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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
Sat Feb 01 2014
Journal Name
World Journal Of Pharmaceutical Sciences
Detection of JAK2V617F Mutation and Serum Levels of Alkaline Phosphatase and Lactate Dehydrogenase in Chronic Myelogenous Leukemia.
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Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm arises from Bcr-Abl gene translocation (called Ph chromosome) in hematopoietic stem cells (HSCs). This genetic abnormality results in constitutive activation of tyrosine kinase and subsequent uncontrol growth and multiplication of granulocytes. The cornerstone in treatment of CML are tyrosine kinase inhibitors, of which imatinib is the most effectively used. JAK2V617F mutation is an acquired single nucleotide polymorphism (SNP) occurs in JAK2 gene and is associated with many hematological malignancy other than CML. It was thought that the two genetic abnormalities (Bcr-Abl and JAK2V617F) occur mutually; however, growing body of evidences suggested the reverse. This study a

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Publication Date
Fri Jul 28 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Levels of Trace and Essential Elements in Sera of Chronic Renal FAilure Patients Before and After Dialysis
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        This study included a group of (15) chronic renal failure patients (CRF), an addition group of (15) healthy individual  was concluded in this study for control. Trace and essential elements ( Zn, Cu , Ca , K , Na) were measured by atomic absorption and flam analyzer in sera of CRF patients pre and post dialysis and control groups. The results showed a significant ( p < 0.05) increase in Zn and k+ concentration in sera of CRF patients pre and post dialysis compared to the control group. While there is a significant decrease for copper concentration in sera of CRF patients pre and post dialysis compared to the control group.       There was no significant alte

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Publication Date
Thu Jun 25 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Comparing the Efficacy of Paracetamol, Diclofenac, and Ketorolac on Post-Appendectomy Outcomes in Children and Adolescents
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Abstract

urgent surgical intervention and appendectomy until now represent standard treatment for uncomplicated cases of appendicitis. Nausea, vomiting and pain after surgery are the most frequent issues facing patients and affecting patient quality of life and responsible for many cases of readmission after surgery. Ketorolac and diclofenac represent the most commonly prescribed non-steroidal anti-inflammatory used in postoperative setting and they cause many side effects as gastrointestinal, kidney and cardiac adverse effect in addition to increased risk of bleeding. Paracetamol is currently among the most frequently prescribed medication worldwide and it can be used safely for all age groups. This study aimed

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Publication Date
Sun Sep 03 2017
Journal Name
Baghdad Science Journal
Preparation and Characterization some New of Naproxen Drug Derivatives
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In this research four steps of the new derivatives of Naproxen drug have been made which are known as a high medicinal effectiveness; the first step involved converting Naproxen into the corresponding ester (A) by reaction Naproxen with methanol absolute in presence H2SO4. While the second step involved treatment methyl Naproxen ester (A) with hydrazine hydrate 80% in presence of ethanol .The third reaction requires synthesis of Schiff bases (C1-C10) by condensation. of Naproxen hydrazide (B) with many substituted aromatic aldehydes . Finally, the fourth step synthesized new tetrazole derivatives ( D1- D10) by the reaction of the prepared Schiff bases (in the third step) with Sodium azide in THF as a solvent .The prepared compounds wer

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Publication Date
Wed Jul 01 2020
Journal Name
Medico-legal Update
Evaluation of technical quality and procedural errors of root canal treatment performed by undergraduate and postgraduate dental students: A retrospective radiographic analysis
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Publication Date
Mon Jun 27 2022
Journal Name
Al-rafidain Journal Of Medical Sciences ( Issn: 2789-3219 )
Self-Reported Sleep Disorder, Anxiety and Depression in Iraqi Patients Post-Myocardial Infraction
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Background: Myocardial infarction (MI) is distinguished by the necrosis of myocardial cells as a result of substantial and prolonged ischemia. Anxiety, problems sleeping, and feelings of depression are some of the most common psychosocial consequences of having a myocardial infarction. Aim: The purpose of this study is to evaluate the effects of post-myocardial infarction on patients' levels of anxiety, depression, and quality of sleep. Method: The collection of data from 94 individuals with MI was carried out according to a descriptive cross-sectional design. Sleep quality, depression, and anxiety were evaluated using standard questionnaires. Results: 69.1% of the participants reported having trouble getting quality sleep. The perc

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Publication Date
Tue Apr 01 2003
Journal Name
Abhath Al- Yarmouk [basic Sciences And Engineering]
Methodology for selecting Nonprestressed Steel in Post- Tensioning Beams
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Publication Date
Mon Feb 03 2020
Journal Name
College Of Islamic Sciences
Rulings of magic  and its treatment in Islam
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Praise be to God, Lord of the worlds, and the best of prayers. He has completed the delivery of our master Muhammad, his family, and all his companions. O God, bring us out from the darkness of illusion, honor us with the light of understanding, open us with knowledge of knowledge, facilitate our morals with dreams, and make us who listen to the saying and follow their best.
And after ..

Since ancient times, magic was mentioned in many books in the history of the civilizations of ancient peoples, where the first emergence of human civilizations, the oldest of which is the Mesopotamian civilization, the Chinese civilization, and the Pharaonic civilization in Egypt, where concepts prevailed based on the charlatans and sorcery an

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Publication Date
Thu Jan 30 2014
Journal Name
Al-kindy College Medical Journal
THE PREVALENCE AND ANTIMICROBIAL RESISTANCE OF PSEUDOMONAS SPECIES IN PATIENTS WITH CHRONIC SUPPURATIVE OTITIS MEDIA
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Background: Chronic suppurative otitis media (CSOM) is the result of aninitial episode of acute otitis media and is characterized by a persistent discharge from the middle ear through a tympanic perforation for at least 2 weeks duration. It is an important cause of preventable hearing loss, particularly in the developing world.Methods. 1. To get an overview on the bacterial ear infection profile in general 2. To assess the antibiotic resistance of Pseudomonal infection (PS) particularly since it is usually the commonest infection to cause otitis media and the most difficult to treat due to the problem of multi drug resistance... A cross sectional study was done which included 405 patient of CSOM patients196 (48%) case were males ,209 (52

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Publication Date
Tue Jun 30 2015
Journal Name
Al-kindy College Medical Journal
The prevalence and antimicrobial resistance of Pseudomonas species in patients with chronic suppurative otitis media
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Background: Chronic suppurative otitis media (CSOM) is the result of an initial episode of acute otitis media and is characterized by a persistent discharge from the middle ear through a tympanic perforation for at least 2 weeks duration. It is an important cause of preventable hearing loss, particularly in the developing world.Objective: To get an overview on the bacterial ear infection profile in general and to assess the antibiotic resistance of Pseudomonal infection (PS) particularly since it is usually the commonest infection to cause otitis media and the most difficult to treat due to the problem of multi drug resistance..Methods: A cross sectional study was done which included 405 patients of CSOM patients, 196 (48%) case were mal

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