Search

A facile synthesis of rGO–CuO nanocomposite was carried out using hydrothermal method. rGO–CuO nanocomposite was incorporated in aerosol forming composite (AFC) for the first time in order to develop the fast fire extinguishant materials. Synthesized nanocomposites were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, scanning electron microscopy (SEM), energy dispersive Xray spectroscopy (EDX) and transmission electron microscopy (TEM). Catalytic activity of rGO–CuO was analysed considering the parameters such as combustion temperature, activation energy, burn rate, combustion efficiency, minimum fire extinguishing concentration (MEC) and fire extinguishing time. Addition of rGO–CuO to base AFC remarkably enhanced the performance of AFC by increasing the combustion efficiency (11.36%) and decreasing the combustion temperature (16.14%) and MEC (19.78%). A tremendous increase in burn rate (47.1%) boosted the fast extinguishment of fire by reducing the fire extinguishment time 78.2%. Developed AFC found promising to meet the faster fire extinguishment requirement of futuristic fire suppression systems. [ABSTRACT FROM AUTHOR]

rGO/Fe2O3 nanocomposites were synthesized using facile and inexpensive hydrothermal route. For the first time, these nanocomposites were incorporated in aerosol forming composites (AFCs), characterized and investigated for ultra-fast fire extinguishing applications. The morphological and structural characteristics were examined using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transmission infrared spectroscopy (FTIR), Raman spectroscopy and energy dispersive X-ray spectroscopy (EDX). AFCs were also characterized for burn rate, combustion efficiency, minimum fire extinguishing concentration, fire extinguishing time, combustion temperature and activation energy. Characterization revealed successful synthesis of rGO/Fe2O3 nanocomposites having Fe2O3 nanoparticles (25–50 nm) over and in-between the graphene oxide nanosheets. Increase in combustion efficiency (9%) and burn rate (35%) and reduction in onset temperature (17.16%), combustion temperature (13.46%) and activation energy (37.71%) were observed on addition of 3% rGO/5.0Fe2O3 nanocomposite to base AFC. Increase in burn rate by 35% led to ultra-fast aerosol generation and faster (50% reduction in fire extinguishing time) fire extinguishment. AFCs found promising for incorporation in condensed aerosol-based fire extinguishing systems to comply futuristic quicker fire extinguishment requirements. [ABSTRACT FROM AUTHOR]

GenoVault is a cloud-based repository for handling Next Generation Sequencing (NGS) data. It is developed using OpenStack-based private cloud with various services like keystone for authentication, cinder for block storage, neutron for networking and nova for managing compute instances for the Cloud. GenoVault uses object-based storage, which enables data to be stored as objects instead of files or blocks for faster retrieval from different distributed object nodes. Along with a web-based interface, a JavaFX-based desktop client has also been developed to meet the requirements of large file uploads that are usually seen in NGS datasets. Users can store files in their respective object-based storage areas and the metadata provided by the user during file uploads is used for querying the database. GenoVault repository is designed taking into account future needs and hence can scale both vertically and horizontally using OpenStack-based cloud features. Users have an option to make the data shareable to the public or restrict the access as private. Data security is ensured as every container is a separate entity in object-based storage architecture which is also supported by Secure File Transfer Protocol (SFTP) for data upload and download. The data is uploaded by the user in individual containers that include raw read files (fastq), processed alignment files (bam, sam, bed) and the output of variation detection (vcf). GenoVault architecture allows verification of the data in terms of integrity and authentication before making it available to collaborators as per the user's permissions. GenoVault is useful for maintaining the organization-wide NGS data generated in various labs which is not yet published and submitted to public repositories like NCBI. GenoVault also provides support to share NGS data among the collaborating institutions. GenoVault can thus manage vast volumes of NGS data on any OpenStack-based private cloud. [ABSTRACT FROM AUTHOR]

