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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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Abstract<sec> <title>Background

Chronic lymphocytic leukaemia (CLL) patients display a highly variable clinical course, with progressive acquisition of drug resistance. We sought to identify aberrant epigenetic traits that are enriched following exposure to treatment that could impact patient response to therapy.

Methods

Epigenome-wide analysis of DNA methylation was performed for 20 patients at two timepoints during treatment. The prognostic significance of differentially methylated regions (DMRs) was assessed in independent cohorts of 139 and 163 patients. Their functional role in drug sensitivity was assessed in vitro.

Results

We identified 490 DMRs following exposure to therapy, of which 31 were CLL-specific and independent of changes occurring in normal B-cell development. Seventeen DMR-associated genes were identified as differentially expressed following treatment in an independent cohort. Methylation of the HOXA4, MAFB and SLCO3A1 DMRs was associated with post-treatment patient survival, with HOXA4 displaying the strongest association. Re-expression of HOXA4 in cell lines and primary CLL cells significantly increased apoptosis in response to treatment with fludarabine, ibrutinib and idelalisib.

Conclusion

Our study demonstrates enrichment for multiple CLL-specific epigenetic traits in response to chemotherapy that predict patient outcomes, and particularly implicate epigenetic silencing of HOXA4 in reducing the sensitivity of CLL cells to therapy.

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Publication Date
Sun Mar 24 2024
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn 2789-3219 )
Correlation between Therapeutic Drug Monitoring of Infliximab Serum Trough Levels and other Biomarkers in Iraqi Patients with Crohn's Disease
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Background: Inflammatory bowel disease (IBD) is a collection of chronic, recurrent inflammatory illnesses of the gastrointestinal system, including Crohn's disease (CD). Infliximab is one of the biological medications used to treat CD. Therapeutic drug monitoring has evolved as a treatment in IBD, aiming to optimize benefit while meeting more demanding, objective end criteria. Objective: To determine the achievement of target trough level (TL), develop anti-drug antibodies (ADAs) to infliximab, assess response to therapy, and study TL relations with different variables. Methods: The present study was cross-sectional and conducted from May 2022 to November 2022. It included 40 CD patients allotted into 2 groups: group 1 patients ach

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Publication Date
Sun Jun 01 2025
Journal Name
Results In Materials
Adsorption, thermodynamic and corrosion study of enalapril malate pharmaceutical drug as corrosion inhibitor for carbon steel in saline solution
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Unused and expired pharmaceutical drugs are a novel type of organic corrosion inhibitor. They are less expensive, more effective, and less harmful than conventional organic corrosion inhibitors. This study investigated the effects of concentration, adsorption mechanism and thermodynamic parameters of enalapril malate (ENAP) as a corrosion inhibitor for carbon steel in a saline solution (3.5 % NaCl). The polarization method was used to determine the corrosion rate and inhibition efficiency. Field emission scanning electron microscopy (FE-SEM) and atomic force spectroscopy (AFM) were used to investigate the surface morphology and topography of carbon steel after immersion in both uninhibited and inhibited media for 24 h. Fourier transform inf

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Publication Date
Sun May 15 2022
Journal Name
Al-kindy College Medical Journal
Impact of Tobacco Use in the Etiology of Chronic Renal Failure Among Sudanese Patients: Tobacco and Renal Failure Among Sudanese Patients
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Background: Chronic renal failure (CRF) is a clinical syndrome that occurs when there is gradual decline in renal operation overtime.

Objective: This study aims to investigate the prevalence of depression among medical students at university of Baghdad, college of medicine in Iraq and the association between some variables and depression.

Aim: This study aimed to identify the impact of tobacco use in the etiology of chronic renal failure among Sudanese patients in Omdurman Military Hospital and Omdurman Kidney Dialysis Center

Materials and methods: This descriptive community-based study was conducted in Khartoum State. A random sample of 100 cases with chronic renal failure and 100

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Publication Date
Tue Nov 17 2020
Journal Name
Journal Of Physics: Conference Series
A trial treatment of Hydatidosis in white mice by Immunization and Chemicals
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The present study was conducted as atrial to treat secondary hydatidosis in white mice of species Mus musculus. (Balb/c strain), experimentally infected with secondary hydatid cysts of sheep origin. The immunization process was carried by using CF/PS antigen which consist hydatid cyst fluid (CF) antigen, and protoscolices (PS) antigen mixed together and by using two concentrations 7.5, 15 mg/ml. Then derivatives of Benzimidazole, Mebendazole (M) and drugs Albendazole (A) were used 10 and 40 μm/gm body weight respectively. The mixture of drugs was used one week after challenged dose. Criteria taken into consideration to define the activity of the immunization and chemotherapy in this study were reduction in the numeral of cysts, the coeffic

