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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 Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Development and in vitro Evaluation of Bioadhesive Vaginal Tablet using Econazole Nitrate as a Model Drug
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         In this study, a bioadhesive dosage form of eoconazole nitrate for vaginal delivery was designed using a combination of bioadhesive polymers: Carbopol 941 p and sodium carboxymethylcellulose or methylcellulose in different ratios. The bioadhesive strength was evaluated by measuring the force required to detach the tablet from sheep vaginal mucosal membrane. It was found that the bioadhesive force was directly proportional to Carbopol 941 p content in the different formulae. The formulae were tested for their swelling behavior using agar gel plate method. The results showed that formulae containing a combination of Carbopol 941 p and sodium carboxymethylcellulose had greater swelling index

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Publication Date
Wed Aug 13 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Comparison of regional bond strength of post space of fiber-reinforced post luted with two types of cements at different testing times
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Back ground: This in vitro study was carried out to investigate the effect of post space regions (coronal, middle and apical), Time and the mode of polymerization (dual, self-cured) of the cements used on the bond strength between translucent fiber post and root dentin by using push-out test. Materials and Methods: Forty eight extracted mandibular first premolars (single root) were instrumented with ProTaper Universal system files (for hand use) and obturated with gutta percha for ProTaper and AH26® root canal sealer following the manufacturer instructions, after 24 hours post space was prepared using FRC postec® plus drills no.3 creating 8 mm depth post space. The prepared samples were randomly divided into two main groups (24 samples ea

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Publication Date
Thu Mar 03 2022
Journal Name
Rawal Medical Journal
Functional outcome of closed reduction of supracondylar humerus fracture with cross Kirschner wire in children
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Objective: To evaluate the functional outcome of percutaneous cross two K wires fixation for Gartland types II and III fractures of humerus. Methodology: This prospective study included80 patients with supracondylar humeral fracture, who underwent closed reduction and fixation by two crossed Kirschner wires. We included children with age < 15 years with closed fractures with Gartland types II and III, while the patient with vascular injury, open, irreducible fractures were excluded. The patients were following up for 6 months and assessed functionally by Flynn’s criteria. Results: The mean age of patients was 8.1 years. Trauma while child playing was the main mechanism of injury in 43 (59.8%) children and 46 (57.5%) fractures were of the

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Publication Date
Sat Oct 01 2022
Journal Name
The Egyptian Journal Of Hospital Medicine
Laminin Is a Promising Predictive Biomarker for Acute and Chronic Toxoplasmosis
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Publication Date
Sat Jan 01 2022
Journal Name
Journal Of Engineering
Serviceability of Post-fire RC Rafters with Openings of Different Sizes and Shapes
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This study deals with the serviceability of reinforced concrete solid and perforated rafters with openings of different shapes and sizes based on an experimental study that includes 12 post-fire non-prismatic reinforced concrete beams (solid and perforated). Three groups were formed based on heating temperature (room temperature, 400 °C, and 700 °C), each group consisting of four rafters (solid, rafters with 6 and 8 trapezoidal openings, and rafter with eight circular openings) under static loading. A developed unified calculation technique for deflection and crack widths under static loading at the service stage has been provided, which comprises non-prismatic beams with or without opening exposed to flexure concentra

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Publication Date
Tue Mar 12 2019
Journal Name
Hematology Reports
Studying Anemia of Chronic Disease and Iron Deficiency in Patients with Rheumatoid Arthritis by Iron Status and Circulating Hepcidin
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Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the two most important types of anemia in rheumatoid arthritis (RA). Functional iron deficiency in ACD can be attributed to overexpression of the main iron regulatory hormone hepcidin leading to diversion of iron from the circulation into storage sites resulting in iron-restricted erythropoiesis. The aim is to investigate the role of circulating hepcidin and to uncover the frequency of IDA in RA. The study included 51 patients with RA. Complete blood counts, serum iron, total iron binding capacity, ferritin, and hepcidin- 25 were assessed. ACD was found in 37.3% of patients, IDA in 11.8%, and combined (ACD/IDA) in 17.6%. Serum hepcidin was higher in ACD than in con

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Publication Date
Thu Jan 01 2004
Journal Name
Ipmj-iraqi Postgraduate Medical Journal
Changes in alkaline phosphatase activity in rat mammary glands from virgin through pregnancy, lactation and post–lactation
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The aim of this investigation is to study the rote of alkaline phosphatase in mammogenesis and lactogenesis. A total of fortyfemalealbino rats were used and divided according to their physiological states into four groups [ten rats each]. From each deeply ether anesthetized rat, the mammary gland was removed, fixed, quenched in liquid nitrogen and sectioned using SLEE cryostat. The sections were employed for routine haematoxylin and eosin stain and alkaline phosphatase demonstration using the calcium–cobalt method. The obvious finding in the mammary glands of pregnant rat was the presence of thick black rings indicating strong alkaline phosphatase activityaround the basal part of the secretory epithelium of the alveoli. In lactating mamma

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Publication Date
Wed Jan 01 2003
Journal Name
Ipmj-iraqi Postgraduate Medical Journal
Changes in acid phosphatase activity in rat’s mammary tissue from virginity, through pregnancy, lactation and post–lactation
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Purpose: Studying the activity of acid phosphatase, which is the marker of lysosomal activity in the mammary glands of rats at different stages of the physiological maturation [virgih, pregnancy, lactation and Post lactation] Methods: Forty, female, albino rats were used in this study. They were divided into four groups according to their physiological states [virgin, pregnancy, lactation and post lactation]. The mammary glands, after suitable fixation and sectioning, were employed for routine haematoxylin and eosin stain and for acid phosphatase demonstration Results: Acid phosphatase activity was weakly diffuse in the secretory tubules of virgin rats, the diffuse and granular activity of this enzyme was increased during pregnancy in the s

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Publication Date
Sat Apr 01 2023
Journal Name
Earth And Environmental Science
Study Functional Properties of the Isolated Protein from Germinated Mung‏
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The functional properties of the defatted powder and protein isolate of germinated mung bean seeds were studied and the estimation of the amino acids was carried out. The results showed a significant increase in the values of the amino acids leucine, lysine, phenylalanine and valine. The results of studying the functional properties of the protein isolate and defatted powder showed that there were significant differences between the sample The defatted and protein isolate, if the water absorption capacity of the defatted mung powder was 2.5% water/gm protein and the water absorption capacity of the protein isolate was 3%ml water/g protein, the fat binding capacity of the defatted powder was 0.3 ml fat/g protein and the isolate The ratio was

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Publication Date
Thu Nov 01 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Impact of functional disability on lifestyle for patients with arthritis
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A descriptive study, which was using an assessment approach, was conducted for the
determination of the impact of rheumatoid arthritis and osteoarthritis patient’s functional disability
upon their life style. The study was carried out at the Rheumatology and outpatients clinics of ALKarama
Teaching Hospital, Baghdad Teaching Hospital AL-Kindey Teaching Hospital and Specialized
surgeries Teaching Hospital for the period of October 15th 2003 through May 13th 2004 in Baghdad
City. A purposive (non-probability) sample of (245) arthritis patients which was comprised (111)
rheumatoid arthritis patients and (134) osteoarthritis patients, was selected out of the early stated
settings. The questionnaire was comprised of

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