Introduction: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spread mainly through respiratory droplets and contact routes. Long-term use of spectacles may prevent repeated touching and rubbing of the eyes. Aim: To know the association between infection with SARSCoV-2 and wearing of spectacles. Materials and Methods: A cross-sectional study was conducted in which 304 patients of Coronavirus Disease-2019 (COVID-19) were selected. Their spectacles wearing behaviour were assessed through a questionnaire. Spectacles wearing behaviour of general population were obtained from older studies (for comparison). Risk of COVID-19 was calculated in long-term spectacles wearers as well as in persons not using spectacles. Chi-Square test was used for statistical analysis. Results: In this study, total 58 patients showed the behaviour of using spectacles continuously during day time and always on outdoor activities. The risk of COVID-19 was found 0.48 in spectacles wearing population as compared to 1.35 in population not using spectacles. The calculated Risk Ratio (RR) was 0.36. It indicates that the risk of COVID-19 was 2-3 times less in spectacles wearing population than the population not using spectacles. The protective effectiveness of the spectacles was found statistically significant (p-value=0.00113). Conclusion: The present study showed that the risk of COVID-19 was about 2-3 times less in spectacles wearing population than the population not wearing those. The nasolacrimal duct may be a route of virus transmission from conjunctival sac to the nasopharynx. [ABSTRACT FROM AUTHOR]

Abstract Enhanced oil recovery (EOR) especially surfactant slug injection has received a great attention as an oil recovery technique. Surfactants are capable in reducing the interfacial tension (IFT) and altering the wettability of rock from subsurface reservoir. Here, a new anionic surfactant was synthesized from Madhuca longifolia (Mahua) oil. The surfactant was characterized using FTIR, GC–MS, FE-SEM and EDX analysis and tested rigorously using IFT, wettability and flooding experiments for its application in EOR. The surfactant showed an ultralow IFT value around 1 × 10−2 at optimal salinity. Thermodynamic parameters were calculated using surface tension as a function of temperature and the studies showed that adsorption of molecules at the interface is favorable over micellization. The surfactant was found to be thermally stable by TGA analysis for its application at high temperature reservoir conditions. It showed the ability to alter the wettability of oil-wet sandstone rock surface to water-wet. The core-flooding experiments were conducted using individual surfactant slug and surfactant-polymer slug injection, which showed an additional recovery of almost 20% over convention water flooding. The experimental results were simulated using computational fluid dynamics (CFD) analysis. The results obtained after simulation study and core-flooding experiment results are very much comparable. The comprehensive evaluation of thermal, interfacial and oil recovery studies provides grounds for potential application in EOR. Graphical abstract Unlabelled Image Highlights • Synthesis of natural surfactant from Madhuca longifolia • Ultralow IFT achieved by surfactant in presence of salt and alkali • Rock wettability is altered using surfactant from oil-wet to water-wet. • Core flooding experiments recovered up to 20% additional recoveries. • Simulation studies of experimental data using computational fluid dynamics [ABSTRACT FROM AUTHOR]

