Convolutional neural network in the classification of COVID-19

Covid-19 spread out rapidly around the world, forcing many countries to full shutdown, and economical and social consequences. Resulting in rapid need for new and effective methods to deal with this crisis and control it. X-ray lung images is considered one of the most effective and safe method for diagnosing Covid-19, since it could provide solid proof of the existing of the disease, and it has limited effect on the health of the human comparing with other radiography methods. In this proposed work, CNN model is designed and trained to classify Covid-19 X-ray images, by using the COVID-19 Radiography Database, which is published and available online. This database is collected by researchers and experts from various universities around the world. The database contains total of 15153 lung x-ray images, divided into three classes. The classification classes are: Normal, Covid-19, and Viral Pneumonia. The model is trained and tested on publicly available dataset. The dataset is divided into three parts: training, validation, and testing datasets. The model is evaluated based on the three of these datasets. Totally, the evaluation metrics include Accuracy, F1-score, Area Under Curve (AUC), Precision, and Recall, with values of greater than 98% for all of the evaluation metrics. Comparing the results with state of arts publications, which used the same dataset, the proposed method outperformed the state of arts publications depending on the evaluation metrics. The number of the trainable parameters in the proposed CNN model is about 25.4 millions

Tumor suppressor function of Bruton tyrosine kinase is independent of its catalytic activity

During B-cell development in the mouse, Bruton tyrosine kinase (Btk) and the adaptor protein SLP-65 (Src homology 2 [SH2] domain-containing leukocyte protein of 65 kDa) limit the expansion and promote the differentiation of pre-B cells. Btk is thought to mainly function by phosphorylating phospholipase Cgamma2, which is brought into close proximity of Btk by SLP-65. However, this model was recently challenged by the identification of a role for Btk as a tumor suppressor in the absence of SLP-65 and by the finding that Btk function is partially independent of its kinase activity. To investigate if enzymatic activity is critical for the tumor suppressor function of Btk, we crossed transgenic mice expressing the kinase-inactive K430R-Btk mutant onto a Btk/SLP-65 double-deficient background. We found that K430R-Btk expression rescued the severe developmental arrest at the pre-B-cell stage in Btk/SLP-65 double-deficient mice. Moreover, K430R-Btk co

Synthesis and Characterization of Spinel Ferrite Co0.8Fe2.2O4 Nanoparticle

Cobalt ferrite Co0.8Fe2.2O4 nanoparticles were prepared using the sol-gel auto combustion process. The effects of calcination temperature on structural, magnetic, and electrical properties were studied. The cubic spinel phase fashioning of ferrite structure was confirmed using Fourier Transform-Infrared Spectroscopy (FT-IR) and X-ray Diffraction Patterns (XRD). The size of the formed crystallite of ferrite samples is ranged from 24.530 to 49.067 nm and it is found to be dependent on calcination. According to the images, which were taken by a Field Emission-Scanning Electron Microscope (FE-SEM), the particle size increases with raising the calcination temperature. Energy Dispersive Spectrum (EDS) was used to confirm the presence of Co, Fe, and O in all samples. A Vibrating Sample Magnetometer (VSM) was used to study the magnetic properties such as coercivity, saturation magnetization, and remanence field for the as-burnt and calcined samples. All samples exhibited ferrimagnetic behavior. As the calcination temperature rises, saturation magnetization (M_s), remanent magnetization (M_r), and squareness ratio (M_r/ M_s) increased. This behavior is related to the spin canting and disturbance in the surface spin. At room temperature, the dielectric loss factor (ε''), dielectric loss angle (tanδ), dielectric constant (ε'), and the conductivity σ_ac of all samples were examined as a function of frequency using the LCR meter. The changes in dielectric properties have been characterized at frequencies ranged from 50Hz to 2MHz based on Koop's theory, Maxwell-Wagner polarization, and electron hopping. As frequency rose, all-dielectric properties exhibited natural behavior

BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition.

Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with leukaemia driven by BCR-ABL1 (ref. 1) and other oncogenic tyrosine kinases. Recent efforts have focused on developing more potent TKIs that also inhibit mutant tyrosine kinases. However, even effective TKIs typically fail to eradicate leukaemia-initiating cells (LICs), which often cause recurrence of leukaemia after initially successful treatment. Here we report the discovery of a novel mechanism of drug resistance, which is based on protective feedback signalling of leukaemia cells in response to treatment with TKI. We identify BCL6 as a central component of this drug-resistance pathway and demonstrate that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukaemia-initiating subclones

Molecular Detection and Genotyping of Human Papilloma Virus Infections in Iraqi Patients with Esophageal Carcinoma.

Background: Molecular DNA hybridization has confirmed more than 120 different human papilloma virus (HPV) genotypes. A small group of them have high- risk oncogenic potential. Many studies have described an association of such high risk-HPV genotypes with a variety of esophageal benign tumors as well as malignant squamous cell carcinomas. Patients and Methods: A total number of 90 tissue specimens were collected from 50 patients with esophageal squamous cell (SCC), adenocarcinoma (AC) and carcinoma in situ (CIS); 20 patients with squamous acanthosis (SA); and 20 individuals with apparently-healthy esophageal tissues (AHET). The molecular detection methods for HPV detection and genotyping were performed by in situ hybridization using cocktailed- and specific high- risk HPV DNA probes, respectively. Results: The overall percentage of HPV in the total group of esophageal carcinoma was 20%.The percentage of HPV DNA in the subgroup of SCC and AC was 26.7% and 13.3%, respectively,. However, neither HPV DNA was detected in CIS subgroup nor in both control groups (SA and AHET).The overall genotyping results showed that HPV 18 constituted the majority of the detected high-risk oncogenic HPV genotypes, followed by HPV 16 then HPV 31/33. Conclusions: Despite the low prevalence of HPV infection and rarity of invasive esophageal carcinoma in the general Iraqi population, the detection of high percentage of such high oncogenic risk- HPV genotypes in these carcinomas indicating for a relevant importance in esophageal carcinogenesis

Immunoglobulin expression in the endoplasmic reticulum shapes the metabolic fitness of B lymphocytes

The major function of B lymphocytes is to sense antigens and to produce protective antibodies after activation. This function requires the expression of a B-cell antigen receptor (BCR), and evolutionary conserved mechanisms seem to exist that ensure that B cells without a BCR do not develop nor survive in the periphery. Here, we show that the loss of BCR expression on Burkitt lymphoma cells leads to decreased mitochondrial function and impaired metabolic flexibility. Strikingly, this phenotype does not result from the absence of a classical Syk-dependent BCR signal but rather from compromised ER expansion. We show that the reexpression of immunoglobulins (Ig) in the absence of the BCR signaling subunits Igα and Igβ rescues the observed metabolic defects. We demonstrate that immunoglobulin expression is needed to maintain ER homeostasis not only in lymphoma cells but also in resting B cells. Our study provides evidence that the expression of BCR components, which is sensed in the ER and shapes mitochondrial function, represents a novel mechanism of metabolic control in B cells

IGLV3-21∗01 is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling

© 2020 National Academy of Sciences. All rights reserved. The prognosis of chronic lymphocytic leukemia (CLL) depends on different markers, including cytogenetic aberrations, oncogenic mutations, and mutational status of the immunoglobulin (Ig) heavy-chain variable (IGHV) gene. The number of IGHV mutations distinguishes mutated (M) CLL with a markedly superior prognosis from unmutated (UM) CLL cases. In addition, B cell antigen receptor (BCR) stereotypes as defined by IGHV usage and complementaritydetermining regions (CDRs) classify ∼30% of CLL cases into prognostically important subsets. Subset 2 expresses a BCR with the combination of IGHV3-21-derived heavy chains (HCs) with IGLV3- 21-derived light chains (LCs), and is associated with an unfavorable prognosis. Importantly, the subset 2 LC carries a single-point mutation, termed R110, at the junction between the variable and constant LC regions. By analyzing 4 independent clinical cohorts through BCR sequencing and by immunophenotyping with antibodies specifically recognizing wild-type IGLV3-21 and R110-mutated IGLV3-21 (IGLV3-21R110), we show that IGLV3-21R110-expressing CLL represents a distinct subset with poor prognosis independent of IGHV mutations. Compared with other alleles, only IGLV3-21∗01 facilitates effective homotypic BCR-BCR interaction that results in autonomous, oncogenic BCR signaling after acquiring R110 as a single-point mutation. Presumably, this mutation acts as a standalone driver that transforms IGLV3-21∗01-expressing B cells to develop CLL. Thus, we propose to expand the conventional definition of CLL subset 2 to subset 2L by including all IGLV3-21R110-expressing CLL cases regardless of IGHV mutational status. Moreover, the generation ofmonoclonal antibodies recognizing IGLV3-21 or mutated IGLV3-21R110 facilitates the recognition of B cells carrying this mutation in CLL patients or healthy donors

