Extension of simple multi-attribute rating technique in uncertainty environment for 5G industry evaluation: Egyptian new administrative capital as a case study.

As is well-known, multicriteria decision-making (MCDM) approaches can aid decision-makers in identifying the optimal alternative based on predetermined criteria. However, it is a big challenge to apply this approach in complex applications such as 5th generation (5G) industry assessment because criteria are challenging and trade-offs between them are hard. Also, assessment of the 5G industry involve strong uncertainty. So, this study is the first to evaluate the 5G industry using a new neutrosophic simple multi-attribute rating technique (N-SMART). Since neutrosophic set considers truth-degree, indeterminacy-degree, and falsity-degree, it is a more accurate instrument for evaluating uncertainty. The 5G assessment issue exemplifies the validity and great performance of our proposed method as: (1) its ability to deal with uncertainty phenomena; (2) its simplicity; and (3) its enhanced capacity to discern alternatives. Also, by considering the 5G service provided in the Egyptian New Administrative capital as a case study, the results showed that Ericsson 5G is the best choice and Nokia 5G is the worst choice.

Bee chitosan nanoparticles loaded with apitoxin as a novel approach to eradication of common human bacterial, fungal pathogens and treating cancer.

Antimicrobial resistance is one of the largest medical challenges because of the rising frequency of opportunistic human microbial infections across the globe. This study aimed to extract chitosan from the exoskeletons of dead bees and load it with bee venom (commercially available as Apitoxin [Api]). Then, the ionotropic gelation method would be used to form nanoparticles that could be a novel drug-delivery system that might eradicate eight common human pathogens (i.e., two fungal and six bacteria strains). It might also be used to treat the human colon cancer cell line (Caco2 ATCC ATP-37) and human liver cancer cell line (HepG2ATCC HB-8065) cancer cell lines. The x-ray diffraction (XRD), Fourier transform infrared (FTIR), and dynamic light scattering (DLS) properties, ζ-potentials, and surface appearances of the nanoparticles were evaluated by transmission electron microscopy (TEM). FTIR and XRD validated that the Api was successfully encapsulated in the chitosan nanoparticles (ChB NPs). According to the TEM, the ChB NPs and the ChB NPs loaded with Apitoxin (Api@ChB NPs) had a spherical shape and uniform size distribution, with non-aggregation, for an average size of approximately 182 and 274 ± 3.8 nm, respectively, and their Zeta potential values were 37.8 ± 1.2 mV and - 10.9 mV, respectively. The Api@ChB NPs had the greatest inhibitory effect against all tested strains compared with the ChB NPs and Api alone. The minimum inhibitory concentrations (MICs) of the Api, ChB NPs, and Api@ChB NPs were evaluated against the offer mentioned colony forming units (CFU/mL), and their lowest MIC values were 30, 25, and 12.5 µg mL-1, respectively, against Enterococcus faecalis. Identifiable morphological features of apoptosis were observed by 3 T3 Phototox software after Api@ChB NPs had been used to treat the normal Vero ATCC CCL-81, Caco2 ATCC ATP-37, and HepG2 ATCC HB-8065 cancer cell lines for 24 h. The morphological changes were clear in a concentration-dependent manner, and the ability of the cells was 250 to 500 µg mL-1. These results revealed that Api@ChB NPs may be a promising natural nanotreatment for common human pathogens.

Physiological, Agronomic, and Grain Quality Responses of Diverse Rice Genotypes to Various Irrigation Regimes under Aerobic Cultivation Conditions.

