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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 Oct 04 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Comparison of fit among different types of post restorations luted with conventional cement
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Background: with the advent of new postmaterial in dentistry, it has become important to measure fitness of post restoration along the horizontal plane of the root space.This study aimed to measure and compare, the cement film thickness of conventional zinc phosphate cement in micrometer between the post and root dentin along horizontal plane at different post space regions (coronal, middle and apical) of four types of posts, by using stereomicroscopy. Material and methods: Thirty-two extracted human maxillary canines, mandibular canines and maxillary central incisors (n=32) were instrumented with ProTaper system files (hand use) and obturated with gutta-percha for ProTaper and AH26® root canal sealer. After 24hrs of incubation at 37ºC, p

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Publication Date
Sun Mar 04 2018
Journal Name
Iraqi Journal Of Science
Effect of maternal exposure of silver nanoparticles on the histogenesis of cerebellum in post-implantation of albino rats embryos
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Publication Date
Sun Mar 04 2018
Journal Name
Iraqi Journal Of Science
Effect of maternal exposure of silver nanoparticles on the histogenesis of cerebellum in post-implantation of albino rats embryos
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The central nervous system is the most important system and is very sensitive to any accidental infection during ontogenesis; it includes brain and spinal cord. The cerebellum is the second largest part of the brain after cerebrum and it’s very sensitive to the abnormal changes during the embryological development. This study was designed to investigate the effect of the maternal exposure of selected concentrations of suspension of nanoparticles on the ontogenesis of the rat cerebellum after embryos implanted in uterus. A total of 60 female pregnant rats were divided in to three groups, each contains 20 females. Group1 (G1) was treated orally with 2mg/kg /body weight (b. wt) of suspension of silver nanoparticles (Ag NPs). While group 2 (G

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Publication Date
Thu Oct 31 2019
Journal Name
Al-kindy College Medical Journal
Assessment of efficacy and safety of dapsone gel 5% in the treatment of acne vulgaris
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ABSTRACTBackground : Acne vulgaris is a
common skin disease, affecting more than 85% of
adolescents and often continuing into adulthood.
People between 11 and 30 years of age and up to
5% of older adults. For most patients acne remains
a nuisance with occasional flares of unsightly
comedones, pustules and nodules. For other less
fortunate persons, the sever inflammatory response
to Propionibacterium acnes (P.acnes) results in
permanent
Methods: Disfiguring scars. (1, 2) Stigmata of sever
acne cane lead to social ostracism, withdrawal
from society and severe psychologic
depression (1-4).
Result Pathogenesis of acne Traditionally, acne
has been thought of as a multifactorial disease of
the fo

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Publication Date
Wed Jul 31 2024
Journal Name
International Journal Of Health &amp; Medical Research
Review Article: Cupping Therapy in Treatment of Certain Diseases
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The research undertaken has provided a comprehensive insight into the practice of cupping therapy, a traditional treatment modality that has seen resurgence in. modern complementary medicine. This exploration, focusing on a spectrum of. Conditions such as migraines, lower back pain, neck pain, knee osteoarthritis, and chronic urticaria, highlights the potential benefits and the necessity for a deeper. Scientific understanding of cupping therapy. Cupping therapy, with its roots deeply embedded in ancient medical practices, offers a unique approach to treatment by promoting healing through increased blood flow and the release of toxins from the body. The application of this therapy in treating migraines has shown promising results, su

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Publication Date
Wed Jul 31 2024
Journal Name
International Journal Of Health &amp; Medical Research
Review Article: Cupping Therapy in Treatment of Certain Diseases
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The research undertaken has provided a comprehensive insight into the practice of cupping therapy, a traditional treatment modality that has seen resurgence in. modern complementary medicine. This exploration, focusing on a spectrum of. Conditions such as migraines, lower back pain, neck pain, knee osteoarthritis, and chronic urticaria, highlights the potential benefits and the necessity for a deeper. Scientific understanding of cupping therapy. Cupping therapy, with its roots deeply embedded in ancient medical practices, offers a unique approach to treatment by promoting healing through increased blood flow and the release of toxins from the body. The application of this therapy in treating migraines has shown promising results, su

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Publication Date
Fri Jan 01 2016
Journal Name
Scholars' Press
Determination of Pollutants in Water Treatment for Petroleum Refinery
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Dora petroleum refinery waste water is the one of the important source of pollution by priority pollutant aromatic compound discharged to Tigris river in Iraq. the station has waste water treatment unit contains many treatment subunits The most important sub units is :skimmer units ,physiochemical unit ,daf unit, biological unit. The aim of research project is to study the ability of unit to remove the priority pollutant aromatic compound and follow up these compounds in river to study ability of river to self removal. A solid phase extraction (SPE) followed by high performance liquid chromatography-ultra violet (HPLC-UV) technique is depicted for the quantitative estimation of benzidines and phenols. Experimental studies were performed to

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Publication Date
Mon Nov 02 2020
Journal Name
Biochemical And Cellular Archives
PHYSIOLOGICAL ROLE OF IMMUNE SYSTEM ELEMENTS IN ORTHODONTIC TREATMENT
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Orthodontic treatment is an inclusive treatment that includes growth adjustment of the craniofacial area and alveolar bone reconstruction that affects the movement of teeth. Apply orthodontic forces to correct teeth anomaly via alveolar bone remodeling includes a combination of cellular and molecular events in the gum. Orthodontic tooth movement is based on force induced periodontal ligament and alveolar bone remodeling. Mechanical motivation on a tooth causes an inflamed response in the gum tissue. Inflammatory immune markers stimulate the biological processes associated with alveolar bone resorption. The aim of this article is shedding light on the significance role inflammatory immune response in orthodontic treatment.

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Publication Date
Fri Dec 01 2017
Journal Name
The Iraqi Postgraduate Medical Journal
Extensive Versus Traditional Phototherapy in Treatment of Neonatal Jaundice
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Publication Date
Sun Feb 03 2019
Journal Name
Journal Of The College Of Education For Women
The Legend between reality and its future Treatment in threatre analytics study
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The Legend between reality and its future Treatment in threatre analytics study

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