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The vast majority of today’s data is collected and stored in enormous databases with a wide range of characteristics that have little to do with the overarching goal concept. Feature selection is the process of choosing the best features for a classification problem, which improves the classification’s accuracy. Feature selection is considered a multi-objective optimization problem with two objectives: boosting classification accuracy while decreasing the feature count. To efficiently handle the feature selection process, we propose in this paper a novel algorithm inspired by the behavior of waterwheel plants when hunting their prey and how they update their locations throughout exploration and exploitation processes. The proposed algorithm is referred to as the binary waterwheel plant algorithm (bWWPA). In this particular approach, the binary search space as well as the technique’s mapping from the continuous to the discrete spaces are both represented in a new model. Specifically, the fitness and cost functions that are factored into the algorithm’s evaluation are modeled mathematically. To assess the performance of the proposed algorithm, a set of extensive experiments were conducted and evaluated in terms of 30 benchmark datasets that include low, medium, and high dimensional features. In comparison to other recent binary optimization algorithms, the experimental findings demonstrate that the bWWPA performs better than the other competing algorithms. In addition, a statistical analysis is performed in terms of the one-way analysis-of-variance (ANOVA) and Wilcoxon signed-rank tests to examine the statistical differences between the proposed feature selection algorithm and compared algorithms. These experiments’ results confirmed the proposed algorithm’s superiority and effectiveness in handling the feature selection process.

Accurate cyclone intensity prediction is crucial for smart cities to effectively prepare and mitigate the potential devastation caused by these extreme weather events. Traditional meteorological models often face challenges in accurately forecasting cyclone intensity due to cyclonic systems’ complex and dynamic nature. Predicting the intensity of cyclones is a challenging task in meteorological research, as it requires expertise in extracting spatio-temporal features. To address this challenge, a new technique, called linear support vector regressive gradient descent Jaccardized deep multilayer perceptive classifier (LEGEMP), has been proposed to improve the accuracy of cyclone intensity prediction. This technique utilizes a dataset that contains various attributes. It employs the Herfindahl correlative linear support vector regression feature selection to identify the most important characteristics for enhancing cyclone intensity forecasting accuracy. The selected features are then used in conjunction with the Nesterov gradient descent jeopardized deep multilayer perceptive classifier to predict the intensity classes of cyclones, including depression, deep depression, cyclone, severe cyclone, very severe cyclone, and extremely severe cyclone. Experimental results have demonstrated that LEGEMP outperforms conventional methods in terms of cyclone intensity prediction accuracy, requiring minimum time, error rate, and memory consumption. By leveraging advanced techniques and feature selection, LEGEMP provides more reliable and precise predictions for cyclone intensity, enabling better preparedness and response strategies to mitigate the impact of these destructive storms. The LEGEMP technique offers an improved approach to cyclone intensity prediction, leveraging advanced classifiers and feature selection methods to enhance accuracy and reduce error rates. We demonstrate the effectiveness of our approach through rigorous evaluation and comparison with conventional prediction methods, showcasing significant improvements in prediction accuracy. Integrating our enhanced prediction model into smart city disaster management systems can substantially enhance preparedness and response strategies, ultimately contributing to the safety and resilience of communities in cyclone-prone regions.

Breast cancer is one of the most common cancers in women, with an estimated 287,850 new cases identified in 2022. There were 43,250 female deaths attributed to this malignancy. The high death rate associated with this type of cancer can be reduced with early detection. Nonetheless, a skilled professional is always necessary to manually diagnose this malignancy from mammography images. Many researchers have proposed several approaches based on artificial intelligence. However, they still face several obstacles, such as overlapping cancerous and noncancerous regions, extracting irrelevant features, and inadequate training models. In this paper, we developed a novel computationally automated biological mechanism for categorizing breast cancer. Using a new optimization approach based on the Advanced Al-Biruni Earth Radius (ABER) optimization algorithm, a boosting to the classification of breast cancer cases is realized. The stages of the proposed framework include data augmentation, feature extraction using AlexNet based on transfer learning, and optimized classification using a convolutional neural network (CNN). Using transfer learning and optimized CNN for classification improved the accuracy when the results are compared to recent approaches. Two publicly available datasets are utilized to evaluate the proposed framework, and the average classification accuracy is 97.95%. To ensure the statistical significance and difference between the proposed methodology, additional tests are conducted, such as analysis of variance (ANOVA) and Wilcoxon, in addition to evaluating various statistical analysis metrics. The results of these tests emphasized the effectiveness and statistical difference of the proposed methodology compared to current methods.

Metamaterials have unique physical properties. They are made of several elements and are structured in repeating patterns at a smaller wavelength than the phenomena they affect. Metamaterials’ exact structure, geometry, size, orientation, and arrangement allow them to manipulate electromagnetic waves by blocking, absorbing, amplifying, or bending them to achieve benefits not possible with ordinary materials. Microwave invisibility cloaks, invisible submarines, revolutionary electronics, microwave components, filters, and antennas with a negative refractive index utilize metamaterials. This paper proposed an improved dipper throated-based ant colony optimization (DTACO) algorithm for forecasting the bandwidth of the metamaterial antenna. The first scenario in the tests covered the feature selection capabilities of the proposed binary DTACO algorithm for the dataset that was being evaluated, and the second scenario illustrated the algorithm’s regression skills. Both scenarios are part of the studies. The state-of-the-art algorithms of DTO, ACO, particle swarm optimization (PSO), grey wolf optimizer (GWO), and whale optimization (WOA) were explored and compared to the DTACO algorithm. The basic multilayer perceptron (MLP) regressor model, the support vector regression (SVR) model, and the random forest (RF) regressor model were contrasted with the optimal ensemble DTACO-based model that was proposed. In order to assess the consistency of the DTACO-based model that was developed, the statistical research made use of Wilcoxon’s rank-sum and ANOVA tests.

Objectives: This study aimed to determine the prevalence of total blood cell abnormalities, hemoglobinopathies and G6PD deficiency and evaluate the efficacy of red blood cell (RBC) indices, mentzer index (MI) and naked-eye single tube red cell osmotic fragility (NESTROF) test as screening tools for diagnosis of β thalassemia trait among Yemeni blood donors., Methods: A cross-sectional study was conducted with 106 volunteer blood donors who met the national standard criterion of blood donation. Various tests were performed, including complete blood count (CBC), serum ferritin, sickling test, G6PD assay, NESTROF test and high-performance liquid chromatography (HPLC)., Results: The prevalence of hematological abnormalities among blood donors reached 68.9%, with functional RBC abnormalities at 51.9%, leukopenia at 10.4%, thrombocytosis at 1.9%, and thrombocytopenia at 4.7%. Additionally, hemoglobinopathies were found in 21.7% of donors, with β-thalassemia trait at 3.8%, sickle cell trait at 1.9%, and suspected α-thalassemia trait at 16%, while G6PD deficiency and iron deficiency were present in 12.3% and 17.9% of donors, respectively. The NESTROF test, MCV and MCH demonstrated a sensitivity rate of 100%. MI and MCH exhibited the highest specificity followed by NESTROF test in the screening of β-thalassemia trait., Conclusions: The prevalence of hemoglobinopathies and G6PD deficiency appear to be common among Yemeni blood donors. These results emphasize the necessity of comprehensive blood donation screening programs to safeguard the blood supply and promote early detection and management of hemoglobinopathies and G6PD deficiency in Yemen.

Background: Mutations in the EPOR gene can disrupt its normal signaling pathways, leading to hematological disorders such as polycythemia vera and other myeloproliferative diseases., Methodology: In this study, a range of bioinformatics tools, including SIFT, PolyPhen-2, SNAP2, SNPs & Go, PhD-SNP, I-Mutant2.0, MuPro, MutPred, ConSurf, HOPE, and Interpro were used to assess the deleterious effects of missense nonsynonymous single nucleotide polymorphisms (nsSNPs) on protein structure and function. Furthermore, molecular dynamics simulations (MDS) were conducted to assess the structural deviations of the identified mutant variants in comparison to the wild type., Results: The results identified two nsSNPs, R223P and G302S, as deleterious, significantly affecting protein structure and function. Both substitutions occur in functionally conserved regions and are predicted to be pathogenic, associated with altered molecular mechanisms. The MDSs indicated that while the wild-type EPOR maintained optimal stability, the G302S and R223P variants exhibited substantial deviations, adversely affecting overall protein stability and compactness., Conclusions: The computational analysis of missense nsSNPs in the EPOR gene identified two missense SNPs, R223P and G302S, as deleterious, occurring at highly conserved regions, and having substantial effects on erythropoietin receptor (EPO-R) protein structure and function, suggesting their potential pathogenic consequences.