Aerobic rice cultivation represents an innovative approach to reduce water consumption and enhance water use efficiency compared to traditional transplanting methods. Simultaneously, cultivating drought-tolerant rice genotypes becomes crucial to ensure their sustainable production under abrupt climate fluctuations. Hence, this study aimed to explore the physiological, agronomic, and grain quality responses of ten diverse rice genotypes to various irrigation levels under aerobic cultivation conditions. A field experiment was performed for two summer seasons of 2019 and 2020 in an arid Mediterranean climate. The irrigation regimes were well watered (13,998 m3/ha), mild drought (10,446 m3/ha), moderate drought (7125 m3/ha), and severe drought (5657 m3/ha). The results revealed considerable variations among rice genotypes under tested irrigation regimes in all physiological, agronomic, and quality traits. According to drought response indices, rice genotypes were classified into three groups (A-C), varying from tolerant to sensitive genotypes. The identified drought-tolerant genotypes (Giza-179, Hybrid-1, Giza-178, and Line-9399) recorded higher yields and crop water productivity with reduced water usage compared to drought-sensitive genotypes. Thus, these genotypes are highly recommended for cultivation in water-scarce environments. Furthermore, their characteristics could be valuable in breeding programs to improve drought tolerance in rice, particularly under aerobic cultivation conditions. The PCA biplot, heatmap, and hierarchical clustering highlighted specific physiological parameters such as relative water content, chlorophyll content, proline content, peroxidase content, and catalase content exhibited robust associations with yield traits under water deficit conditions. These parameters offer valuable insights and could serve as rapid indicators for assessing drought tolerance in rice breeding programs in arid environments.

A 3D scaling law for supravalvular aortic stenosis suited for stethoscopic auscultations.

In this study a frequency scaling law for 3D anatomically representative supravalvular aortic stenosis (SVAS) cases is proposed. The law is uncovered for stethoscopy's preferred auscultation range (70-120 Hz). LES simulations are performed on the CFD solver Fluent, leveraging Simulia's Living Heart Human Model (LHHM), modified to feature hourglass stenoses that range between 30 to 80 percent (mild to severe) in addition to the descending aorta. For physiological hemodynamic boundary conditions the Windkessel model is implemented via a UDF subroutine. The flow-generated acoustic signal is then extracted using the FW-H model and analyzed using FFT. A preferred receiver location that matches clinical practice is confirmed (right intercostal space) and a correlation between the degree of stenosis and a corresponding acoustic frequency is obtained. Five clinical auscultation signals are tested against the scaling law, with the findings interpreted in relation to the NHS classification of stenosis and to the assessments of experienced cardiologists. The scaling law is thus shown to succeed as a potential quantitative decision-support tool for clinicians, enabling them to reliably interpret stethoscopic auscultations for all degrees of stenosis, which is especially useful for moderate degrees of SVAS. Computational investigation of more complex stenotic cases would enhance the clinical relevance of this proposed scaling law, and will be explored in future research.

A CFD-FFT approach to hemoacoustics that enables degree of stenosis prediction from stethoscopic signals.

In this paper, we identify a new (acoustic) frequency-stenosis relation whose frequencies lie within the recommended auscultation threshold of stethoscopy (< 120 Hz). We show that this relation can be used to extend the application of phonoangiography (quantifying the degree of stenosis from bruits) to widely accessible stethoscopes. The relation is successfully identified from an analysis restricted to the acoustic signature of the von Karman vortex street, which we automatically single out by means of a metric we propose that is based on an area-weighted average of the Q-criterion for the post-stenotic region. Specifically, we perform CFD simulations on internal flow geometries that represent stenotic blood vessels of different severities. We then extract their emitted acoustic signals using the Ffowcs Williams-Hawkings equation, which we subtract from a clean signal (stenosis free) at the same heart rate. Next, we transform this differential signal to the frequency domain and carefully classify its acoustic signatures per six (stenosis-)invariant flow phases of a cardiac cycle that are newly identified in this paper. We then automatically restrict our acoustic analysis to the sounds emitted by the von Karman vortex street (phase 4) by means of our Q-criterion-based metric. Our analysis of its acoustic signature reveals a strong linear relationship between the degree of stenosis and its dominant frequency, which differs considerably from the break frequency and the heart rate (known dominant frequencies in the literature). Applying our new relation to available stethoscopic data, we find that its predictions are consistent with clinical assessment. Our finding of this linear correlation is also unlike prevalent scaling laws in the literature, which feature a small exponent (i.e., low stenosis percentage sensitivity over much of the clinical range). They hence can only distinguish mild, moderate, and severe cases. Conversely, our linear law can identify variations in the degree of stenosis sensitively and accurately for the full clinical range, thus significantly improving the utility of the relevant scaling laws... Future research will investigate incorporating the vibroacoustic role of adjacent organs to expand the clinical applicability of our findings. Extending our approach to more complex 3D stenotic morphologies and including the vibroacoustic role of surrounding organs will be explored in future research to advance the clinical reach of our findings.

