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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 Mar 15 2018
Journal Name
Journal Of Baghdad College Of Dentistry
Assessment of Salivary Total Antioxidants Capacity Levels of Patients with Chronic Periodontitis in Comparison to Healthy Control
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Background: Chronic periodontitis (CP) is greatly prevalent condition of inflammatory behavior. Salivary biomarker total antioxidants capacity (T-AOC) status, may be related to both periodontal condition and oral hygiene. Aims of the study: To assess the level of salivary T-AOC of patients with chronic periodontitis in comparison to healthy control and to correlate between the level of this marker with the clinical periodontal parameters (plaque index (PLI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL)). Materials and Methods: Ninety subjects of males and females with an age ranged between (35-55) years were participated in this study. Participants were divided into two grou

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Publication Date
Tue Oct 02 2018
Journal Name
Iraqi Journal Of Physics
Enhancement the sensitivity of humidity sensor based on an agarose infiltration reflection-type photonic crystal fiber interferometer
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Photonic Crystal Fiber Interferometers (PCFIs) are widely used for sensing applications. This work presents the fabrication and study the characterization of a relative humidity sensor based on a polymer-infiltrated photonic crystal fiber that operates in a Mach- Zehnder Interferometer (MZI) reflection mode. The fabrication of the sensor only involves splicing and cleaving Photonic Crystal Fiber (PCF) with Single Mode Fiber (SMF). A stub of (LMA-10) PCF spliced to SMF (Corning-28). In the splice regions. The PCFI sensor operation based on the adsorption and desorption of water vapour at the silica-air interface within the PCF. The sensor shows a high sensitivity to RH variations from (27% RH - 95% RH), with a change in its reflected powe

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Publication Date
Thu Nov 02 2017
Journal Name
Iraqi Journal Of Laser
Enhancement the Sensitivity of Humidity Sensor Based on an Agarose Coating Transmission-Type Photonic Crystal Fiber Interferometer
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Photonic Crystal Fiber Interferometers (PCFIs) are widely used for sensing applications. This work presents the fabrication and the characterization of a relative humidity sensor based on a polymer-coated photonic crystal fiber that operates in a Mach- Zehnder Interferometer (MZI) transmission mode. The fabrication of the sensor involved splicing a short (1 cm) length of Photonic Crystal Fiber (PCF) between two single-mode fibers (SMF). It was then coated with a layer of agarose solution. Experimental results showed that a high humidity sensitivity of 29.37 pm/%RH was achieved within a measurement range of 27–95%RH. The sensor also showed good repeatability, small size, measurement accuracy and wide humidity range. The RH sensitivity o

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Publication Date
Fri Sep 27 2019
Journal Name
Journal Of Baghdad College Of Dentistry
The Impact of Chronic Periodontitis on Mother-Infant Bonding Status in Relation to Salivary Tumor Necrosis Factor Alpha and Interleukin-6
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Background: Chronic periodontitis is a bacterial infection that result in bone destruction associated with the increasing level of salivary tumor necrosis alpha and interleukin6 that affect Mother-infant bonding status. The aim of the present study was to assess the relationship between the Mother-infant bonding status in mothers with chronic periodontitis in relation to Salivary Tumor necrosis factor alpha and Salivary Interleukin6. Materials and Methods: The selected sample consisted of mothers with chronic periodontitis compared with mothers with healthy periodontium in postpartum period, their age ranged between 30-40 years. Both groups were subjected to postpartum Bonding Questionnaire (PBQ). Periodontal health status was assessed f

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Publication Date
Tue Dec 20 2022
Journal Name
Iraqi Journal Of Biotechnology
Synergistic Effect of Conocarpus erectus Extract and some Antibiotics against Multi-Drug Resistant Pseudomonas aeruginosa
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Over the past few decades, the health benefits are under threat as many commonly used antibiotics have become less and less effective against certain illnesses not only because many of them produce toxic reactions but also due to the emergence of drug-resistant bacteria. The clinical use of a combination of antibiotic therapy for Pseudomonas aeruginosa infections is probably more effective than monotherapy. The present study aims to estimate the antibacterial and antibiofilm activity of Conocarpus erectus leaves extracts against multi-drug resistant P. aeruginosa isolated from different hospitals in Baghdad city. One hundred fifty different clinical specimens were collected from patients from September 2021 to January 2022. All samples were

