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Background/Objectives: Oxidative stress, the Warburg effect, and resistance to apoptosis are key hallmarks driving colorectal tumorigenesis. This study aimed to develop novel multi-target compounds capable of modulating these pathways. Methods: A library of 24 newly synthesized compounds—incorporating annulated thiophene, thiazole, quinazolinone, 2-oxoindoline, and 1,2,3-oxadiazole scaffolds, as well as N-(1-(4-hydroxy-3-methoxyphenyl)-3-oxo-3-(2-(phenylcarbamothioyl)hydrazineyl) prop-1-en-2-yl)benzamide—was evaluated for antioxidant activity (DPPH assay), PDK-1 and LDHA inhibition, cytotoxic effects against LoVo and HCT-116 colon carcinoma cells, with parallel assessment of safety profiles on normal HUVECs. The underlying anticancer mechanism of the most active compound was investigated through analysis of cell cycle distribution, apoptosis induction, intracellular reactive oxygen species levels, mitochondrial membrane potential disruption, and expression levels of apoptosis-related genes. Molecular docking assessed binding interactions within LDHA and PDK-1 active sites. The physicochemical, drug-likeness, and ADMET properties of the multi-bioactive candidates were predicted in silico. Results: Among the synthesized compounds, thiophenes 3b and 3d exhibited potent PDK-1/LDHA and DPPH/LDHA inhibitions, along with significant cytotoxic effects on LoVo/HCT-116 cells (IC50 in µM: 190.30/170.21 and 156.60/160.96, respectively), while showing minimal cytotoxicity toward HUVECs. Molecular docking revealed favorable interactions with key amino acid residues within the LDHA and/or PDK-1 active sites. Compound 3d notably induced G2/M (LoVo) and G1 (HCT-116) arrest and promoted apoptosis via enhancing ROS generation, modulating Bax/Bcl-2 expressions, disrupting mitochondrial membrane potential, and ultimately activating caspses-3. In silico predictions indicated their promising drug-likeness and pharmacokinetics, though high lipophilicity, poor solubility (especially for 3b), and potential toxicity risks were identified as limitations. Conclusions: Thiophenes 3b and 3d emerged as promising multi-target candidates; however, structural optimization is warranted to enhance their solubility, bioavailability, and safety to support further development as lead anti-colon cancer agents.

This paper deals with a cartonnage mummy mask that is now preserved in the El-Ashmounin Museum Magazine, in Minia Governorate. This unpublished mummy mask was not studied or included in any studies concerning cartonnage mummy masks. The piece in question is made of linen and painted plaster. The cartonnage consists of a mask and three breast pieces, except for the ruined lower side parts of the mask; the piece is in a good state of preservation. The paper also aims to suggest the provenance of the cartonnage. Based on the features of Egyptian profane art during the Graeco- Roman period, this paper studies the depicted mythological scenes as well as the accompanying inscriptions. The dating of the mask goes back to the Roman era, where the face bears the features of the deceased in terms of the face, eyes, and fringes of hair, and depicted on the funeral mask scenes bearing the Egyptian traditions according to the common Egyptian funerary art style during the Graeco-Roman Period.