Ovarian reserve in adolescent girls with autoimmune thyroiditis

ABSTRACT Objectives: To assess serum anti-Müllerian hormone (AMH) levels as an ovarian reserve marker in adolescent girls with autoimmune thyroiditis (AIT) and explore the relationship of this marker with autoimmunity and thyroid function biomarkers. Subjects and methods: This study included 96 adolescent girls with newly diagnosed AIT and 96 healthy, age- and sex-matched controls. All participants were evaluated with detailed history taking and physical examination, thyroid ultrasound, and measurement of levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies (TPOAb), antithyroglobulin antibody (TGAb), estradiol, total testosterone, and anti-Müllerian hormone (AMH) levels. The LH/FSH ratio was also calculated. Among 96 patients evaluated, 78 were overtly hypothyroid and 18 were euthyroid. AMH levels were significantly lower in participants with overt hypothyroidism and euthyroidism compared with controls. Results: Serum levels of AMH correlated negatively with age, body mass index (BMI) standard deviation score (SDS), and TPOAb, TGAb, and TSH levels but positively with FT4 levels. In multivariate analysis, AMH levels correlated significantly with age (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.18-2.32, p = 0.05), BMI SDS (OR = 2.3, 95% CI, 2.23-3.50, p = 0.01), TSH (OR = 2.43, 95% CI 1.5-2.8, p = 0.01), and TPOAb (OR = 4.1, 95% CI 3.26-8.75, p = 0.001). Conclusions: Ovarian reserve of adolescent girls with AIT, as measured by serum AMH levels, is affected by thyroid autoimmunity and hypothyroidism, indicating a possible need for ovarian reserve monitoring in these patients.

Automated guided vehicles with a mounted serial manipulator: A systematic literature review.

Automated Guided Vehicles (AGVs) have become a vital part of the automation sector and a key component of a new industrial revolution that promises to: i. automate the entire manufacturing process, ii. increase productivity rates, iii. develop safer workplaces, while iv. maximising profits and reducing running costs for businesses. However, several concerns arise in the face of this very promising revolution. A major issue is how to ensure that AGVs function effectively and safely during interactions with humans. Another one concerns the ethical desirability of pervasive, continuous, and multidimensional couplings (or interactions) between humans and robots. Generally speaking, automated systems, in virtue of their vast sensing capabilities, may pose privacy challenges to their users. This is because such systems can seamlessly gather information about people' behaviors, without people's consent or awareness. To tackle the important issues abovementioned, we performed a systematic literature review [SLR] on AGVs with mounted serial manipulators. We used as an input 282 papers published in the relevant scientific literature. We analysed these papers and selected 50 papers based on certain criteria to find out trends, algorithms, performance metrics used, as well as potential ethical concerns raised by the deployment of AGVs in the industry. Our findings suggest that corporations can effectively rely on AGVs with mounted manipulators as an efficient and safe solution to production challenges.

Endothelial dysfunction in children with newly diagnosed Graves' disease.