Introduction: Antimicrobial resistance is a critical global issue, and medicinal plants, as a key source of therapeutic agents, offer potential solutions by offering new antibacterial agents. Acacia polyacantha tree, known as Al Kakamout in Sudan, is a significant source of Gum Arabic and has been traditionally used to treat bacterial diseases. This study aimed to investigate a hydro-ethanol extract of Kakamout stem bark through GC-MS analysis, evaluate its antibacterial activity against two standard bacterial strains, and conduct molecular docking and ADME studies., Methods: The stem bark of the plant was extracted by maceration using a hydro-ethanol solvent and analyzed via GC-MS. The antibacterial activity of the extract was evaluated against Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 using the well diffusion method. The identified compounds were studied in silico to investigate their binding affinities with the target bacterial proteins. The ADMET properties were predicted for the top scoring compounds., Results: GC-MS analysis revealed the presence of 11 compounds, with the major ones being dopamine, N, N-dimethyl-, dimethyl ether (43.76%), 4-O-methylmannose (23.27%), sucrose (8.09%), 1,4,7-triazacyclononane, 1-benzoyl- (5.41%), and lupeol, trifluoroacetate (5.24%). The extract demonstrated significant effectiveness against both bacterial strains, even at a low concentration of 50 mg/mL. Molecular docking showed that compounds 1, 3, 4, and 6 had the best docking scores with enoyl-acyl carrier protein reductase (FabI) (PDB ID: 3GR6) from S. aureus (-6.142, -10.843, -6.218 and -7.14 Kcal/mol). Similarly, compounds 1-6 exhibited favorable binding energies with LasR-TP4 complex (PDB ID: 3JPU) from P. aeruginosa (-10.025, -9.127, -8.623, -7.092, -7.722, and -6.019 Kcal/mol)., Conclusion: This study provides the first GC-MS analysis of Acacia polyacantha stem bark, identifying potential antibacterial compounds. Molecular docking and ADMET predictions suggest several promising compounds for further investigation as antibacterial agents., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Hammad et al.)

This study examines the potential impacts of energy efficiency and renewable energy on economic growth proxies by gross domestic product and environmental quality proxies by carbon dioxide emissions across eight selected Asian countries from 2000 to 2020. This study contributes by calculating green total factor productivity and carbon total factor productivity based on the famous Solow's residual via employing a modified extensive growth accounting model that internalized ignored factors such as energy efficiency and renewable energy. The employed panel cointegration techniques confirm that all variables are co-integrated with carbon dioxide emissions and economic growth. The pooled mean group/autoregressive distributed lag model analysis results indicate that energy efficiency is positively associated with both environmental quality and economic growth. Renewable energy hurts economic growth but has a positive effect on environmental quality which suggests the necessity of implementing an effective strategy for renewable energy alongside energy efficiency measures to enhance economic growth and environmental quality in the selected Asian countries. The findings from the fully modified ordinary least squares estimator are consistent with the environmental quality model. The average growth rate of green total factor productivity is positive despite negative contributions from energy efficiency and renewable energy. Similarly, the average growth rate of carbon total factor productivity is negative despite positive contributions from labor and capital. This discrepancy may be attributed to the beneficial effects of labor and capital as input productivity-driven. Embracing renewable energy sources can take significant steps toward improving environmental quality for future generations. Focusing on green technologies that enhance energy efficiency can substantially promote environmental quality and stimulate sustainable economic growth through innovation and climate change integration to achieve Sustainable Development Goals., (© 2024. The Author(s).)

Introduction: Brodie's abscess is a form of localized sub-acute osteomyelitis that rarely occurs in the humerus. Its diagnosis stems from clinical, laboratory, and imaging findings, especially magnetic resonance imaging (MRI). The current paper describes the first case in the literature of humeral paddle Brodie's abscess., Case Report: This report describes the first case of Brodie's abscess in the humeral paddle of a 12-year-old boy, revealed by swelling and pain in the right elbow. Radiographs and computerized tomography (CT) scans showed a well-defined cavitary surrounded by a rim of sclerosis, alongside evidence of cortical expansion and periosteal reaction. The patient was treated with debridement and curettage of the cavity combined with antibiotics. They resulted in the complete disappearance of the cavity. After 1 year of follow-up, the patient can practice daily activities with no pain, and imaging showed no signs of recurrence., Conclusion: The present case highlights the utility of CT scans in diagnosing Brodie's abscesses when an MRI is either unavailable or contraindicated. CT scans serve as a valuable alternative diagnostic modality in such cases., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most abundantly used classes among therapeutic agents in medicine. NSAIDs inhibit the enzyme cyclooxygenase (COX), which is responsible for the conversion of arachidonic acid to prostaglandins. Meanwhile, non-selective NSAIDs are considered as a double-edged weapon since inhibition of COX-1 can lead to gastrointestinal side effects and kidney damage, whereas selective COX-2 inhibition provides anti-inflammatory effects without gastrointestinal toxicity. The detection of COX-2 role in inflammation process launched a new era in its management. Several trials have been established to proceed towards selectivity of well-defined anti-inflammatory members. COX-2 selective inhibitors are evidently safer on the gastrointestinal tract than non-selective NSAIDs. Nevertheless, their unexpected cardiovascular risks cannot be ignored. This review article highlights the latest trials aimed at developing new compounds with promising selective COX-2 activity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Interest has been piqued in c-Met and Pim-1, potential new cancer treatment targets. A variety of triazolo[4,3- b ]pyridazine derivatives were synthesized to create powerful dual c-Met/Pim-1 inhibitors having the pharmacophoric elements of both enzyme inhibitors. All derivatives were screened for their cytotoxic effects on 60 cancer cell lines. Compounds 4g and 4a, had strong antiproliferative cytotoxic impacts on tumor cells, with mean GI% values of 55.84 and 29.08%, respectively. Research revealed that 4g has more powerful inhibitory activity against c-Met and Pim-1, with IC 50 of 0.163 ± 0.01 and 0.283 ± 0.01 μM, respectively than the reference and derivative 4a. Moreover, compound 4g was the subject of an additional investigation into biological processes. The findings showed that compound 4g caused MCF-7 cells to arrest in the S stage of the cell cycle. Also, it accelerated the progress of apoptosis 29.61-fold more than the control. Compound 4g demonstrated a significantly higher level of caspase-9 and a decreased level of p -PI3K, p -AKT, and p -mTOR compared to staurosporine. Later, analysis of 4g showed good drug-ability and pharmacokinetic properties. A similar mode of interaction at the ATP-binding site of c-Met and Pim-1 compared to the docked ligands was suggested by additional docking studies of compound 4g., Competing Interests: The authors have no conflicts of interest. This manuscript's content and writing are the sole responsibility of its authors., (This journal is © The Royal Society of Chemistry.)

Rift Valley Fever Virus (RVFV) is an arbovirus that circulates among animals and can be transmitted to humans. Mosquitoes are the primary vectors that allow RVFV to spread vertically and horizontally. Egypt was exposed to frequent outbreaks with devastating economic consequences. RVFV has a high incidence of worldwide dissemination and no specific vaccine or therapy. Linear Human Cathelicidin (LL-37), is a natural antimicrobial peptide with antiviral activity against numerous viruses. In addition to immunomodulatory effects, LL-37 directly influences viral encapsulation. This study aimed to evaluate the antiviral activity of LL-37 against RVFV in vitro. The post-entry and pre-incubation of LL-37 within Vero cells were assessed in the absence and presence of RVFV. LL-37 activity was assessed using a TCID50 endpoint test, qRT-PCR, and a western blot. When genomic RVFV was quantified, it resulted in a 48% direct inactivation of the viral envelope and a 36% reduction when the virus was pre-incubated with LL-37 before infection. LL-37 decreased viral infection by 75% and protected Vero cells against RVFV infection by 47% at a 1.25 µg/ml dosage. These findings imply that LL-37 exerts antiviral efficacy against RVFV by restricting virus entrance through direct disruption of the virus envelope and indirectly by triggering an immunological response. The effect of LL-37 is time-dependent. As a result, LL-37 may provide rapid and affordable therapies for RVFV infection in Egypt, both during outbreaks and as a preventive strategy.

