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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 Jul 30 2023
Journal Name
Pakistan Heart Journal
Evaluation of nurses Practice toward Children Safety Post Cardiac Catheterization Procedure
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Publication Date
Fri May 01 2015
Journal Name
Journal Of The Faculty Of Medicine
Gentamycin injection in disc space during lumbar discectomy (aiming to prevent post - operative discitis)
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AW Ali T, Journal of the Faculty of Medicine, 2015 - Cited by 3

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Publication Date
Tue Jan 01 2019
Journal Name
Indian Journal Of Public Health Research &amp; Development
Post-Traumatic Stress Disorder among Women with Breast Cancer in Iraq: A Preliminary Report
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Publication Date
Sun Mar 26 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Spectrophotometric Determination of Nitrofurantoin Drug in its Pharmaceutical Formulations Using MBTH as a Coupling Reagent
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A direct, sensitive and efficient spectrophotometric method for the determination of nitrofurantoin
drug (NIT) in pure as well as in dosage form (capsules) was described. The suggested method was
based on reduction NIT drug using Zn/HCl and then coupling with 3-methyl-2-benzothiazolinone
hydrazone hydrochloride (MBTH) in the presence of ammonium ceric sulfate. Spectrophotometric
measurement was established by recording the absorbance of the green colored product at 610 nm.
Using the optimized reaction conditions, beer’s law was obeyed in the range of 0.5-30 μg/mL, with
good correlation coefficient of 0.9998 and limits of detection and quantitation of 0.163 and 0.544
μg/mL, respectively. The accuracy and

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Publication Date
Thu Mar 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of Salivary Total Antioxidants Capacity Levels of Patients with Chronic Periodontitis in Comparison to Healthy Control
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Background: Chronic periodontitis (CP) is greatly prevalent condition of inflammatory behavior. Salivary biomarker total antioxidants capacity (T-AOC) status, may be related to both periodontal condition and oral hygiene. Aims of the study: To assess the level of salivary T-AOC of patients with chronic periodontitis in comparison to healthy control and to correlate between the level of this marker with the clinical periodontal parameters (plaque index (PLI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL)). Materials and Methods: Ninety subjects of males and females with an age ranged between (35-55) years were participated in this study. Participants were divided into two grou

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Publication Date
Sun Jan 01 2017
Journal Name
Al–bahith Al–a'alami
Advertises of Advertising Mail Post of Emirate of Dubai as a sample
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                The advertising mail is considered as one of potential tools that followed to transfer the printed messages to the consumers and public customers whom are located at homes or works. This type of advertising is preferable due to the zero expense to receive the announcements of products, which became recently one of the successful procedures to create new customers and keep them in touch with direct communication. It is also possible to send them to specific group of people who can be classified by the advertisers to select even by name their own clients to give the personality to the clients for a long term of communication.

&

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Publication Date
Fri Feb 01 2019
Journal Name
Journal Of Economics And Administrative Sciences
Work pressure of the administrative and academic members of Biskra University, its sources and its relation to some personal and functional variables
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  The study aimed to highlight the reality of the functional pressures with its dimensions (role ambiguity, role conflict, role burden, glass ceiling, and discrimination in composition). The researchers also relied on the questionnaire as a essential tool for data collection. The field study was conducted at the University of Mohammed Khiedr - Biskra -, the study was conducted on the basis of the total survey, which included all the workers of the 6 faculties of Biskra University (523 female employees).

     After the analyzing of the data using the version 21 of the statistical program Spss, The study reached a number of results, the most of them is the low level of the functiona

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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
Mon Mar 07 2022
Journal Name
Journal Of Educational And Psychological Researches
The Impact of Cognitive Behavior Program Based on Meichenbaum Theory in Reducing the Negative Emotional Sensitivity among the Intermediate Stage Students
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The aim of this research is to construct a cognitive behavior program based on the theory of Meichenbaum in reducing the emotional sensitivity among Intermediate school students. To achieve the aims of the research, two hypotheses were formulated and the experimental design with equal groups was chosen. The population of research and its sample are determined. The test of negative emotional sensitivity, which is constructed by the researcher, was adopted. The test contains (20) items proved validity and reliability as a reliable test by presenting it to a group of arbitrators and experts in education and psychology. An educational program is constructed based on the theory of Meichenbaum. The test was applied to a sample of (60) second i

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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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