The most frequent cause of hyperthyroidism in children is Graves' disease (GD). Vascular endothelium is a specific target of thyroid hormone. The purpose of this study is to assess flow-mediated dilatation (FMD)% and serum von Willebrand factor (vWF) levels in children with newly diagnosed GD to reflect the extent of endothelial dysfunction in those children. In this study, 40 children with newly discovered GD and 40 children who were healthy served as the control group. Both patients and controls had anthropometric assessment, as well as measurements of fasting lipids, glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), TSH, and free thyroxine (FT4 and FT3), thyrotropin receptor antibodies TRAbs and vWF. Noninvasive ultrasound was utilized to quantify the carotid arteries' intima-media thickness and the brachial artery's FMD. Patients reported significantly reduced FMD response and greater vWF and hs-CRP levels compared to controls (P = 0.001 for each). In multivariate analysis, we reported that vWF was significantly correlated with TSH (OR 2.5, 95% CI 1.32-5.32, P = 0.001), FT3 (OR 3.4, 95% CI 1.45-3.55, P = 0.001), TRAb (OR 2.1, 95% CI 1.16-2.23, P = 0.01), and FMD% (OR 4.2, 95% CI 1.18-8.23, P = 0.001).  Conclusions: Children with newly diagnosed GD have endothelial dysfunction, which is shown by impaired FMD and increased vWF. These findings support the idea that GD may need to be treated as soon as possible. What is Known: • Graves' disease is the most common cause of hyperthyroidism in children. • vWF is a reliable marker for detection of vascular endothelial dysfunction. What is New: • Children with newly diagnosed Graves' disease may have endothelial dysfunction as reflected by impairment of FMD and raised vWF level. • Measurement of vWF level in children with newly diagnosed Graves' disease can be used for early detection of endothelial dysfunction.

Outflow Reconstruction in Right Lobe Living Donor Liver Transplant: Middle Hepatic Vein Reconstruction Versus Separate Tributaries to Inferior Vena Cava Anastomosis.

OBJECTIVES: In right lobe living donor liver transplant, proper reconstruction of the segment 5 vein and segment 8 vein is essential. Herein, we compared 2 different techniques for segment 5 vein reconstruction. MATERIALS AND METHODS: This prospective nonrandomized study included all recipients of modified right lobe living donor liver transplant who had reconstruction of the segment 5 vein, with or without segment 8 veins, from October 2018 to October 2021. Patients were grouped into group A (classical technique) and group B (modified technique). For group A, the segment 5 (and segment 8, if present) vein was anastomosed in an end-to-side fashion to a polytetrafluoroethylene synthetic graft positioned parallel to the cut surface of the liver graft; then, during implant, its proximal end was anastomosed to recipient's middle hepatic or middle-left hepatic veins unified orifice. In group B (modified technique), the stumps of segment 5 (and segment 8 if present) were anastomosed in an end-to-end fashion to 2 different polytetrafluoroethylene grafts; then during implant, the other ends of the segment 5 grafts were anastomosed directly to the inferior vena cava. Postoperative segment 5 vein patency and graft recovery were compared. RESULTS: Forty patients were included: 22 in group A and 18 group B. There were no significant differences in the demographic data or characteristics of donors, grafts, and recipients between the groups. There was better patency in segment 5 synthetic grafts in group A at all time points compared with group B, but this difference was statistically significant only at 1 month (18 [81.8%] vs 9 [50%, respectively; P = .046).There was no statistically significant difference in the markers of graft recovery in both groups. CONCLUSIONS: Reconstruction of the segment 5 vein by polytetrafluoroethylene synthetic graft in a fashion to resemble the native middle hepatic vein in modified right lobe living donor liver transplant has better patency than anastomosis of the segment 5 vein in an end-to-end fashion to the synthetic graft and then to the inferior vena cava. Both techniques did not affect graft recovery.

Ovarian reserve in adolescent girls with autoimmune thyroiditis.

