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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
Thu Jan 07 2021
Journal Name
Indian Journal Of Forensic Medicine &amp; Toxicology
Efficacy and Safety of Sacral Neuromodulation in Treatment of Refractory Overactive Bladder
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Publication Date
Mon Feb 21 2022
Journal Name
Open Access Macedonian Journal Of Medical Sciences
Prospective Descriptive Study of Radiological and Functional Outcomes of Volar Barton’s Fracture Fixed by Volar Locked Plate
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BACKGROUND: Volar Barton’s fracture is a shearing mechanism of injury that results in fracture and subluxation of distal end radius in which volar rim of the distal radius is displaced with hand and carpus. Open reduction and volar plate fixation ensure more stable change of displacement, preservation of reduction, and early mobilization. AIM: This study aims to assess the functional and radiological outcome results of volar Barton’s fracture treated by volar buttress plate using the demerit points system of Gartland and Werley. PATIENTS AND METHODS: This study is a prospective descriptive observational study on 32 patients who were treated with ORIF by volar buttress plate for isolated volar Barton’s fractures between Fe

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Publication Date
Tue Mar 03 2020
Journal Name
International Journal Of Psychosocial Rehabilitation
A Study of Some Biochemical Variables and Functional Indicators and Their Relationship to the Achievement of 200m Young Runners
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ES Hussein

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Publication Date
Sat Oct 20 2018
Journal Name
Journal Of Economics And Administrative Sciences
Measurement and analysis of financial liberalization in Iraq
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Abstract :                                                                                                            

In light of the trend of the countries of t

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Publication Date
Sat Jul 01 2023
Journal Name
Journal Of Engineering
Using of Constructed Wetlands in The Treatment of Wastewater: A Review for Operation and Performance: Review for Using of Constructed Wetlands in The Treatment of Wastewater: Operation and Performance
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Wastewater recycling for non-potable uses has gained significant attention to mitigate the high pressure on freshwater resources. This requires using a sustainable technique to treat natural municipal wastewater as an alternative to conventional methods, especially in arid and semi-arid rural areas. One of the promising techniques applied to satisfy the objective of wastewater reuse is the constructed wetlands (CWs) which have been used extensively in most countries worldwide through the last decades. The present study introduces a significant review of the definition, classification, and components of CWs, identifying the mechanisms controlling the removal process within such units. Vertical, horizontal, and hybrid CWs

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Publication Date
Thu Sep 15 2022
Journal Name
Journal Of Baghdad College Of Dentistry
The effect of sweet and salty taste sensitivity on gin-gival health in relation to salivary serotonin among type1 diabetic patients aged 12-14 years
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Background: This study was conducted among diabetic persons to assess the sweet and salty taste sensitivity with its effect on gingival health in relation to salivary serotonin levels. Materials and methods: A cross-sectional comparative study design was used. All patients with diabetes aged 12-14 years that attend the Paediatric hospital at Baghdad medical city with specific inclusion criteria were involved in the sample of the present study (patients group 50 patients) compared with non-diabetic persons matched in age and gender of the study sample (control group 70 patients) who were attending dental unit in the college of dentistry/university of Baghdad. A two-alternative forced choice question including each component presented at f

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Publication Date
Fri Dec 15 2023
Journal Name
Al-academy
Utilising modelling software to convert functional utensils into ceramic art.
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Contemporary art has been widely affected by technology, and ceramics production is no exception. As an ancient art that originates from clay and other humble materials found in the ground, ceramics is considered one of the most adaptable art forms. Once it is realised how flexible ceramics as a material is, it can be easily altered into endless forms and shapes. Therefore, it is vital for ceramics practitioners to find a relationship between this wonderful material and the media of contemporary art, culture and modelling software or technology in general so that they can take their deformable art pieces to a whole new level. Such a relationship is worth investigating. Thus, for the purposes of this research, several ceramic pieces were

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Publication Date
Wed Dec 30 2015
Journal Name
College Of Islamic Sciences
Living Dengue (Cause and treatment)
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This research dealt with the modern dengue living in its linguistic meaning and where this dengue will be, and its cause and treatment, then concluded the talk about the search with the results envisaged from this research, has been shown that the main reason in living dengue: is after the slave of the book of God and the Sunnah of the Prophet peace be upon him Him.

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Publication Date
Wed Apr 30 2025
Journal Name
International Journal Of Environmental Impacts
Analysis of the Effect of Heavy Elements in Polluted Industrial Water and its Environmental Treatment: An Applied Study on the Gas Power Plant/ 1 (Central Region) in Southern Baghdad and its Discharge into the Tigris River
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Water produced from power plants is one of the most important sources of water pollution, especially for areas like Baghdad, Contaminated industrial wastewater is a major environmental challenge due to the rapid growth of industries, leading to increased accumulation of harmful pollutants in water resources, the work is intended to study the impact of water generated from a power plant in the south on the level of heavy metals before and after the treatment process and after its discharge to the Tigris River. Objective is to determine the extent of heavy metals such as iron, copper, chromium, and zinc concentration in water extracted from various points and subsequently study the monthly variations of these elements with a view to assessmen

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Treatment of polycyclic armoatic hydrocarbone in agriculture
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Despite the multiple sources of polycyclic compounds in the agricultural environment, this study suggests that it is possible to adopt the events of plants and their associated microorganisms in the soil, such as mushrooms and bacteria in the decomposition of these compounds can also use harvested plants such as barley and alfalfa grown for animal feed

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