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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
Sun Jan 11 2026
Journal Name
Iraqi Journal Of Science
Effect of Diode Laser (805) nm on alpha-toxin production and antibiotic sensitivity of Staphylococcus aureus
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Publication Date
Mon Jan 23 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
Estimation of SLC25A3 Gene Expression in Chronic Myelogenous Leukemia Iraqi Patients
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Background: Chronic myelogenous leukemia is a malignant hematological disease of hematopoietic stem cells. It is difficult to adapt treatment to each patient's risk level because there are currently few clinical tests and no molecular diagnostics that may predict a patient's clock for the advancement of CML at the time of chronic phase diagnosis. Biomarkers that can differentiate people based on the outcome at diagnosis are needed for blast crisis prevention and response improvement. Objective: This study is an effort to exploit the SLC25A3 gene as a potential biomarker for CML. Methods: RT-qPCR was applied to assess the expression levels of the SLC25A3 gene. Results: In comparison to the mean ΔCt of the control group, which was found to b

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Publication Date
Thu Jan 30 2014
Journal Name
Al-kindy College Medical Journal
Microbiology of active chronic otitis media: in comparison with abroad studies
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Background: Chronic otitis media (COM) of mucosal or squamous type is a common problem in otolaryngology practice, the active form of COM is characterized by discharge of pus and is treated by antibiotics to start with, the appropriate antibiotic should be prescribed to avoid antibiotic abuse and guarantee good outcome. Objectives:The objective of this study is to identify the causative organisms of active chronic active otitis media both (mucosal, squamous) type and test their sensitivity to various anti- microbial agents &compare with abroad studies.Methods:A prospective study was done on eighty patients, different ages and sexes were taken and carful history and examination was done, examination under microscope was done with carf

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Publication Date
Wed Dec 30 2015
Journal Name
Al-kindy College Medical Journal
Evaluation Study of Patients Infected with Chronic Hepatitis C in Iraq
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Background: ;Hepatitis C virus (HCV) is a major cause of chronic liver disease. Approximately 85% of patients acutely infected with HCV progress to chronic liver disease with persistence of HCV-RNA for more than 6 months Among patients with chronic HCV infection , 15-20% progress to end-stage liver disease main transmission methods of the virus is by : blood and blood products ; sharing needles and acupuncture .Objective: To evaluate Iraqi patients infected with chronic HCV, including their treatment, and factors that affect their response to treatment .Methods :This study was performed at Gastroenterology and Hepatology hospital in Baghdad from January 2011 to March 2012.The study enrolled 90 patients with HCV Antibody positive (Ab +ve)

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Publication Date
Fri Jan 01 2021
Journal Name
Annals Of Parasitology
The role of intestinal protozoa in chronic obstructive pulmonary disease exacerbation
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chronic obstructive pulmonary disease (COPD) is a common respiratory disease with episodes of exacerbation. Variable factors including infectious pathogen can predispose for this exacerbation. The aim of this study is to evaluate the role of intestinal protozoa in COPD exacerbation. A total of 56 patients with COPD were included in this study. Patients were categorized into two groups based on the frequency of exacerbation during the last 6 months: those with ≤1 exacerbation (32 patients) and those with ≥2 exacerbations (24 patients). Stool specimens from each patient were collected two times (one week interval) examined for intestinal parasite. In univariate analysis, rural residence and parasitic infection were more common among patie

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Publication Date
Sun Mar 15 2020
Journal Name
Journal Of Baghdad College Of Dentistry
Influence of smoking on salivary interleukin-8 levels in chronic periodontitis
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Background: Smoking is the major environmental risk factor that has been associated with the pathogenesis and progression of periodontal diseases. Interleukin-8 (IL-8), has been associated with the immunopathology of periodontitis. Objectives: To determine the influence of smoking on salivary Interleukin-8 level from smokers and non-smokers with periodontitis and periodontally healthy control subjects.

Materials and Methods: Un-stimulated saliva samples were collected of 90 participants: 30 smokers and 30 non-smokers with chronic periodontitis, as well as 30 periodontally healthy control subjects. The clinical parameters such as the pocket depth, clinical attachment loss, plaque index, and gingiv

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Publication Date
Fri Jan 01 2021
Journal Name
Academy Of Strategic Management Journal
Prospects and Challenges for Iraqi SMES Sector Post-Isis
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Iraq faces significant economic challenges, owing in part to its reliance on oil revenue and the country's overburdened public sector. The supremacy of State-Owned Enterprises (SOEs), obstructive rules, a lack of access to finance, a shortage of skilled labor, and inadequate infrastructure all impede private sector growth. This research relied mainly on information from global development organizations, most markedly the World Bank, as well as policy documents, and it discovered a scarcity of pertinent educational writings. The following are the key findings of this research: Recent economic growth has not resulted in poverty reduction; the stretched history of war and insecurity in Iraq has hampered progress and development; the private se

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Publication Date
Mon Feb 03 2020
Journal Name
College Of Islamic Sciences
Rulings of magic  and its treatment in Islam
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Praise be to God, Lord of the worlds, and the best of prayers. He has completed the delivery of our master Muhammad, his family, and all his companions. O God, bring us out from the darkness of illusion, honor us with the light of understanding, open us with knowledge of knowledge, facilitate our morals with dreams, and make us who listen to the saying and follow their best.
And after ..

Since ancient times, magic was mentioned in many books in the history of the civilizations of ancient peoples, where the first emergence of human civilizations, the oldest of which is the Mesopotamian civilization, the Chinese civilization, and the Pharaonic civilization in Egypt, where concepts prevailed based on the charlatans and sorcery an

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Publication Date
Thu Sep 15 2022
Journal Name
Bionatura
Chronic Myeloid Leukemia: A retrospective study of clinical and pathological features
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Chronic myeloid leukemia (CML), is one of the myeloproliferative disorders with a characteristic cytogenetic abnormality resulting in the BCR-ABL fusion gene. Imatinib Mesylate is an effective agent for treating patients in all stages of CML. According to the annual Iraqi cancer registry 2019, the total number of chronic myeloproliferative disorders was 338. The percentage and incidence rates were 0.94% and 0.86%, respectively, with a higher incidence rate in males than females (1.12 in males and 0.60 in females). In this registry, no details about CML, so this study aimed to estimate the number of CML patients who attended the national center of hematology from 2005 until 2020 and investigate their epidemiological and clinic-pathol

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Publication Date
Wed Jan 30 2013
Journal Name
Al-kindy College Medical Journal
Chronic Kidny Disease and Risk of coronary Artery Disease,Aprospective study
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AbstractBackground:Reduced glomeular filtration rate isassociated with increasedmorbidity in patientswith coronary arterydisease.Objectives :To analyze the declining eGFR andmortality risks in a patients with Chronic KidneyDisease and have had Coronary Artery Diseaseincluding risk factors .Patientsand Methods:The study included (160)patientsbetween the ages of 16 and 87years.Glomerular filtration rate was estimated (eGFR)using the Modification of Diet in Renal Diseaseequationand was categorized in the ranges<60 mL· min−1 per 1.73 m2and≥ 60 ml/min/1.73 m2.Baseline risk factors were analyzed by category ofeGFR,.The studied patients in emergencydepartment, were investigatedusing Coxproportional hazard models adjusting for traditiona

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