Objective: To assess serum anti-Müllerian hormone (AMH) levels as an ovarian reserve marker in adolescent girls with autoimmune thyroiditis (AIT) and explore the relationship of this marker with autoimmunity and thyroid function biomarkers. Subjects and methods: This study included 96 adolescent girls with newly diagnosed AIT and 96 healthy, age- and sex-matched controls. All participants were evaluated with detailed history taking and physical examination, thyroid ultrasound, and measurement of levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies (TPOAb), antithyroglobulin antibody (TGAb), estradiol, total testosterone, and anti-Müllerian hormone (AMH) levels. The LH/FSH ratio was also calculated. Among 96 patients evaluated, 78 were overtly hypothyroid and 18 were euthyroid. AMH levels were significantly lower in participants with overt hypothyroidism and euthyroidism compared with controls. Results: Serum levels of AMH correlated negatively with age, body mass index (BMI) standard deviation score (SDS), and TPOAb, TGAb, and TSH levels but positively with FT4 levels. In multivariate analysis, AMH levels correlated significantly with age (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.18-2.32, p = 0.05), BMI SDS (OR = 2.3, 95% CI, 2.23-3.50, p = 0.01), TSH (OR = 2.43, 95% CI 1.5-2.8, p = 0.01), and TPOAb (OR = 4.1, 95% CI 3.26-8.75, p = 0.001). Conclusion: Ovarian reserve of adolescent girls with AIT, as measured by serum AMH levels, is affected by thyroid autoimmunity and hypothyroidism, indicating a possible need for ovarian reserve monitoring in these patients.

Phytochemistry and Biological Properties of Salvia verbenaca L.: A Comprehensive Review.

The family Lamiaceae contains several plants used in traditional medicine to fight against different diseases. Salvia verbenaca L. (S. verbenaca) is one of the Lamiaceae species distributed around the Mediterranean regions. This plant exhibits different bioactive properties, including antibacterial, anticancer, antioxidant, antileishmanial, antidiabetic, immunomodulatory, and wound healing. This review was conducted to revise previous studies on S. verbenaca addressing its botanical description, geographical distribution, and phytochemical, pharmacological, and toxicological properties. Moreover, the main pharmacological actions of S. verbenaca major compounds were well investigated. Literature reports have revealed that S. verbenaca possesses a pivotal role in medicinal applications. The findings of this work noted that S. verbenaca was found to be rich in chemical compound classes such as terpenoids, phenolics, fatty acids, sterols, and flavonoids. Numerous studies have found that S. verbenaca essential oils and extracts have a wide range of biological effects. These results support the potential pharmacological properties of S. verbenaca and its traditional uses. This analysis can constitute a scientific basis for further refined studies on its pure secondary metabolites. Therefore, the outcome of the present work may support the perspective of identifying new therapeutical applications with detailed pharmacological mechanisms of S. verbenaca to prevent the development of some diseases such as neurodegenerative disorders. However, toxicological investigations into S. verbenaca are needed to assess any potential toxicity before it can be further used in clinical studies.

Attractive study of the antimicrobial, antiviral, and cytotoxic activity of novel synthesized silver chromite nanocomposites.

Antibiotic resistance is a global problem. This is the reason why scientists search for alternative treatments. In this regard, seven novel silver chromite nanocomposites were synthesized and assayed to evaluate their antimicrobial, antiviral, and cytotoxic activity. Five bacterial species were used in this study: three Gram-positive (Bacillus subtilis, Micrococcus luteus, and Staphylococcus aureus) and two Gram-negative (Escherichia coli and Salmonella enterica). Three fungal species were also tested: Candida albicans, Aspergillus niger, and A. flavus. The MIC of the tested compounds was determined using the bifold serial dilution method. The tested compounds showed good antibacterial activity. Maximum antibacterial activity was attained in the case of 15 N [Cobalt Ferrite (0.3 CoFe2O4) + Silver chromite (0.7 Ag0.5Cr2.5O4)] against M. luteus. Concerning antifungal activity, C. albicans was the most susceptible fungal species. The maximum inhibition was recorded also in case of 15 N [Cobalt Ferrite (0.3 CoFe2O4) + Silver chromite (0.7 Ag0.5Cr2.5O4)]. The most promising antimicrobial compound 15 N [Cobalt Ferrite (0.3 CoFe2O4) + Silver chromite (0.7 Ag0.5Cr2.5O4)] was assayed for its antiviral and cytotoxic activity. The tested compound showed weak antiviral activity. The cytotoxic activity against Mammalian cells from African Green Monkey Kidney (Vero) cells was detected. The inhibitory effect against Hepatocellular carcinoma cells was detected using a MTT assay. The antimicrobial effect of the tested compounds depends on the tested microbial species. The tested compounds could be attractive and alternative antibacterial compounds that open a new path in chemotherapy.