The current research is motivated by the controversy between the proponents and opponents of privatizing SOEs in LDCs concerning its impact on the MCSs designed and implemented in these companies. On the one hand, proponents expect privatization to foster the design and implementation of market-based, consensual and transparent MCSs. On the other hand, opponents are more critical about the 'actual' changes that privatization might entail to SOEs' MCSs as they expect it to entail the design and implementation of non-transparent, coercive MCSs. When examined closely, this conflict was found to be rooted in the different theoretical perspectives adopted by each side. While proponents base their arguments, mostly, on 'traditional' agency and property-rights theories that underplay the role of structure in shaping the MCSs designed and implemented in privatized companies, many of the opponents base their arguments on neo-Marxist theories that underplay the role of agency in that process (namely labour process theory- LPT). The current research contributes to this debate through developing a power-informed theoretical model that acknowledges the role of both agency and structure in shaping the nature of the pre- and post-privatization MCSs designed and implemented in companies operating in LDCs. The model provides an attempt to develop the Hopper et al (2009) model through integrating into it a theory of power informed by the works of Lukes (1974 and 2005) and Gaventa (1980 and 2007) while adopting the integrative agency-structure approach suggested by Mahoney and Snyder (1999).Once developed, the model is used to guide the analysis of the relevant literature pertaining to Egypt's supra-national and national power relations and structural factors throughout its state and market capitalism eras as a first step towards comparatively analysing the pre- and post-privatization power relations and MCSs manifesting in two Egyptian companies. The empirical data was mainly collected through conducting semi-structured interviews in the two companies and with some of the government officials involved in their privatization. Other sources of data include the companies' internal records and financial reports, government publications, and newspapers. The comparative analysis shows how the power-informed model can help shed more light onto the nature of, and the dynamics of change in, MCSs transformations in LDCs; without having to abandon LPT as one of the main theoretical perspectives informing the analysis. While doing so, the nature of a company's MCSs (be it coercive, consensual, or irrelevant) is found to reflect the power relations manifesting in that company (namely, powerful management, comparatively powerful management and labour, or powerful labour, respectively). Furthermore, as the comparative analysis shows, it is found that privatization is more likely to result in changing the nature of a SOE's MCSs when it entails altering the power relations shaping these MCSs.

Background Extracellular vesicles (EVs) are a promising biomarker and play a vital role in cell–cell communication. This study aimed (I) to identify and characterize EVs from low volume uterine lavage (LVL) and serum in mares with endometritis, compared to healthy controls and (II) to measure serum levels of interleukin 6 (IL-6), and prostaglandins (PGF 2α and PGE 2 ). Mares were divided into 30 sub-fertile (endometritis) and 20 fertile (controls). Serum and LVL was collected for EV isolation, and determination of serum levels of inflammatory mediators. Characterization and visualization of EVs were done by electron microscopy, dynamic light scattering and flow cytometry. Results Serial ultracentrifugation of LVL and use of a commercial kit for serum were strategies for EVs isolation. Mares with endometritis released higher amounts of larger size EVs. The EVs from mares with endometritis differentially expressed CD9 and CD63, compared to controls. Mares suffering from endometritis evoked higher levels of inflammatory mediators. Conclusions Thus, EVs could be used for a better understanding the regulatory mechanisms associated with developing endometritis in mares.

So far the intimate link between serum microRNA (miRNA) and uterine inflammation in mares is unknown. We aimed (I) to investigate expression profile of eca-miR-155, eca-miR-223, eca-miR-17, eca-miR-200a, and eca-miR-205 (II) and to measure concentrations of interleukin 6 (IL-6), and prostaglandins (PGF2α and PGE2) in serum of mares with healthy and abnormal uterine status (endometritis). This study was conducted on 80 Arabian mares: young (4–7 years), and old (8–14 years). Mares were divided into 48 sub-fertile (endometritis) and 32 fertile (control) at stud farms. Serum was collected for measuring IL-6, PGF2α, and PGE2, as well as miRNA isolation and qRT-PCR. Concentrations of IL-6, PGE2, and PGF2α were higher in mares with endometritis compared to control. Age of mares had a remarkable effect on IL-6, PGE2, and PGF2α concentrations. Relative abundance of eca-miR-155, eca-miR-223, eca-miR-17, eca-miR-200a, and eca-miR-205 was higher in both young and old mares with endometritis. We noticed that eca-miR-155, eca-miR-223, eca-miR-200a, and eca-miR-205 revealed higher expression level in old than young mares with endometritis. This is the first study that has revealed the changes in cell free miRNA and serum inflammatory mediators during endometritis, and these findings could be used for a better understanding the pathophysiology mechanisms of endometritis in equine.

