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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
Fri Mar 31 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Efficacy of Topically Applied Silymarin in the Treatment of Herpes Labialis Ulcers
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Herpes labialis is an infection caused by the herpes simplex virus, characterized by an eruption of small and usually painful blisters on the skin of the lips, mouth, gums, or the skin around the mouth. Although there is no successful treatment available, the local use of compounds with effective anti-inflammatory and cytoprotective effects may be of value in this respect. This project was designed to evaluate clinically the local use of silymarin, a group of flavonoids with powerful antioxidant, anti-inflammatory and cytoprotective activity, in the treatment of herpes simplex ulcer. Fifty three patients with herpes labialis ulcers (HLU) were enrolled in this randomized, single blinded, placebo controlled clinical study, and they were al

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Publication Date
Thu Jun 15 2017
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation Of Stainless Steel Intermaxillary Fixation Screws In Treatment Of Favorable Mandibular Fractures
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Background: Numerous methods have been described for achievement of Intermaxillary fixation in the treatment of fractures of facial skeleton. Conventional methods like Erich arch bars and eyelet wires are currently the most common methods for achieving intermaxillary fixation (IMF), however, they have their own disadvantages. Since 1989, IMF using intraoral self-tapping IMF screws has been introduced for treatment of mandibular fractures. The aim of this study was to evaluate the efficacy, advantages, disadvantages and potential complications associated with using of self-tapping IMF screws in the treatment of mandibular fractures. Material and Methods: Twenty patients with favorable mandibular fractures, attended to Oral and Maxillofacial

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Publication Date
Thu Aug 01 2024
Journal Name
Al-kindy College Medical Journal
Efficacy of Gamma Knife Stereotactic Radiosurgery in the Treatment of Primary Trigeminal Neuralgia
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Background: Trigeminal neuralgia (TN), or Tic Douloureux, is one of the most common neuropathic pains. Gamma knife stereotactic radiosurgery (GNSRS) has been considered one of the procedures for treating primary TN. Objective: This study evaluates the effectiveness of GNSRS in treating primary TN in patients who are unresponsive to medical treatment in a single-center experience. Subjects and Methods: This study was conducted on 180 patients from January 2018 to October 2021. The study utilized the Barrow Neurological Institute (BNI) pain intensity score to assess pain before and after GNSRS treatment. Results: A total of 180 patients with primary TN were included in this study, 108 female with a 1.5:1 female: male ratio.  Results

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Publication Date
Thu Oct 12 2017
Journal Name
Iraqi Journal Of Laser
A Comparative Evaluation of Post-Operative Pain and Function after Gingival Depigmentation Using 940 Nm Diode Laser And Conventional Bur Method: 6 Months Study
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The aim of the study was to evaluate the efficacy of diode laser (λ=940 nm) in the management of gingival hyperpigmentation compared to the conventional bur method. Materials and methods: Eighteen patients with gingival hyperpigmentation were selected for the study with an age between 12-37 years old. The site of treatment was the upper gingiva using diode laser for the right half and the conventional method for the left half. All patients were re-evaluated after the following intervals: 3 days, 7 days, 1 month and 6 months post-operation. Pain and functions were re-evaluated in each visit for a period of 1 day, 3 days and 1 week post-operation. Laser parameters included 1.5 W in continuous mode with an initiated tip (400 μm) placed in

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Publication Date
Sun Sep 26 2021
Journal Name
Modern Sport
The effect of physical exertion exercises using electrical muscle stimulation on the development of some physical and functional characteristics of women aged (40-45) years
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The researchers have recently noticed the interest in the problem of overweight and how to find solutions to it until it is now at the forefront in terms of innovating various and different methods and treatment methods, and the interest in developing health fitness is one of the most important requirements of physical activity for the trainees, which led to the multiplicity of sports activities that promote the health aspect For the individual, in addition to the aesthetic aspect, the problem lies in not adopting training programs according to codified scientific foundations aiming, in addition to reducing weight, to raise the general health level of the trainee participating in fitness institutes, as the trainers do not follow the