Background Cardiac manifestations of neonatal lupus (cardiac NL) include congenital heart block and cardiomyopathy. Several candidate biomarkers were evaluated in cases at risk for cardiac NL on the basis of potential roles in inflammation, fibrosis, and cardiac dysfunction: C-reactive protein (CRP); NT-pro-B-type natriuretic peptide (NT-proBNP); troponin I; matrix metalloproteinase (MMP)-2; urokinase plasminogen activator (uPA); urokinase plasminogen activator receptor (uPAR); plasminogen; and vitamin D. Objectives Identification of maternal and fetal biomarkers associated with development and morbidity of cardiac NL should provide clues to pathogenesis with translational implications for management. Methods Cord (139) and maternal (135) blood samples collected during pregnancies at risk for cardiac NL were available for study. Levels of cord and maternal CRP, cord NT-proBNP, and cord troponin I were evaluated using multiplex assays. Cord and maternal vitamin D were assessed by liquid chromatography-mass spectrometry. MMP-2, uPA, uPAR, and plasminogen were evaluated using ELISA. Results Cord CRP, NT-proBNP, MMP-2, uPA, uPAR, and plasminogen levels were higher in cardiac NL-affected fetuses than in unaffected cases, independent of maternal rheumatic disease, season at highest risk of cardiac NL development, and medications taken during pregnancy. These biomarkers were positively associated with a disease severity score derived from known risk factors for mortality in cardiac NL. Maternal CRP and cord troponin I levels did not differ between the groups. Cord and maternal vitamin D levels were not significantly associated with cardiac NL, but average maternal vitamin D level during pregnancy was positively associated with longer time to postnatal pacemaker placement. Conclusions These data support the association of fetal reactive inflammatory and fibrotic components with development and morbidity of cardiac NL. Following CRP and NT-proBNP levels after birth can potentially monitor severity and progression of cardiac NL. MMP-2 and the uPA/uPAR/plasminogen cascade provide therapeutic targets to decrease fibrosis. Although decreased vitamin D did not confer increased risk, given the positive influence on postnatal outcomes, maternal levels should be optimized. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) play a pivotal role in suppressing immune responses regulating behavior and gene expression in effector T cells, macrophages, and dendritic cells. Tregs infiltrate the infarcted myocardium; however, their role the inflammatory and reparative response after myocardial infarction remains poorly understood. We used FoxP3EGFP reporter mice to study Treg trafficking in the infarcted heart and examined the effects of Treg depletion on postinfarction remodeling using an anti-CD25 antibody. Moreover, we investigated the in vitro effects of Tregs on cardiac fibroblast phenotype and function. Low numbers of Tregs infiltrated the infarcted myocardium after 24-72 h of reperfusion. Treg depletion had no significant effects on cardiac dysfunction and scar size after reperfused myocardial infarction but accelerated ventricular dilation and accentuated apical remodeling. Enhanced myocardial dilation in Treg-depleted animals was associated with increased expression of chemokine (C-C motif) ligand 2 and accentuated macrophage infiltration. In vitro, Tregs modulated the cardiac fibroblast phenotype, reducing expression of a-smooth muscle actin, decreasing expression of matrix metalloproteinase-3, and attenuating contraction of fibroblast-populated collagen pads. Our findings suggest that endogenous Tregs have modest effects on the inflammatory and reparative response after myocardial infarction. However, the anti-inflammatory and matrix-preserving properties of Tregs may suggest a role for Treg-based cell therapy in the attenuation of adverse postinfarction remodeling. [ABSTRACT FROM AUTHOR]

Aims The CXC chemokine CXCL10 is up-regulated in the infarcted myocardium and limits cardiac fibrosis by inhibiting growth factor-mediated fibroblast migration. CXCL10 signals by binding to its receptor CXCR3; however, recently CXCR3-independent CXCL10 actions have been suggested. Our study explores the role of CXCR3 signalling in myocardial infarction and investigates its involvement in mediating the anti-fibrotic effects of CXCL10. Methods and results Wild-type and CXCR3 null mice underwent reperfused infarction protocols. CXCL10 was markedly induced in the infarct; in contrast, expression of the other two CXCR3 ligands, CXCL9 and CXCL11 was extremely low. CXCR3 loss did not affect scar size, geometric ventricular remodelling, collagen deposition, and systolic dysfunction of the infarcted heart. CXCR3 null mice had increased peak neutrophil recruitment and delayed myofibroblast infiltration in the infarcted heart, but exhibited comparable myocardial expression of pro-inflammatory cytokines and chemokines. In vitro, CXCL10 did not modulate Transforming Growth Factor (TGF)-β signalling, but inhibited basic fibroblast growth factor (bFGF)-induced cardiac fibroblast migration in both wild-type and CXCR3 null cells. Treatment of fibroblasts with heparinase and chondroitinase to cleave glycosaminoglycan chains abrogated the inhibitory effects of CXCL10 on cell migration. Conclusion CXCR3 signalling does not critically regulate cardiac remodelling and dysfunction following myocardial infarction. The anti-fibrotic effects of CXCL10 in the healing infarct and in isolated cardiac fibroblasts are CXCR3-independent and may be mediated through proteoglycan signalling. Thus, administration of CXCR3-defective forms of CXCL10 may be an effective anti-fibrotic strategy in the remodelling myocardium without activating a potentially injurious, CXCR3-driven T cell response. [ABSTRACT FROM AUTHOR]