Five new pyridazine scaffolds were synthesized and assessed for their inhibitory potential against both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) compared with indomethacin and celecoxib. The majority of the synthesized compounds demonstrated a definite preference for COX-2 over COX-1 inhibition. Compounds 4c and 6b exhibited enhanced potency towards COX-2 enzyme with IC 50 values of 0.26 and 0.18 µM, respectively, compared to celecoxib with IC 50  = 0.35 µM. The selectivity index (SI) of compound 6b was 6.33, more than that of indomethacin (SI = 0.50), indicating the most predominant COX-2 inhibitory activity. Consequently, the in vivo anti-inflammatory activity of compound 6b was comparable to that of indomethacin and celecoxib and no ulcerative effect was detected upon the oral administration of compound 6b, as indicated by the histopathological examination. Moreover, compound 6b decreased serum plasma PEG2 and IL-1β. To rationalize the selectivity and potency of COX-2 inhibition, a molecular docking study of compound 6b into the COX-2 active site was carried out. The COX-2 inhibition and selectivity of compound 6b can be attributed to its ability to enter the side pocket of the COX-2 enzyme and interact with the essential amino acid His90. Together, these findings suggested that compound 6b is a promising lead for the possible design of COX-2 inhibitors that could be employed as safe and effective anti-inflammatory drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Different dyes are discharged into water streams, causing significant pollution to the entire ecosystem. The present work deals with the removal of acid red 2 dye (methyl red-as an anionic dye) by green sorbents based on chitosan derivatization. In this regard, two classes of chitosan derivatives-a total of six-were prepared by gamma irradiation at 30 kGy. The first group (group A) constitutes a crosslinked chitosan/polyacrylamide/aluminum oxide with different feed ratios, while the second group, identified as group B, is composed of crosslinked carboxymethyl chitosan/polyacrylamide/aluminum oxide with different ratios. Glycerol was added to soften the resultant hydrogels. The products were characterized by different tools, including FTIR for confirming the chemical modification, TGA for investigating their thermal properties, and XRD for verifying their crystalline structure. The morphology of the prepared derivatives was studied through SEM, while their topography before and after dye adsorption was monitored via the AFM. The removal efficiencies of the prepared sorbents were verified at different operation conditions, such as pH, temperature, adsorbent dose, initial concentration of dye solutions, and contact time. The data revealed that the optimum conditions for maximum dye uptake were as follows: pH 4, contact time 120 min, 0.1-g sorbent dose, and 50-ppm dye concentration. Additionally, the prepared sorbents demonstrated potent adsorption capacity and removal efficiency. It was found that the elements of the second group displayed higher performance than their counterparts. The data showed also that the adsorption process best fits with the Freundlich model and obeyed pseudo-first-order kinetic isotherm. In addition, the synthesized composites showed observable antibacterial potency toward E. coli as a Gram-negative bacterium and S. aureus as a Gram-positive bacterium., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Polyunsaturated fatty acids (PUFA), including n-6 and n-3 fatty acids, are essential for enhancing the performance and health of poultry. Avian species lack desaturase enzymes for endogenous synthesis of n-6 and n-3 fatty acids. This work aimed to determine the impacts of including soybean oil (SO) and linseed oil (LO) in quail diets on growth, lipid profile, hepatic and renal functions, immunity, and antioxidant status. A total of 350 Japanese quail chicks (1-wk-old) were randomly arranged into 7 dietary treatment groups. Seven isocaloric and isonitrogenous experimental basal diets were formed based on the nutritional requirements of growing Japanese quail. Group 1, the control, received a basal with no oils, while groups 2 to 7 received a basal diet containing either 1% SO, 1.5% SO, 2% SO, 1% LO, 1.5% LO, or 2% LO, respectively. Quail groups that consumed diets containing LO at all levels showed significantly greater live body weight (LBW) at 5th wk of age than other experimental groups. The dietary incorporation of 1.5 or 2% SO or LO at all levels yielded significant improvements in body weight gain (BWG) and feed conversion ratio (FCR) through 3 to 5 and 1 to 5 wk of age. Different dietary oil sources and levels have no significant impacts on feed intake (FI) and carcass yield parameters. Lipid profile parameters were improved by adding SO and LO in quail diets, with LO having a higher effect than SO. The hepatic and renal functionality were improved by adding SO and LO in quail diets. The lowest uric acid (UA) bloodstream concentrations were recorded in the quail group fed a diet with 2% LO. Values of Gamma globulins (G-GLO) and immunoglobulins (G, M, and A) were increased by adding SO or LO to quail diets. Blood levels of MDA and TAC were improved significantly by including LO in quail diets. The activity of the superoxide dismutase (SOD) enzyme was significantly increased by adding SO or LO to quail diets. Generally, adding SO or LO to growing quail diets up to 2% could yield favorable effects on growth performance, blood lipids, hepatic and renal functions, immunity, and antioxidant status; however, LO seems to have better effects than SO., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Heavy metals exist in different water resources and can threaten human health, inducing several chronic illnesses such as cancer and renal diseases. Therefore, this work dealt with the fabrication of highly efficient nanomembranes based on silver nanoparticle (Ag NP)-doped hybrid polyvinyl chloride (PVC) by dapsone (DAP) using an in situ method. Fourier-transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD) analysis were used to confirm the hybridization of PVC as well as the crystalline structure of hybrid PVC nanocomposites. Three varying proportions of Ag NPs ( i.e. , 0.1, 0.2, and 0.3%) were used to fabricate hybrid PVC-DAP nanomembranes. The Brunauer-Emmet-Teller (BET) method was used to estimate membrane surface area, porosity and distribution of pore volume. The mechanical strength and antibacterial properties of the cased films notably improved when Ag NPs were added depending on the NP ratio inside the matrix. Results obtained from adsorption experiments of PVC-DAP nanomembranes at 35 °C revealed that the optimum nanomembrane was achieved at 0.2% NPs and its percentage of removal effectiveness ranged from 71 to 95% depending on the ion type. The surface morphology of the PVC-DAP-0.2 Ag NPs before and after the adsorption process of the metal ions was analyzed using SEM-EDX. Moreover, the impact of other parameters such as the initial concentrations, pH media, temperature, and contacting time, on the adsorption efficiency of PVC-DAP-0.2 Ag NPs was also investigated. Furthermore, kinetic and adsorption isotherm models were suggested to describe the adsorption efficiency of the PVC-DAP-0.2 Ag NP membrane, and the uptake mechanism of metal ion removal was studied. The obtained outcomes for these fabricated nanomembranes demonstrated that they could be potential candidates for water purification and other potential purposes including biomedical areas., Competing Interests: The authors have no conflict of interest to declare in this study., (This journal is © The Royal Society of Chemistry.)

Aplasia cutis congenita (ACC) is a rare congenital disorder defined as a congenital skin defect, characterized by the absence of all skin layers at birth. The most frequent presentation is a small erythematous ulcerated or scar-like alopecic ectodermal lesion on the scalp vertex. However, extensive cutis aplasia of the trunk is extremely uncommon. Clinical and radiological evaluation defined the appropriate treatment. We herein report a rare case of a large aplasia cutis congenita of the trunk occurring in a male newborn managed with sulfadiazine silver 1% dressing, complete healing was achieved in about a month. The report highlights that conservative treatment is a highly effective and practical option for managing non-scalp extensive ACC., Competing Interests: The authors declare no competing interests., (Copyright: El Mouloua Ahmed et al.)

Sugar esters display surface-active properties, wetting, emulsifying, and other physicochemical phenomena following their amphipathic nature and recognize distinct biological activity. The development of nutritional pharmaceuticals and other applications remains of great interest. Herein, three novel homologous series of several N-mono-fatty acyl amino acid glucosyl esters were synthesized, and their physicochemical properties and biological activities were evaluated. The design and preparation of these esters were chemically performed via the reaction of glucose with different fatty acyl amino acids as renewable starting materials, with the suggestion that they would acquire functional characteristics superior and competitive to certain conventional surfactants. The synthesized products are characterized using FTIR, 1 H-NMR, and 13 C-NMR spectroscopy. Further, their physicochemical properties, such as HLB, CMC, Γ max , γ CMC , and A min, were determined. Additionally, their antimicrobial and anticancer efficiency were assessed. The results indicate that the esters' molecular structure, including the acyl chain length and the type of amino acid, significantly influences their properties. The measured HLB ranged from 8.84 to 12.27, suggesting their use as oil/water emulsifiers, wetting, and cleansing agents. All esters demonstrate promising surface-active characteristics, with moderate to high foam production with good stability. Notably, compounds 6-O-(N-dodecanoyl, tetradecanoyl cysteine)-glucopyranose (34, 35), respectively and 6-O-(N-12-hydroxy-9-octadecenoyl cysteine)-glucopyranose (38) display superior foamability. Wetting efficiency increased with decreasing the chain length of the acyl group. The storage results reveal that increasing the fatty acyl hydrophobe length enhances the derived emulsion's stability for up to 63 days. Particularly, including cysteine in these glucosyl esters improves wetting, foaming, and emulsifying potentialities. Furthermore, the esters exhibit antibacterial activity against several tested Gram-positive and Gram-negative bacteria and fungi. On the other hand, they show significant antiproliferative effects on some liver tumor cell lines. For instance, compounds 6-O-(N-12-hydroxy-9-octadecenoylglycine)-glucopyranose (28), 6-O-(N-dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoylvaline)- glucopyranose (29, 31, 32 and 33), respectively in addition to the dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoyl cysteine glucopyranose (34, 36, 37 and 38), respectively significantly inhibit the examined cancer cells., (© 2024. The Author(s).)

