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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 Nov 01 2020
Journal Name
Journal Of Green Engineering
Eco-Friendly Enhancement of Fire Tube Boiler Control in Oil Factory Using Functional Block Diagram
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This research is a continued efforts for a project on the fire tube boiler control for Al Rasheed edible oil factory. The aim is to enhance the control system with new integral control one. A functional blocks diagram (FBD) was built and simulated. With Schneider smart relays, FBD differs than ladder logic programming in which the PID option is active. An extensive work was done to understand the operation sequence, emergency shutdown, and faults causing the trips. A control program was designed to control logical sequence of operation. Furthermore temperature is controlled via cascade control with fuel and air controllers. The temperature controller output is send as remote set point to the fuel controller in a serial cascade manner. The f

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Publication Date
Fri Jan 01 2021
Journal Name
Annals Of Tropical Medicine & Public Health
Newly developed method for determination of methyldopa drug using ammonium ceric (IV) nitrate by continuous flow injection analysis via homemade NAG-ADF-300-2 analyser
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A new, simple, sensitive and fast developed method was used for the determination of methyldopa in pure and pharmaceutical formulations by using continuous flow injection analysis. This method is based on formation a burgundy color complex between methyldopa andammonium ceric (IV) nitrate in aqueous medium using long distance chasing photometer NAG-ADF-300-2. The linear range for calibration graph was 0.05-8.3 mmol/L for cell A and 0.1-8.5 mmol/L for cell B, and LOD 952.8000 ng /200 µL for cell A and 3.3348 µg /200 µL for cell B respectively with correlation coefficient (r) 0.9994 for cell A and 0.9991 for cell B, RSD % was lower than 1 % for n=8. The results were compared with classical method UV-Spectrophotometric at λ max=280 n

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Publication Date
Sun Dec 04 2016
Journal Name
Baghdad Science Journal
Effect of the Clenbuterol drug in some physiological parameters in male rabbits(Oryctolagus cuniculs)
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This study was designed to investigate the effect of the Clenbuterol drug in some physiological parameters of Liver, Kidney function and lipidprofie concentration. Fourty adult male rabbits were used in this study. The animals were randomly divided into four groups,the first group was given distilled water (control) ,while the other third groups were given (2,4,6 µg/kg) of Clenbuterol drug for 30 days. Blood samples were collected after 14 and 30 days of the treatment for biochemical study. Drug caused non significant increase(P<0.05)in the AST and ALT enzymeactivity in second and third groups during treatment period ,while we note a significant increase(P<0.05) in both AST,ALT enzyme level in fourth group compared with control group , as

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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 Aug 23 2022
Journal Name
International Journal Of Health Sciences
Correlation between paraoxonase-1 arylesterase activities and clopidogrel drug in patients with coronary artery disease
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Background: Coronary artery disease (CAD) is one of the leading causes of death worldwide. Clopidogrel, antiplatelet drug, has been widely used for management of CAD. Arylesterase, the activity of Paraoxonase-1 (PON-1), is mainly contributed in the biotransformation of clopidogrel to its active thiol form. The purpose of this study was to investigate the effect of receiving clopidogrel drug on the arylesterase activities in CAD patients. The effect of receiving clopidogrel drug on the antioxidant activity of arylesterase was also monitored by determination of malondialdehyde (MDA) level. Methods: One hundred CAD patients, who were followed-up for 5 days after reciving clopidogrel, and 50 healthy volunteers were included in our study

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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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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Effect of Aspirin drug in Liver tissue of swiss white mice Mus musculus
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This study was designed to identify the extent of the effect of drug Acetylsalicylic acid (aspirin) on histological structure of liver in Swiss albino mice Mus musculus.(16) mice were used and divided into two groups. The first groupwas orally treated with )0.5ml(of aspirinat concentration of (50 mcg / kg) and the second group was considered as control group Treated with distiled water lasted for 30 days. Treatment with Aspirin led to the occurrence of histopathological cases included liver necrosis ,cellular infilitration, congestion in central vein and a case of Hemorrhage. The results also showed the absence of radial arrangement of the constituents of hepatic cells from tissue due to these changes with the control group.

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Publication Date
Sun Sep 15 2019
Journal Name
Al-academy
Aesthetic and Functional Dimensions of Environmental Waste in the Products of Students of the Department of Art Education: فردوس خضر الجوفي
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The practice of art is an inevitable result imposed by the circumstances surrounding the human being, as he needs some knowledge associated with raw materials, tools and methods to develop skills in the formation of elements of the work of art in new ways that give a decent artistic appearance to the work of art. Through the exploratory study carried out by the researcher, which included asking the following question to the third grade students, Department of Art Education:

What types of materials are used in handicrafts and from which sources are they obtained? Through the answers, the problem of research was founded as follows:

-Are the products of students of the Department of Art Education in the handicraft material d

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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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