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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
Mon Jun 03 2013
Journal Name
Al-kindy College Medical Journal
Conservative Treatment of Closed Fracture Shaft Humerus in Adult Patients
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Background: Fractures of the humeral shaft accounting for approximately 3% of all fractures. There is a wide array of good options for their treatment and controversy over the best methods. Although good techniques of osteosynthesis are available, the aim of this article is toemphasize on the benefit and good outcome of conservative treatment for properly selected cases to decrease the cost and avoid the complications of surgery. Method : During the period from February 2011 to June 2012 fifty-five fractures of humeral shaft were treated at orthopedicdepartment in the ALKindyteaching hospital. 22 fractures considered suitable for the study. The patients treatedconservatively by using the‘U’ shaped coaptation slab. Then we shift to POP c

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Publication Date
Wed Jan 30 2013
Journal Name
Al-kindy College Medical Journal
Conservative Treatment of Closed Fracture Shaft Humerus in Adult Patients
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Background: Fractures of the humeral shaft
accounting for approximately 3% of all
fractures. There is a wide array of good
options for their treatment and controversy
over the best methods. Although good
techniques of osteosynthesis are available, the
aim of this article is toemphasize on the benefit
and good outcome of conservative treatment
for properly selected cases to decrease the cost
and avoid the complications of surgery.

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Publication Date
Sun Jun 03 2012
Journal Name
Baghdad Science Journal
Evaluation of the functional response of Chrysoperla carnea (Stephens) (Neuroptera:Chrysopidae) larvae feeding on cabbage aphid, Brevicoryne brassicae (L.)(Homoptera: Aphididae) in laboratory
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This study evaluated the functional response of the larva of the predator Chrysoperla carnea by offering varying densities of cabbage aphid, Brevicoryne brassicae (L.) . Results showed conformity with type–II functional response, where the number of prey killed approaches asymptote hyperbolically as prey density increases (declining proportion of prey killed or the inverse density dependent) till it reached the stability stage determined by handling time and predator satiation. Also, the values of attack rate and handling time changed with age progress for both predator and prey. It has been observed an increase in the attack rate and reduction in handling time with the progress of the predator age when feeding on a particular nymphal in

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Publication Date
Sat Oct 04 2025
Journal Name
Modern Sport
Impact style of the changeable resistance in the development some of physical &amp; functional changes for the National team for the badminton
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Publication Date
Thu Sep 01 2022
Journal Name
Neuroquantology
Evaluation of using of square flap in treatment of Postburn Contracture
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Background: One of the most common problems that encountered is postburn contracture which has both functional and aesthetic impact on the patients. Various surgical methods had being proposed to treat such problem. Aim: To evaluate the effectiveness of square flap in management of postburn contracture in several part of the body. Patients and methods: From April 2019 to June 2020 a total number of 20 patients who had postburn contracture in various parts of their body were subjected to scar contracture release using square flap. The follow up period was ranging between 6 months to 12 months. Results: All of our patients had achieved complete release of their band with maximum postoperative motion together with accepted aesthetic outcome. A

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Publication Date
Thu Feb 07 2019
Journal Name
Iraqi Journal Of Laser
In Growing Toenail Treatment using Carbon Dioxide Laser
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An ingrowing toenail is a common problem affecting mainly adolescents and young adults, with a male predominance of 3:1. The disorder generally occurs in big toes. It is painful and often chronic and it affects work and social activities. Most patients initially complain of pain and later discharge, infection and difficulty in walking occur. The Objectives: The purpose of the study was to evaluate the efficacy and safety of (10600nm) CO2 laser in the treatment of ingrowing toe nail. Patients, Materials & Methods: This study was done in laser medicine research clinics from July 2013 to the end of December 2013; 10 patients including 7(70%) males and 3 (30%) females with age ranging from 18 years to 70 years with mean age of 44 years o

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Publication Date
Sun Jan 01 2023
Journal Name
2nd International Conference Of Mathematics, Applied Sciences, Information And Communication Technology
Spatial and temporal analysis of the spread of Covid-19 in Iraq
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Publication Date
Sun Mar 15 2020
Journal Name
Journal Of Baghdad College Of Dentistry
Comparative study of the antioxidant effects of lavender and flax oils in recurrent aphthous ulceration treatment
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Background: Recurrent aphthous ulceration (RAU) is an inflammatory condition of unknown etiology characterized by painful recurrent (single or multiple) ulcerations of the oral mucosa. It is one of the most common and poorly understood mucosal disorders. It occurs more frequently in times of stress. Local and systemic conditions, genetic, immunologic, microbial factors, and oxidative stress may play a role in the pathogenesis of RAU. The objective of this study was to evaluate the free radical metabolism and antioxidant activity of RAU patients treated by lavender or flax oil paint.

Materials and Methods: Sixty-six RAU patients were enroll

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Publication Date
Thu May 05 2022
Journal Name
Al-kindy College Medical Journal
Evaluation of podophyllin and Trichloroacetic acid for the treatment of genital warts in Iraqi female patients
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Background: human paillomavirus infections (genital warts) are the most frequent sexually transmitted viral infections. a wide range of treatment options is available with different efficacy.

Objective: To evaluate the efficacy of podophyllin, trichloracetic acid (TCA) in the treatment of genital warts and side effects of them.

Subjects and methods: a total of sixty patients with genital warts were randomly selected, 30 in each group, in the Department of Dermatology, medical city for a Duration of 11 months from January 2009 to December 2009 treated with 35 % podophyllin in the tincture of benzoin or 50%  TCA) .Forty-eight patients were followed up for three months.

Results: wart

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Publication Date
Wed Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
The Efficacy of Polidocanol foam Sclerotherapy in Treatment of Infantile Hemangioma and Slow-Flow Vascular Malformation
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Background: Sclerotherapy is a simple treatment modality for treatment of infantile hemangioma and slow-flow vascular malformations; Polidocanol is a mild sclerosing agent that is traditionally used in treatment of varicose veins. This study aims to evaluate the effectiveness, treatment outcome, and complications of polidocanol foam sclerotherapy for infantile hemangioma and slow-flow vascular malformations. Materials and methods: Between March 2013 and December 2014, seventeen patients with infantile hemangioma and slow-flow vascular malformations treated with polidocanol 1% foam sclerotherapy. Foam was prepared by Tessari’s method. Injection performed under general or local anesthesia, injections were repeated (if necessary) on mon

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