B cell antigen receptor expression and phosphatidylinositol 3-kinase signaling regulate genesis and maintenance of mouse chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a frequent lymphoproliferative disorder of B cells. Although inhibitors targeting signal proteins involved in B cell antigen receptor (BCR) signaling constitute an important part of the current therapeutic protocols for CLL patients, the exact role of BCR signaling, as compared to genetic aberration, in the development and progression of CLL is controversial. To investigate whether BCR expression per se is pivotal for the development and maintenance of CLL B cells, we used the TCL1 mouse model. By ablating the BCR in CLL cells from TCL1 transgenic mice, we show that CLL cells cannot survive without BCR signaling and are lost within eight weeks in diseased mice. Furthermore, we tested whether mutations augmenting B cell signaling influence the course of CLL development and its severity. The Phosphatidylinositol-3-kinase (PI3K) signaling pathway is an integral part of the BCR signaling machinery and its activity is indispensable for B cell survival. It is negatively regulated by the lipid phosphatase PTEN, whose loss mimics PI3K pathway activation. Herein, we show that PTEN has a key regulatory function in the development of CLL, as deletion of the Pten gene resulted in greatly accelerated onset of the disease. By contrast, deletion of the gene TP53, which encodes the tumor suppressor p53 and is highly mutated in CLL, did not accelerate disease development, confirming that development of CLL was specifically triggered by augmented PI3K activity through loss of PTEN and suggesting that CLL driver consequences most likely affect BCR signaling. Moreover, we could show that in human CLL patient samples, 64% and 81% of CLL patients with a mutated and unmutated IgH VH, respectively, show downregulated PTEN protein expression in CLL B cells if compared to healthy donor B cells. Importantly, we found that B cells derived from CLL patients had higher expression levels of the miRNA-21 and miRNA-29, which suppresses PTEN translation, compared to healthy donors. The high levels of miRNA-29 might be induced by increased PAX5 expression of the B-CLL cells. We hypothesize that downregulation of PTEN by increased expression levels of miR-21, PAX5 and miR-29 could be a novel mechanism of CLL tumorigenesis that is not established yet. Together, our study demonstrates the pivotal role for BCR signaling in CLL development and deepens our understanding of the molecular mechanisms underlying the genesis of CLL and for the development of new treatment strategies

An optimized derivative of an endogenous CXCR4 antagonist prevents atopic dermatitis and airway inflammation

Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes such as cancer and inflammatory diseases. A natural fragment of serum albumin, named EPI-X4, has previously been identified as endogenous peptide antagonist and inverse agonist of CXCR4 and is a promising compound for the development of improved analogues for the therapy of CXCR4-associated diseases. To generate optimized EPI-X4 derivatives we here performed molecular docking analysis to identify key interaction motifs of EPI-X4/CXCR4. Subsequent rational drug design allowed to increase the anti-CXCR4 activity of EPI-X4. The EPI-X4 derivative JM#21 bound CXCR4 and suppressed CXCR4-tropic HIV-1 infection more efficiently than the clinically approved small molecule CXCR4 antagonist AMD3100. EPI-X4 JM#21 did not exert toxic effects in zebrafish embryos and suppressed allergen-induced infiltration of eosinophils and other immune cells into the airways of animals in an asthma mouse model. Moreover, topical administration of the optimized EPI-X4 derivative efficiently prevented inflammation of the skin in a mouse model of atopic dermatitis. Thus, rationally designed EPI-X4 JM#21 is a novel potent antagonist of CXCR4 and the first CXCR4 inhibitor with therapeutic efficacy in atopic dermatitis. Further clinical development of this new class of CXCR4 antagonists for the therapy of atopic dermatitis, asthma and other CXCR4-associated diseases is highly warranted