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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
Fri Apr 01 2016
Journal Name
Water
The Effect of UV and Combined Chlorine/UV Treatment on Coliphages in Drinking Water Disinfection
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Publication Date
Thu Dec 10 2009
Journal Name
Iraqi Journal Of Laser
Diagnosis and Treatment of Cervical Intraepithelial Neoplasia with Carbon Dioxide Laser Therapy in Selected Patients
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Female infection with HPV (human papilla virus) has been established as an essential cause of CIN (cervical intraepithelial neoplasia). The danger of transformation from CIN to frank malignancy should be considered. Objective: The goal of this study is to evaluate the effectiveness of CO2 laser vaporization of ectocervical lesion high grade squamous intraepithelial lesion (HGSIL). Patients and Methods: Four Female out of 150 affected with HGSIL lesions were submitted to CO2 laser vaporization and followed up in 4 months later, and 10 women with HGSIL lesion submitted to electrocautery diathermy for the comparison. Results: Among women treated by CO2 laser vaporization, 3 women had negative results (clear cervix), at 4 months follow up; o

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Publication Date
Wed Feb 22 2023
Journal Name
Iraqi Journal Of Science
The Acute and Chronic Toxicity of Copper on The Behavioral Responses and Hematological Parameters of Freshwater Fish, Common Carp (Cyprinus carpio L.)
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The present study was conducted to examine toxicological effects of copper sulfate (Cu) in common carp fish (Cyprinus carpio L.). The LC50 (median lethal concentrations) of copper on Cyprinus carpio were 3.64, 3.36, 3.04, 2.65 mg/L respectively. In general, behavioral responses of the fishes exposed to copper included uncontrolled swimming, erratic movements, loss of balance, swam near the water surface with sudden jerky movements. Haematological parameters such, red blood cells (RBC), white blood cells (WBC), haemoglobin (Hb), Packed cell volume (PCV), mean cell volume (MCV) mean cell haemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were studied. The obtained results indicated that the (RBC) and (WBC) have increas

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Publication Date
Wed Dec 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Dental Caries and Treatment Needs among Kindergarten Children in Al-Basrah Governorate/Iraq
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Background: Dental caries is a disease occurs in the world in both developed and developing countries, it is still widespread among children and it can be controlled but not eliminated , most of tooth loss occurs due to dental caries and its complications. The aim of this study was to estimate the occurrence, and severity of dental caries and treatment needs among kindergarten children in Al-Basrah governorate. Materials and methods: The sample consisted of 1000 kindergarten children at age of 4-5 years old (445 boys and 555 girls) from urban areas in Al-Basrah city. Diagnosis and recording of dental caries and treatment needs were done according to the criteria of WHO (1987). Results: The percentage of dental caries was (80.8%) of the tota

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Publication Date
Wed Jan 30 2013
Journal Name
Al-kindy College Medical Journal
The efficacy and tolerability of 10mg and 20mg/day isotretinoinin the treatment of acne vulgaris in Iraqi patients
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Back ground: Oral isotretinoin is recommended
for sever nodulocystic acne in the doses 0.5-
2mg/kg/day which is usually associated with higher
incidence of adverse effects. To reduce the
incidence of side-effects and to make it more costeffective,
the lower dose regimen of isotretinoin has
been used.
Aim: To compare the efficacy and tolerability of
oral isotretinoin 10mg and 20mg/day in acne
vulgaris.
Methods: one hundred and twenty patients with
acne vulgaris were randomized into two treatment
regimens each consisting of 60 patients. The first
was treated with 10mg/day and the second group
with 20mg/day for 24 weeks. Fifty five patients
from the first group and 47 patients from the second

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Publication Date
Sat Jun 15 2019
Journal Name
Journal Of Baghdad College Of Dentistry
Taste Detection Thresholds in Relation to Salivary and Serum Zinc in Patients on Simvastatin Treatment
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Background: Hyperlipidemia is an elevated fat (lipids), mostly cholesterol and triglycerides, in the blood. These lipids usually bind to proteins to remain circulated so-called lipoprotein. Aims of the study: To determine taste detection threshold and estimate the trace elements (zinc) in serum and saliva of those patients and compare all of these with healthy control subjects. Methods: Eighty subjects were incorporated in this study, thy were divided into two groups: forty patients on simvastatin treatment age between (35-60) years, and forty healthy control of age range between (35-60) years. Saliva was collected by non-stimulated technique within 10 minutes. Serum was obtained from each subject. Zinc was estimated in serum and saliva

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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
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
Wed Sep 30 2015
Journal Name
College Of Islamic Sciences
Treatment of the general budget deficit in Islamic economic system
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In the name of God the Merciful
 Praise be to God and the Hall and Peace Uncle Prophet Muhammad and blindness Alo and companions
 Money is the lifeblood and a reason for living. An individual cannot live without money to make it
It is only through the necessities of life and the state that it can perform its duties and functions only
As money is so important, the state must regulate the balance of revenues
And expenses in order to avoid failure in Mizanitia, but perhaps the country may be exposed to crises
An exception that leads to misappropriation in the general Mizanitia and the Islamic Shari'ah is valid for Makkah
Time and place for all circumstances has created several ways to address the budget defici

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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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