Background There are few epidemiological data to support rehabilitation programs for cerebral palsy (CP). Scarce international studies described the developmental anomalies (DAs) among children with CP. To our knowledge, the Arab countries did not publish data regarding this topic. This study aimed to describe the percentage of DAs among children with CP and detect the association between clinical subtypes and impairment severity in children with various DAs. We collected registry data of 679 children with cerebral palsy, between 2014 and 2019, from Armed Forces Hospitals, Taif, Kingdom of Saudi Arabia (KSA). We recorded demographic, perinatal, postnatal, developmental anomalies, subtypes, and impairment characteristics. We utilized the chi-square test to calculate the differences between groups. Results We reported significant differences between the children with and without anomalies regarding the percentages of consanguinity, preterm labor, low birth weight, and neonatal intensive care unit admission ( P = 0.001, 0.002, 0.003, 0.005, respectively). Congenital dysplasia of the hip and hydrocephalus was the most frequent skeletal and nervous anomalies among children with DAs (19.1% and 12.8%, respectively). The spastic bilateral pattern was significantly higher among children with skeletal anomalies than the central nervous system/other groups ( P < 0.001). The nervous anomalies group had higher frequencies of severe intellectual, motor, speech, and visual disabilities and a higher percentage of seizures than all other groups. Conclusions The frequency of children with anomalies in this study was comparable to previous studies. Children with CP and nervous system anomalies had more severe motor disabilities and associated impairments.

Introduction Hepatitis C virus (HCV) infection has detrimental effects on patient and graft survival after kidney transplantation. In the pre‐direct‐acting antiviral (DAA) era, treatment of HCV infection was associated with low response rates, poor tolerance, and increased risk of allograft rejection. However, DAAs have revolutionized HCV treatment. The aims of this study were to determine the impact of DAA on the sustained virologic response (SVR), renal function, and calcineurin inhibitor (CNI) levels and assess the tolerability to treatment in kidney transplant recipients with HCV infection in Qatar. Methods This retrospective study included the medical records of all kidney transplant recipients with confirmed HCV infection before January 1, 2020. All data were obtained from the patients’ electronic medical records; these included patient demographics; virologic responses to treatment; serum creatinine levels during treatment; urine protein to creatinine ratios and CNI levels before, during, and after treatment; and side effects related to DAA therapy. Results A total of 27 kidney transplant recipients with HCV were identified, 23 of whom received DAA therapy. The length of treatment ranged from 12 to 24 weeks, and 52% of patients had HCV genotype 1 infection. The median log10 HCV RNA was 6.6 copies per milliliter. None of the patients had liver cirrhosis, and all of them achieved SVR. There was no statistically significant difference in the glomerular filtration rate before, during, and after treatment. Most patients had stable CNI trough levels during treatment and did not require dose adjustment. Conclusions HCV infection was successfully eradicated by DAA therapy in kidney transplant recipients, with a 100% SVR rate. Moreover, DAA therapy was well‐tolerated, and kidney function remained stable without an increased risk of rejection. These results are expected to drive the eradication of hepatitis C from the entire country. Direct‐acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment. The aims of this study were to determine the impact of DAA on the sustained virologic response (SVR), renal function, and calcineurin inhibitor (CNI) levels and assess the tolerability to treatment in kidney transplant recipients with HCV infection in Qatar. We believe that our study makes a significant contribution to the literature because, in line with the WHO vision, we were able to achieve the eradication of HCV infection among kidney transplant recipients in Qatar by administering DAA therapy, which yielded a complete treatment response in all recipients infected with HCV.

