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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 Sep 03 2020
Journal Name
مجلة العلوم السياسية
The Requirement of the National Democratic project in Iraq post Daesh Terrorist Group Stage
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This study aims at re-transmit the spirit of the national democratic project of Iraq post of the chaos left by the Daesh terrorist group stage(The Islamic State of Iraq and Syria, ISIS) , Which controlled large parts of Iraq, and had an adverse effect on the political scene in Iraq, inspired everyone that there are deficiencies in the political, economic, religious and ethnic structure of the Iraqi people in non-response to democratic thought.The researcher relied on the hypothesis that " the requirements of building a democratic project are based on the need to provide the requirements ranging from two interrelated aspects, like the institutional aspect and the aspect that related to the general and necessary requirements for the e

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Publication Date
Sun May 03 2020
Journal Name
Systematic Reviews In Pharmacy
Therapeutic Effect of Pumpkin ( Cucurbita pepo L.) on Post Burn Injury in White Mice
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Publication Date
Tue Nov 06 2018
Journal Name
Iraqi National Journal Of Nursing Specialties
Assessment of Factors Contributing to Abdominal Post-Operative Wound Infections in Sulaimani Teaching Hospital
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Objectives: The study aims to assess some of the contributing factors to abdominal postoperative wound infection and
to find out the relationship between postoperative wound infections and some socio-demographic characteristics such as
age, gender, level of education, occupation and residential area.
Methodology: A descriptive study was carried out in Sulaimani Teaching Hospital (Kurdistan Region). The study has
started from January 15th up to October 31th, 2009. To achieve the study objectives, a purposive "non probability"
sample of (100) patients who have abdominal postoperative wound infection, Adult female and male patients who were
admitted to Sulaimani Teaching Hospital was selected.
The data were collected th

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Publication Date
Mon Jul 01 2024
Journal Name
Journal Of The Faculty Of Medicine Baghdad
The Burden of Chronic Obstructive Pulmonary Disease COPD in Stable Patients and its Association with Inflammatory Biomarkers and Body Mass Index
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Background: Chronic obstructive pulmonary disease (COPD) is a progressive airflow limitation that is preventable but not curable. It is associated with persistent symptoms that cause a considerable burden on individual productivity at work, and daily activities, and reduced quality of life, also burdening the healthcare system and society. Objectives: The study aims to measure the burden of COPD on patients in terms of daily activities and work productivity. It also seeks to investigate some inflammatory biomarkers' levels and their correlation with selected outcomes. Patients and Methods: A cross-sectional study on 120 stable COPD patients who were diagnosed and treated according to the GOLD guidelines at Kirkuk General Hospital's

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Publication Date
Sun Dec 21 2025
Journal Name
Journal Of Baghdad College Of Dentistry
An Assessment of Salivary Leptin and Resistin Levels in Type Two Diabetic Patients with Chronic Periodontitis (A Comparative Study)
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Background: Type 2 diabetes mellitusand chronic periodontitis hold a close relationship that has been the focus of many researches. Currently there is an appreciation to the role of adipose tissue-derived substances "the adipokines" in immune-inflammatory responses; also, there is an interest in using the simple non-invasive saliva in diagnosing and linking oral and general health problems. The current study aims to determine the periodontal health status in the chronic periodontitis patients with and without poorly or well controlled type 2 diabetes mellitus, measure the salivary levels of two adipokines "leptin and resistin", pH and flow rate and then correlate between these clinical periodontal, biochemical and physical parameters in eac

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Publication Date
Tue Oct 01 2024
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Evaluation of Interleukin-31 Serum Levels in Patients with Chronic Kidney Disease on Hemodialysis with and without Uremic Pruritus
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الخلاصة: الحكة اليوريمية لدى مرضى غسيل الكلى يؤثر على أكثر من 40٪ من المرضى. وربما ترتبط الحكة المستمرة بمستويات عالية من الإنترلوكين 31. الاهداف: النظر إلى مستويات مصل إنترلوكين 31 لدى مرضى غسيل الكلى المصابين بمرض الكلى في المرحلة النهائية، سواء مع أو بدون حكة يوريمية. النتائج: لم يكن مستوى المصل [الوسيط (] لـ IL-31 في المرضى الذين يعانون من الحكة اليوريميةأو بدون حكة في عينة مصل ما قبل غسيل الكلى مختلفًا بشكل م

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Publication Date
Mon Jun 15 2020
Journal Name
Journal Of Baghdad College Of Dentistry
Effect of diabetes mellitus on periodontal health status, salivary flow rate and salivary pH in patients with chronic periodontitis
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Background: Diabetes and periodontitis are considered as chronic diseases with a bidirectional relationship between them. This study aimed to determine and compare the severity of periodontal health status and salivary parameters in diabetic and non-diabetic patients with chronic periodontitis. Materials and Methods: Seventy participants were enrolled in this study. The subjects were divided into three groups: Group I: 25 patients had type 2 diabetes mellitus with chronic periodontitis, Group 2: 25 patients had chronic periodontitis and with no history of any systemic diseases, Group 3: 20 subjects had healthy periodontium and were systemically healthy. Unstimulated whole saliva was collected for measurement of salivary flow rate and pH.

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Publication Date
Mon Apr 04 2022
Journal Name
Journal Of Educational And Psychological Researches
Fear of Intimacy and its Relationship with Post-Traumatic Stress Disorder among Yazidis Women
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The current research aims to identify the fear of intimacy and post-traumatic stress disorder among Yazidi women and the correlation between them. To achieve the objectives of the research, the researcher adopted the Descutner, 1991 & (Thelen) scale, which consisted of (35) items. The researcher also adopted the post-traumatic stress disorder scale for (Davidson, 1995) translated by (Abdul Aziz Thabet), which consists of (17) items. These two scales were administered to a sample of (200) individuals. Then, the researcher analyzes the data using the Statistical Package for Social Sciences (SPSS). The results showed that the research sample of Yazidi women has a fear of intimacy. The research sample of Yazidi women is characterized by

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Publication Date
Wed Jan 02 2019
Journal Name
International Journal Of Research In Social Sciences And Humanities
MUSLIM AMERICANS DELIMMA POST 9/11 IN LAILA HALABY’S ONCE IN A PROMISED LAND
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September 11th attacks held the biggest tragedy in American history. It was a day of grief, and it proved that America was not immune to attacks and threat. Afterwards life has changed not only for the American Muslims but also American Christians and Jews and to people from other religions. The cruelty of that day has left its shed particularly on the Muslims’ life in America who in reality had nothing to do with the attacks. Arab American Muslim writer Laila Halaby’s novel, Once in a Promised Land, intensely displays the problems that Arab Muslims went through after September 11th attacks. This paper discusses this issue through analysing Halaby’s novel, where she deals with the issues such as discrimination, stereotype, and prejudi

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Publication Date
Sun Dec 01 2013
Journal Name
Journal Of Al-nahrain University
Spectrophotometric Determination of Ketotifen Drug in Pure form and Pharmaceutical Preparation Using Bromothymol Blue Via Ion-Pair Formation
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