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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 Jun 29 2025
Journal Name
Al-academy
The Narrative Treatment of The Climate Change Topic in Film
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لم تولد الجماهيرية العالية للسينما من فراغ، إنّما تحققت من إيمان المتلقي العميق، بأن الفيلم أبعد من محاولة للترفيه، فالسينما هي فلسفة العصر، التي تتناول القضايا المهمة لتقدمها عبر حكايتها مؤطّرة بمنطق محدّد ومدفوعة ببناء عاطفي مؤثر، يهيئ المتلقي للاهتمام بهذه القضايا واستيعابها، والتغير المناخي واحد من أهم المواضيع التي بدأت السينما في الحقبة السابقة بتبنيها وتقديمها ضمن بنى حكائية تزيد من وعي المتل

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Publication Date
Mon Jan 01 2018
Journal Name
Association Of Arab Universities Journal Of Engineering Sciences
Treatment of Sulfate in Sand by Using Magnetic Water Process
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One of the most important problems in concrete production in Iraq and other country is the high sulfate content in sand that led to damage of concrete and hence reduces its compressive strength and may leads to cracking due to internal sulfate attack and delay ettringite formation. The magnetic water treatment process is adopted in this study. Many samples with different SO3 content are treated with magnetic water (12, 8, 4 and 2)L that needed for each 1kg of sand with the magnetic intensity (9000 and 5000) Gaus. The magnetic water needed is reduced with less SO3 content in sand. The ACI 211.1-91 concrete mix design was used in this research with slump range (75- 100) mm and the specified compressive strength (35MPa). The compressive streng

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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
Thu Feb 01 2018
Journal Name
Association Of Arab Universities Journal Of Engineering Sciences
Effect of High Temperature (Fire Flame) on the Behavior of Post-tensioned Concrete Beams
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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
Thu May 05 2022
Journal Name
Al-kindy College Medical Journal
Safety profile of immediate post-partum intrauterine device insertion during caesarean delivery – a clinical trial with three years of follow up: Utility of Immediate Post Placental Insertion of Intrauterine Device During Cesarean Delivery
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Background: Many countries recommend the use of long-acting reversible contraceptive intrauterine device immediately after cesarean delivery. The cesarean delivery rate in Iraqi public hospitals is 32.2% and may reach 85.8% in private hospitals. Immediate post-partum intrauterine device insertion at cesarean is rarely done in Iraq.

Objectives: To assess the safety and practicality of immediate post-partum intrauterine device insertion during cesarean delivery for family planning and pregnancy spacing in Iraqi women.

Subjects and Methods: A single arm clinical trial included 150 eligible women who attended Al-‎Elwiyah Maternity Teaching Hospital or Al Hayat Rahibat Hospita

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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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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
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
Sat Dec 28 2019
Journal Name
International Journal Of Environmental Research And Public Health
Predominant Mechanisms in the Treatment of Wastewater Due to Interaction of Benzaldehyde and Iron Slag Byproduct
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Iron slag is a byproduct generated in huge quantities from recycled remnants of iron and steel factories; therefore, the possibility of using this waste in the removal of benzaldehyde from contaminated water offers an excellent topic in sustainability field. Results reveal that the removal efficiency was equal to 85% for the interaction of slag and water contaminated with benzaldehyde at the best operational conditions of 0.3 g/100 mL, 6, 180 min, and 250 rpm for the sorbent dosage, initial pH, agitation time, and speed, respectively with 300 mg/L initial concentration. The maximum uptake capacity of iron slag was 118.25 mg/g which was calculated by the Langmuir model. Physical sorption may be the major mechanism for the removal of

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