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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
Wed Nov 20 2024
Journal Name
Journal Of Baghdad College Of Dentistry
Evaluation of fracture strength of endodontically treated teeth restored by milled zirconia post and core with different post and core systems (An in vitro comparative study)

Background: Restoration of root canal treated teeth with a permanent restoration affect in the success of endodontically treated teeth. This in vitro study was performed to evaluate and compare the fracture strength of endodontically treated teeth restored by using custom made zirconium posts and cores, prefabricated carbon fiber, glass fiber and zirconium ceramic posts. Materials and method: Forty intact human mandibular second premolars were collected for this study and were divided into five groups. Each group contains 8 specimens: Group1: Teeth restored with Carbon Fiber Posts; Group2: Teeth restored with Glass Fiber Posts; Group3: Teeth restored with Zirconium Ceramic prefabricated Posts; Group4: Teeth restored with Zirconium Posts

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Publication Date
Wed Dec 15 2021
Journal Name
Iraqi Journal Of Science
Study the Effect of some Medical Plants in Biofilm Formation and Antibiotic Sensitivity for Klebsiella Pneumoniae

Twenty clinical and fecal samples (ten clinical samples from patients attending to
Imam Ali Hospital and ten chicken faeces samples collected from local poultry farm
in Baghdad city) collected during December 2015, for isolated Klebsiella
pneumoniae. All K. pneumoniae isolates were extended-spectrum β- lactamase
producers and biofilm formation. The activities of two selected K. pneumoniae
isolates for their biofilm formation and susceptibility to antibiotics after treatment
with several plants extracts were investigated. The results of water and 60% ethanol
extracts for Matricaria chamomile flowers, Alhagi maurorum leafs, Syzygium
aromaticum buds (clove) and Arctium minus leafs were showed reduction of biofilm

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Publication Date
Wed Sep 01 2021
Journal Name
Baghdad Science Journal
Isolation, Screening and Antibiotic Sensitivity of Pseudomonas species from Kelana Jaya Lake Soil in Selangor Malaysia

Pathogenic microorganisms from hospitals, communities, and the environment remain great threats to human health. The increasing concern about antibiotic resistance has also necessitated the search for robust alternatives. Therefore, this study aims to isolate, screen and evaluate the antibiotic susceptibility of Pseudomonas aeruginosa isolated from a soil sample taken from northern, western and eastern parts of Kelana Jaya Lake against four antibiotics (gentamycin, tetracycline, ampicillin, and penicillin) on a Mueller-Hinton Agar media plate. Pseudomonas identification was done by using API 20 kit. Disc diffusion was employed as well as the oxidase test. From the positive oxidase result, the isolated bacteria were identified as Burkhold

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Publication Date
Sun Mar 01 2020
Journal Name
Periodicals Of Engineering And Natural Sciences
Employment of the genetic algorithm in some methods of estimating survival function with application

Intended for getting good estimates with more accurate results, we must choose the appropriate method of estimation. Most of the equations in classical methods are linear equations and finding analytical solutions to such equations is very difficult. Some estimators are inefficient because of problems in solving these equations. In this paper, we will estimate the survival function of censored data by using one of the most important artificial intelligence algorithms that is called the genetic algorithm to get optimal estimates for parameters Weibull distribution with two parameters. This leads to optimal estimates of the survival function. The genetic algorithm is employed in the method of moment, the least squares method and the weighted

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Publication Date
Sun Jun 20 2021
Journal Name
Baghdad Science Journal
Hypothyroidism and Leptin in Iraqi Patients with Chronic Kidney Disease

The present study aims at assessing the effects of chronic kidney disease (CKD) on thyroid hormone and leptin by evaluating the level of: leptin hormone along with thyroid hormone in CKD patients. The study has been conducted on  70 subjects, 50 patients with an age range between 20-50 years (25  males and 25 females) who were diagnosed to have CKD stage-5, and 20 normal controls whose ages ranged between 20-48 years (10  males and 10 females), who attended  the Nephrology and Transplant Center in Medical City of Baghdad- Iraq from April  2018  to July  2018. The study showed a highly significant (P<0.01) increase in TSH level in CKD patients in comparison with controls. While T3 and T4 levels observed highly significant decrea

