[Abstract unavailable

Computer-aided diagnosis for the reliable and fast detection of coronavirus disease (COVID-19) has become a necessity to prevent the spread of the virus during the pandemic to ease the burden on the healthcare system. Chest X-ray (CXR) imaging has several advantages over other imaging and detection techniques. Numerous works have been reported on COVID-19 detection from a smaller set of original X-ray images. However, the effect of image enhancement and lung segmentation of a large dataset in COVID-19 detection was not reported in the literature. We have compiled a large X-ray dataset (COVQU) consisting of 18,479 CXR images with 8851 normal, 6012 non-COVID lung infections, and 3616 COVID-19 CXR images and their corresponding ground truth lung masks. To the best of our knowledge, this is the largest public COVID positive database and the lung masks. Five different image enhancement techniques: histogram equalization (HE), contrast limited adaptive histogram equalization (CLAHE), image complement, gamma correction, and balance contrast enhancement technique (BCET) were used to investigate the effect of image enhancement techniques on COVID-19 detection. A novel U-Net model was proposed and compared with the standard U-Net model for lung segmentation. Six different pre-trained Convolutional Neural Networks (CNNs) (ResNet18, ResNet50, ResNet101, InceptionV3, DenseNet201, and ChexNet) and a shallow CNN model were investigated on the plain and segmented lung CXR images. The novel U-Net model showed an accuracy, Intersection over Union (IoU), and Dice coefficient of 98.63%, 94.3%, and 96.94%, respectively for lung segmentation. The gamma correction-based enhancement technique outperforms other techniques in detecting COVID-19 from the plain and the segmented lung CXR images. Classification performance from plain CXR images is slightly better than the segmented lung CXR images; however, the reliability of network performance is significantly improved for the segmented lung images, which was observed using the visualization technique. The accuracy, precision, sensitivity, F1-score, and specificity were 95.11 %, 94.55 %, 94.56 %, 94.53 %, and 95.59 % respectively for the segmented lung images. The proposed approach with very reliable and comparable performance will boost the fast and robust COVID-19 detection using chest X-ray images.

Cationic antimicrobial peptides (CAMPs) are important components of the innate host defense system against microbial infections and microbial products. However, the human pathogen Neisseria meningitidis is intrinsically highly resistant to CAMPs, such as polymyxin B (PxB) (MIC > 512 g/ml). To ascertain the mechanisms by which meningococci resist PxB, mutants that displayed increased sensitivity (>4-fold) to PxB were identified from a library of mariner transposon mutants generated in a meningococcal strain, NMB. Surprisingly, more than half of the initial PxB-sensitive mutants had insertions within the mtrCDE operon, which encodes proteins forming a multidrug efflux pump. Additional PxB-sensitive mariner mutants were identified from a second round of transposon mutagenesis performed in an mtr efflux pump-deficient background. Further, a mutation in lptA, the phosphoethanolamine (PEA) transferase responsible for modification of the lipid A head groups, was identified to cause the highest sensitivity to PxB. Mutations within the mtrD or lptA genes also increased meningococcal susceptibility to two structurally unrelated CAMPs, human LL-37 and protegrin-1. Consistently, PxB neutralized inflammatory responses elicited by the lptA mutant lipooligosaccharide more efficiently than those induced by wild-type lipooligosaccharide. mariner mutants with increased resistance to PxB were also identified in NMB background and found to contain insertions within the pilMNOPQ operon involved in pilin biogenesis. Taken together, these data indicated that meningococci utilize multiple mechanisms including the action of the MtrC-MtrD-MtrE efflux pump and lipid A modification as well as the type IV pilin secretion system to modulate levels of CAMP resistance. The modification of meningococcal lipid A head groups with PEA also prevents neutralization of the biological effects of endotoxin by CAMP.

The biological response to endotoxin mediated through the Toll-like receptor 4 (TLR4)-MD-2 receptor complex is directly related to lipid A structure or configuration. Endotoxin structure may also influence activation of the MyD88-dependent and -independent signaling pathways of TLR4. To address this possibility, human macrophage-like cell lines (THP-1, U937, and MM6) or murine macrophage RAW 264.7 cells were stimulated with picomolar concentrations of highly purified endotoxins. Harvested supernatants from previously stimulated cells were also used to stimulate RAW 264.7 or 23ScCr (TLR4-deficient) macrophages (i.e., indirect induction). Neisseria meningitidis lipooligosaccharide (

Meningococcal lipopoly(oligo)saccharide (LOS) is a major inflammatory mediator of fulminant meningococcal sepsis and meningitis. Highly purified wild-type meningococcal LOS and LOS from genetically defined mutants of Neisseria meningitidis that contained specific mutations in LOS biosynthesis pathways were used to confirm that meningococcal LOS activation of macrophages was CD14/Toll-like receptor 4 (TLR4)-MD-2 dependent and to elucidate the LOS structural requirement for TLR4 activation. Expression of TLR4 but not TLR2 was required, and antibodies to both TLR4 and CD14 blocked meningococcal LOS activation of macrophages. Meningococcal LOS ␣ or ␤ chain oligosaccharide structure did not influence CD14/TLR4-MD-2 activation. However, meningococcal lipid A, expressed by meningococci with defects in 3-deoxy-D-mannooctulosonic acid (KDO) biosynthesis or transfer, resulted in an ϳ10-fold (P < 0.0001) reduction in biologic activity compared to KDO 2 -containing meningococcal LOS. Removal of KDO 2 from LOS by acid hydrolysis also dramatically attenuated cellular responses. Competitive inhibition assays showed similar binding of glycosylated and unglycosylated lipid A to CD14/TLR4-MD-2. A decrease in the number of lipid A phosphate head groups or penta-acylated meningococcal LOS modestly attenuated biologic activity. Meningococcal endotoxin is a potent agonist of the macrophage CD14/TLR4-MD-2 receptor, helping explain the fulminant presentation of meningococcal sepsis and meningitis. KDO 2 linked to meningococcal lipid A was structurally required for maximal activation of the human macrophage TLR4 pathway and indicates an important role for KDO-lipid A in endotoxin biologic activity.