Toxoplasma gondii holds significant therapeutic potential; however, its nonspecific invasiveness results in off-target effects. The purpose of this study is to evaluate whether T. gondii specificity can be improved by surface display of scFv directed against dendritic cells' endocytic receptor, DEC205, and immune checkpoint PD-L1. Anti-DEC205 scFv was anchored to the T. gondii surface either directly via glycosylphosphatidylinositol (GPI) or by fusion with the SAG1 protein. Both constructs were successfully expressed, but the binding results suggested that the anti-DEC-SAG1 scFv had more reliable functionality towards recombinant DEC protein and DEC205-expressing MutuDC cells. Two anti-PD-L1 scFv constructs were developed that differed in the localization of the HA tag. Both constructs were adequately expressed, but the localization of the HA tag determined the functionality by binding to PD-L1 protein. Co-incubation of T. gondii displaying anti-PD-L1 scFv with tumor cells expressing/displaying different levels of PD-L1 showed strong binding depending on the level of available biomarker. Neutralization assays confirmed that binding was due to the specific interaction between anti-PD-L1 scFv and its ligand. A mixed-cell assay showed that T. gondii expressing anti-PD-L1 scFv predominately targets the PD-L1-positive cells, with negligible off-target binding. The recombinant RH-PD-L1-C strain showed increased killing ability on PD-L1+ tumor cell lines compared to the parental strain. Moreover, a co-culture assay of target tumor cells and effector CD8+ T cells showed that our model could inhibit PD1/PD-L1 interaction and potentiate T-cell immune response. These findings highlight surface display of antibody fragments as a promising strategy of targeting replicative T. gondii strains while minimizing nonspecific binding.

A sequence of dye-sensitized solar cells is proposed, utilizing TiO 2 @Zn/Al-layered double hydroxide (LDH) as their starting materials, in which Ruthenizer N719 was used as a photon absorber. The anticipated system was turned into sheet-like TiO 2 @mixed metal oxide (MMO) via post-processing treatment. The crystal quality indicated a relation to power conversion efficiency (PCE); this was combined with a comparable morphology profile. In detail, the optimum DSSC device exhibited average sheet-like thickness and a dye loading amount of 43.11 nm and 4.28 ×10-3 mM/cm -2 , respectively. Concurrently, a considerable PCE enhancement of the optimum DSSC device (TiO 2 @MMO-550°) was attained compared to pristine MMO (0.91%), which could be due to boosted electron transfer efficiency. Of the fabricated devices, DSSC fabricated at 550° exhibited the highest PCE (1.91%), with a 35.6% enhancement compared to that obtained at 450°, as a result of its increased open-circuit voltage (3.29 mA/cm 2 ) and short-circuit current (0.81 V). The proposed work delivers an enhanced efficiency as compared to similar geometries.

Background: Peripheral insulin resistance and compromised insulin secretion from pancreatic β-cells are significant factors and pathogenic hallmarks of diabetes mellitus (DM). NF-κβ/TLR-4 and SERCA/Ca 2+ pathways have been identified as potential pathways regulating insulin synthesis by preserving pancreatic β-cell functioning. The current study aimed to evaluate the therapeutic effect of aged garlic extract (AGE) against DM in a streptozotocin (STZ)-induced rat model with particular emphasis on pancreatic β-cell functioning., Methods: AGE was characterized by gas chromatography-mass spectrometry (GC-MS), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) to evaluate its physio-chemical characteristics followed by in-vitro anti-diabetic and antioxidant potential. This was followed by the induction of DM in laboratory animals for investigating the therapeutic action of AGE by evaluating the role of NF-κβ/TLR-4 and the SERCA/Ca 2+ pathway. The parameters assessed in the present experimental setup encompassed antioxidant parameters, metabolic indicators, insulin concentration, intracellular calcium levels, apoptotic markers (CCK-8 and Caspase Glo-8), and protein expression (P-62 and APACHE-II)., Results: AGE characterization by SEM, GC-MS, and X-ray diffraction (XRD) revealed the presence of phenylalanine, alliin, S-allylmercaptocysteine (SAMC), tryptophan, 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid as major bioactive constituents of AGE. Metabolic studies, including intraperitoneal glucose tolerance test (IPGTT), revealed significantly lower blood glucose levels in the AGE group compared to the disease control group. In contrast, the intraperitoneal insulin tolerance test (ITT) exhibited no significant difference in insulin sensitivity between the AGE supplementation group and the DM control group. Interestingly, AGE was found to have no significant effect on fasting glucose and serum insulin levels. In contrast, AGE supplementation was found to cause significant hypoglycaemia in postprandial blood glucose and insulin levels. Importantly, AGE causes restoration of intracellular Ca 2+ levels by modulation of SERCA/Ca 2 functioning and inhibition NF-κB/TLR-4 pathway. AGE was found to interact with and inhibit the DR-5/ caspase-8/3 apoptotic complex. Furthermore, microscopic studies revealed degeneration and apoptotic changes in pancreatic β-cells of the DM control group, while supplementation of AGE resulted in inhibition of apoptotic pathway and regeneration of pancreatic β-cells., Conclusion: The current study suggests that AGE enhance glucose homeostasis by exerting their effects on pancreatic β-cells, without ameliorating peripheral sensitivity. Moreover, AGEs promote an increase in β-cell mass by mitigating the apoptosis of pancreatic β-cells. These findings suggest that AGE could aid in developing a viable alternative therapy for diabetes mellitus (DM)., (© 2024. The Author(s).)

Diabetes mellitus (DM) represents a problem for the healthcare system worldwide. DM has very serious complications such as blindness, kidney failure, and cardiovascular disease. In addition to the very bad socioeconomic impacts, it influences patients and their families and communities. The global costs of DM and its complications are huge and expected to rise by the year 2030. DM is caused by genetic and environmental risk factors. Genetic testing will aid in early diagnosis and identification of susceptible individuals or populations using ATP-sensitive potassium (K ATP ) channels present in different tissues such as the pancreas, myocardium, myocytes, and nervous tissues. The channels respond to different concentrations of blood sugar, stimulation by hormones, or ischemic conditions. In pancreatic cells, they regulate the secretion of insulin and glucagon. Mutations in the KCNJ11 gene that encodes the Kir6.2 protein (a major constituent of K ATP channels) were reported to be associated with Type 2 DM, neonatal diabetes mellitus (NDM), and maturity-onset diabetes of the young (MODY). Kir6.2 harbors binding sites for ATP and phosphatidylinositol 4,5-diphosphate (PIP2). The ATP inhibits the K ATP channel, while the (PIP2) activates it. A Kir6.2 mutation at tyrosine330 (Y330) was demonstrated to reduce ATP inhibition and predisposes to NDM. In this study, we examined the effect of mutations on the Kir6.2 structure using bioinformatics tools and molecular dynamic simulations (SIFT, PolyPhen, SNAP2, PANTHER, PhD&SNP, SNP&Go, I-Mutant, MuPro, MutPred, ConSurf, HOPE, and GROMACS). Our results indicated that M199R, R201H, R206H, and Y330H mutations influence Kir6.2 structure and function and therefore may cause DM. We conclude that MD simulations are useful techniques to predict the effects of mutations on protein structure. In addition, the M199R, R201H, R206H, and Y330H variant in the Kir6.2 protein may be associated with DM. These results require further verification in protein-protein interactions, Kir6.2 function, and case-control studies.

Insulin gene mutations affect the structure of insulin and are considered a leading cause of neonatal diabetes and permanent neonatal diabetes mellitus PNDM. These mutations can affect the production and secretion of insulin, resulting in inadequate insulin levels and subsequent hyperglycemia. Early discovery or prediction of PNDM can aid in better management and treatment. The current study identified potential deleterious non-synonymous single nucleotide polymorphisms nsSNPs in the INS gene. The analysis of the nsSNPs in the INS gene was conducted using bioinformatics tools by implementing computational algorithms including SIFT, PolyPhen2, SNAP2, SNPs & GO, PhD-SNP, MutPred2, I-Mutant, MuPro, and HOPE tools to investigate the prediction of the potential association between nsSNPs in the INS gene and PNDM. Three mutations, C96Y, P52R, and C96R, were shown to potentially reduce the stability and function of the INS protein. These mutants were subjected to MDSs for structural analysis. Results suggested that these three potential pathogenic mutations may affect the stability and functionality of the insulin protein encoded by the INS gene. Therefore, these changes may influence the development of PNDM. Further researches are required to fully understand the various effects of mutations in the INS gene on insulin synthesis and function. These data can aid in genetic testing for PNDM to evaluate its risk and create treatment and prevention strategies in personalized medicine.