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Publication Date
Tue Mar 30 2021
Journal Name
Baghdad Science Journal
Hypothyroidism and AMH in Iraqi Patients with Chronic Kidney Disease

This study was conducted to investigate thyroid function and Anti-Müllerian hormone (AMH) in (Chronic kidney disease) CKD patients by evaluating their levels in CKD patients, 50 patients were diagnosed to have CKD stage-5, their ages ranged between 20-50 years (25 males and 25 females) who attended the Nephrology and Transplant Center in Medical City of Baghdad- Iraq, they were recruited from April 2018 to July 2018 and were enrolled into the study. The control group consisted of 20 healthy individuals, their ages ranged between 20-48 years (10 males and 10 females). The study showed non-significant (p>0.05) increase in AMH level in CKD patients compared to the control group. On the other hand, TSH was recorded a highly significant (

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Publication Date
Sun Oct 03 2010
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Role of Pro-inflammatory and Immunoregulatory Cytokines in Pathogenesis of Chronic Gastritis

Background: Chronic gastritis (CG) is histopathological entity characterized by chronic inflammation of the stomach that mostly caused by Helicobacter pylori, development of
inflammation in gastric mucosa result in release of pro- and anti- inflammatory cytokines .This study aimed to shed light on the role of cytokines (IFN-γ, IL-8, IL-4, IL-10, and GM-CSF) in the
development and prognosis of CG among Iraqi patients.
Patients and methods: 100 Iraqi patients with CG (61 male and 39 female) with age range (10-79) year, were involved in this stady while attending Specialist Hospital of Disease of Liver and Gastrointestinal System at Baghdad Medical City from Nov. 2007 to Apr. 2008. Patients divided accordi

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Publication Date
Sat Jun 30 2012
Journal Name
Al-kindy College Medical Journal
Management of Chronic Osteomylitis

Background : Bone infections is one of the most challenging orthopaedic complications, with considerable morbidity. There is significant impact on the life of the patients; socially, financially, physically, and mentally and it could be a limb-threatening complication. Osteomyelitis is a bone infection usually caused by bacteria, including mycobacteria, but mainly Staphylococcus aureus which is the most commonly responsible bacteria . Aim of study: To evaluate our management policy of chronic osteomylitis (C.O.M).
Methods : 32 patients presented with different types &forms of chronic osteomyelitis in many sites of long & flat bones such as tibia , femur, ,humerus ,iliac bones and knee joint , which are not response to previous

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Publication Date
Thu Aug 06 2020
Journal Name
Cuestiones PolĂ­ticas
Political structure and the administration of political system in Iraq (post-ISIS)

The objective of the investigation was to analyze the structure and administration of the political system in Iraq (post-ISIS). After 2003, the Iraqi political system suffered the fundamental problem of its failure to achieve the political and social inclusion that characterizes democratic systems, to guarantee the establishment of a "state for all", while respecting differences. Political representation has moved from the system of sectarian ethnic components, under the title of consensual democracy, to the representation of leaders and the realization of their interests and the interests of their parties at the expense of the groups that claim to represent them, which complicates the problem. In this sense, the new political syste

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Publication Date
Fri May 01 2020
Journal Name
Civil Engineering Journal
Post-Fire Behavior of Post-Tensioned Segmental Concrete Beams under Monotonic Static Loading

This paper presents a study to investigate the behavior of post-tensioned segmental concrete beams that exposed to high-temperature. The experimental program included fabricating and testing twelve simply supported beams that divided into three groups depending on the number of precasting concrete segments. All specimens were prepared with an identical length of 3150 mm and differed in the number of the incorporated segments of the beam (9, 7, or 5 segments). To simulate the genuine fire disasters, nine out of twelve beams were exposed to a high-temperature flame for one hour. Based on the standard fire curve (ASTM – E119), the temperatures of 300◦C (572◦F), 500◦C (932◦F), and 700◦C (1292◦F) were adopted. Consequently,

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