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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 Oct 01 2006
Journal Name
Modern Sport
The effect of using a treadmill with different incline angles in developing some functional variables among Diyala University basketball team players
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تعد لعبة كرة السلة من الألعاب الرياضية التي تحتاج متطلبات بدنية ووظيفية خاصة بها، وذلك من خلال الانتقال داخل الملعب بالكرة أو بدونها والسبل للتخلص من ملاحقة الخصم أثناء الدفاع وكيفية المناورة أثناء الهجوم مع إجادة التصويب بكافة أنواعه داخل الملعب، ومن هنا تكونت مشكلة البحث في كيفية تطوير تلك العوامل الوظيفية والتي لها الأثر في الارتقاء بمستوى أداء اللاعب أثناء اللعب، وعن طريق استخدام الباحثان لطريقة جهاز ا

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Publication Date
Fri Jun 01 2012
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Phenomena of corruption and money laundering: and causes and risks and their role in the financing of terrorism in Iraq and finding ways of treatment
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Iraq  is Suffering nowadays from the criminal triad represented by the fiscal and administrative corruption, money laundering and terrorism, which are intertwined in a very related relations, as each of them support the other . Since the over growth has been one of its characteristics leaving behind a very dangerous negative effects whether it was social , economic or even political impacts . As a result , this trial is now represents a high risk that threatens the present and the future of Iraq . On the political , economic and social level , it is well to mention that the poor direct investment , the increasing rates of poverty , unemployment , inflation as well as the smuggling of goreign currency an

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Publication Date
Tue Dec 23 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
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
Fri Dec 23 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Impact and Association of Anaemia Severity and Its Treatment With Quality of Life of Breast Cancer Patients in Malaysia
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Anaemia is a crucial issue among cancer patients and need to be treated properly. High incidence of anaemia in patients with cancer have been associated with several physiological manifestations, leading to decreased quality of life (QOL).

The current study aimed to assess the severity of anaemia, evaluate the current treatment guideline of anaemia, and to determine the association between the level of anaemia and its treatment on quality of life of breast cancer patients in Malaysia. This prospective study conducted among breast cancer patients in multicancer centers in Malaysia including three follow ups after receiving their chemotherapy. Clinical data were collected from their medical records and at each follow up, they asked

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Publication Date
Wed Oct 10 2018
Journal Name
Al-kindy College Medical Journal
Microfracture Arthroscopy Efficacy In Treatment Of Articular Cartilage Insult Of Knee
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Background: The treatment of articular cartilage defects is one of the most clinical challeng for orthopedic surgeons. Articular cartilage is a highly organized tissue with complex biomechanical properties and substantial durability. However, it has a poor ability for healing, and damage from trauma or degeneration can result in morbidity and functional impairment. debilitating joint pain, dysfunction, and degenerative arthritis                                                 &nbs

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Publication Date
Wed Oct 10 2018
Journal Name
Al-kindy College Medical Journal
Microfracture Arthroscopy Efficacy In Treatment Of Articular Cartilage Insult Of Knee
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Background: The treatment of articular cartilage defects is one of the most clinical challeng for orthopedic surgeons. Articular cartilage is a highly organized tissue with complex biomechanical properties and substantial durability. However, it has a poor ability for healing, and damage from trauma or degeneration can result in morbidity and functional impairment. debilitating joint pain, dysfunction, and degenerative arthritis                                                                           Objectives: The purpose of study is to show effectiveness of micro fracture arthroscopy as a method of treatment for such problem . Type of the study: Cros

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Publication Date
Thu Jan 30 2014
Journal Name
Al-kindy College Medical Journal
Efficacy & safety of Desmopressin in the treatment of pediatric nocturnal enuresis
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Back ground: primary nocturnal enuresis (PNE) is a socially distressing condition that can be troubling for children & their families. It affects 15-26% of five years olds. Several approaches are used to treat PNE including behavioral modification, alarms & drug therapy. Aim of the study: to determine the efficacy and safety of nasal desmopressin treatment in children with PNEPatients : fifty-four children with primary nocturnal enuresis with a mean age of ( 8.2) years ( range 6-15), underwent a 2 week observation period followed by entrance into a randomized controlled study, comparing desmopressin & placebo, lasting 4 weeks. The efficacy of the drug was measured in reduction of the number of wet nights per week. The enureti

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Publication Date
Fri Oct 12 2018
Journal Name
International Journal Of Medical Research & Health Sciences
A Comparison of Fear Levels of Endodontic Treatment in Iraqi Population
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Introduction: Dental fear is defined as the patient’s specific reaction towards stress related to dental treatment in which the stimulus is unkn..

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Publication Date
Mon Jun 30 2014
Journal Name
Al-kindy College Medical Journal
Efficacy of atorvastatin in treatment of Iraqi obese patients with hypercholesterolemia
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ABSTRACTBackground: dyslipidemia plays a crucial rule in the development of cardiovascular disease, which has become the leading cause of death in most developed countries as well as in developing countries (1). The effects of reducing low density lipoprotein – C (LDL-C) concentrations on the prevention of cardiovascular events and stroke have been well reported in many clinical trials.Objectives: Evidence supports the use of statins for lipid modifications in the primary prevention of coronary artery disease, morbidity and mortality. This study aims to determine the effectiveness of atorvastatin in treating dyslipidemia in Iraqi obese patients.Methods: 200 overweight and obese patients with hypercholesterolemia, according to NCEP ATP

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