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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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
Mon Jul 01 2024
Journal Name
Indian Journal Of Clinical Biochemistry
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Publication Date
Sun Feb 01 2015
Journal Name
Journal Of Economics And Administrative Sciences
The Relationship between Growth and Economic Reformation in Iraq: Post 2003

There were many ideas and opinions on the linkage between growth and economic reform  in both developed and developing countries. The relationship is, of course, existed. Therefore, this research comes to analyses it in the Iraqi economy. This study is based on a hypothesis that the economic reformation in Iraq leads to lag level of growth with the of high rates of inflation. However, the study is designed to be included five sections. It found a positive relationship between the economic reformation and slowing of economic growth, in which the specified hypothesis is not fit to the economic reality in Iraq after 2003                  &

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Publication Date
Sun Jun 05 2016
Journal Name
Baghdad Science Journal
Serum Cortisol and BMI in Chronic Diseases and Increased Early Cardiovascular Diseases

The purpose of this study was to examine the role of cortisol, and it is related to BMI in the chronic diseases which may increase early cardiovascular disease (CVD) in old Iraqi. The subjects were 116 adults, aged 51-71 years. Body Mass Index (BMI), Waist Circumferences (WC) and Waist Hip Ratio (WHR) were used as a measure of adiposity. Investigation showed highly significant difference between patients in BMI ranges, most of male were in an obese weight range (48.5%), as well in women. There were no significant correlations between serum cortisol concentration and age both gender groups. While there were highly significant correlations between cortisol level and BMI, waist, and WHR (except in female subjects), also there were highly signi

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Publication Date
Fri Oct 30 2020
Journal Name
Journal Of Economics And Administrative Sciences
Estimate The Survival Function By Using The Genetic Algorithm

  Survival analysis is the analysis of data that are in the form of times from the origin of time until the occurrence of the end event, and in medical research, the origin of time is the date of registration of the individual or the patient in a study such as clinical trials to compare two types of medicine or more if the endpoint It is the death of the patient or the disappearance of the individual. The data resulting from this process is called survival times. But if the end is not death, the resulting data is called time data until the event. That is, survival analysis is one of the statistical steps and procedures for analyzing data when the adopted variable is time to event and time. It could be d

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Publication Date
Wed Feb 27 2019
Journal Name
Iraqi Journal Of Science
Effect of Ph on the Growth and Survival of Juvenile Common Carp (Cyprinus Carpio L.)

Common carp ( Cyprinus carpio L.) juveniles  averaging 7.68± 0.25 - 8.12± 1.14 g in weight were  used for 6 weeks to investigate their survival and growth preferences. The experimented carp were stocked at 12 tanks formerly adjusted with different pH levels values as: 6.0, 7.0, 8.0 and 9.0.  Growth and survival of common carp was assessed every Sunday of each week. Growth rates significantly (P < 0.05 ) increased  at pH 7 and  pH8 respectively. Therefore, the results suggest that the water with pH ranged from 7 to 8 was the best range for growth performance and survival rate of carp. Feed conversion ratio (FCR) improved at pH 6  and 9 respectively. In general, the results indicated that water p

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Publication Date
Wed Jan 30 2013
Journal Name
Al-kindy College Medical Journal
Chronic Plaque Pso riasis and Metabolic Syndrome

AbstractBackground:Psoriasis is an inflammatorydiseasewhichcan be associated with otherdiseases, which may have amajor impact onpatientslife. Psoriasis has also been reported tobe associated with metabolic disorders.Metabolic syndrome(MS)isa combination ofmedicaldisorders that, when occurring together,increasesthe risk of development ofcardiovasculardiseasesanddiabetes.It affectsone in five people in the United States andtheprevalence increases with age. Some studieshave showntheprevalencein the USA to be anestimated 25% of the population.Objective:To investigate the prevalence ofmetabolic syndrome in patients with psoriasis.Methods: We performed a hospital-based case-

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Publication Date
Tue Dec 06 2022
Journal Name
Iraqi National Journal Of Nursing Specialties
Quality of Life of Children age from (8- lessthan13) years with Acute Lymphocytic Leukemia Undergoing Chemotherapy at Hematology Center in Medical City

Objective (s): To assess the QoL of children age from (8- lessthan13) years with acute lymphocytic leukemia undergoing chemotherapy and to find out the relationship between the QoL of children with acute lymphocytic leukemia and their illness history.

Methodology:  A descriptive study included (40) children with acute lymphocytic leukemia who were ranged between (8 - less than 13 years) at the Hematology Center in Medical City for the period from 4th March 2021 to 1st September 2021. The sample was non-probability (purposive) sample of children (male and female). A questionnaire designed with 2 main parts was used. The first part focused on sociodemographic characterist

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Publication Date
Mon Mar 15 2021
Journal Name
Al-academy
Icon, Symbol and Values of Functional and Aesthetic Communication in Industrial Product Design: زياد حاتم حربي العامري

The icon and the symbol represent the constituents of the communication process, through their intellectual and philosophical concepts that have been addressed by the current research that it has touched upon their importance in conveying the design idea for the recipient and showing the specificity of each one of them in the communication process. The research problem has been limited by the following question: what are the communication roles that the symbol and the icon present for the user in designing the industrial product?
The research objective is to reveal the theoretical visualization that describes the icon and the symbol in the industrial product and its importance in the communication process through stating the of simil

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Publication Date
Thu Jan 13 2022
Journal Name
Journal Of Water And Land Development
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Publication Date
Mon Nov 05 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Evaluation and Comparison of Complete Dentures’ Complaints: Post-insertion

Aims: This study aims to compare patients’ complaints and problems of wearing complete dentures.
Methodology: The sample included 40 Iraqi patients who are wearing complete dentures from about five years ago. They
were selected randomly with a age range between (55–65) years. The questions asked to the patients were listed according
to the recent classification of post-insertion problems.
Result: The results showed that the percentage of patient's complaint from adaptation problems (62.1%) was higher than
looseness problems (61.3%) and discomfort problems (39.3%) as followed.
Recommendation: Dentists need thorough knowledge of anatomy, physiology, pathology and psychology. The assessing
of the psyche and emotions

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