Determining the optimal feature set is a challenging problem, especially in an unsupervised domain. To mitigate the same, this paper presents a new unsupervised feature selection method, termed as densest feature graph augmentation with disjoint feature clusters. The proposed method works in two phases. The first phase focuses on finding the maximally non-redundant feature subset and disjoint features are added to the feature set in the second phase. To experimentally validate, the efficiency of the proposed method has been compared against five existing unsupervised feature selection methods on five UCI datasets in terms of three performance criteria, namely clustering accuracy, normalized mutual information, and classification accuracy. The experimental analyses have shown that the proposed method outperforms the considered methods. [ABSTRACT FROM AUTHOR]

This paper proposes a novel approach for selecting a subset of features in semi-supervised datasets where only some of the patterns are labeled. The whole process is completed in two phases. In the first phase, i.e., Phase-I, the whole dataset is divided into two parts: The first part, which contains labeled patterns, and the second part, which contains unlabeled patterns. In the first part, a small number of features are identified using well-known maximum relevance (from first part) and minimum redundancy (whole dataset) based feature selection approaches using the correlation coefficient. The subset of features from the identified set of features, which produces a high classification accuracy using any supervised classifier from labeled patterns, is selected for later processing. In the second phase, i.e., Phase-II, the patterns belonging to the first and second part are clustered separately into the available number of classes of the dataset. In the clusters of the first part, take the majority of patterns belonging to a cluster as the class for that cluster, which is given already. Form the pairs of cluster centroids made in the first and second part. The centroid of the second part nearest to a centroid of the first part will be paired. As the class of the first centroid is known, the same class can be assigned to the centroid of the cluster of the second part, which is unknown. The actual class of the patterns if known for the second part of the dataset can be used to test the classification accuracy of patterns in the second part. The proposed two-phase approach performs well in terms of classification accuracy and number of features selected on the given benchmarked datasets. [ABSTRACT FROM AUTHOR]

Background: Neonatal sepsis significantly contributes to neonatal mortality and morbidity in developing countries. The delay in diagnosis due to the time-consuming gold standard blood culture necessitates rapid, accessible, and cost-effective diagnostic markers. Aims: This study aimed to evaluate the sensitivity and specificity of Micro-ESR for early neonatal sepsis diagnosis and compare its effectiveness with other standard markers. Methodology: Conducted at D.Y. Patil Hospital's Department of Pediatrics in Navi Mumbai, this prospective observational study included 200 neonates suspected of sepsis. Blood samples were analyzed for CBC, CRP, Micro-ESR, and bacterial culture before antibiotic initiation. Micro-ESR's diagnostic performance was assessed against other markers based on confirmed sepsis cases via blood culture. Results: Among 200 neonates, 16 had a positive blood culture. Micro-ESR showed a sensitivity of 87.5% and specificity of 28.80%. In comparison, Total Leucocyte Count (TLC) and Absolute Neutrophil Count (ANC) demonstrated higher specificity (91.25% and 70% respectively) but lower sensitivity. Platelet count and CRP indicated high specificity (94.56%) and sensitivity (100%) respectively, albeit with low predictive values. Conclusions: While CRP exhibited the highest sensitivity, TLC and platelet count showed superior specificity. Despite its lower specificity, Micro-ESR's high sensitivity suggests its utility as a supportive early diagnostic marker alongside CBC, CRP, and ANC. Blood culture remains the definitive diagnostic standard. [ABSTRACT FROM AUTHOR]

