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Arafat, Y.

Publications and source records attributed to Arafat, Y..

4 recordsLinked to original sources

Harnessing Immunoinformatic for HIV-2: Multi-Epitope Vaccine Design Targeting the env Protein (CAA28914.1)

A[Formula][s][t]rac[t]O_ST_ABSBackgroundC_ST_ABSHIV-2 is a major threat to human health because of its rising global incidence. As a result, the development of effective immunostimulatory molecules for vaccine design against HIV-2 has garnered increasing interest. ObjectiveThe main objective was to make a multi Targeting epitoptpic vaccine for HIV-2 envelope protein using immunoinformatic approaches. MethodsSequence were retrieved from NCBI. B & T-cell epitopes were predicted with assessments of antigenicity, allergenicity, and cytokine-inducing potential. Physicochemical properties, docking studies, and codon optimization for expression was also performed using different software tools. FindingsThe designed vaccine construct (477 amino acids, molecular weight of 54 kDa) showed a strong antigenicity with VaxiJen score of 0.7146 which was non-allergenic and non-toxic with favorable physicochemical parameters (Mw: [~]53 kDa; pI: 9.89; stable and soluble). The construct demonstrated broad population coverage for MHC-I (West Africa: 69.51%, Pakistan: 78%, Global: 82%) and MHC-II (Global: 99%). Out of 16 peptides analyzed, 7 were predicted as IL-10 inducers 2 as a strong IL-4 inducer, and 2 were IFN-{gamma} inducing epitopes. Structural validation confirmed high-quality folding (96% residues in favored regions; ERRAT score: 84.35). Docking results revealed a strong binding affinity to TLR2 (PDB ID: 2AOZ; energy: -1481.1 kcal/mol). MD simulation confirmed structural stability (RMSD [~]1.37 nm; Rg [~]3.65 nm). Immune simulation predicted robust humoral and cellular responses with sustained antibody production and cytokine activation. Codon optimization is given to a Codon Adaptation Index (CAI) of 0.628 with a guanine (G) and cytosine (C) nucleotides content of 65.48%, suitable for E. coli expression. ConclusionThis vaccine construct is immunogenic, stable, and able to elicit both antibody-mediated immunity and cell-mediated immunity responses. Furthermore, In-vitro or In-Vivo Validations are recommended to verify its effectiveness O_FIG O_LINKSMALLFIG WIDTH=178 HEIGHT=200 SRC="FIGDIR/small/658249v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@c3660corg.highwire.dtl.DTLVardef@60cc61org.highwire.dtl.DTLVardef@10a1e87org.highwire.dtl.DTLVardef@15a5aa1_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

RAS-PI3K Pathway in CAFs Shapes Physicochemical Properties of Tumor ECM and restrains Tumor progression

Cancer-associated fibroblasts display extensive functional plasticity, yet the signaling mechanisms that stabilize distinct CAF states remain poorly understood. Here, we identify stromal RAS-PI3K signaling as a key regulator of myofibroblastic CAF identity and matrix competence in lung cancer. Genetic disruption of the RAS-PI3K interaction in fibroblasts preserved upstream responsiveness to activating cues but impaired cytoskeletal remodeling, contractile execution and acquisition of a matrix-remodeling CAF program. As a result, RAS-PI3K-deficient CAFs generated extracellular matrices with defective collagen and fibronectin organization, reduced stiffness, altered microstructural properties and broad compositional remodeling of the matrisome, including changes in ECM glycoproteins and glycosylation-associated enzymes. These altered matrices failed to efficiently provide directional, adhesive and proliferative cues to tumor cells, attenuated EMT-associated programs and increased sensitivity to cisplatin plus pemetrexed. In vivo, fibroblast-specific RAS-PI3K disruption reduced tumor burden, decreased tumor cell proliferation, prolonged survival and improved chemotherapy response. Loss of RAS-PI3K signaling did not simply suppress CAF activation, but redirected CAFs toward a STAT3/NF-{kappa}B-linked immunomodulatory state associated with IL6, CXCL12 and PDGFR induction. Functionally, this altered stromal state promoted iNOS-associated macrophage features and was accompanied in vivo by reduced macrophage accumulation and increased CD8 T cell infiltration. These findings establish RAS-PI3K signaling as a stromal state-control mechanism that couples myofibroblastic matrix competence to tumor-supportive microenvironmental function while restraining alternative immunomodulatory CAF programs.