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Publication Date
Wed Dec 18 2019
Journal Name
Baghdad Science Journal
The Dissemination of Multidrug Resistance (MDR) and Extensively Drug Resistant (XDR) among Uropathogenic E. coli (UPEC) Isolates from Urinary Tract Infection Patients in Babylon Province, Iraq
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Antibiotic resistance is a problem of deep scientific concern both in hospital and community settings. Rapid detection in clinical laboratories is essential for the judicious recognition of antimicrobial resistant organisms. So, the growth of Uropathgenic Escherichia coli (UPEC) isolates with Multidrug-resistant (MDR) and Extensively Drug-resistant (XDR) profiles that thwart therapy for (UTIs) has been detected and has straight squeezed costs and extended hospital stays. This study aims to detect MDR- and XDR-UPEC isolates. Out of 42 UPEC clinical isolates were composed from UTI patients. The bacterial strains were recognized by standard laboratory protocols. Susceptibility to antibiotic was measured by the standard disk diffusi

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Publication Date
Thu Jul 14 2022
Journal Name
Egyptian Journal Of Medical Human Genetics
A single-nucleotide polymorphism of IL12A gene (rs582537 A/C/G) and susceptibility to chronic hepatitis B virus infection among Iraqi patients
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A case–control study (80 patients with chronic hepatitis B virus [HBV] infection and 96 controls) was performed to evaluate the association of an IL12A gene variant (rs582537 A/C/G) with HBV infection. Allele G showed a signifcantly lower frequency in patients compared to controls (31.2 vs. 46.9%; probability [p]=0.009; corrected p [pc]=0.027) and was associated with a lower risk of HBV infection (odds ratio [OR]=0.49; 95% confdence interval [CI]=0.29–0.83). A similar lower risk was associated with genotypes CG (17.5 vs. 29.2; OR=0.25; 95% CI=0.08–0.81; p=0.02) and GG (10.0 vs. 16.7; OR=0.25; 95% CI=0.07–0.91; p=0.036), but the pc value was not signifcant (0.12 and 0.126, respec‑ tively). Serum IL35 levels showed signifcant difere

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Publication Date
Thu Nov 21 2019
Journal Name
Journal Of Engineering
Comparative Permeability Estimation Method and Identification of Rock Types using Cluster Analysis from Well Logs and Core Analysis Data in Tertiary Carbonate Reservoir-Khabaz Oil Field
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Characterization of the heterogonous reservoir is complex representation and evaluation of petrophysical properties and application of the relationships between porosity-permeability within the framework of hydraulic flow units is used to estimate permeability in un-cored wells. Techniques of flow unit or hydraulic flow unit (HFU) divided the reservoir into zones laterally and vertically which can be managed and control fluid flow within flow unit and considerably is entirely different with other flow units through reservoir. Each flow unit can be distinguished by applying the relationships of flow zone indicator (FZI) method. Supporting the relationship between porosity and permeability by using flow zone indictor is ca

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Publication Date
Fri Jun 12 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Root resorption and anti-dentine antibody level in serum and saliva of well-controlled type ? diabetic patients undergoing orthodontic treatment
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Background: Diabetic mellitus type ? is a metabolic disorder of diverse etiological factors, characterized by hyperglycemia resulting from an absolute deficiency of insulin affected childhood and adolescent. Some of these patients seek an orthodontic care .The orthodontist who is treating these medically compromised patients should have a working knowledge of the multitude of medically complex problems. This information will support and enable for delivery of high standards of dental care in general and orthodontic care in particular. The aim of this study was to analyze serum IgG levels and salivary secretory IgA (sIgA) levels in human dentine extract (HDE) before (T0) and 6 months after (T6) orthodontic treatment and to correlate anti-HDE

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Publication Date
Tue Nov 01 2022
Journal Name
Bulletin Of National Institute Of Health Sciences
Using of Propolis on the treated rats induced with Polysystic ovarian syndrome by Litrozol drug
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