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Epigenome-wide analysis reveals functional modulators of drug sensitivity and post-treatment survival in chronic lymphocytic leukaemia
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 13 2024
Journal Name
Iraqi Journal Of Science
Stability Analysis of A stage Structure Prey-Predator Model with Hollimg Type IV Functional Response

In this paper a stage structure prey-predator model with Hollimg type IV functional response is proposed and analyzed. The local stability analysis of the system is carried out. The occurrence of a simple Hopf bifurcation and local bifurcation are investigated. The global dynamics of the system is investigated with the help of the Lyapunov function. Finally, the analytical obtained results are supported with numerical simulation and the effects of parameters system are discussed. It is observed that, the system has either stable point or periodic dynamics.

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Publication Date
Sun Jan 01 2017
Journal Name
Journal Of Clinical And Diagnostic Research
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Publication Date
Wed Oct 09 2019
Journal Name
Engineering, Technology &amp; Applied Science Research
Numerical Analysis of Segmental Post Tensioned Concrete Beams Exposed to High Fire Temperature

The main objective of this study is to characterize the main factors which may affect the behavior of segmental prestressed concrete beams comprised of multi segments. The 3-D finite element program ABAQUS was utilized. The experimental work was conducted on twelve simply supported segmental prestressed concrete beams divided into three groups depending on the precast segments number. They all had an identical total length of 3150mm, but each had different segment numbers (9, 7, and 5 segments), in other words, different segment lengths. To simulate the genuine fire disasters, nine beams were exposed to high-temperature flame for one hour, the selected temperatures were 300°C (572°F), 500°C (932°F) and 700°C (1292°F) as recomm

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Publication Date
Sun Jan 04 2009
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Evaluation of T- Helper (Th-1) Cytokines during the Treatment Responses of chronic Hepatitis C Virus

Background:It is widely assumed that cellular immune response and cytokine (especially proinflammatory cytokines) production play an important role in the course and treatment effectiveness of chronic hepatitis C infection. <br />Aim of the study: evaluate the level of Th-1 cytokines during treatment of chronic HCV infection and their dynamic changes in response to treatment.<br />Patients and methods: The study was performed on sixty patients with chronic HCV infection, the patients were recruited from medical city gastroenterology and hepatology teaching hospital for the period from February 2007 till February 2008 and 50 healthy control group. Diagnosis was made using third generation ELISA-based screening test, RIBA-based

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Publication Date
Wed Jun 15 2022
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of salivary immunoglobulin A, interleu-kin-6 and C-reactive protein in chronic kidney dis-ease patients on hemodialysis and on conservative treatment

Background: Chronic kidney disease is a gradual loss of kidney function with diabetes and hypertension as the leading cause. Chronic kidney disease is one of these systemic diseases that can affect salivary contents. Aims: This study aimed to assess salivary immunoglobulin A, interleukin-6 and C- reactive protein in chronic kidney disease patients on hemodialysis and those on conservative treatment in comparison with control subjects. Materials and methods: Ninety subjects were included in this study divided into three groups: 30 patients with chronic kidney disease on hemodialysis for at least 6 months ago; 30 patients with chronic kidney disease on conservative treatment and 30 healthy control subjects. Secretory immunoglobulin A, inte

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Publication Date
Tue Feb 27 2024
Journal Name
Pharmacia
Association of the rs1801133 and rs1801131 polymorphisms in the MTHFR gene and the adverse drug reaction of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients

Background: Methotrexate is one of the mainstays for treating rheumatoid arthritis (RA) with a wide range of adverse drug reactions, however, it’s the relationship between adverse drug reactions and genetic polymorphism remains to be highlighted, and there is a lack of studies concerning Arabic Iraqi population regarding this aspect.

Objective: Evaluate the association between genetic mutations in the MTHFR gene in SNPs (rs1801133G&gt;A and rs1801131T&gt;G) on the adverse drug reaction for RA Iraqi patients.

Methods: An observational study, that involved 95 Iraqi RA patients with established RA. Patien

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Publication Date
Tue Nov 19 2024
Journal Name
Journal Of Baghdad College Of Dentistry
The association of crevicular albumin level with the severity of periodontal destruction in chronic periodontitis patients after initial periodontal treatment

Background: Gingival crevice fluid (GCF) is a mixture of substances derived from serum, leukocytes, and structural cells of periodontium and oral bacteria. These substances possess a great potential for serving as indicators of periodontal disease and healing after therapy the main purpose of this study was to find if there is a difference in albumin concentration between healthy and diseased periodontal tissues and to compare between diseased group according to pocket depth Materials and methods: total sample composed of 60 pockets found in 35 patients all of them had no history of any systemic disease, The samples were divided in to three main group that include two diseased groups divided according to the depth of the periodontal pocket

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Publication Date
Tue Dec 01 2020
Journal Name
Gulf Economist
The Bayesian Estimation in Competing Risks Analysis for Discrete Survival Data under Dynamic Methodology with Application to Dialysis Patients in Basra/ Iraq

Survival analysis is one of the types of data analysis that describes the time period until the occurrence of an event of interest such as death or other events of importance in determining what will happen to the phenomenon studied. There may be more than one endpoint for the event, in which case it is called Competing risks. The purpose of this research is to apply the dynamic approach in the analysis of discrete survival time in order to estimate the effect of covariates over time, as well as modeling the nonlinear relationship between the covariates and the discrete hazard function through the use of the multinomial logistic model and the multivariate Cox model. For the purpose of conducting the estimation process for both the discrete

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Publication Date
Fri Jan 13 2023
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Impact of sociodemographic characteristics and drug-related side effects on quality of life of patients with hepatocellular carcinoma receiving sorafenib treatment in Iraqi hospitals

Background: Sorafenib is an oral multikinase inhibitor which has been given approval by the United States Food and Drug Administration for the treatment of patients diagnosed with hepatocellular carcinoma and advanced renal cell carcinoma . However, measuring quality of life and patient-reported symptoms may provide further information for evaluating and comparing treatment efficacy and toxicity profiles during cancer treatment. Despite the critical importance of patients' quality of life while receiving anticancer treatment, neither Iraqi patients undergoing anti-cancer medications in general nor those receiving Sorafenib in particular had any published data evaluating this important parameter.

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Publication Date
Fri Jul 01 2022
Journal Name
Structures
Reliability analysis of deteriorated post-tensioned concrete bridges: The case study of Ynys-y-Gwas bridge in UK

Concrete structures are exposed to aggressive environmental conditions that lead to corrosion of the embedded reinforcement and pre-stressing steel. Consequently, the safety of concrete structures may be compromised, and this requires a significant budgets to repair and maintain critical infrastructure. Prediction of structural safety can lead to significant reductions in maintenance costs by maximizing the impact of investments. The aim of this paper is to establish a framework to assess the reliability of existing post-tensioned concrete bridges. A time-dependent reliability analysis of an existing post-tensioned involving the assessment of Ynys-y-Gwas bridge has been presented in this study. The main cause of failure of this bridge was c

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