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Publication Date
Tue Jun 01 2021
Journal Name
Baghdad Science Journal
Mesoporous Silica Nanoparticles as a System for Ciprofloxacin Drug Delivery; Kinetic of Adsorption and Releasing
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Mesoporous silica (MPS) nanoparticle was prepared as carriers for drug delivery systems by sol–gel method from sodium silicate as inexpensive precursor of silica and Cocamidopropyl betaine (CABP) as template. The silica particles were characterized by SEM, TEM, AFM, XRD, and N2adsorption–desorption isotherms. The results show that the MPS particle in the nanorange (40-80 nm ) with average diameter equal to 62.15 nm has  rods particle morphology, specific surface area is 1096.122 m2/g, pore volume 0.900 cm3/g, with average pore diameter 2.902 nm, which can serve as efficient carriers for drugs. The adsorption kinetic of Ciprofloxacin (CIP) drug was studied and the data were analyzed and found to match well with

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Publication Date
Sun Dec 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Design and Evaluation of Solid Lipid Nanoparticle Eye Drops Containing VRN for Ocular Drug Delivery
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As a well-known oral and intravenous antifungal, voriconazole (VRN) has an extensive history of usage in the medical field. Solid lipid nanoparticles (SLNs) have been produced to treat ocular fungal keratitis in the eye. A 32Box-behnken design was used to produce a variety of new formulas for hot-melt extrusion. The SLNs were evaluated by entrapment efficiency (EE percent), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). A series of in-vitro and in-vivo studies were carried out on the new formula. The produced vesicles’ EE, PS, PDI, and ZP values were all good. SLNs eye drops were numerically adjusted to include carbopol, a stabilizer, lipids, and a surfactant, among other substances. ZP of -36.5 ± 0.20 m

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Publication Date
Thu May 28 2020
Journal Name
Journal Of Generic Medicines: The Business Journal For The Generic Medicines Sector
Determinants of national drug products acceptance across patients, pharmacists, and manufacturers: A mixed method study
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Introduction

The national pharmaceutical industry is pivotal for both the health sector and the national economy. This study aims to identify determinants of national drug products acceptance. The objectives of this study were to quantitatively measure the level of patient and community pharmacist acceptance of national drug products available in community pharmacies and to qualitatively explore the barriers facing national pharmaceutical companies and investigate the suggested solutions.

Methods

This cross-sectional study used an explanatory mixed method design. It was conducted in Baghdad, Iraq from July through October 2018. The stud

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Publication Date
Sun Jun 21 2020
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Nanotechnology-Based Topical Drug Delivery Systems for Management of Dandruff and Seborrheic Dermatitis: An overview
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Dandruff and seborrheic dermatitis (SD) are common skin disorders affecting the scalp and extending to other body sites in the case of SD. They are associated with pruritus and scaling, causing an esthetical disturbance in the population affected.   Treatment of such conditions involves using a variety of drugs for long terms, thus optimizing drug formulation is essential to improve therapeutic efficacy and patient compliance. Conventional topical formulations like shampoos and creams have been widely used but their use is associated with disadvantages. To overcome such effects, novel topical nanotechnology-based formulations are currently under investigation. In the following article, we highlight recently published formulatio

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Publication Date
Tue Jun 15 2021
Journal Name
Al-academy
Forms of post-modernism in performance of Iraqi theatre "dream of Baghdad exam": عمار عبد سلمان محمد
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  The effects of postmodernism on theatrical form was managed by the director (Anas Abdul Samad) to be employed in the Iraqi play (Dream in Baghdad) and the researcher sought to study this problem and divided it into four chapters dealt with in the first chapter the problem of research and its need, the importance of research, As well as the definition of terminology, either Chapter II theoretical framework divided by the researcher to the first two is the postmodernism in the theater is the most prominent reference references and the second most important postmodern applications in the world play and then the researcher concluded the second chapter of the most important indicators. In the third chapter, the researcher identified th

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