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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 Jan 01 2023
Journal Name
8th Engineering And 2nd International Conference For College Of Engineering – University Of Baghdad: Coec8-2021 Proceedings
Serviceability performance of high-strength concrete flexural members with internally unbonded post-tensioning strands
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Publication Date
Fri Jun 20 2025
Journal Name
Ournal Of Kufa For Chemical Sciences
Hemorrhagic Fever history, Diagnosis and Treatment: review article
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hemorrhagic fever (VHF), one of which is Filoviridae. The Filoviridae family includes the Ebola virus , is responsible for the current VHF outbreak in West Africa. Viral hemorrhagic fevers (VHFs) occur in various regions around the world, yet traditional diagnostic testing for these diseases has typically been conducted in major reference laboratories located in Europe and the United States. In this review, we explore the current understanding of the mechanisms driving the pathogenesis of viral hemorrhagic fevers (VHFs) and examine the progress in developing preventive and therapeutic strategies for these infections.

Publication Date
Wed Dec 13 2017
Journal Name
Al-khwarizmi Engineering Journal
Produced Water Treatment Using Ultrafiltration and Nanofiltration Membranes
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The application of ultrafiltration (UF) and nanofiltration (NF) processes in the handling of raw produced water have been investigated in the present study. Experiments of both ultrafiltration and nanofiltration processes are performed in a laboratory unit, which is operated in a cross-flow pattern. Various types of hollow fiber membranes were utilized in this study such as poly vinyl chloride (PVC) UF membrane, two different polyether sulfone (PES) NF membranes, and poly phenyl sulfone PPSU NF membrane. It was found that the turbidity of the treated water is higher than 95 % by using UF and NF membranes. The chemical oxygen demand COD (160 mg/l) and Oil content (26.8 mg/l) were found after treatment according to the allowable limits set

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Publication Date
Sun Oct 07 2012
Journal Name
Journal Of Educational And Psychological Researches
Bullying and its relation to parental treatment style
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The current research aims to know the relationship between bullying and parental treatment. (200) pupils were selected randomly from the fifth and sixth grades of primary schools.

Two instruments were used. The first was to measure bullying and it included 19 items. To measure parental treatment, the researchers adopted (Aletaby 2001) scale.

Statistical analysis showed that correlation between bullying , wiggle and Firm treatment style was positive Statistically significant .Bulling was correlated negatively with (neglect, careless, and Authoritarian treatment style.

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Publication Date
Sun Mar 04 2012
Journal Name
Baghdad Science Journal
Oilfield Produced Water Management: Treatment, Reuse and Disposal
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Produced water is accompanied with the production of oil and gas especially at the fields producing by water drive or water injection. The quantity of these waters is expected to be more complicated problem with an increasing in water cut which is expected to be 3-8 barrels water/produced barrel oil.Produced water may contain many constituents based on what is present in the subsurface at a particular location. Produced water contains dissolved solids and hydrocarbons (dissolved and suspended) and oxygen depletion. The most common dissolved solid is salt with concentrations range between a few parts per thousand to hundreds parts per thousand. In addition to salt, many produced waters also contain high levels of heavy metals like zinc, bari

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Publication Date
Wed Oct 07 2020
Journal Name
Journal Of Interdisciplinary Mathematics
Discrete an SIS model with immigrants and treatment
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In this paper, a discrete SIS epidemic model with immigrant and treatment effects is proposed. Stability analysis of the endemic equilibria and disease-free is presented. Numerical simulations are conformed the theoretical results, and it is illustrated how the immigrants, as well as treatment effects, change current model behavior

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Publication Date
Sun Jun 12 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Understanding the Experience of Hospital Pharmacists with the Effectiveness, Safety, Adverse Drug Reaction Reporting and Interchangeability of Biopharmaceutical Medicines
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The study objectives were to 1) explore the real-world experience of hospital pharmacists with the differences in effectiveness safety, and interchangeability between biosimilar medicines and their reference biological counterparts, 2) reveal pharmacist recommendations to enhance the safety of biopharmaceutical medicines in public hospitals.

The study has a mixed-method design where the core component was qualitative (interviews) and the supplemental component was quantitative (adverse drug reaction, ADR, reports). This qualitative component included semi-structured (mostly face-to-face) interviews involving hospital pharmacists from different hospitals with experience with biological or biosimilar medicines. The interviews were c

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Publication Date
Fri Dec 23 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Aspirin Derivatives Exploration: A Review on Comparison Study with Parent Drug
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In recent decades, drug modification is no longer unusual in the pharmaceutical world as living things are evolving in response to environmental changes. A non-steroidal anti-inflammatory drug (NSAID) such as aspirin is a common over-the-counter drug that can be purchased without medical prescription. Aspirin can inhibit the synthesis of prostaglandin by blocking the cyclooxygenase (COX) which contributes to its properties such as anti-inflammatory, antipyretic, antiplatelet and etc. It is also being considered as a chemopreventive agent due to its antithrombotic actions through the COX’s inhibition. However, the prolonged use of aspirin can cause heartburn, ulceration, and gastro-toxicity in children and adults. This review article hi

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Publication Date
Fri Dec 23 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Impact and Association of Anaemia Severity and Its Treatment With Quality of Life of Breast Cancer Patients in Malaysia
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Anaemia is a crucial issue among cancer patients and need to be treated properly. High incidence of anaemia in patients with cancer have been associated with several physiological manifestations, leading to decreased quality of life (QOL).

The current study aimed to assess the severity of anaemia, evaluate the current treatment guideline of anaemia, and to determine the association between the level of anaemia and its treatment on quality of life of breast cancer patients in Malaysia. This prospective study conducted among breast cancer patients in multicancer centers in Malaysia including three follow ups after receiving their chemotherapy. Clinical data were collected from their medical records and at each follow up, they asked

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Publication Date
Fri Jul 26 2019
Journal Name
Dental Materials Journal
Semi-interpenetrating network composites reinforced with Kevlar fibers for dental post fabrication
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