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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
Tue Jan 01 2019
Journal Name
Journal Of Global Pharma Technology
Analytical Study for the Ability of Some Polymers to Gain Transitional Elements Ionsions in Different Temperature, PH Acidity Functional and Time Situations
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The compound [K1] was synthesized from the reaction of dichloromethane with linear alkyl benzene (Lab9) using ethanol as a solvent, and from(chloro methyl)-4-nonylbenzene) [K1] it was possible to synthesize the compound Z(4-(nonan-3-yl)phenyl) methane amine) [K2] containing the amine group by synthesized from [K2] reaction with appropriate phenolic aldehydes and using Ethanol as a solvent in the preparation of vinyl chloride4-(((4-nonylbenzyl)imino)methyl)phenol-4-(((4-nonylbenzyl)imino methyl)benzene-1,3diol) [K3-K4] bases has been used. Preparation of a number of Phenolic polymers4-(2- hydroxy-3.5-dimethylbenzyl)-2-methyl-6-(((4-4-(2hyroxy-3, 5-dimethylbenzyl)-2-methyl-6(((4 nonylbenzyl) imino) methyl) benzene-phenolnonylbenzyl) imino) me

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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
Mon Jan 01 2024
Journal Name
Scripta Medica
Effect of proteolytic enzymes and insulin sensitiser in treatment of joint osteoarthritis in diabetic patients
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Background/Aim: Knee osteoarthritis is a frequently crippling chronic condition. Numerous pharmacological medications have been successfully utilised to treat knee osteoarthritis. This research aimed to compare the efficiency of metformin and serratiopeptidase in treating and preventing osteoarthritis development via distinct mechanisms. Methods: Between 1 January and 30 May 2019, a randomised-clinical-trial was done at Al-Kindy Hospital on 80 osteoarthritis patients, divided in two groups. Group I was given metformin 850 mg orally, whereas Group II was given serratiopeptidase 20 mg and metformin 850 mg orally. Parameters in these groups were compared with forty healthy normal controls. Results: Following treatment, patients in Grou

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Publication Date
Wed Jan 01 2025
Journal Name
Mediators Of Inflammation
Evaluating the Association Between Neutrophil Gelatinase‐Associated Lipocalin Levels and Periodontal Health Status in Patients With Chronic Kidney Disease
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Background: Chronic kidney disease (CKD) is one of the significant public health problems that is characterized by structural and functional changes due to various causes. Periodontal disease has risen as a nontraditional risk factor for CKD since it is considered a source of inflammatory products in systemic disease.

Objective: The objective of the study was to investigate the association between serum and salivary levels of neutrophil gelatinase‐associated lipocalin (NGAL) and the periodontal health status of patients with CKD.

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Publication Date
Mon Oct 17 2022
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Focus Assessment of Transthoracic Echocardiography post septostomy Procedure in Patients Undergoing Ablation of Left Atrial Supraventricular Tachycardia
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Background: Echocardiography has an important role to follow up patients with Iatrogenic atrial septaldefect (IASD) and after Catheter ablation during electro-physiological study.Objectives: evaluating the impact of non-invasive Transthoracic Echocardiography (TTE) parameters(LAVI, LVEF, ASD size and E/e`) post radiofrequency ablation of left atrial arrhythmia.Patients and methods: for the evaluation of the atrial septal defect, a transthoracic echocardiography(TTE) was used in patients who underwent left atrial arrhythmia ablation, enrolled in prospective studyin the Iraqi center for cardiac diseases, in cooperation with university of Baghdad /college of medicineResults: The outcomes of the present study were assessed according to

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Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
The formation, structure, and electronic properties of Lansoprazol drug and cucurbit [7]urils complex (Theoretical Study)
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The current study deals with host-guest complex formation between cucurbit [7] urils as host and lansoprazole as guesti using PM3 (semi empirical molecules orbital calculations) also DFT calculations. In this complex, the formation of hydrogen bonding may be occurred through portal oxygen atoms(O2) of cucurbit [7] urils and amine groups (NH 2 )of the drug. The energies of HOMO and LUMO orbital’s have been computed for the host guest complex and its components. The result of the stabilization energy explained a complex formation.

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Publication Date
Fri Sep 27 2019
Journal Name
Journal Of Baghdad College Of Dentistry
The Impact of Chronic Periodontitis on Mother-Infant Bonding Status in Relation to Salivary Tumor Necrosis Factor Alpha and Interleukin-6
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Background: Chronic periodontitis is a bacterial infection that result in bone destruction associated with the increasing level of salivary tumor necrosis alpha and interleukin6 that affect Mother-infant bonding status. The aim of the present study was to assess the relationship between the Mother-infant bonding status in mothers with chronic periodontitis in relation to Salivary Tumor necrosis factor alpha and Salivary Interleukin6. Materials and Methods: The selected sample consisted of mothers with chronic periodontitis compared with mothers with healthy periodontium in postpartum period, their age ranged between 30-40 years. Both groups were subjected to postpartum Bonding Questionnaire (PBQ). Periodontal health status was assessed f

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Publication Date
Thu Mar 28 2024
Journal Name
Nigerian Journal Of Parasitology
Evaluation of hormones and other biochemical parameters among chronic liver disease patients infected with Toxoplasma gondii
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This study was conducted in Baghdad, Iraq from December 2021 to May 2022. The goal was to determine the effect of Toxoplasma gondii on liver function by examining the relationship between Toxoplasma infection and hormones. One hundred and twenty male patients with Chronic liver disease (CLD) (age:14-75 years) and 120 control males (age: 24-70 years) participated in this study. Serum samples were taken from all individuals and were then analysed for anti-Toxoplasma antibodies. Hormonal tests were conducted for all participants which included (Cortisol, testosterone, prolactin, insulin, and thyroid-stimulating hormone TSH). Biochemical tests included (Prothrombin time PT, international normalized ratio INR and albumin); liver enzymes

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Publication Date
Mon Jun 06 2022
Journal Name
International Journal Of Health Sciences
effect of a training curriculum for the development of some functional variables and the level of achievement in the effectiveness of air rifle shooting
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There are significant differences between the pre and post-tests in favor of the post-test in the tests) stroke volume (S.V), cardiac thrust (C.O.P), left ventricular volume, maximum oxygen consumption Vo2max), which indicates the effect of the proposed training approach.There are significant differences between the pre and post-tests in favor of the post-test in the achievement level test with air rifle shooting for young female shooters, which indicates the effect of the proposed training curriculum.There are no significant differences between the pre and post-tests in the tests (heart rate (HR) before exercise, heart rate (HR) after exercise, systolic blood pressure rate before exercise, systolic blood pressure rate after exercis

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