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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
Fri May 01 2020
Journal Name
Civil Engineering Journal
Post-Fire Behavior of Post-Tensioned Segmental Concrete Beams under Monotonic Static Loading

This paper presents a study to investigate the behavior of post-tensioned segmental concrete beams that exposed to high-temperature. The experimental program included fabricating and testing twelve simply supported beams that divided into three groups depending on the number of precasting concrete segments. All specimens were prepared with an identical length of 3150 mm and differed in the number of the incorporated segments of the beam (9, 7, or 5 segments). To simulate the genuine fire disasters, nine out of twelve beams were exposed to a high-temperature flame for one hour. Based on the standard fire curve (ASTM – E119), the temperatures of 300◦C (572◦F), 500◦C (932◦F), and 700◦C (1292◦F) were adopted. Consequently,

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Publication Date
Sun Sep 01 2019
Journal Name
Baghdad Science Journal
An Analysis of a Partial Temporary Immunity SIR Epidemic Model with Nonlinear Treatment Rate

     A partial temporary immunity SIR epidemic model involv nonlinear treatment rate is proposed and studied. The basic reproduction number  is determined. The local and global stability of all equilibria of the model are analyzed. The conditions for occurrence of local bifurcation in the proposed epidemic model are established. Finally, numerical simulation is used to confirm our obtained analytical results and specify the control set of parameters that affect the dynamics of the model.

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Publication Date
Sun Jan 01 2023
Journal Name
Journal Of Complementary Medicine Research
Principles and Advantages of New Drug Delivery Technologie

Advanced drug delivery systems offer undeniable benefits for drug delivery. In the past three decades, new methods have been proposed to develop a novel carriers for drug delivery. Nowadays, the major goal is to maximize therapeutic benefit while minimizing side effects. Drug delivery technique is clearly shifting from the micro to nanoscale. Nano-drug delivery systems (NDDSs) are the most promising approach utilized to improve the accuracy of drug delivery and the efficacy of drugs.In this narrative review article, we evaluate how delivery challenges associated with commercial marketed products and discuss newer DDS is being carried out to overcome these challenges .Different colloidal carrier systems such as carbon nanotube ,li

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Publication Date
Sun Sep 22 2019
Journal Name
Baghdad Science Journal
Estimation of Survival Function for Rayleigh Distribution by Ranking function:-

In this article, performing and deriving te probability density function for Rayleigh distribution is done by using ordinary least squares estimator method and Rank set estimator method. Then creating interval for scale parameter of Rayleigh distribution. Anew method using   is used for fuzzy scale parameter. After that creating the survival and hazard functions for two ranking functions are conducted to show which one is beast.

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Publication Date
Mon Jul 31 2023
Journal Name
International Journal Of Sustainable Development And Planning
Monitoring and Prediction Functional Change of Land Uses Toward Urban Sustainability

Urban land uses are in a dynamic state that varies over time, the city of Karbala in Iraq has experienced functional changes over the past 100 years, as the city is characterized by the presence of significant tourist and socio-economic activity represented by religious tourism, and it occur due to various reasons such as urbanization. The purpose of this study is to apply a Markov model to analyze and predict the behavior of transforming the use of land in Karbala city over time. This can include the conversion of agricultural land, or other areas into residential, commercial, industrial land uses. The process of urbanization is typically driven by population growth, economic development, based on a set of probabilities and transitions bet

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Publication Date
Wed Jan 01 2020
Journal Name
Annals Of Tropical Medicine And Public Health
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Publication Date
Sun Jul 03 2016
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Synthetic vertebral body implantation Functional outcome in management of spinal disorders

Background: Synthetic vertebral body replacement has been widely used recently to treat different spinal conditions affecting the anterior column. They arrange from trauma, infections and even tumor conditions
Objective: To assess the functional outcome of this modality in different spinal conditions.
Patients and Methods: twenty-seven cases operated from Oct. 2010 to Dec. 9 cases had spinal fractures, 8 cases with spinal tuberculosis, and 10 cases with spinal tumors. They were followed clinically for a mean period of 36 months.
Results: All the cases approached anteriorly. 5 cases had postoperative infection. No neurological worsening reported. we had dramatic neurological improvement in all spinal tuberculo

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Publication Date
Mon Dec 31 2018
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Neonatal mortality post ISIS conflict in Iraq

Neonatal mortality is an indicator to assess maternal and neonatal care.1 Iraq has been suffering from wars, economic hardship, terrorism and internal displacement for last 4 decades.2 The impact of such suffering on health was reported.3 However, the impact of terrorism on health infrastructure which in turn manifested in neonatal mortality was neglected. This study carried out to demonstrate the effect of war against terrorism on neonatal mortality in Iraq.

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Publication Date
Sat Dec 30 2023
Journal Name
Al-kindy College Medical Journal
Health System in Iraq Post 2003 War

Background: War represents a major human crisis; it destroys communities and results in ingrained consequences for public health and well-being

Objective: We set this study to shed light on the public health status in Iraq after the successive wars, sanctions, sectarian conflicts, and terrorism, in light of certain health indicators.

Design: The primary source of data for this analysis comes from the Iraqi Ministry of Health, and The World Health Organization disease surveillance.

Results: Most of the morbidity indicators are high, even those that are relatively declining recently, are still higher than those repor

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Publication Date
Sun Mar 07 2010
Journal Name
Baghdad Science Journal
Safety method, Spectrophotometric Determination of Sulfamethaxazole drug in bulk and Pharmaceutical Preparations

A simple, cheap, fast, accurate, Safety and sensitive spectrophotometric method for the determination of sulfamethaxazole (SFMx), in pure form and pharmaceutical dosage forms. has been described The Method is based on the diazotization of the drug by sodium nitrite in acidic medium at 5Cº followed by coupling with salbutamol sulphate (SBS) drug to form orange color the product was stabilized and measured at 452 nm Beer’s law is obeyed in the concentration range of 2.5-87.5 ?g ml-1 with molar absorptivity of 2.5x104 L mole-1 cm-1. All variables including the reagent concentration, reaction time, color stability period, and sulfamethaxazole /salbutamol ratio were studied in order to optimize the reaction conditions. No interferences were

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