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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
Tue Feb 01 2022
Journal Name
Baghdad Science Journal
Study the Inhibition Effect of Amoxicillin Drug for Corrosion of Carbon Steel in Saline Media
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          Potentiostatic polarization and weight loss methods have been used to investigate the corrosion behavior of carbon steel in sodium chloride solution at different concentrations (0.1, 0.4 and 0.6) M under the influence of temperatures ( 293, 298, 303, 308 and 313) K. The inhibition efficiency of the amoxicillin drug on carbon steel in 0.6 M NaCl has also been studied based on concentration and temperature. The corrosion rate showed that all salt concentrations ( NaCl solution) resulted in corrosion of carbon steel in varying ratio and 0.6 M of salt solution  was the highest rate (50.46 g/m².d). The results also indicate that the rate of corrosion increases at a temperature of 313 K.. Potentiodynamic polarization studi

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Publication Date
Sun Dec 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Effect of Zinc drug on amino acid concentration in liver of white mice, Mus musculus
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Zinc is one of the essential trace elements, it plays a key role in many biochemical and functional processes. It is less harmful than many other minerals, in the case of exposure to high doses of zinc, poisoning occurs, and this poisoning may mostly result from the accidental ingestion of household products containing zinc or nutritional supplements, this study was conducted to find out the effects of zinc on the concentration of amino acid. A total of 30 adult white mouse males were taken and divided into three groups; the first group (control) of 10 mice taken with distilled water for 30 days, the second group includes 10 mice that were dose with Zn drug concentration of 50 mg/kg/day for 30 days, the third group includes 10 mice that wer

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Publication Date
Mon Dec 03 2018
Journal Name
The Iraqi Postgraduate Medical Journal
Operative Treatment by Plate and Screws Versus Conservative Treatment of Closed Displaced Fracture of the Mid Third of Clavicle in Adults: Comparative Study
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BACKGROUND: Clavicle fractures are common injuries in young active individuals, the mid third of the clavicle is most commonly fractured part(80% of clavicle fracture) OBJECTIVE: To compare the outcomes of operative and non operative management of displaced and or comminuted closed fracture of the mid third of clavicle in young adults PATIENTS AND METHODS: This prospective observational study of 24 patients of fracture of the mid third of the clavicle was conducted in Alkindy teaching hospital from July 2015 to January 2017 and divided into two groups; one managed by operative treatment with plate and screws and the other by non operative sling immobilization after taking the consent and the patients were seen at 2, 4, 6 weeks,3, 6, and 9 m

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Publication Date
Wed Dec 30 2020
Journal Name
Journal Of Planner And Development
The preferences of planning bridges of Al-Mosul city post war
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The study started from the problems of wars and the damage that result from deterioration and destruction of infrastructure and the absence of planning and urban reconstruction. The study aims to address the condition of the bad destroyed bridges that have paralyzed traffic from the right and left sides of the city of Mosul. The study is based on the assumption that the reconstruction of bridges will improve the transportation network in the city of Mosul. The study relied on several approaches, including: the historical approach by reviewing global and local experiences and the descriptive approach to review the reality of the state of Mosul after the liberation process, through maps and the analytical approach through statistics and da

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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
Sun May 15 2022
Journal Name
Al-kindy College Medical Journal
Impact of Tobacco Use in the Etiology of Chronic Renal Failure Among Sudanese Patients: Tobacco and Renal Failure Among Sudanese Patients
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Background: Chronic renal failure (CRF) is a clinical syndrome that occurs when there is gradual decline in renal operation overtime.

Objective: This study aims to investigate the prevalence of depression among medical students at university of Baghdad, college of medicine in Iraq and the association between some variables and depression.

Aim: This study aimed to identify the impact of tobacco use in the etiology of chronic renal failure among Sudanese patients in Omdurman Military Hospital and Omdurman Kidney Dialysis Center

Materials and methods: This descriptive community-based study was conducted in Khartoum State. A random sample of 100 cases with chronic renal failure and 100

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Publication Date
Thu Jun 28 2018
Journal Name
Journal Of The College Of Education For Women
The function and Formation of NORTH ATLANTIC TREATY ORGANZIAITON as (NATO) Post Cold War Period
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The problem of this study lies in that NATO was formed in the first place to protect Europe from Warsaw Pact. The geographical and military strategy have been changed with the change of its mission and expanding its operation scope with the leadership of the USA in the international scens. The latter has made this organization as the military arm to tighten its control over strategic regions.

            The research supposes that NATO state members confront security concerns and political and military issues that push to expand the organization. The importance of this study lies in knowing the new roles of NATO imposed by the United States. Therefore, the continuity and affi

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Publication Date
Mon Sep 01 2025
Journal Name
Civil Engineering Journal
Pre- and Post-Cracking Resistance of Steel Fiber Reinforced Concrete Flexural Members with GFRP Bars
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This research investigates the pre- and post-cracking resistance of steel fiber-reinforced concrete specimens with Glass Fiber Reinforced Polymer (GFRP) bars subjected to flexural loading. The purpose is to modify the ductility and cracking resistance of GFRP-reinforced beams, which are prone to early cracking and excessive deflections instigated by the low modulus of elasticity of GFRP. Six self-compacting concrete specimens (1500×240×200 mm), incorporating steel fibers of two lengths (25 mm and 40 mm) with varying distribution depths, were tested to assess their structural performance. The results indicate significant enhancements in cracking resistance, stiffness, energy absorption, ductility, and flexural strength. Tested beam

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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
Sat Jun 15 2019
Journal Name
Journal Of Baghdad College Of Dentistry
Oral hygiene status in relation to salivary estradiol hormone level among pre-menopausal and post-menopausal Iraqi women
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Background: The menopause is physiological changes in women that give rise to adaptive changes at both systemic and oral level. During menopause, ovarian function declines and the production of sex steroid hormones reduces significantly affecting the oral tissues and periodontal structures leading to chronic inflammation of the gingiva, increased risk of tooth loss. Aim of study: The present study was designed to estimate the oral hygiene status in relation to salivary estradiol level among pre and post-menopausal women. Materials and Methods: Ninety women aged 48-52 years old, the control group consisted of 45 pre-menopausal women and the study group consisted of 45 post-menopause were examined for gingival index, plaque index and calcu

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