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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
Wed Nov 20 2024
Journal Name
Journal Of Baghdad College Of Dentistry
Bone density determination for the maxilla and the mandible in different age groups by using computerized tomography (Part I)

Background: Mini implant stability is primarily related to local bone density; no studies have evaluated bone density related to mini implant placement for orthodontic anchorage between different age groups in the maxilla and the mandible. The present research aims to evaluate side, gender, age, and regional differences in bone density of the alveolar bone at various orthodontic implant sites. Materials and method: Fifty three individuals who were divided into two groups according to their age into: group I (ages 16-20 years) and group II (ages 21-29 years) had subjected to clinical examination, then 64-multislice computed tomography scan data were evaluated and bone density was measured in Hounsfield unit at 102 points (51 in the maxilla

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Publication Date
Sun Mar 28 2021
Journal Name
Journal Of The College Of Education For Women
Unplanned Urbanization and Agricultural Land Degradation in Baghdad City from 2003 to 2017: احمد عباس كاظم , ليث زيد عباس

Several problems have emerged as a result of urban expansion or the connection of urban areas with rural areas. This process has led to the urbanization of rural areas, and to have overlapping edges and margins of areas, which were outside the basic design of the city. Accordingly, the present research assumes that the accelerating growth of Baghdad population has contributed significantly to the process of unplanned urbanization. Thus, the study aims to examine the factors that have led to an increase of urban sprawl at the expense of the agricultural land. The study has thus adopted the descriptive, analytical, and historical approaches relying on the simple linear regression method to predict the phenomenon of urban expansion and its

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Publication Date
Thu Feb 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
Brokerage Firms under Information Asymmetry and its Effect on Common Stock Trade : Applied Research in the Iraq Stock Exchange

The research aims to Applied Study in the nature of the impact of information asymmetry for brokerage firms in the common stock trading, The research included the theoretical concepts associated with each of the brokerage firms ,information asymmetry and common stock trading, It used the financial methods on the practical side of the information asymmetry for brokerage firms based in the sector as well as trading volume and spread for common stock , The community of the research included the Iraq Stock Exchange,the sample of research the companies listed which have been trading on its stock for the period August 2015 until December 2015 as well as brokerage firms

amounting to 47 brokerage firm. The resea

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Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Nitric Oxide, Peroxynitrite and Malondialdehyde Levels as Markers for Nitrosative/Oxidative Stress in Iraqi Patients with Systemic Lupus Erythematosus

Systemic lupus Erythematosus is an autoimmune disease of unknown aetiology affecting multiple organ system. Reactive nitrogen and oxygen species are claimed to play a role in this disease. However, the potential of Nitrosative/Oxidative Stress to elicit an autoimmune, response remain till now largely unexplored in humans. This study was done to investigate the status and contribution of nitrosative/oxidative stress in Iraqi patients for systemic lupus erythematosus. Blood samples from 19 patients with systemic lupus erythematosus and 19 age-and sex- matched apparently healthy controls were evaluated for serum levels of nitrosative/oxidative stress markers including nitric oxide, peroxynitrite and malondialdehyde. Nitric oxide levels were

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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)
Comparative Study between Oral Hypoglycemic Drugs Repaglinide, Glibenclamide and Rosiglitazone on Some Biochemical Parameters in Type 2 Diabetic Patients

Type 2 diabetes mellitus is often characterized by hyperglycemia as a result of increased insulin resistance in hepatic/peripheral tissues and pancreactic B-cell dysfunction. Approximately 92% of patients with type 2 diabetes mellitus demonstrate insulin resistance, however hyperglycemia is always a consequence of insulin deficiency. This study was done on 120 patients newly diagnosed diabetes type 2 characterized by dyslipidemia that is increased triglycerides and decreased HDL. Hypoglycemia and weight gain are common problem with oral sulfonyl urea drugs. In this work three different oral hypoglycemic drugs repaglinide and glibenclamide (insulin secretagogues) and rosiglitazone (insulin sensitizer) were used for treatment of patients w

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Publication Date
Mon Apr 01 2019
Journal Name
Applied Water Science
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Publication Date
Mon Jan 01 2018
Journal Name
Blood Research
Relationship between liver iron concentration determined by R2-MRI, serum ferritin, and liver enzymes in patients with thalassemia intermedia

4 Blood Res 2018;53:314-319. Received on August 11, 2018 Revised on August 30, 2018 Accepted on August 30, 2018 Background Iron overload is a risk factor affecting all patients with thalassemia intermedia (TI). We aimed to determine whether there is a relationship of serum ferritin (SF) and alanine ami- notransferase (ALT) with liver iron concentration (LIC) determined by R2 magnetic reso- nance imaging (R2-MRI), to estimate the most relevant degree of iron overload and best time to chelate in patients with TI. Methods In this cross-sectional study, 119 patients with TI (mean age years) were randomly se- lected and compared with 120 patients who had a diagnosis of thalassemia major (TM). Correlations of LIC, as determined by R2-MRI, with SF

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Publication Date
Sun Apr 30 2023
Journal Name
Al-kindy College Medical Journal
Comparison between Reference Infliximab (Remicade) and its Biosimilar (Remsima) in Patients with Ankylosing Spondylitis: A Field-based Pharmacoeconomic Study

Background: Ankylosing spondylitis is a chronic inflammatory disease that mostly involves the spine and sacroiliac joints. It is associated with a decreased quality of life. Biological medicines such as infliximab and its biosimilar are the mainstay treatments for active ankylosing spondylitis.

Objective: The study objective was to conduct a pharmacoeconomic study comparing the cost-effectiveness of the reference infliximab with its biosimilar in ankylosing spondylitis patients visiting public hospitals.

Subjects and Method: This is a two-center pharmacoeconomic study performed at two large teaching governmental hospitals in Baghdad, Iraq, which s

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Publication Date
Mon Jun 01 2020
Journal Name
Iraqi Journal Of Physics
Monitoring dust storm using Normalized difference dust index (NDDI) and brightness temperature variation in Simi arid areas over Iraq

Dust storms are a natural phenomenon occurring in most areas of Iraq. In recent years, the study of this phenomenon has become important because of the danger caused by increasing desertification at the expense of the green cover as well as its impact on human health. In this study  is important to devote the remote sensing of dust storms and its detection.Through this research, the dust storms can be detected in semi-arid areas, which are difficult to distinguish between these storms and desert areas. For the distinction between the dust storm pixels in the image with those that do not contain dust storm can be applied the Normalized Difference Dust Index (NDDI) and Brightness Temperature variation (BTV). MODIS sensors that carried

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Publication Date
Thu Jun 29 2023
Journal Name
Farmacia
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