Objective: To investigate long‐term safety and tolerability of anifrolumab, a human monoclonal antibody to the type I interferon (IFN) receptor subunit 1, in patients with moderate‐to‐severe systemic lupus erythematosus (SLE). Methods: This 3‐year, multinational, open‐label extension study included adult patients who completed treatment (48 weeks of anifrolumab or placebo; 12‐week follow‐up) in the MUSE phase IIb randomized controlled trial (RCT). Patients initially received 1,000 mg of anifrolumab intravenously every 4 weeks, which was reduced to 300 mg every 4 weeks based on the benefit/risk profile established in the MUSE trial. Adverse events (AEs) were assessed monthly. Exploratory end points included the SLE Disease Activity Index 2000 (SLEDAI‐2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), pharmacodynamics, and health‐related quality of life (HRQoL). Results: Of the 246 patients who completed the RCT, 218 (88.6%) enrolled in the open‐label extension study, of which 139 (63.8%) completed 3 years of treatment. Approximately 69.7% of patients reported ≥1 AE during the first year of open‐label extension treatment. Frequency and patterns of serious AEs and AEs of special interest over 3 years were consistent with those reported for 1 year of treatment in the RCT. Few patients (6.9%) discontinued treatment due to AEs. No new safety signals were identified. Improvement in the SLEDAI‐2K was sustained over 3 years. SDI and Short Form 36 health survey scores remained stable. Neutralization of type I IFN gene signatures was maintained in the IFN‐high population, and C3, C4, and anti–double‐stranded DNA showed trends toward sustained improvement. Conclusion: Long‐term anifrolumab treatment demonstrates an acceptable safety profile with sustained improvement in SLE disease activity, HRQoL, and serologic measures. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a chronic neurodegenerative disease that causes brain cells to degenerate, resulting in decreased physical and mental abilities and, in severe cases, permanent memory loss. It is considered as the most common and fatal form of dementia. Although mild cognitive impairment (MCI) precedes Alzheimer's disease (AD), it does not necessarily show the obvious symptoms of AD. As a result, it becomes challenging to distinguish between mild cognitive impairment and cognitively normal. In this paper, we propose an ensemble of deep learners based on convolutional neural networks for the early diagnosis of Alzheimer's disease. The proposed approach utilises simple averaging ensemble and weighted averaging ensemble methods. The ensemble-based transfer learning model demonstrates enhanced generalization and performance for AD diagnosis compared to traditional transfer learning methods. Extensive experiments on the OASIS-3 dataset validate the effectiveness of the proposed model, showcasing its superiority over state-of-the-art transfer learning approaches in terms of accuracy, robustness, and efficiency. [ABSTRACT FROM AUTHOR]

