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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 Jul 11 2023
Journal Name
Journal Of Educational And Psychological Researches
Functional Engagement and Its Relationship to Hope-Based Thinking for Kindergarten Teachers
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The research aims to identify the level of functional engagement and hope-based thinking of kindergarten teachers, identify if there is a significant difference in functional engagement and hope-based thinking in terms of specialization and years of service for kindergarten teachers, identify if there is a significant correlation between functional engagement and hope-based thinking of kindergarten teachers. The current research is determined by kindergarten teachers in the Second Rusafa Baghdad Education Directorate for the academic year (2022-2023). In order to achieve the objectives of the research, the researcher prepared a functional engagement scale, which consists of (45) items in three areas: Perceptual and functional engagement

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Publication Date
Sat Dec 31 2016
Journal Name
Al-kindy College Medical Journal
Diagnostic Value Of Post Exercise Systolic Blood Pressure Response In Ischemic Heart Disease
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 Background: The normal decline in systolic blood pressure during recovery phase of treadmill exercise dose not occur in most patients with coronary artery disease, in others recovery values systolic blood pressure may even exceed the peak exercise value. Objectives: Treadmill exercise test parameters indicating the presence and extent of coronary artery disease have traditionally included such as exercise duration, blood pressure and ST-segment response to exercise. The three –minute systolic blood pressure ratio is another important indicator of presence and significance of coronary artery disease is useful and obtainable measure that can be applied in all patients who are undergoing stress testing for evaluation of suspected is

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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 Oct 08 2026
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of serum levels of MMP-8 and hs CRP in chronic periodontitis patients in relation to atherosclerotic cardiovascular disease
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Background: Periodontitis and Atherosclerosis Cardiovascular disease are chronic inflammatory diseases which are highly prevalent. During the last two decades, there has been an increasing interest in the impact of oral health on atherosclerosis and subsequent cardiovascular disease.Aims of the study wereto evaluate the periodontal health status in study groups (Atherosclerotic cardiovascular disease patients with chronic periodontitis and patients having chronic periodontitis),to estimate the serum levels of Matrixmetalloproteinase-8(MMP-8) and high sensitive C-reactive protein(hs CRP) in study and control groups and compare between them. Also,test the correlation between the serum levels of MMP-8 and hs CRP with clinical periodontal par

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Publication Date
Fri Sep 18 2020
Journal Name
Infection And Immunity
Brucella abortus and Pregnancy in Mice: Impact of Chronic Infection on Fertility and the Role of Regulatory T Cells in Tissue Colonization
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Stealthy intracellular bacterial pathogens are known to establish persistent and sometimes lifelong infections. Some of these pathogens also have a tropism for the reproductive system, thereby increasing the risk of reproductive disease and infertility. To date, the pathogenic mechanism involved remains poorly understood. Here, we demonstrate thatBrucella abortus, a notorious reproductive pathogen, has the ability to infect the nonpregnant uterus, sustain infection, and induce inflammatory changes during both acute and chronic stages of infection.

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Publication Date
Mon Oct 17 2022
Journal Name
Journal Of The Faculty Of Medicine Baghdad
the incidence and the clinical significance of gray zone in the clinical phases of chronic hepatitis B infection
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Background: five clinical phases were described in patients with chronic (HBV) infection: HBeAg- positive HBV infection, HBeAg- positive chronic HB, HBeAg negative HBV infection, HBeAg-negative CHB and occult HBV infection. Aim: This study aimed to determine the incidence of the unclassified phase (gray zone) in chronic hepatitis B patients and its significant in the clinical practice. Patients and methods: The study was conducted retrospectively on 109 patients' who have HBsAg positive for more than 6 months. The data recorded include; HbeAg and anti-HBe Ab, ultrasound of the abdomen, HBV DNA load and alanine aminotransferase (ALT), accordingly; we classify the patients to known clinical phases. Patients who were unfit one of these phases

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Publication Date
Tue Dec 01 2026
Journal Name
Clinical Immunology Communications
Chemokine network dysregulation in EGFR-mutant NSCLC: impact on tumor immunity and drug resistance
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EGFR-mutant non–small cell lung cancer (NSCLC) initially responds well to EGFR tyrosine kinase inhibitors (EGFR-TKIs), yet resistance is nearly inevitable and responses to immune checkpoint inhibitors (ICIs) remain limited. In a retrospective cohort of 57 patients with advanced EGFR-mutant NSCLC treated with nivolumab or pembrolizumab, the objective response rate was 12.3%, although responses were concentrated in a small subgroup with concurrent high PD-L1 expression and dense intratumoral CD8⁺ immune-cell infiltration. Emerging evidence links these outcomes to chemokine-network dysregulation that alters immune trafficking and spatial organization. Oncogenic EGFR signaling shifts chemokine networks away from effector T-cell recruitment

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Publication Date
Sat Sep 03 2022
Journal Name
International Journal Of Health Sciences
Correlation between oxidative stress and clopidogrel drug in Iraqi patients with coronary artery disease
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Background: Coronary Artery Disease (CAD) is one of the largest causes of mortality worldwide. Clopidogrel, antiplatelet drug, has been widely used for management of CAD. The current study aimed to investigate the effect of clopidogrel on the oxidative stress in CAD patients. Methods: One hundred CAD patients, who were followed-up for 5 days after receiving clopidogrel, and 50 healthy volunteers were included in this study. Parameters include catalase (CAT), total antioxidant capacity (TAC), total oxidant capacity (TOC), total protein, albumin, and globulins were determined before and after treatment with clopidogrel. Results: CAT, TAC, and Tp were significantly decreased (P<0.0001) in CAD patients compared to healthy control and

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Publication Date
Tue Jun 15 2021
Journal Name
Al-academy
Social Graphic Design and its Reflection in Combating Drug Abuse: محمد عباس مظهر الزيدي
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Social graphic design is the design that realizes the role and responsibility of the designer in society, and the use of graphic design in bringing about social change, especially as it is a professional contribution that plays an important role in the behavioral development of societies, and through the above, the researcher found a logical justification for his research problem, which is summarized by the following question: (What is the concept of Social Graphic Design and its implications in the fight against drug abuse)
While the two objectives of the research were identified in defining the social graphic design and its effect on combating drug abuse, and the theoretical framework was divided into two topics, the first study dea

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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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