Soqotra, an island situated at the mouth of the Gulf of Aden in the northwest Indian Ocean between Africa and Arabia, is home to ~60,000 people subsisting through fishing and semi-nomadic pastoralism who speak a Modern South Arabian language. Most of what is known about Soqotri history derives from writings of foreign travellers who provided little detail about local people, and the geographic origins and genetic affinities of early Soqotri people has not yet been investigated directly. Here we report genome-wide data from 39 individuals who lived between ~650 and 1750 CE at six locations across the island and document strong genetic connections between Soqotra and the similarly isolated Hadramawt region of coastal South Arabia that likely reflects a source for the peopling of Soqotra. Medieval Soqotri can be modelled as deriving ~86% of their ancestry from a population such as that found in the Hadramawt today, with the remaining ~14% best proxied by an Iranian-related source with up to 2% ancestry from the Indian sub-continent, possibly reflecting genetic exchanges that occurred along with archaeologically documented trade from these regions. In contrast to all other genotyped populations of the Arabian Peninsula, genome-level analysis of the medieval Soqotri is consistent with no sub-Saharan African admixture dating to the Holocene. The deep ancestry of people from medieval Soqotra and the Hadramawt is also unique in deriving less from early Holocene Levantine farmers and more from groups such as Late Pleistocene hunter-gatherers from the Levant (Natufians) than other mainland Arabians. This attests to migrations by early farmers having less impact in southernmost Arabia and Soqotra and provides compelling evidence that there has not been complete population replacement between the Pleistocene and Holocene throughout the Arabian Peninsula. Medieval Soqotra harboured a small population that showed qualitatively different marriage practices from modern Soqotri, with first-cousin unions occurring significantly less frequently than today., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In this study, we developed a novel nanocomposite, polyurethane foam impregnated with zero-valent iron nanoparticles (PU@nZVI), for the effective removal of chromium(VI) from various water sources. The characterization of nanocomposite (PU@nZVI) was performed by XRD, SEM-EDS, TEM and FT-IR techniques. Using the response surface methodology, we optimized the removal conditions, achieving an optimal pH of 2 and a dose of 0.5 g/L. The PU@nZVI demonstrated an excellent maximum adsorption capacity of 600.0 mg/g for Cr 6+ . The adsorption kinetics and isotherms were best described by the pseudo-second-order model and the Freundlich isotherm, respectively. Significantly, the nanocomposite removed 99.98% of Cr 6+ from tap water, 96.81% from industrial effluent, and 94.57% from treated sewage wastewater. Furthermore, the PU@nZVI maintained its efficiency over five adsorption-desorption cycles, highlighting its reusability. These results suggest that the PU@nZVI nanocomposite is a highly efficient and sustainable option for chromium(VI) removal in water treatment applications., (© 2024. The Author(s).)

The cytotoxic effects of Cymbopogon schoenanthus L. aerial part ethanol extract were examined against some cancer cell lines, and HUVEC normal cell lines using MTT assay. The ethanolic extract was prepared by ultrasonic-assisted extraction and analyzed by GC-MS and HPLC. The extract was found to be rich in terpene compounds. The extract proved to be highly selective and effective against breast and prostate cancer cell lines (MDA-MB-435, MCF-7, and DU 145) with IC 50 as low as 0.7913 ± 0.14, 12.841 ± 0.21, and 30.51 ± 0.18 µg/ml, respectively. In silico modeling was performed to investigate the binding orientation and affinity of the major identified compounds against Polo-like kinase (PLK1 protein) a cancer molecular target using molecular docking and molecular dynamic whereas eudesm-5-en-11-ol, piperitone, and 2,3-dihydrobenzofuran displayed better binding affinity and stability against PLK1 compared to the reference drug. These findings encourage further in vivo studies to assess the anti-cancer effects of C. schoenanthus extract and its components.

Two innovative series derived from nicotinic acid scaffold were synthesized and evaluated for their anti-inflammatory activity. Ibuprofen, celecoxib and indomethacin were used as standard drugs. All the newly synthesized compounds were in vitro screened for their anti-inflammatory activity adopting 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide dye (MTT), as well as Griess assays. The results showed that all compounds exhibited significant anti-inflammatory activity without affecting the viability of the macrophages compared to ibuprofen. In addition, compounds 4d, 4f, 4g, 4h and 5b exhibited the most potent nitrite inhibition activity and consequently superior anti-inflammatory activity with MTT results ranging between values 86.109 ± 0.51 to 119.084 ± 0.09. The most active compounds were subjected to evaluation of TNF-α, IL-6, iNOS and COX-2 levels in LPS/INF γ-stimulated RAW 264.7 macrophage cells in comparison to ibuprofen as a reference compound. The five compounds showed comparable inhibition potency of these inflammatory cytokines compared to ibuprofen. Same compounds were further in vivo evaluated for their anti-inflammatory activity via carrageenan induced arthritis in rats. Regarding the ulcerogenic profile, compound 4h showed mild infiltration of gastric mucosa superb to compound 5b displayed severe gastritis. Molecular docking of 4h and 5b in the COX-2 active site was performed to evaluate their preferential COX-2 inhibitory potency. The docking results were in accordance with the biological findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Redo sternotomy aortic root surgery is technically demanding, and the evidence on outcomes is mostly from retrospective, small sample, single-centre studies. We report the trend, early clinical results and outcome predictors of redo aortic root replacement over 20 years in the United Kingdom., Methods: We retrospectively analysed collected data from the UK National Adult Cardiac Surgery Audit (NACSA) on all redo sternotomy aortic root replacements performed between 30th January 1998 and 19th March 2019. We analysed trends in the volume of operations, characteristics of hospital survivors vs. non-survivors, and predictors of in-hospital outcomes., Results: During the study period, 1,107 redo sternotomy aortic root replacements were performed (median age 59, 26% of patients were females). Eighty-four per cent of cases ( N  = 931) underwent a composite root replacement, 11% ( N  = 119) had homograft root replacement and valve-sparing root replacement was performed in 5.1% ( N  = 57) of cases. There was a steady increase in the volume of redo sternotomy root replacements beyond 2006, from an annual volume of 22 procedures in 2006 to 106 procedures in 2017. Hospital mortality was 17% ( n  = 192), postoperative stroke or TIA occurred in 5.2% ( n  = 58), and postoperative dialysis was required in 11% ( n  = 109) of patients. Return to the theatre for bleeding/tamponade was required in 9% ( n  = 102) and median in-hospital stay was 9 days. Age >59 (OR: 2.99, CI: 1.92-4.65, P  < 0.001), recent myocardial infarction (OR: 6.42, CI: 2.24-18.41, P  = 0.001) were associated with increased in-hospital mortality. Emergency surgery (OR: 3.95, 2.27-6.86, P  < 0.001), surgery for endocarditis (OR: 2.05, CI: 1.26-3.33, P  = 0.001), salvage coronary artery bypass grafting (OR: 2.20, CI: 1.37-3.54, P  < 0.001), arch surgery (OR: 2.47, CI: 1.30-3.61, P  = 0.018) and aortic cross-clamp longer than 169 min (OR: 2.17, CI: 1.00-1.01, P  = 0.003) were associated with increased risk of mortality. We found no effect of the centre or surgeon volume on mortality ( P  > 0.05)., Conclusions: Redo sternotomy aortic root replacement still carries significant morbidity and mortality and is sporadically performed across surgeons and centres in the UK., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Fudulu, Dong, Kota, Sinha, Chan, Rajakaruna, Dimagli, Angelini and Ahmed.)

Diabetes mellitus (DM) is characterized by an absolute decline in insulin secretion and peripheral resistance and is the most prevalent metabolic and endocrine disorder. However, the pathogenesis of DM also includes adipocyte insulin resistance, increased glucagon secretion, increased renal glomerular glucose absorption, and neurotransmitter dysfunction. Although there is a wide spectrum of therapeutics available for glycemic control, owing to the identification of various pathogenic determinants of DM, management of DM remains challenging and complex. Current therapeutic interventions against DM focus mostly on glycemic control without considering the other pathological determinants that eventually lead to treatment failure and the progression of DM. Furthermore, long-term use of these conventionally available anti-diabetic drugs leads to various side effects, henceforth development of novel drugs against DM remains an unending search strategy for researchers. Various studies conducted in various parts of the world have proposed that these novel therapeutic interventions target multiple and alternate pathogenic hotspots involved in DM. The current review article discusses novel therapeutic options that hold particular promise to support their safety and discuss the side effects resulting from their use so that these novel candidate drugs can be effectively fabricated into potential drugs for the treatment of DM.