Abstract The boreal forests of Alberta have extensive networks of legacy seismic exploration lines that have been linked to the decline of boreal woodland caribou (Rangifer tarandus caribou) populations throughout the region. In order to improve habitat quality for caribou, energy companies are investing significant resources in the restoration of many of these seismic lines in key areas, however, frequent large and intense wildfires may compromise the effectiveness of these conservation measures. To minimize the wildfire risk, managers need to know the likelihood of wildfire and the effectiveness of mitigation measures. We undertook a wildfire risk assessment across the Cold Lake caribou range where we used the Burn-P3 model to determine: a) burn probability; b) wildfire risk to restored seismic line areas; and c) the effectiveness of mitigation measures. The burn probability of the landscape was highly heterogeneous, and recent large burns and some waterbodies provided "shields" that reduced burn probability on their leeward sides. We designed mitigation scenarios to mimic the shielding effect of waterbodies and large recent burns by modeling the effects of increase suppression activity and fuel conversion within intensive management zones upwind of the resources to be protected. We found that these intensive management zones reduced the burn probability and wildfire hazard in the restored habitat areas but the effect declined rapidly as distance from the treatment zones increased. If land managers want to minimize the risk of losing their investments in caribou conservation to wildfire, it would be preferable to have mitigation measures spatially targeted closer to the conservation areas. Furthermore, it would be advisable to have redundancy in any conservation measures and wildfire-risk mitigations to ensure that losses due to wildfire on one area do not jeopardize all conservation projects within the landscape. Highlights • Locations for conservation often based on current landscape conditions. • Assessments often ignore wildfire risk, which can destroy habitat restoration. • Use Burn Probability Modeling to examine fire risk to caribou conservation projects. • Intensive management reduces burn probability and fire hazard. • These effects decline as the distance from the treated area increases. [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid arthritis (RA) is considered to be a prototypical autoimmune disorder. Several mechanisms have been proposed for the known pathologic function of B cells in RA, including antigen presentation, cytokine secretion, and humoral immunity. The aim of this study was to address the function of B lymphocytes in experimental arthritis. Methods: We mapped the adaptive immune response following collagen‐induced arthritis (CIA). We subsequently monitored these responses and disease outcomes in genetically modified mouse strains that lack mature B cell or germinal center (GC) functionality in a B cell–intrinsic manner. Results: Following primary immunization, the draining lymph nodes broadly reacted against type II collagen (CII) with the formation of GCs and T cell activation. Mice that lacked mature B cell function were fully protected against CIA and had a severely attenuated ability to mount isotype‐switched humoral immune responses against CII. Almost identical results were observed in mice that were selectively deficient in GC responses. Importantly, GC‐deficient mice were fully susceptible to collagen antibody–induced arthritis. Conclusion: We identified GC formation and anticollagen antibody production as the key pathogenic functions of B cells in CIA. The role of B cells in RA is likely to be more complex. However, targeting the GC reaction could allow for therapeutic interventions that are more refined than general B cell depletion. [ABSTRACT FROM AUTHOR]

In recent times Gallbladder cancer (GBC) incidences increased many folds in India and are being reported from arsenic hotspots identified in Bihar. The study aims to establish association between arsenic exposure and gallbladder carcinogenesis. In the present study, n = 200 were control volunteers and n = 152 confirmed gallbladder cancer cases. The studied GBC patient's biological samples-gallbladder tissue, gallbladder stone, bile, blood and hair samples were collected for arsenic estimation. Moreover, n = 512 gallbladder cancer patients blood samples were also evaluated for the presence of arsenic to understand exposure level in the population. A significantly high arsenic concentration (p < 0.05) was detected in the blood samples with maximum concentration 389 µg/L in GBC cases in comparison to control. Similarly, in the gallbladder cancer patients, there was significantly high arsenic concentration observed in gallbladder tissue with highest concentration of 2166 µg/kg, in gallbladder stones 635 µg/kg, in bile samples 483 µg/L and in hair samples 6980 µg/kg respectively. Moreover, the n = 512 gallbladder cancer patient's blood samples study revealed very significant arsenic concentration in the population of Bihar with maximum arsenic concentration as 746 µg/L. The raised arsenic concentration in the gallbladder cancer patients' biological samples—gallbladder tissue, gallbladder stone, bile, blood, and hair samples was significantly very high in the arsenic exposed area. The study denotes that the gallbladder disease burden is very high in the arsenic exposed area of Bihar. The findings do provide a strong link between arsenic contamination and increased gallbladder carcinogenesis. [ABSTRACT FROM AUTHOR]

In this paper, a novel approach is proposed to improve the classification performance of a polynomial neural network (PNN). In this approach, the partial descriptions (PDs) are generated at the first layer based on all possible combinations of two features of the training input patterns of a dataset. The set of PDs from the first layer, the set of all input features, and a bias constitute the chromosome of the real-coded genetic algorithm (RCGA). A system of equations is solved to determine the values of the real coefficients of each chromosome of the RCGA for the training dataset with the mean classification accuracy (CA) as the fitness value of each chromosome. To adjust these values for unknown testing patterns, the RCGA is iterated in the usual manner using simple selection, crossover, mutation, and elitist selection. The method is tested extensively with the University of California, Irvine benchmark datasets by utilizing tenfold cross validation of each dataset, and the performance is compared with various well-known state-of-the-art techniques. The results obtained from the proposed method in terms of CA are superior and outperform other known methods on various datasets. [ABSTRACT FROM PUBLISHER]