Nano Matrix Soft Confectionary for Oral Supplementation of Vitamin D: Stability and Sensory Analysis.

Vitamin D deficiency distresses nearly 50% of the population globally and multiple studies have highlighted the association of Vitamin D with a number of clinical manifestations, including musculoskeletal, cardiovascular, cerebrovascular, and neurological disorders. In the current study, vitamin D oil-in-water (O/W) nanoemulsions were developed and incorporated in edible gummies to enhance bioavailability, stability, and patient compliance. The spontaneous emulsification method was employed to produce a nano-emulsion using corn oil with tween 20 and lecithin as emulsifiers. Optimization was carried out using pseudo-ternary phase diagrams and the average particle size and polydispersity index (PDI) of the optimized nanoemulsion were found to be 118.6 ± 4.3 nm and 0.11 ± 0.30, respectively. HPLC stability analysis demonstrated that the nano-emulsion prevented the degradation and it retained more than 97% of active vitamin D over 15 days compared to 94.5% in oil solution. Similar results were obtained over further storage analysis. Vitamin D gummies based on emulsion-based gelled matrices were then developed using gelatin as hydrocolloid and varying quantities of corn oil. Texture analysis revealed that gummies formulated with 10% corn oil had the optimum hardness of 3095.6 ± 201.7 g on the first day which remained consistent on day 45 with similar values of 3594.4 ± 210.6 g. Sensory evaluation by 19 judges using the nine-point hedonic scale highlighted that the taste and overall acceptance of formulated gummies did not change significantly (p > 0.05) over 45 days storage. This study suggested that nanoemulsions consistently prevent the environmental degradation of vitamin D, already known to offer protection in GI by providing sustained intestinal release and enhancing overall bioavailability. Soft chewable matrices were easy to chew and swallow, and they provided greater patient compliance.

Intranasal Cerium Oxide Nanoparticles Ameliorate Cognitive Function in Rats with Alzheimer's via Anti-Oxidative Pathway.

Cerium oxide nanoparticles (CNPs), owing to their antioxidant property, have recently emerged as therapeutic candidate for Alzheimer's disease (AD). However, intravenous CNPs are limited due to their poor physicochemical properties, rapid blood clearance and poor blood-brain penetration. Thus, we developed intranasal CNPs and evaluated its potential in experimental AD. CNPs were synthesized using homogenous precipitation method and optimized through Box-Behnken Design. The formation of CNPs was confirmed by UV spectroscopy and FTIR. The optimized CNP were spherical, small (134.0 ± 3.35 nm), uniform (PDI, 0.158 ± 0.0019) and stable (ZP, -21.8 ± 4.94 mV). The presence of Ce in CNPs was confirmed by energy-dispersive X-ray analysis. Further, the X-ray diffraction spectra revealed that the CNPs were nano-crystalline. The DPPH assay showed that at concentration of 50 µg/mL, the percentage radical scavenging was 95.40 ± 0.006%. Results of the in vivo behavioral studies in the scopolamine-induced Alzheimer rat model showed that intranasal CNPs dose dependently reversed cognitive ability. At dose of 6 mg/kg the morris water maze results (escape latency, path length and dwell time) and passive avoidance results (retention latency) were significantly different from untreated group but not significantly different from positive control group (rivastigmine patch, 13.3 mg/24 h). Further, biochemical estimation showed that intranasal CNP upregulated the levels of SOD and GSH in brain. In conclusion, intranasal CNPs, through its antioxidant effect, could be a prospective therapeutics for the treatment of cognitive impairment in AD.