Background: Surgical pulmonary embolectomy is rarely used for the treatment of massive acute pulmonary embolism. The aim of this study was to assess the incidence and outcomes of this operation by undertaking a retrospective analysis of a large national registry in the UK., Methods: All acute pulmonary embolectomies performed between 1996 and 2018 were captured in the National Institute of Cardiovascular Outcomes Research central database. Trends in the number of operations performed during this interval and reported in-hospital outcomes were analysed retrospectively. Multivariable logistic regression was used to identify independent risk factors for in-hospital death., Results: All 256 patients treated surgically for acute pulmonary embolism during the study interval were included in the analysis. Median age at presentation was 54 years, 55.9% of the patients were men, 48.0% had class IV heart failure symptoms, and 37.5% had preoperative cardiogenic shock. The median duration of bypass was 73 min, and median cross-clamp time was 19 min. Cardioplegic arrest was used in 53.1% of patients. The median duration of hospital stay was 11 days. The in-hospital mortality rate was 25%, postoperative stroke occurred in 5.4%, postoperative dialysis was required in 16%, and the reoperation rate for bleeding was 7.5%. Risk-adjusted multivariable analysis revealed cardiogenic shock (OR 2.54, 95% c.i. 1.05 to 6.21; P = 0.038), preoperative ventilation (OR 5.85, 2.22 to 16.35; P < 0.001), and duration of cardiopulmonary bypass exceeding 89 min (OR 7.82, 3.25 to 20.42; P < 0.001) as significant independent risk factors for in-hospital death., Conclusion: Surgical pulmonary embolectomy is rarely performed in the UK, and is associated with significant mortality and morbidity. Preoperative ventilation, cardiogenic shock, and increased duration of bypass were significant predictors of in-hospital death., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nephrolithiasis is a prevalent issue around the globe, particularly in hot climates such as Saudi Arabia. This analysis's objectives were to investigate the characteristics of kidney stones in Eastern Saudi Arabia and to provide the following findings: urinary stone composition, gender and age distribution, seasonal variations in stone formation, coexisting diseases linked to stone development, and urinary stone incidence. With comparisons to European and American populations, the primary risk factors for nephrolithiasis in Asian populations are to be determined through this systematic review and meta-analysis. We synthesized data from 13 geographically different studies using a thorough literature search through PubMed, ScienceDirect, and ResearchGate following the Preferred Reporting Items of Systematic Reviews and Meta-Analyses criteria. Potential targets for specialized public health programs were highlighted by the elucidation of differences in health-care-seeking behavior and disparities in health-care access. The results of this systematic analysis give doctors, researchers, and policymakers a thorough understanding of the condition of nephrolithiasis care in Saudi Arabia today. In addition, to maximize the care of nephrolithiasis in this particular group, this review identifies information gaps and highlights the necessity of context-specific guidelines and future research initiatives. All things considered, this systematic review addresses the unique possibilities and problems that exist within the Saudi Arabian health-care sector while also adding to the worldwide conversation on nephrolithiasis., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Urology Annals.)

Background: To determine whether there is any difference in graft rerupture rates and clinical outcomes between cases having vancomycin graft presoaking vs. no vancomycin presoaking in anterior cruciate ligament (ACL) reconstruction (ACLR)., Methods: Systematic review and meta-analysis. PubMed, Embase, CINAHL, and Cochrane CENTRAL were searched. Full published studies reporting on the relation between vancomycin graft presoaking and rates of graft rerupture and/or clinical outcomes in ACLR surgery vs. no vancomycin graft presoaking were included. Data extraction and quality appraisal were performed. Meta-analysis was conducted using a random effects model. The study's protocol was prospectively registered with PROSPERO (CRD42021290608)., Results: The literature search identified 907 records. After removing duplicates and those not meeting inclusion criteria, 8 studies were included. Meta-analysis showed that the estimated risk of hamstring graft rerupture was lower in cases presoaked with vancomycin vs. those having no presoaking (3.2% vs. 6.2% rerupture rate, risk ratio [RR] = 0.507, 95% CI, 0.39-0.737, p < 0.001). Similarly, the estimated risk of graft rerupture was lower in cases presoaked with vancomycin vs. those having no presoaking when the analysis included various ACL graft types (2.7% vs. 3.9% rerupture rate, RR = 0.557, 95% confidence interval [CI], 0.403-0.771, p < 0.001). Meta-analysis also showed that vancomycin graft presoaking was associated with similar International Knee Documentation Committee scores as compared with no presoaking when looking at hamstring grafts (estimated mean difference 0.112, 95% CI, -2.359 to 2.582, p = 0.929) or when considering various graft types (estimated mean difference 0.933, 95% CI, -0.140 to 2.006, p = 0.088)., Conclusion: Vancomycin graft presoaking is a safe practice and does not compromise ACL graft rerupture rates or clinical outcomes., Level of Evidence: Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B42)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

This study comprises the design and synthesis of novel nicotinic acid-based cytotoxic agents with selective inhibitory efficacy against the vascular endothelial growth factor receptor-2 (VEGFR-2). Screening of novel compounds for cytotoxicity was assessed against 60 human cancer cell lines. The two most active compounds, 5b and 5c, and the reference drugs sorafenib and doxorubicin were investigated against HCT-15, PC-3, and CF-295 cancer cell lines. Compound 5c exhibited the highest cytotoxic potential compared to doxorubicin against the HCT-15 and PC-3 tumor cell lines. Moreover, it exhibited higher cytotoxic potential and selectivity toward the HCT-15 cell panel compared with sorafenib. Compound 5c demonstrated promising VEGFR-2 inhibition (concentration needed to inhibit cell viability by 50%, IC 50  = 0.068 μM) and superior VEGFR-2 selectivity over the epidermal growth factor receptor and platelet-derived growth factor receptor-β enzymes. It also reduced the total and phosphorylated VEGFR-2 and induced apoptosis, as evidenced by a 4.3-fold rise in caspase-3 levels. The antioxidant potential of the new compounds was determined via measuring the superoxide dismutase (SOD) levels, among which compound 5c exhibited an SOD level almost comparable to ascorbic acid. These results suggested that compound 5c exhibited dual cytotoxic and antioxidant activities. Docking of 5c into the VEGFR-2 pocket showed a similar binding mode to sorafenib. Moreover, the ADME (absorption, distribution, metabolism, and excretion) profile of 5c outlined drug-likeness. Finally, The density functional theory calculations displayed an increased binding affinity of 5c to the target enzyme., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

Selective cyclooxygenase (COX)-2 inhibitors have several advantages over nonselective COX inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]), including the absence of adverse effects (renal and hepatic disorders) associated with the long-term use of standard NSAIDs, as well as an improved gastrointestinal profile. The pyridazine nucleus is regarded as a promising scaffold for the development of powerful COX-2 inhibitors, particularly when selectively functionalized. This article summarizes some methods for the synthesis of pyridazine derivatives. Furthermore, it covers all of the pyridazine derivatives that have appeared as selective COX-2 inhibitors, making it useful as a reference for the rational design of novel selective COX-2 inhibitors., (© 2023 Wiley Periodicals LLC.)

The objective of the current study was to extract 2-(benzhydryl sulfinyl)-N-sec-butylacetamide), a novel compound from fig, and then determine its role in enhancing trastuzumab-triggered phagocytic killing of SKOV-3 cancer cells. In this study, Soxhlet was used to extract the compound from the mature and air-dried fig fruits. The production of the isolated extracts was enhanced by using polar and non-polar solvents. Several solvents, such as methanol, ethyl acetate, chloroform, and n-hexane, were used to isolate the effective compound 2-(benzhydryl sulfinyl)-N-sec-butylacetamide) from the organic layer. UV-spectroscopy, FT-IR, 1 H-NMR, and 13 C-NMR were applied to identify the purified compound. The in vitro and in vivo assays demonstrated that the 2-(benzhydryl sulfinyl)-N-sec-butylacetamide) can increase the activity of the phagocytic cells, via the interaction with FcY receptors, along with trastuzumab, and the pathway can use a model for the therapeutic strategy for effective treatment of ovarian cancer cells.

Background: Currently, there are many techniques available for repairing hypospadias in urogenital reconstructive surgery., Aim: The purpose of this survey is to determine the preferred age of hypospadias repair patients, as well as the preferred surgical techniques among Saudi urologic and pediatric surgeons., Materials and Methods: An E-mail questionnaire was sent to urologic and pediatric surgeons throughout Saudi Arabia., Results: Forty-six participants from the Saudi regions returned completed questionnaires. Sixty-five percent of participants preferred age to do surgery on 6-18 months. While, 50% preferred meatal advancement and glanduloplasty techniques for coronal/glandular hypospadias, and 46% participate that tubularized incised plate (TIP). It was found that 86% of the participants admitted to using TIP procedure for subcoronal/distal penile hypospadias, whereas the majority of them (63%) used TIP for midpenile/proximal hypospadias with significant value P < 0.05. Ninety-eight percentage of surgeons stated that they prefer performing the chordee repair simultaneously. As a final note, 91% of participants have been omitted preoperative androgen in their protocols., Conclusions and Recommendation: We concluded from the surgeons' preferences regarding hypospadias repair in this study, that their preferences are highly successful rate and have few complications; however, we highly recommend using this study as a basis for future studies., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Urology Annals.)

