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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 Nov 09 2018
Journal Name
International Journal Of English Linguistics
A Discourse Analysis Study of Comic Words in the American and British Sitcoms
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DBN Rashid, International Journal of English Linguistics, 2019 - Cited by 2

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Publication Date
Thu May 05 2022
Journal Name
Al-kindy College Medical Journal
Time-Trend Analysis of Bladder Cancer and its Association with Bilhariziasis in Egypt
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Background: Both bladder cancer and schistosomiasis are endemic in Egypt. The former has a unique epidemiological pattern, which has been linked to bladder infestation by Schistosoma. The last decades have witnessed a great reduction in the infection rate of schistosomiasis and a decline in the incidence and changes in the patterns of bladder cancer. Whether these changes are linked to each other or a co-incidence is a subject of investigations.

Method: Literature on epidemiological data of bladder cancer and Schistosoma in Egypt was searched for in Medline, Scopus, PubMed, and Google Scholar. Furthermore, a hand search for literature and reports released by the Egyptian government and involved agencies was perfo

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Publication Date
Thu Jun 16 2022
Journal Name
Al-khwarizmi Engineering Journal
Estimate and Analysis the Availability of Generator in Electric Power Plant Using ANN
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The large number of failure in electrical power plant leads to the sudden stopping of work. In some cases, the necessary reserve materials are not available for maintenance which leads to interrupt of power generation in the electrical power plant unit. The present study, deals with the determination of availability aspects of generator in unit 5 of Al-Dourra electric power plant. In order to evaluate this generator's availability performance, a wide range of studies have been conducted to gather accurate information at the level of detail considered suitable to achieve the availability analysis aim. The Weibull Distribution is used to perform the reliability analysis via Minitab 17, and Artificial Neural Networks (ANNs) by approaching o

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Publication Date
Thu Jun 16 2022
Journal Name
Al-khwarizmi Engineering Journal
Comparative study of vibration analysis in rotary shafts between Rayleigh's and Dunkerley's methods
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The importance of vibrations in rotating rotors in engineering applications has been examined, as has the best approach to interpreting vibration data. The most extensively used analytical approaches for rotating shaft vibration analysis have been investigated. In this research, a detailed study was made of the Rayleigh and Dunkerley methods due to their importance in the special calculations to find the amplitude of vibrations in the rotation system. The multi-node method was used to calculate both Dunkerley's and Rayleigh's methods. An experimental platform was built to study the vibrations that occur in the rotating shafts, and the results were compared with theoretical calculations and with different distances of the bearings. It pro

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Publication Date
Fri Sep 27 2019
Journal Name
Journal Of Baghdad College Of Dentistry
Clinical Assessment and Cytomorphometric Analysis of Buccal Mucosal Cells in Behçet’s Disease Patients
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Background: Behçet’s disease (BD) is a disorder of systemic inflammatory condition. Its important features are represented by recurrent oral, genital ulcerations and eye lesions. Aims. The purpose of the current study was to evaluate and compare cytological changes using morphometric analysis of the exfoliated buccal mucosal cells in Behçet’s disease patients and healthy controls, and to evaluate the clinical characteristics of Behçet’s disease. Methods. Twenty five Behçet’s disease patients have been compared to 25 healthy volunteers as a control group. Papanicolaou stain was used for staining the smears taken from buccal epithelial cells to be analyzed cytomorphometrically. The image analysis software has been used to

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Publication Date
Sun Oct 01 2023
Journal Name
Baghdad Science Journal
Numerical Investigation, Error Analysis and Application of Joint Quadrature Scheme in Physical Sciences
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In this work, a joint quadrature for numerical solution of the double integral is presented. This method is based on combining two rules of the same precision level to form a higher level of precision. Numerical results of the present method with a lower level of precision are presented and compared with those performed by the existing high-precision Gauss-Legendre five-point rule in two variables, which has the same functional evaluation. The efficiency of the proposed method is justified with numerical examples. From an application point of view, the determination of the center of gravity is a special consideration for the present scheme. Convergence analysis is demonstrated to validate the current method.

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Publication Date
Sat Jan 01 2022
Journal Name
Ssrn Electronic Journal
The Prospective of Artificial Neural Network (ANN’s) Model Application to Ameliorate Management of Post Disaster Engineering Projects
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Currently and under the COVID-19 which is considered as a kind of disaster or even any other natural or manmade disasters, this study was confirmed to be important especially when the society is proceeding to recover and reduce the risks of as possible as injuries. These disasters are leading somehow to paralyze the activities of society as what happened in the period of COVID-19, therefore, more efforts were to be focused for the management of disasters in different ways to reduce their risks such as working from distance or planning solutions digitally and send them to the source of control and hence how most countries overcame this stage of disaster (COVID-19) and collapse. Artificial intelligence should be used when there is no practica

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Publication Date
Tue Dec 01 2015
Journal Name
Journal Of Engineering
Importance of New Use of Concrete in Iraq Analysis of Development And Use of Concrete in Architecture
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Since its invention by the Ancient Romans and later developed during the mid-18th century, the concrete structure and finish, has been considered as the most powerful, practical, economic and constructional material that meets the building’s architectural and aesthetical requirements. By creating unique architectural forms, the pioneer architects used concrete widely to shape up their innovative designs and buildings.

The pre-mixed ultra-high performance concrete which manufactured by Lafarge.

The transparent concrete and cement that allow the light beams to pass through them, introduces remarkable well-lit architectural spaces within the same structural criteria. This product is a recyclable, sustainab

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Publication Date
Thu Jan 20 2022
Journal Name
Journal Of Clinical Medicine
Comparison of the Safety and Efficacy of Laser Versus Pneumatic Intracorporeal Lithotripsy for Treatment of Bladder Stones in Children
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This study aimed to compare the safety and efficacy of laser lithotripsy and pneumatic lithotripsy, the two most commonly used transurethral lithotripsy methods for treating bladder stones in children in Iraq. Between January 2013 and December 2016, 64 children with bladder stones were included in this prospective randomized study, after ethical committee approval and written consent from the children’s parents or caregivers were obtained. Patients were assigned randomly by computer software to two groups treated with either pneumatic cystolithotripsy or laser lithotripsy. A 9 Fr. semirigid ureteroscope was used to pass the lithotripter through and fragment the stone. A catheter of 8–12 Fr. was then introduced and kept in place

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Publication Date
Tue Jun 11 2019
Journal Name
Al-kindy College Medical Journal
Conservative Treatment of Tuberculosis of the Spine in Patients with no Neurological Deficits
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Background: Patients who have both neurological impairment and kyphotic deformity can be treated medically, and this treatment can be achieved with anti-tuberculous drugs alone.

Objective: To evaluate conservative medical management of patients with tuberculosis of the spine (Pott disease). The prognostic significance of various clinical, radiological, and long-term follow-up findings in these patients was also evaluated.

Methods: Between January 2009 and January 2018 data were collected prospectively at The Neurosciences Hospital/ Baghdad/ Iraq in 44 patients with Pott disease in the thoracic and lumbar spine. These patients had no major neurological deficits or

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