Potential Use of Tailored Citicoline Chitosan-Coated Liposomes for Effective Wound Healing in Diabetic Rat Model.

PURPOSE: This study aimed to formulate citicoline-loaded chitosan-coated liposomes (CT-CS-LPs) for topical administration and evaluated for wound healing in a diabetic animal model. METHODS: CT-LPs were formulated via a thin-film hydration approach and coated with chitosan (CS). Box-Behnken statistical design investigated the effects of lipid amount, chitosan concentration, and cholesterol amount on vesicle diameter, surface charge, and entrapment efficiency. The potential of the optimized CT-CS-LPs gel for wound healing was further evaluated in streptozocin-induced diabetic rats. The different healing stages were evaluated by several techniques, including general and special staining techniques, in addition to antibody immunohistochemistry. RESULTS: The optimized CT-CS-LPs obtained had a mean size of 211.6 nm, a 50.7% entrapment efficiency, and a positive surface charge of 32.1 mV. In addition, the optimized CT-CS-LPs exhibited in vitro sustained release behavior. The in vivo experiments revealed that treatment with the optimized CT-CS-LPs boosts the healing process of the skin wound in diabetic rats by reducing inflammation, accelerating re-epithelization, angiogenesis, fibroblast proliferation, and connective tissue remodeling, leading to rapid wound closure. CONCLUSION: Chitosan-coated liposomes containing citicoline have emerged as a potential approach for promoting the healing process in diabetic rats. However, the therapeutic effectiveness of the suggested approach in diabetic patients needs to be investigated.

New cell cycle checkpoint pathways regulators with 2-Oxo-indoline scaffold as potential anticancer agents: Design, synthesis, biological activities and in silico studies.

3-Arylidene-2-oxo-indoline derivatives are at the heart of a wide range of clinically, medicinally and biologically important compounds among the 2-oxo-indolines. A number of 3-arylidene-2-oxo-indolines have been approved for clinical application. Accordingly, the current work describes the structural based design of 3-arylidene-2-oxindole derivatives through docking of their structures in the active site of CDK2 as one of the dominant enzyme checkpoints. Based on the docking studies a range of 3-arylidene-2-oxindole derivatives, 5(a-n) and 6(a-x), with variable substituents at positions 1 and 5 of the 2-oxindole as well as 3 and 4 of the aryl moieties were synthesized. These molecules exist in either E or Z diastereomer about the exocyclic double bond at position 3 of oxindole nucleus. Their structures were confirmed by spectral and elemental methods of analyses and the E/Z-configuration of the diastereomers was confirmed by 2D NOE analysis. In vitro cytotoxicity of these molecules was tested against four cancerous cell lines, namely, breast cancer cell line (MCF7), liver carcinoma cell line (HepG2), cervix carcinoma cell line (HeLa), colon cancer cell line (HCT116) in addition to the diploid human normal non-cancerous cell line (F180) using SRB and MTT assays. The tested molecules showed variable cytotoxic effects on the four cancer cell lines with pronounced selectivity compared to the normal one (F180) with no significant difference between E and Z diastereomers. Compounds 5a, 5b, 5e1, 5m, 6f and 6j were tested for the effect on the expression on CDK2, p53, caspase-3 and caspase-9 proteins, and revealed variable activities compared to the positive controls Sunitinib and Staurosporine. These molecules seem to have multiple cellular targets as they induced expression of p53 and caspases while inhibited that of CDK2. Apoptotic effect of compound 6j was further investigated using annexin V-FITC/PI dual staining assay and showed that cells treated with 6j have nearly 15 folds greater apoptotic effect than that of the control cells. Furthermore, inhibitory activity of compounds 5a, 5b, 5e1, 5m, 6f and 6j on CDK2 enzyme were tested and revealed that compound 6f, with the N-4-flourobenzyl- 2-oxindole and 3-p-chlorobenzylidene moieties, has a comparable inhibitory activity to the reference drug sunitinib.