BackgroundThe use of immune checkpoint inhibitors (ICIs) has led to a paradigm change in cancer management. Many patients may have inherent primary resistance to ICIs or develop secondary resistance after initial response. The impact of using novel therapeutic combinations of checkpoint blockade (avelumab) with immune stimulating agonists such as anti-OX40 and/or anti-4-1BB on the tumor microenvironment and modulation of the immune response is an intriguing strategy to evaluate how these agents interact and whether the hypothetical rationale for combinations can be translated into augmentation of anti-tumor immunity in solid tumors.MethodsWe performed whole exome sequencing (WES), bulk RNAseq, multiplex immunofluorescence (mIF) and chromogenic assay immunohistochemistry (IHC) on tumor tissue and flow cytometry of the peripheral blood to study changes between post and pre-treatment longitudinal changes following the combination of avelumab with utomilumab (a 4-1BB agonist) (arm A), PF-04518600 (an OX40 agonist) (arm B), utomilumab and PF-04518600 (arm C) and utomilumab and radiotherapy (arm D) in phase I/II study (NCT03217747). Wilcoxon signed rank test was applied.ResultsWe observed low tumor mutation burden (TMB<6) (median: 1.88), alteration of RTK-RAS, TP53, PI3K and WNT pathways across the cohorts. Mutations in TP53, TTN and KRAS (mostly p.G12C, p.G12D) genes and copy number variations (CNV) were found in PIK3CA, CCNE1 and KRAS. Interferon gamma signaling pathway was only enriched early on-treatment after immune stimulating agonists in tumors from patients with colorectal and pancreatic cancers with in arm C. Patients deriving clinical benefit (CR/PR/SD≥4 months) displayed higher T- cell lymphocytes frequencies at baseline (p=0.0157), C1D15 (p=0.0086), and C3D15 (p=0.0070) than patients without clinical benefit in mIF data.ConclusionsOur findings, though limited, highlight genomic differences between histologic subsets and outcome as well as the need for combination strategies that drive the recruitment and/or priming of anti-tumor T cells and address low immune permissive tumor states in patients with advanced solid tumors.Trial RegistrationNCT03217747AcknowledgementsThe study was financially supported by Pfizer as part of a previous alliance between Pfizer and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID:10.13039/100009945)Ethics ApprovalThe study was approved by the institutional review board at The University of Texas MD Anderson Cancer Center.

In 2010, Qatar adopted the target of reducing hepatitis B prevalence to < 1% in children by 2015. The World Health Organization Region for the Eastern Mediterranean is identified with intermediate hepatitis B virus (HBV) endemicity, ranging from 2% to 7%. It is estimated that 4.3 million individuals are living with HBV infection in the Region. This study was conducted to assess hepatitis B seroprevalence in children, hepatitis B vaccination coverage, potential exposure to risk factors, and knowledge among parents/guardians about hepatitis B infection. We carried out this cross-sectional study in Qatar during the academic year 2015/16. Multistage cluster sampling was used to select a nationally representative sample of 2735 grade 1 school students aged ≥ 5 years. Blood was collected by finger prick and tested using the point-of-care test/rapid test. A self-administered, precoded questionnaire was used to assess parent/guardian knowledge about HBV and collect information on the child's HBV vaccination coverage. All blood samples were HBsAg negative. Qataris had a vaccination card and were totally vaccinated but 17.7% of non-Qataris did not hold a vaccination card and most parents/guardians were not aware of the vaccination status of their children. Children were exposed to various hepatitis B risk practices. Knowledge about hepatitis B among parents/ guardians was low. Qatar has averted the hepatitis B threat and maintained high vaccination coverage for children.

Méthodes: La présente étude transversale a été réalisée au Qatar pendant l'année scolaire 2015-2016. L'échantillonnage en grappe à plusieurs niveaux a été la technique utilisée pour sélectionner un échantillon national représentatif de 2735 élèves de première année du primaire, âgés de cinq ans ou plus. Un prélèvement de sang a été réalisé par piqûre au doigt et un dépistage a été effectué à l'aide d'un test sur le lieu de soins/test rapide. Un questionnaire auto-administré précodé a été utilisé pour évaluer les connaissances des parents/tuteurs en matière d'hépatite B et recueillir des informations sur la couverture vaccinale des enfants contre l'hépatite B.