Alpha synuclein (α-Syn) is a neuronal protein encoded by the SNCA gene and is involved in the development of Parkinson's disease (PD). The objective of this study was to examine in silico the functional implications of non-synonymous single nucleotide polymorphisms (nsSNPs) in the SNCA gene. We used a range of computational algorithms such as sequence conservation, structural analysis, physicochemical properties, and machine learning. The sequence of the SNCA gene was analyzed, resulting in the mapping of 42,272 SNPs that are classified into different functional categories. A total of 177 nsSNPs were identified within the coding region; there were 20 variants that may influence the α-Syn protein structure and function. This identification was made by employing different analytical tools including SIFT, PolyPhen2, Mut-pred, SNAP2, PANTHER, PhD-SNP, SNP&Go, MUpro, Cosurf, I-Mut, and HOPE. Three mutations, V82A, K80E, and E46K, were selected for further examinations due to their spatial positioning within the α-Syn as determined by PyMol. Results indicated that these mutations may affect the stability and function of α-Syn. Then, a molecular dynamics simulation was conducted for the SNCA wildtype and the four mutant variants (p.A18G, p.V82A, p.K80E, and p.E46K). The simulation examined temperature, pressure, density, root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), and radius of gyration (Rg). The data indicate that the mutations p.V82A, p.K80E, and p.E46K reduce the stability and functionality of α-Syn. These findings highlight the importance of understanding the impact of nsSNPs on α-syn structure and function. Our results required verifications in further protein functional and case-control studies. After being verified these findings can be used in genetic testing for the early diagnosis of PD, the evaluation of the risk factors, and therapeutic approaches.

New benzothienopyran and benzothienopyranopyrimidine derivatives were synthesized based on the structural requirements of topoisomerase I inhibitors. All target compounds exhibited strong cytotoxic activity with GI 50 range of 70.62 %-87.29 % in one dose NCI (USA) screening against 60 human tumor cell lines. Among the tested derivatives, eight compounds namely 4d, 4e, 4f, 5b, 5e, 6b, 6d, and 6f demonstrated broad spectrum and potent anticancer efficacy in five dose screening against all tested panels. DNA relaxation assay for the latter compounds showed that 4d, 5b, and 6f exhibited excellent inhibitory activity with IC 50 range of 2.553-4.495 µM as compared to indenoisoquinoline reference drug (IC 50  = 3.911 ± 0.21 µM). Moreover, the most active compounds were investigated for being topoisomerase poisons or catalytic inhibitors using DNA nicking assay. Compounds 4d and 6f were found to be potential Topo I poisons, whereas compound 5b has acted as Topo I suppressor. Analyzing cell cycle and induction of apoptosis for the most active compound 4d, revealed growth arrest at the S phase in MDA-MB-435 cells similarly to indenoisoquinoline reference drug. Additionally, in silico molecular modeling study for eight most active cytotoxic compounds in five dose screening demonstrated interaction with DNA as well as distinctive binding pattern similar to the reference indenoisoquinoline, indicating that the newly discovered targets are supposed to be promising candidates as Topo I inhibitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: In testicular neoplasms, the interrelationship of elevations of the novel serum tumor marker microRNA-371a-3p (M371) and traditional markers with other clinical features is still incompletely understood. The present study evaluated marker expression rates in relation to various other clinical parameters., Methods: The following data were retrospectively registered from 641 consecutive patients with testicular neoplasms: histology, such as seminoma (n = 365), nonseminoma (n = 179), benign tumor (n = 79), other malignant tumor (n = 18); patients age (years); clinical stage (CS1, CS2a/b, CS2c, CS3); and preoperative elevation of beta HCG, AFP, LDH, M371 (yes/no). Descriptive statistical methods were employed with comparisons of various subgroups to disclose associations of marker expression rates with age, histology and CS, and of age with histology., Results: The histologic subgroups revealed significantly different expression rates of tumor markers. M371 performed best with expression rates of 82.69% and 93.58% in seminoma and in nonseminoma, respectively. In germ cell tumors, all markers had significantly higher expression rates in metastasized stages than in localized disease. All markers except LDH have significantly higher expression rates in younger than in older patients. Nonseminoma is most prevalent in the youngest age category, seminoma predominates in patients > 40 years, other malignancies were restricted to patients > 50 years., Conclusion: The study documented significant associations of serum marker expression rates with histology, age and clinical staging, with highest rates in nonseminomas, young age and advanced clinical stages. M371 showed significantly higher expression rates than other markers suggesting its superior clinical usefulness., (© 2023. The Author(s).)

To date, there is limited data about the genetic relationship of Escherichia coli between wild birds and cattle because these birds act as silent vectors for many zoonotic bacteria. This study aimed to elucidate the role of rooming wild birds in the vicinity of cattle farm in transmission of the same pathogenic E. coli variants, identifying their virulence, resistance traits and genetic similarities of fimH virulence gene. About 240 faecal/cloacal swabs were collected from both species and examined bacteriologically. Escherichia coli was yielded in 45.8% and 32.5%, respectively, of examined cattle and wild birds. The most prevalent detected E. coli serovar was O26. High tetracycline and chloramphenicol resistance were recorded; however, gentamycin and ciprofloxacin exhibited the highest sensitivity rates. Polymerase chain reaction (PCR) conserved genotypic resistance (tetA and blaCTX-M) and virulence attributes (fimH, stx1, eaeA and ompA) of E. coli isolates were discussed in detail. The fimH gene revealed 100% sequence similarity when comparing with different E. coli isolates globally and locally. Finally, a close genetic association of E. coli with both wild birds and cattle was detected, thus strengthening its role in the dissemination of the infection via environment. Prevention and conservative policy should be carried as E. coli constitute enormous significant zoonotic risks to livestock and animal workers. Also, further studies to the whole genome sequencing of fimH, other virulence and resistance genes of E. coli are recommended trying to limit the possibilities of co-infection and transfer among different species.Contribution: The current study recorded updated data about the critical infectious role of wild birds to livestock, including cattle farms in Egypt. It also delivered some recommendations for good hygienic practices in cattle farms which must be implemented for handling animal manure.

Introduction: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients., Methods: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology., Results and Conclusion: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion ( p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers' expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

Background: Rift Valley Fever Virus (RVFV) is an arbovirus, a zoonotic disease that resurfaces as a potential hazard beyond geographic boundaries. Fever that can proceed to encephalitis, retinitis, hemorrhagic fever, and death is the main manifestation observed in human infections. RVFV has no authorized medication. The RNA interference (RNAi) gene silencing pathway is extremely well conserved. By targeting specific genes, small interfering RNA (siRNA) can be used to suppress viral replication. The aim of this study was to design specific siRNAs against RVFV and evaluate their prophylactic and antiviral effects on the Vero cells., Methods and Results: Various siRNAs were designed using different bioinformatics tools. Three unique candidates were tested against an Egyptian sheep cell culture-adapted strain BSL-2 that suppressed RVFV N mRNA expression. SiRNAs were transfected a day before RVFV infection (pre-transfection), and 1 h after the viral infection (post-transfection), and were evaluated to detect the silencing activity and gene expression decrease using real-time PCR and a TCID50 endpoint test. The degree of N protein expression was determined by western blot 48 h after viral infection. D2 which targets the (488-506 nucleotides), the middle region of RVFV N mRNA was the most effective siRNA at 30 nM concentration, it almost eliminates N mRNA expression when utilized as antiviral or preventive therapy. siRNAs had a stronger antiviral silencing impact when they were post-transfected into Vero cells., Conclusion: Pre and post-transfection of siRNAs significantly reduced RVFV titer in cell lines, offering novel and potentially effective anti-RVFV epidemics and epizootics therapy., (© 2023. The Author(s).)

Background : LGR5 is one of the most important stem cell markers for colorectal cancer (CRC), as it potentiates Wnt/Β-catenin signaling. The well-characterized deregulation of Wnt/Β-catenin signaling that occurs during adenoma/carcinoma sequence in CRC renders LGR5 a hopeful therapeutic target. We assessed the immunohistochemical expression of LGR5 and Β-catenin in normal colonic and tumorous lesions with a clinicopathological correlation. Methods : Tissue blocks and clinical data of 50 selected cases were included: 8 from normal mucosa, 12 cases of adenoma, and 30 cases of CRC, where sections were cut and re-examined and the immunohistochemical technique was conducted using anti-LGR5 and anti-Β-catenin to measure the staining density. Results : There was no expression of LGR5 in normal mucosa compared to samples of adenoma and CRC samples. The association analysis showed that CRC specimens were more likely to have strong LGR5 and Β-catenin expressions than the other two groups ( p = 0.048 and p < 0.001, respectively). Specimens with high-grade dysplastic adenoma were more likely to express moderate-to-strong expression of LGR5 and Β-catenin ( p = 0.013 and p = 0.036, respectively). In contrast, there were no statistically significant associations between LGR5 and Β-catenin expression with grade and stage. Conclusion : These results suggest and support the possible role of LGR5 as a potential marker of cancer stem cells in sporadic colorectal carcinogenesis in addition to a prognostic value for LGR5 and Β-catenin in adenomatous lesions according to immunohistochemical expression density. A potential therapeutic role of LGR5 in CRC is suggested for future studies based on its role in pathogenesis.

