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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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
Thu Mar 30 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Effect of Chronic Exposure of Cadmium Chloride in Drinking Water on Structural and Functional Aspects of Thyroid Gland in Mature Male Rabbits

The effect of chronic exposure to two different levels of cadmium chloride (CdCl2) 30 ppb and 40 ppb in drinking water for 12 weeks on thyroid function of mature male rabbits was studied. Eighteen mature male rabbits  were randomly divided into three groups (each of six ) , control group (group I ): were offered ordinary tap water , and treated groups (II and III ) were offered tap water containing 30ppb and 40 ppb respectively for 12 weeks .Serum concentration of  thyroxin (T4 ) and triiodothyronine (T3) were measured every six weeks ,as an index  of  thyroid function , further more ,  section of thyroid gland were prepared for histological studies. The results showed that  chronic exposure of male rabbits

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Publication Date
Sun Mar 01 2015
Journal Name
Baghdad Science Journal
Histopathological Changes caused by The Chronic Effect of Nitrofurantoin Drug in The Testes of Albino Mice

The present study was conducted to determine histopathological changes caused by chronic effect of Nitrofurantoin(NFT) in The albino mice Testes. The Study included 40 mice were divided on the five groups: the first group taken distilled water and become control group . the remaining group which are exposure with NFT drug in concentration (100-150-200-250) mg / kg, respectively, Doses were given orally for a period (month and two months). The results of histopathological changes included occurrence of congestion in the blood vessel and degeneration of spermatogonia and aggregation of spermatids in the lumen of semineferous tubules and inhibition of spermatogensis process and decrease of sperm inside the lumen

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Publication Date
Wed Jul 20 2022
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Study of Acute and Chronic Sinusitis – Symptoms, Diagnosis and Treatment: A Review article

Background: Sinusitis is an inflammatory condition that affects the mucous membrane lining the airways. Chronic rhinosinusitis and acute rhinosinusitis are the two types. Rhinosinusitis is characterized by facial pain, congestion, and headache. Due to the widespread prevalence of sinusitis, there must be an evaluation of the case because the diagnoses are more serious in the advanced stages of the disease and impact the outcome of care. Objectives: The objective of this study was to conduct a literature evaluation of chronic and acute rhinosinusitis, risk factors, symptoms and signs of sinusitis, diagnostic, sinusitis treatment, and antibiotic treatment, as well as new databases. Conclusion:

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Publication Date
Mon Mar 23 2020
Journal Name
Journal Of Engineering
Post-buckling Analysis of Cold-form Steel Column

For the time being, the cold-formed sections are widely used due to their simple manufacturing and construction processes. To be feasible, the strength of cold-formed columns should be determined based on their post-buckling behavior. Post-buckling relations are cumbersome and need design aids similar to those of American Iron and Steel Institute (AISI) to be applicable. These design aids have been developed to sections and materials other than those available in the local market. Therefore, this paper tries to develop a general finite element model to simulate the postbuckling behavior of cold-formed steel columns. Shell element has been used to discretize the web, flanges, and lips of the column. A linear bucking analy

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Publication Date
Fri Dec 01 2017
Journal Name
Mustansiriya Medical Journal
Publication Date
Tue Jan 03 2017
Journal Name
Al- Ustath: Quarterly Scientific Journal
A Linguistic Analysis of Halliday&#39;s Systemic- Functional Theory in Political Texts

BN Rashid, AKF Jameel, Al- Ustath: Quarterly Scientific Journal, 2017 - Cited by 15

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Publication Date
Fri Jun 02 2017
Journal Name
International Journal Of Medical Research & Health Sciences
Publication Date
Mon May 01 2023
Journal Name
Wiadomości Lekarskie Medical Advances
EVALUATION OF VEST-OVER-PANT TECHNIQUE IN THE TREATMENT OF POST-HYPOSPADIAS URETHROCUTANEOUS FISTULA

The aim: In this study, we present and evaluate the vest-over-pants technique as a simple way to correct urethrocutaneous fistulas after hypospadias. Materials and methods: Between October 2018 and June 2020, twenty male patients aged 5 to 20 years came to us with post hypospadias repair fistula, these patients underwent vest-over-pant repair of their fistula. The size of fistula was ranging between 2.5-5 mm. The distribution of fistula was coronal (3 patients), distal penile (9 patients), midshaft (2 patients) and proximal penile (6 patients). In 14 patients there were single fistula and 6 patients had more than one fistula. Eleven of patients were exposed to a previous failed fistula repair procedure. Results: Six months after the operati

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Publication Date
Wed Oct 30 2019
Journal Name
Journal Of Legal Sciences
Legal regulation of Specialized Medical facilities for treatment of drug addiction

       The increasing use of narcotic drugs and psychotropic substances in the recent period and the accompanying increase in the number of addicts recently on these substances obliged the administration to pay attention to this issue to protect the public health from the dangers of drugs and psychotropic substances.                                                                  &nb

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Publication Date
Sat Aug 31 2019
Journal Name
Iraqi Journal Of Physics
Investigation the effect of post deposition thermal treatment on properties P3HT and P3HT:PCBM blend.

  This work reports the study of heat treatment effect on the structural, morphological, optical and electrical properties of poly [3-hexylthiophene] and its blend with [6,6]-phenyl C61 butyric acid methyl ester ( P3HT:PC61BM). X-ray diffraction (XRD) measurements show that the crystallinity of the films increased with annealing. The evaluation of surface roughness and morphology was investigated using atomic force microscope (AFM), and field emission scanning microscope(FESEM). The optical properties were emphasized a strong optical absorption of P3HT compared with the blend. Hall effect measurement was used to study the electrical properties which revealed there is an increase in the electrical conductivity and Hall mobility of th

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