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Publication Date
Sun Jun 30 2013
Journal Name
Al-kindy College Medical Journal
Cognitive Effects of Tumor and Surgical Treatment in Patients with Cerebral Gliomas
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Background: Quality of life in brain tumor patients is an emerging issue and has prompted neurosurgeons to recon¬sider the need for cognitive assessment in the course of treatment. To date there has been a lack of comprehensive neuropsychological assessment performed preoperatively and in the acute postoperative period in our hospitals.Objectives: to establish the effects of tumors and their surgical treatment, from a neuropsychological perspective, on cognitive functioning in patients with cerebral Gliomas. Methods: This is a prospective study conducted in the Neurosurgical Hospital in Baghdad, Iraq, during the period from January 1999 to January 2001. Any patient admitted during the period of the study with clinical history, signs, sy

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Publication Date
Wed Jan 30 2019
Journal Name
Modern Sport
Evaluation of training programs according to some physical abilities, functional indicators and achievement for men's 200m runners
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The effectiveness of (200 m) of the events of extreme intensity and this is characterized by training in the anaerobic energy system prevailing in the result of this privacy as these are based on the physical abilities and functional indicators identified in this direction and hence the importance of research in the evaluation of training programs on the basis of physical abilities and some indicators of the functionality of the hostile 200 m . The study aimed to: 1. Evaluation of training programs according to physical abilities and some functional indicators of hostile men.The researchers used the descriptive analytical method to suit the nature of the research. The researchers selected them research sample by the deliberate method of the

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Publication Date
Mon Jan 30 2023
Journal Name
Iraqi Journal Of Science
Study the Effect of Oxygen on Coronene Electronic and Spectroscopic Properties via the Density Functional Theory (DFT)
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    The electronic properties (such as energy gap HOMO levels. LUMO levels, density of state and density of bonds in addition to spectroscopic properties like IR spectra, Raman spectra, force constant and reduced masses as a function of frequency) of coronene C24 and reduced graphene oxide C24OX , where x=1-5, were studied.. The  methodology employed was  Density Functional Theory (DFT) with Hybrid function B3LYP and 6-311G** basis sets. The energy gap was calculated for C24 to be 3.5 eV and for C24Ox was from 0.89 to 1.6862 eV  for x=1-5 ,respectively.   These energy gaps values are comparable to the measured gap of Graphene (1-2.2 eV). The spectroscopic properties were  compared with experimental measurements, specificall

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Publication Date
Sun Feb 17 2019
Journal Name
Iraqi Journal Of Physics
A Study of the electronic structure of CdS Nanocrystals using density functional theory
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Density Functional Theory at the generalized-gradient approximation level coupled with large unit cell method is used to simulate the electronic structure of (II-VI) zinc-blende cadmium sulfide nanocrystals that have dimensions 2-2.5 nm. The calculated properties include lattice constant, conduction and valence bands width, energy of the highest occupied orbital, energy of the lowest unoccupied orbital, energy gap, density of states etc. Results show that lattice constant and energy gap converge to definite values. However, highest occupied orbital, lowest unoccupied orbital fluctuates indefinitely depending on the shape of the nanocrystal.

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Publication Date
Thu Jun 28 2018
Journal Name
Journal Of The College Of Education For Women
The function and Formation of NORTH ATLANTIC TREATY ORGANZIAITON as (NATO) Post Cold War Period
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The problem of this study lies in that NATO was formed in the first place to protect Europe from Warsaw Pact. The geographical and military strategy have been changed with the change of its mission and expanding its operation scope with the leadership of the USA in the international scens. The latter has made this organization as the military arm to tighten its control over strategic regions.

            The research supposes that NATO state members confront security concerns and political and military issues that push to expand the organization. The importance of this study lies in knowing the new roles of NATO imposed by the United States. Therefore, the continuity and affi

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Publication Date
Mon Sep 01 2025
Journal Name
Civil Engineering Journal
Pre- and Post-Cracking Resistance of Steel Fiber Reinforced Concrete Flexural Members with GFRP Bars
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This research investigates the pre- and post-cracking resistance of steel fiber-reinforced concrete specimens with Glass Fiber Reinforced Polymer (GFRP) bars subjected to flexural loading. The purpose is to modify the ductility and cracking resistance of GFRP-reinforced beams, which are prone to early cracking and excessive deflections instigated by the low modulus of elasticity of GFRP. Six self-compacting concrete specimens (1500×240×200 mm), incorporating steel fibers of two lengths (25 mm and 40 mm) with varying distribution depths, were tested to assess their structural performance. The results indicate significant enhancements in cracking resistance, stiffness, energy absorption, ductility, and flexural strength. Tested beam

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