Effect of mutation and vaccination on spread, severity, and mortality of COVID-19 disease.

Coronavirus disease 2019 (COVID-19) has had different waves within the same country. The spread rate and severity showed different properties within the COVID-19 different waves. The present work aims to compare the spread and the severity of the different waves using the available data of confirmed COVID-19 cases and death cases. Real-data sets collected from the Johns Hopkins University Center for Systems Science were used to perform a comparative study between COVID-19 different waves in 12 countries with the highest total performed tests for severe acute respiratory syndrome coronavirus 2 detection in the world (Italy, Brazil, Japan, Germany, Spain, India, USA, UAE, Poland, Colombia, Turkey, and Switzerland). The total number of confirmed cases and death cases in different waves of COVID-19 were compared to that of the previous one for equivalent periods. The total number of death cases in each wave was presented as a percentage of the total number of confirmed cases for the same periods. In all the selected 12 countries, Wave 2 had a much higher number of confirmed cases than that in Wave 1. However, the death cases increase was not comparable with that of the confirmed cases to the extent that some countries had lower death cases than in Wave 1, UAE, and Spain. The death cases as a percentage of the total number of confirmed cases in Wave 1 were much higher than that in Wave 2. Some countries have had Waves 3 and 4. Waves 3 and 4 have had lower confirmed cases than Wave 2, however, the death cases were variable in different countries. The death cases in Waves 3 and 4 were similar to or higher than Wave 2 in most countries. Wave 2 of COVID-19 had a much higher spread rate but much lower severity resulting in a lower death rate in Wave 2 compared with that of the first wave. Waves 3 and 4 have had lower confirmed cases than Wave 2; that could be due to the presence of appropriate treatment and vaccination. However, that was not reflected in the death cases, which were similar to or higher than Wave 2 in most countries. Further studies are needed to explain these findings.

Architectural distortion outcome: digital breast tomosynthesis-detected versus digital mammography-detected.

OBJECTIVES: To compare the outcome for DBT-detected and DM-detected suspicious AD, to evaluate the risk of malignancy and if is affected by the US or MRI imaging correlation. METHODS: All cases with suspicious AD (ultimately assigned BI-RADS 4 or 5 categories) were retrospectively included. Two radiologists independently reviewed DM and DBT images in two sessions for detection (DM vs. DBT). US and MRI imaging correlation findings were recorded. Pathologic results were compared between DBT-detected and DM-detected AD. RESULTS: Among 137 detected ADs, 103 (75.2%) were DM-detected, and 34 (24.8%) were only DBT-detected (p = 0.01). The malignancy rate was lower for DBT-detected than DM-detected AD (14.7% vs. 45.6%) (p = 0.01). Malignancy rate was higher with US-positive than US-negative correlation at DM-detected AD (49.4% vs. 27.8%) (p = 0.01). Malignancy rate was not different for DBT-detected AD with (16.7%) or without (12.5%) sonographic correlation. NPV based on radiologists' level of suspicion was high (86.2%-97.2%) but not sufficient enough to forgo biopsy. Of 34 sonographically occult ADs, a positive-MRI correlation was identified in 19 (55.9%) ADs (7 were malignant, 12 were benign). A negative-MRI correlation was identified in 15 (44.1%) ADs; all had a benign outcome (p = 0.01). CONCLUSIONS: DBT-detected AD is less likely to represent malignancy than does DM-detected; however, the risk of malignancy is not low enough to forgo biopsy. MRI-negative correlation in sonographically occult AD was significantly associated with benign outcomes and can avoid unnecessary interventions.