ochre and forming hematization. Euhedral cubic pyrite is of magmatic origin and was formed in the early stages and accumulated in jasperoid by epigenetic Si-rich magmatic-derived hydrothermal fluids; pyritization is considered a magmatic–hydrothermal stage, followed by silicification and then hematization as post-magmatic stages. The euhedral apatite crystals in jasperoid are used to estimate the saturation temperature of their crystallization from the melt at about 850 °C. The chondrite (C1)-normalized REE pattern of the jasperoids shows slightly U–shaped patterns with a slightly negative Eu anomaly (Eu/Eu* = 0.43–0.98) due to slab-derived fluid metasomatism during their origin; these jasperoids are also rich in LILEs (e.g., K, Pb, and Sr) and depleted in HFSEs (e.g., Nb and Ta), reflecting their hydrothermal origin in the island arc tectonic setting. The source of silica in the studied jasperoids is likely derived from the felsic dyke and a nearby volcanic vent, where the resultant Si-rich fluids may circulate along the NW–SE, NE–SW, and E–W major faults and shear zones in the surrounding metavolcanics to leach Fe, S, and Si to form hydrothermal jasperoid lenses and veins. Full article

A networked microgrid is composed of multiple nearby microgrids linked together to gain additional flexibility for resilient operations. Networked microgrids collaborate to prevent power shortages in microgrid clusters by sharing critical renewable and energy storage resources. However, controlling the local resources of each microgrid, including the energy storage systems’ charging and discharging, maintaining the DC bus voltage, and even overseeing the power shared by multiple microgrids, is challenging. Therefore, a microgrid control technique and distributed energy management are used cooperatively in this study to handle the shared power between a system of networked microgrids incorporating photovoltaics and battery energy storage systems. Numerical simulation results from a networked microgrid system verify the accuracy and soundness of the suggested distributed energy management under several operating conditions, including renewable uncertainties and sequential load variations in different zones. The applicability of the suggested technique is confirmed by hardware implementation, and several operational scenarios further evaluate the proposed system on a practical two-microgrid system located in the Florida International University (FIU) testbed. Full article

The reliance on more sustainable refrigeration systems with less electricity consumption attracts a lot of attention as the demand for refrigeration increases due to population growth and global warming threats. This study examines the use of a cascade vapor-compression/adsorption refrigeration system in hot weather, focusing on condensing temperatures of 50, 55, and 60 °C, whereas an air-cooled condenser is in use due to practical considerations. A fully coupled transient model is developed using COMSOL Multiphysics to simulate the integrated system, considering the practical limitations of the vapor compression system (VCS) and the dynamic nature of the adsorption system (ADS). The model combines a lumped model for the ADS with the manufacturer’s data for a VCS compressor at different condensing and evaporating temperatures. It was found that the VCS is more sensitive to the change in the ADS’s condensing temperature, since when the temperature is raised from 50 °C to 60 °C, the VCS’s COP decreases by 29.5%, while the ADS’s COP decreases by 7.55%. Furthermore, the cycle time of ADS plays an important role in providing the cooling requirements for the bottoming cycle (VCS), and it can be optimized to maximize the energy conversion efficiency of the VCS. At optimum cycle time and compared to the conventional VCS, the cascade system can boost the cooling capacity of the VCS by 18.2%, lower the compressor power by 63.2%, and greatly enhance the COP by 221%. These results indicate that the application of the cascade VCS/ADS in such severe conditions is a more sustainable and energy-efficient solution to meet the growing need for refrigeration. Full article

Although primary open-angle glaucoma (POAG) is a major cause of blindness worldwide, patients’ immune response and its relation to the disease course have not been fully unraveled in terms of analyses of circulating B-cell subsets, as well as the association of these subsets with the severity of POAG clinical features. Subjects and Methods: Flow cytometry was used to determine B-cell subset frequencies from 30 POAG patients grouped by hierarchical cluster analysis or the mean deviation (MD) of the visual field (VF) and correlated with the patients’ clinical and pathological data, as well as with BSF-2(IL-6) and CSIF:TGIF(IL-10), which were quantified in peripheral blood samples of patients and controls by ELISA. Results: The total B-cell frequency was increased in the POAG group in comparison to the control group (n = 30). Frequencies of specific B-cell subsets, such as double-negative (DN) and naïve B-cell subsets, were increased in relation to the severity of the POAG disease. However, the unswitched memory B compartment subset decreased in the POAG group. Other non-typical B-cell subsets such as DN B cells also showed significant changes according to the POAG disease severity course. These differences allow us to identify POAG severity-associated inflammatory clusters in patients with specifically altered B-cell subsets. Finally, ocular parameters, biomarkers of inflammation, and other glaucoma-related or non-clinical scores exhibited correlations with some of these B-cell subpopulations. Conclusion: The severity of the POAG disease course is accompanied by changes in the B-cell subpopulation, namely, DN B cells. Furthermore, the existing relationship of the B-cell subset frequencies with the clinical and the inflammatory parameters BSF-2(IL-6), CSIF:TGIF(IL-10), and the BSF-2(IL-6) to CSIF:TGIF(IL-10) ratio suggests that these B lymphocyte cells could serve as potential molecular bio-markers for assessing POAG disease severity and/or progression. Full article