cancer biology↗

Fibre tracing in biomedical images: An objective comparison between seven algorithms

Obtaining the traces and the characteristics of elongated structures is an important task in computer vision pipelines. In biomedical applications, the analysis of traces of vasculature, nerves or fibres of the extracellular matrix can help characterise processes like angiogenesis or the effect of a certain treatment. This paper presents an objective comparison of six existing methodologies (Edge detection, CT Fire, Scale Space, Twombli, U-Net and Graph Based) and one new approach called Trace Ridges to trace biomedical images with fibre-like structures. Trace Ridges is a fully automatic and fast algorithm that combines a series of image-processing algorithms including filtering, watershed transform and edge detection to obtain an accurate delineation of the fibre-like structures in a rapid time. To compare the algorithms, four biomedical data sets with very different characteristics were selected. Ground truth was obtained by manual delineation of the fibre-like structures. Three pre-processing filtering options were used as a first step: no filtering, Gaussian low-pass and DnCnn, a deep-learning filtering. Three distance error metrics (total, average and maximum distance from the obtained traces to the ground truth) and processing time were calculated. It was observed that no single algorithm outperformed the others in all metrics. For the total distance error, which was considered the most significative, Trace Ridges ranked first, followed by Graph Based, U-Net, Twombli, Scale Space, CT Fire and Edge Detection. In terms of speed, Trace Ridges ranked second only slightly slower than Edge Detection. Code is freely available at github.com/youssefarafat/Trace Ridges.

cancer biology↗

Low birth weight in Bangladesh and associated maternal and socioeconomic factors: results from a recent nationally-representative survey

ObjectivesLittle is known about the relative contributions of maternal and socioeconomic factors on low birth weight in Bangladesh and whether they differ by sex. We examined the prevalence and associated maternal and socioeconomic factors of low birth weight separately among boys and girls. Design and settingsThis is a cross-sectional study based on the Bangladesh Demographic and Health Survey 2014. ParticipantsA total of 4728 children with information on birth size were included in this study. Outcome measureLow birth weight was defined according to mothers perception of birth size of their children. Logistic regression analysis was used to estimate the association between maternal and socioeconomic factors with low birth weight. ResultsThe overall prevalence of low birth weight was 17.8% among boys and 22.4% among girls. Low birth weight was associated with maternal factors like maternal age of <20 years at birth (adjusted OR vs. 20-29 years: 1.40, 95% CI 1.09-1.78), and maternal undernutrition (adjusted OR 1.33, 95% CI 1.05-1.69) among boys while only the association with maternal undernutrition was significant among girls. The association for no antenatal care visit was explained by socioeconomic factors. Lower level of mothers education and poorest wealth index were found to be associated with low birth weight in both sexes. ConclusionOur study identifies that maternal factors are associated with increased risk of having low birth weight babies, which cannot be explained by socioeconomic factors, and vice versa. Community-based interventions to reduce low birth weight in Bangladesh should focus on these factors. Strengths and limitations of this studyO_LITo the best of our knowledge our study is the first study in Bangladesh that has looked at the factors for low birth weight separately among boys and girls. C_LIO_LIWe used multiple logistic regression to examine the associations of maternal and socioeconomic factors with low birth weight in a large and nationally-representative sample. C_LIO_LIThis study is limited because we used mothers perception of childs size at birth to define low birth weight. C_LIO_LIWe did not have information about gestational age and thereby could not take prematurity into account in our study. C_LI

epidemiology↗