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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 Aug 01 2018
Journal Name
Journal Of Pharmaceutical Sciences
Schiff base complexes of some drug substances (Review)
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Schiff bases (SBs) represent multipurpose ligands that can be prepared from the concentration of prime amines with carbonyl clusters. Creation of SB transition metal compounds via as ligands has opportunity of attaining coordination complexes of abnormal arrangement and stability. These transition metal compounds have extraordinary attention as a consequence of their dynamic portion in metalloenzymes and as biomimetic prototypical complexes as a result of their proximity to usual enzymes and proteins. These complexes are imperative in medicinal disciplines owing to their widespread range of biological actions. They mostly exhibit organic actions involving antifungal, antibacterial, antitumor, antidiabetic, herbicidal, antiproliferative, ant

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Publication Date
Tue Nov 01 2016
Journal Name
World J. Pharmaceut. Res
Histological study on kidney affected by carbamazepine drug in postnatal rat
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Background: The use of antiepileptic drugs (AEDs) during pregnancy warrants several side effects and also deleterious effects on fetal development, the antiepileptic drugs have potential to affect the fetal development throughout the pregnancy although, the majority of infants born to epileptic pregnant women are normal but more expose to the malformations. Aim: The present study aimed to investigate the effect of carbamazepine drug on the kidney development at day 7 postnatally in the Albino Rat (Rattus rattus) as a mammalian model. Material & Methods: 20 healthy pregnant female rats were divided into two groups, 10 pregnant rats in each group; group one served as control group administrated distal water while group two used as experimenta

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Publication Date
Tue Jun 05 2018
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Preparation and characterization of timed drug delivery system of sumatriptan using natural polymers
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Pulsatile drug delivery systems are time-controlled dosage forms which are designed to release the active pharmaceutical ingredient after a predetermined lag time to synchronize the disease circadian rhythm. A migraine shows circadian rhythm with a marked increase in attacks between 6 a.m. and 8 a.m.

Sumatriptan is a selective agonist at serotonin (5-Hydroxy tryptamine1  (5-HT1))receptors, is an effective treatment for acute migraine attacks.

The aim of this work is to prepare time-controlled press-coated tablet with a lag time of 5.45 hrs.

Six formulas of fast dissolving core tablets and three formulas of press-coated tablets were prepared by using direct compression method using different variables to prepa

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Publication Date
Sun Mar 02 2008
Journal Name
Baghdad Science Journal
Orthogonal Functions Solving Linear functional Differential EquationsUsing Chebyshev Polynomial
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A method for Approximated evaluation of linear functional differential equations is described. where a function approximation as a linear combination of a set of orthogonal basis functions which are chebyshev functions .The coefficients of the approximation are determined by (least square and Galerkin’s) methods. The property of chebyshev polynomials leads to good results , which are demonstrated with examples.

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Publication Date
Mon Jun 01 2020
Journal Name
Comparative Immunology, Microbiology And Infectious Diseases
Drug resistance and virulence traits of Acinetobacter baumannii from Turkey and chicken raw meat
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Publication Date
Tue Oct 13 2026
Journal Name
Al-rafidain University College For Sciences
Uncertainty types and theories of treatment
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In this research the researcher had the concept of uncertainty in terms of types and theories of treatment and measurement as it was taken up are three types of indeterminacy and volatility and inconsistency

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Publication Date
Mon Apr 04 2022
Journal Name
Journal Of Educational And Psychological Researches
Fear of Intimacy and its Relationship with Post-Traumatic Stress Disorder among Yazidis Women
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The current research aims to identify the fear of intimacy and post-traumatic stress disorder among Yazidi women and the correlation between them. To achieve the objectives of the research, the researcher adopted the Descutner, 1991 & (Thelen) scale, which consisted of (35) items. The researcher also adopted the post-traumatic stress disorder scale for (Davidson, 1995) translated by (Abdul Aziz Thabet), which consists of (17) items. These two scales were administered to a sample of (200) individuals. Then, the researcher analyzes the data using the Statistical Package for Social Sciences (SPSS). The results showed that the research sample of Yazidi women has a fear of intimacy. The research sample of Yazidi women is characterized by

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Publication Date
Tue Oct 13 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Phototoxic effect of visible blue light on Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis in patients with chronic periodontitis (An in-vitro study)
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Background: The aim of this study was to determine phototoxic effect of visible blue light on anaerobic periodontal pathogens namely Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Materials and methods: Strains of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis were isolated from pockets of systemically healthy patients aged between 35-55 years old with pocket depths of 5-6 mm, the bacteria cultured on special blood Agar plates solid media, then subjected to visible blue light emitted from commercially available light cure devise (LED curing light); that emits blue light (400-500nm) of 1000mw energy at different periods of time exposures, then the CFU of each plate was measured by direct colony count

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Publication Date
Sun Dec 22 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Knowledge, Attitudes and Experience of off-label Drug Prescribing Practice among Physicians in Baghdad City Hospitals
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Abstract

The present study aims to assess the knowledge, attitude, and experience of off-label prescribing practice among physicians in Baghdad city hospitals. This cross-sectional study was performed through the period from November 1st 2018 to March 2019 at 17 hospitals, a self-administered questionnaire was utilized to collect data from the physicians, and the targeted hospitals were randomly selected at different regions in Baghdad City area. Out of the 400 distributed questionnaires to the physicians, 383 of them were returned completed, 57.2% indicated that they were reasonably familiar with the term “off label drug”, 57.7% mentioned that the most common medical reasons for the prescribing o

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Publication Date
Wed Sep 30 2015
Journal Name
European Journal Of Chemistry
Reaction pathways and transition states of the C-C and C-H bond cleavage in the aromatic pyrenemolecule - A Density Functional study
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The activation and reaction energies of the C-C and C-H bonds cleavage in pyrene molecule are calculated applying the Density Functional Theory and 6-311G Gaussian basis. Different values for the energies result for the different bonds, depending on the location of the bond and the structure of the corresponding transition states. The C-C bond cleavage reactions include H atom migration, in many cases, leading to the formation of CH2 groups and H-C≡C- acetylenic fragments. The activation energy values of the C-C reactions are greater than 190.00 kcal/mol for all bonds, those for the C-H bonds are greater than 160.00 kcal/mol. The reaction energy values for the C-C bonds range between 56.497 to 191.503 kcal/mol. As for the C-H cleavage rea

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