Background: Ward rounds are a cornerstone in the educational experience of junior doctors and an essential part of teaching patient care. Here, we aimed to assess the doctors' perception of ward rounds as an educational opportunity and to identify the obstacles faced in conducting a proper ward round in Sudanese hospitals., Method: A cross-sectional study was conducted from the 15 th to the 30 th of January 2022 among house officers, medical officers, and registrars in about 50 teaching and referral hospitals in Sudan. House officers and medical officers were considered the learners, while specialist registrars were considered the teachers. Doctors' perceptions were assessed using an online questionnaire, with a 5-level Likert scale to answer questions., Results: A total of 2,011 doctors participated in this study (882 house officers, 697 medical officers, and 432 registrars). The participants were aged 26.9 ± 3.2 years, and females constituted about 60% of the sample. An average of 3.1 ± 6.8 ward rounds were conducted per week in our hospitals, with 11.1 ± 20.3 h spent on ward rounds per week. Most doctors agreed that ward rounds are suitable for teaching patient management (91.3%) and diagnostic investigations (89.1%). Almost all the doctors agreed that being interested in teaching (95.1%) and communicating appropriately with the patients (94.7%) make a good teacher in ward rounds. Furthermore, nearly all the doctors agreed that being interested in learning (94.3%) and communicating appropriately with the teacher (94.5%) make a good student on ward rounds. About 92.8% of the doctors stated that the quality of ward rounds could be improved. The most frequently reported obstacles faced during ward rounds were the noise (70%) and lack of privacy (77%) in the ward environment., Conclusion: Ward rounds have a special value in teaching patient diagnosis and management. Being interested in teaching/learning and having good communication skills were the two major criteria that make a good teacher/learner. Unfortunately, ward rounds are faced with obstacles related to the ward environment. It is mandatory to ensure the quality of both ward rounds' teaching and environment to optimize the educational value and subsequently improve patient care practice., (© 2023. The Author(s).)

The study aims to verify the factorial structure of the self-compassion scale across different cultural contexts. The sample included 1039 students, divided into 521 students from Zagazig University (ZU) and 518 from Princess Nourah University (PNU) in the Kingdom of Saudi Arabia (KSA), which were chosen randomly. Exploratory factor analysis was used to test the stability of items on the dimensions. The results showed stability along with kindness with self, isolation, common humanity, and self-judgment factors. On the other hand, confirmatory factor analysis demonstrated that the results of this study yielded the best fit for the total sample. Then factor analysis across the two groups was used to verify the existence of differences between Saudi and Egyptian cultures. The analysis results revealed that the Egyptian environment model is superior to its Saudi counterpart and that there are no differences between the two cultures using the factorial differences indicators RMSEA, NNFI, GFI, and SRMR. This study's outcomes can have global implications for promoting self-compassion as a tool for improving mental health and well-being across cultures.

Objectives: To evaluate programmed death-ligand 1 immunohistochemical expression in the available variants of urinary bladder carcinoma, and to correlate its expression with the available clinicopathological features., Method: The retrospective study was conducted at the Faculty of Medicine, Kafrelsheikh University, Egypt, from February 2020 to April 2021, and comprised formalin-fixed and paraffin-embedded specimens of urinary bladder carcinoma belonging to patients who had no history of radiotherapy or chemotherapy. Immunohistochemicalstaining of all cases was done using anti-programmed death-ligand 1 antibody. Data was analysed using SPSS 20., Results: Of the 70 specimens, 58(82.86%) had been obtained through transurethral resection of bladder tumours and 12(17.14%) through radical cystectomy. Also, 53(75.7%) specimens belonged to males and 27(24.3%) to females. The age of the cases ranged 34-83 years, and 59(84.3%) were aged ≥45 years. There were 27(38.6%) noninvasive bladder tumours and 43(61.4%) were infiltrating bladder carcinomas. Positive programmed death-ligand 1 expression was detected in 42(60%) cases. Age, gender and histopathological type were not significantly associated with the expression of programmed death-ligand 1., Conclusions: Programmed death-ligand 1 could be considered a predictive marker for aggressive bladder carcinoma and its immunohistochemical expression may aid in identifying selective patients for targeted immunotherapy.

Objectives: To evaluate epidermal growth factor receptor and Ki-67 immunohistochemical expression in colorectal adenoma and carcinoma cases, and to relate their expression with the available clinicopathological data., Method: The retrospective study was conducted at the Faculty of Medicine, Kafrelsheikh University, Egypt, from September 2019 to October 2020, and comprised formalin-fixed and paraffin-embedded specimens related to cases of colorectal adenoma and those of colorectal carcinoma, who had no previous radiation or chemotherapeutic treatment. Immunohistochemical staining of all thecases was done using anti-epidermal growth factor receptor and anti-Ki-67 antibodies. Data was analysed using SPSS 20., Results: Of the 70 cases, 20(28.5%) were of colorectal adenoma; mean age 52.95±13.47 years, and male-to-female ratio 1:1. The remaining 50(71.5%) cases had colorectal carcinoma; mean age 51.08±13.49 years, and male-to-female ratio 1.17:1. Epidermal growth factor receptor and Ki-67 overexpression related significantly to villous histopathological type and high-grade dysplasia in colorectal adenoma cases(p<0.05). In colorectal carcinoma cases, epidermal growth factor receptor overexpression related significantly to tumour grade (p<0.05). Ki-67 overexpression related significantly to increased pathological stage (p<0.05)., Conclusions: Overexpression of epidermal growth factor receptor and Ki-67 was found to be an ominous sign of colorectal adenoma aggressiveness, and the risk of progression to colorectal carcinoma.

The study planned to estimate biological parameters linked to rheumatoid arthritis (RA) patients, detecting the influence of MTX and biotherapy treatments on these parameters and synthesizing methotrexate bovine serum albumin nanoparticles linked to folate (FA-MTX-BSA NPs) to reduce the overwhelming expression of inflammatory cytokines. Inflammatory parameters showed significant increases in newly diagnosed and MTX-receiving groups while no changes were observed in the biotherapy-maintained group. MTX-loaded BSA nanoparticles were fabricated by the desolvation method and further linked to activated folic acid to obtain FA-MTX-BSA NPs. FA-MTX-BSA NPs were successfully characterized within the nanoscale range using different screening techniques. FA-MTX-BSA NPs showed an in vitro release in a sustained manner. The potential of MTX, MTX-BSA NPs, and FA-MTX-BSA NPs in inducing cytokine level reduction was detected. Significant decreases in interleukin- 1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels were obtained in cultures treated with FA-MTX-BSA NPs compared to the untreated culture in a dose-dependent pattern. Furthermore, FA-MTX-BSA NPs comparing with MTX and MTX-BSA NPs exhibited a significant advanced effect in decreasing cytokines levels. Accordingly, the conjunction of BSA NPs and MTX linked to folate potentially reduced cytokines manifestation in RA.

Introduction: Although widespread, BCC is still relatively poorly understood in regards to pathogenesis and prognosis, particularly the lesions formed on anatomical sites away from sun exposure. With the aim of deepening our understanding of the pathogenesis and clinico-pathological correlations of BCCs, we conducted this study., Methods: Tissue blocks and data of 52 Egyptian patients diagnosed with BCC were retrieved for clinical information and inclusion criteria, then re-examined histologically; p16 immunostaining was carried out and evaluated for analysis and comparison between the two groups, i.e., sun-exposed and sun-protected., Results: Sex, age, clinical suspicion, tumor size, recurrence status, and histologic variants did not show a significant difference between the sun-protected and sun-exposed groups; however, the mean ages recorded were 67.2 vs. 62.7 for the sun-protected and sun-exposed groups, respectively. A total of 52% of BCCs were positive for p16. The sun-protected lesions showed p16 positivity in 61% of cases, whereas 49% of the sun-exposed lesions were positive with no significant difference. There was a significant difference in p16 expression between the recurrent and non-recurrent lesions., Conclusions: A significant difference was seen in the case of cancer recurrence, where all the recurrent BCCs in this study demonstrated negative p16 immunostaining of the primary lesions; however, the positively stained cases in total were 52% of BCCs. The mean patient age of the sun-protected group was much higher than in previous peer studies. We assume that the biological, prognostic, and clinical aspects of p16 protein expression in BCCs are still far from being clearly understood. Further studies are highly recommended, with more focus on its role in the pathogenesis and the prognostic factors.