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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
Wed Sep 01 2021
Journal Name
Journal Of Engineering
Water Treatment With Conventional and Alternative Coagulants: A Review
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There is no access to basic sanitation for half the world's population, leading to Socioeconomic issues, such as scarcity of drinking water and the spread of diseases. In this way, it is of vital importance to develop water management technologies relevant to the target population. In addition, in the separation form of water treatment, the compound often used as a coagulant in water treatment is aluminum sulfate, which provides good results for raw water turbidity and color removal. Studies show, however, that its deposition in the human body, even Alzheimer's disease, can cause serious harm to health and disease development. The study aims to improve the coagulation/flocculation stage related to the amount of flakes, i

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Publication Date
Thu Oct 01 2020
Journal Name
Biochemical And Cellular Archives
Study on the effect of methotraxate drug on Retinol-Binding Protein 4 (RBP4), nesfatin and some trace elements in Iraqi male patients with rheumatoid arthritis
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Methotrexate (MTX) is one of the most effective medications to treat rheumatoid arthritis (RA).Aserum of 60 Iraqi male patients suffering from RA as (G1) was newly diagnosis and the same patient in G1 after taking MTX as G2 and 40 Iraqi male healthy control as G3. Nesfatin-1 (Nf-1) is belong to the adipokine family withpleiotropic effect. Nf-1 has been found in different tissues, including stomach, pancreas, bone cells, cartilage and heart. Retinol binding protein (RBP4) was known as transpoter of retinol from its storage sites in the liver to the extrahepatic tissues. Moreover, RBP4 acts as adipokine and contributes in the pathophsyology of prototypic inflammatory disease, rheumatoid arthritis (RA). The results showed a significant increas

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Publication Date
Tue Oct 04 2022
Journal Name
Cureus
The Impact of Angiotensin Converting Enzyme-2 (ACE-2) on Bone Remodeling Marker Osteoprotegerin (OPG) in Post-COVID-19 Iraqi Patients
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Publication Date
Fri Jan 31 2025
Journal Name
Aip Conference Proceedings
Classification of oral cavity cancer using linear discriminant analysis (LDA) and principal component analysis (PCA)
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Publication Date
Sun Mar 06 2011
Journal Name
Baghdad Science Journal
Effect of Waste Water Bacteria and some chemical properties on drinking Water in AL-Mada,in Treatment Plan Station
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Three stations were chosen on the water treatment plan of al- madaan .The Samples collected from the (Raw water) and the Sedimentation, filtration and storage water and the drinking water of outlet. Coliform densities T.S and F.C and TS and F.S and total bacterial count as bacteriological pollution indicators, as moste probable number (MPN) method was studied in test. Also some of the chemical characteristics of the water like pH , total suspended solid T.S.S, T.D.D.and S04 , T.Hardness , Ca++ , Mg++ . From the results it were indicated . The study showed the drinking water of outlet (distriputed in system) was agree with WHO criteria and Iraqi limits standards .

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Publication Date
Tue Nov 09 2021
Journal Name
Journal Of Accounting And Financial Studies ( Jafs )
Financial technology as one of the recovery strategies of the Iraqi banking sector in the post-Covid-19 stage: An exploratory study
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The research aims to employ one of the most important strategies for recovery from the crisis of the Covid-19 pandemic, which ravaged the economies of the entire world and its various sectors, including the banking sector, through financial technology that is based on digital transformation to achieve financial sustainability and the creation of innovative financial value chains in light of the decline in the banking sector as a result of The negative effects of the Covid-19 pandemic, be guided by the relevant international accounting standards to control the risks associated with financial technology. To recover from the Covid-19 crisis, the research came out with a set of recommendations, most notably financial technology from

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Publication Date
Sun Mar 01 2020
Journal Name
Journal Of Engineering
Performance Evaluation of Trickling Filter and Extended Aeration of Wastewater Treatment Plants
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In recent decades, there has been increasing interest in wastewater treatment because of its direct impact on the environment and public health. Over time, other forms of treatment have been developed and modified, including extended aeration. This process is included in the suspended growth system. In this paper, a comparative study was conducted between the efficiency of the extended aeration plant and that of the trickling filter plant in removal of BOD and COD.  The method of comparison was done by knowing the value of the pollutant before and after the treatment and then extract the removal ratio of each pollutant within each plant. The results showed that the percentage of removal of BOD in the trickling filte

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Publication Date
Sun Oct 30 2022
Journal Name
Egyptian Journal Of Hospital Medicine
Antibiofilm Activity of Conocarpus erectus Leaves Extract and Assessment Its Effect on pelA and algD Genes on Multi-drug Resistant Pseudomonas aeruginosa
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Due to its various resistance mechanisms, Pseudomonas aeruginosa is the most prevalent opportunistic infection that kills hospitalized patients. Thus, therapeutic options become limited. Objective: The study aimed to estimate the antibiofilm effectiveness of Conocarpus erectus leaf extracts against MDR P. aeruginosa isolates and examines pelA and algD gene expression. Subjects and Methods: One hundred-fifty clinical samples were collected from five Baghdad hospitals between September 2021 and January 2022. Samples were grown on different mediums. Despite cetrimide agar's ability to detect P. aeruginosa, only 83 isolates developed at 42°C. VITEK 2 compact system identification followed. This study examined 83 of P. aeruginosa isolates for r

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Publication Date
Thu Apr 01 2021
Journal Name
Annals Of The Romanian Society For Cell Biology
Evaluation of Nesfatin – 1 and Other Biochemical Markers in diabetic Neuropathy Iraqi patients before and after treatment with tegretol
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Diabetic neuropathy is a form of nerve damage that can occur in people who have diabetes. High blood sugar (glucose) induced nerve damage in every part of the body. The nerves in the legs and feet were the most frequently affected. The extent to which a diabetic patient's body is impaired is calculated by the degree of nervosa harm.The purpose of this present study is estimation BMI,IL-10 , nesfatin-1 and HS-CRP in Iraqi DN patients before and after treatment via tegretol as well as it is the first study sheds light on the relationship between Nesfatin -1 and other parameters ( BMI,IL-10 and HS-CRP) also predication of Nesfatin-1 as a newly biomarker in patients with diabetic neuropathy. The present study consist of from 30 cohort G1 as hea

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Publication Date
Fri Jun 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of Alendronate Treatment on Salivary Levels of Osteoprotegrin and TNF-α in Postmenopausal Woman with Osteoporosis and Periodontal Diseases
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Background: All diseases concerning bone destruction such as osteoporosis and periodontal diseases share common pattern in which the osteoclast cells are absolutely responsible for bone resorption that occurred when osteoclast activity exceeds osteoblast activity. Osteoprotegrin (OPG) considered as novel soluble decoy receptor known as “bone protector” since it prevents extreme bone resorption through inhibition of differentiation and activity of osteoclast by competing for binding site. It binds to receptor activator of nuclear factor kappa-B ligand (RANKL) and prevent its interaction with receptor activator of nuclear factor kappa-B (RANK), thus inhibits osteoclast formation. TNF-α is a pro-inflammatory cytokines having

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