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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 Sep 01 2024
Journal Name
Green Analytical Chemistry
Green methods for determination of paracetamol in drug samples: A comparative study
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Publication Date
Sun Jun 12 2011
Journal Name
Baghdad Science Journal
Study the effective of annealing on the structural and sensitivity properties for SnO2 thin films to CO2 Gas
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In this research thin films from SnO2 semiconductor have been prepared by using chemical pyrolysis spray method from solution SnCl2.2H2O at 0.125M concentration on glass at substrate temperature (723K ).Annealing was preformed for prepared thin film at (823K) temperature. The structural and sensing properties of SnO2 thin films for CO2 gas was studied before and after annealing ,as well as we studied the effect temperature annealing on grain size for prepared thin films .

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Publication Date
Fri Jun 30 2017
Journal Name
Journal Of Madenat Al-elem University College
Study the toxic effect of the herbicide Gold topik (80EC) on survival and behavior of mosquito fish (Gambusia holbrooki Girard 1859)
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Publication Date
Thu Sep 01 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of alkaline phosphatase, salivary flow rate and salivary potential of hydrogen in relation to severity of chronic periodontitis
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Publication Date
Wed Sep 14 2016
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of Alkaline Phosphatase, Salivary Flow Rate and Salivary Potential of Hydrogen in Relation to Severity of Chronic Periodontitis
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Background: The cells of periodontium contain many intracellular enzymes like (alkaline phosphatase ALP) that are released outside into the saliva and gingival crevicular fluid (GCF) after destruction of periodontal tissue. The aim of study was to determine the activity of this enzyme in saliva and its relation to the salivary flow rate, PH and clinical periodontal parameters in patients with chronic periodontitis. Subject, Materials and methods: Sample population consist of 75 individuals ;divided into four groups , the first group (15):control subject, the second group (20):mild chronic periodontitis, the third group(20) moderate chronic periodontitis and the fourth group (20) sever chronic periodontitis, Measurements of plaque index (PL

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Publication Date
Tue Jan 02 2018
Journal Name
International Journal Of Science& Nature
HYPOTHYROIDISM IN PEDIATRIC PATIENTS: MODE OF PRESENTATION AND TREATMENT OUTCOME
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ABSTRACT The present study was conducted to determine the mode of presentation of hypothyroidism in pediatric patients and the effects of timing of diagnosis and therapy on the patient’s outcome. The study involved review and evaluation of the medical records of 41 registered patients in the Endocrine clinic of Children Welfare Teaching Hospital in Baghdad during the period from January 1991 to July 2007. Forty one patients included in this study. Twenty four (58.5%) were males and17 (41.4%) were females with a male to female ratio of 1.4:1, their age range is 40 days to12.3 years. The majority of the studied patients were infants 19(47%). The most commonly observed presenting features were growth retardation and short stature. The best t

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Publication Date
Sat Apr 01 2023
Journal Name
Earth And Environmental Science
Study Functional Properties of the Isolated Protein from Germinated Mung‏
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The functional properties of the defatted powder and protein isolate of germinated mung bean seeds were studied and the estimation of the amino acids was carried out. The results showed a significant increase in the values of the amino acids leucine, lysine, phenylalanine and valine. The results of studying the functional properties of the protein isolate and defatted powder showed that there were significant differences between the sample The defatted and protein isolate, if the water absorption capacity of the defatted mung powder was 2.5% water/gm protein and the water absorption capacity of the protein isolate was 3%ml water/g protein, the fat binding capacity of the defatted powder was 0.3 ml fat/g protein and the isolate The ratio was

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Publication Date
Thu Nov 01 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Impact of functional disability on lifestyle for patients with arthritis
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A descriptive study, which was using an assessment approach, was conducted for the
determination of the impact of rheumatoid arthritis and osteoarthritis patient’s functional disability
upon their life style. The study was carried out at the Rheumatology and outpatients clinics of ALKarama
Teaching Hospital, Baghdad Teaching Hospital AL-Kindey Teaching Hospital and Specialized
surgeries Teaching Hospital for the period of October 15th 2003 through May 13th 2004 in Baghdad
City. A purposive (non-probability) sample of (245) arthritis patients which was comprised (111)
rheumatoid arthritis patients and (134) osteoarthritis patients, was selected out of the early stated
settings. The questionnaire was comprised of

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Publication Date
Mon Aug 17 2026
Journal Name
Baghdad Science Journal
Molecular Characterization and Genotypic Distribution of Hepatitis B Virus Isolates in Iraq: Prevalence of Drug Resistance Mutations
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Hepatitis B virus (HBV) remains one of the most pervasive viral threats worldwide, posing a significant risk to millions. Due to the absence of proofreading activity during reverse transcription, HBV exhibits a high genetic variability. To date, ten distinct HBV genotypes have been identified globally, associated with varying disease outcomes, including progression to cirrhosis and carcinoma, as well as responses to antivirals. Consequently, genotypic analysis and molecular characterization of HBV are critical for optimizing therapeutic strategies. This study aimed to investigate the distribution of HBV genotypes among Iraqi patients and to characterize their molecular profiles. Therefore, a modified protocol was used to improve seq

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Publication Date
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Effect of Chronic Renal Failure on Thyroid Hormones
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       Chronic renal failure (CRF) affects thyroid function in multiple ways, including low circulating thyroid hormone concentration, altered peripheral hormone metabolism, disturbed binding to carrier proteins, possible reduction in tissue thyroid hormone content, and increased iodine store in thyroid glands.The target of study is to find a relationship between chronic renal failure and thyroid function.In addition, we tried to study the effect of CRF on serum creatinine dependent on the level of thyroid hormones (T3 and T4) and thyroid stimulating hormones(TSH). Forty patients with chronic renal failure (20 male, 20 female) were enrolled in this study in addition to forty healthy individual as control gro

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