Objective: Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in phase II and phase III of the belimumab trials was not reflective of the racial distribution observed in the lupus population. This study was undertaken to assess the efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self‐identified Black race. Methods: EMBRACE (GSK Study BEL115471; ClinicalTrials.gov identifier: NCT01632241) was a 52‐week multicenter, double‐blind, placebo‐controlled trial in adults of self‐identified Black race with active SLE who received monthly belimumab 10 mg/kg IV, or placebo, plus standard therapy. The optional 26‐week open‐label extension phase included patients who completed the double‐blind phase. The primary end point of the study was SLE Responder Index (SRI) response rate at week 52 with modified proteinuria scoring adapted from the SLE Disease Activity Index 2000 (SLEDAI‐2K) (SRI–SLEDAI‐2K). Key secondary end points included SRI response rate at week 52, time to first severe SLE flare, and reductions in prednisone dose. Results: The modified intent‐to‐treat population comprised 448 patients, of whom 96.9% were women and the mean ± SD age was 38.8 ± 11.42 years. The primary end point (improvement in the SRI–SLEDAI‐2K response rate at week 52) was not achieved (belimumab 48.7%, placebo 41.6%; odds ratio 1.40 [95% confidence interval 0.93, 2.11], P = 0.1068); however, numerical improvements favoring belimumab were observed, in which the SRI–SLEDAI‐2K response rates were higher in those who received belimumab compared with those who received placebo, especially in patients with SLE who had high disease activity or renal manifestations at baseline. The safety profile of belimumab was generally consistent with that observed in previous SLE trials. Adverse events were the primary reasons for double‐blind phase withdrawals (belimumab 5.4%, placebo 6.7%). Conclusion: The primary end point of this study was not achieved, but improvement with belimumab versus placebo was observed, suggesting that belimumab remains a suitable treatment option for SLE management in patients of Black African ancestry. [ABSTRACT FROM AUTHOR]

Objective: To characterize patients with systemic lupus erythematosus (SLE) affected by coronavirus disease 2019 (COVID‐19) and to analyze associations of comorbidities and medications on infection outcomes. Methods: Patients with SLE and reverse transcriptase–polymerase chain reaction–confirmed COVID‐19 were identified through an established New York University lupus cohort, query of 2 hospital systems, and referrals from rheumatologists. Data were prospectively collected via a web‐based questionnaire and review of medical records. Data on baseline characteristics were obtained for all patients with COVID‐19 to analyze risk factors for hospitalization. Data were also collected on asymptomatic patients and those with COVID‐19–like symptoms who tested negative or were not tested. Statistical analyses were limited to confirmed COVID‐19–positive patients. Results: A total of 226 SLE patients were included: 41 with confirmed COVID‐19, 19 who tested negative for COVID‐19, 42 with COVID‐19–like symptoms who did not get tested, and 124 who remained asymptomatic without testing. Of the SLE patients with confirmed COVID‐19, hospitalization was required in 24 (59%) and intensive care unit–level of care in 4, and 4 died. Hospitalized patients tended to be older, nonwhite, Hispanic, have higher body mas index (BMI), history of nephritis, and at least 1 comorbidity. An exploratory (due to limited sample size) logistic regression analysis identified race, presence of at least 1 comorbidity, and BMI as independent predictors of hospitalization. Conclusion: In general, the variables predictive of hospitalization in our SLE patients were similar to those identified in the general population. Further studies are needed to understand additional risk factors for poor COVID‐19 outcomes in patients with SLE. [ABSTRACT FROM AUTHOR]

Background: Experimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro-mediated congenital heart block (CHB).Objectives: Hydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB.Methods: This multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon's optimal approach. Anti-SSA/Ro-positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1° CHB at birth and skin rash.Results: By intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4).Conclusions: These prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573). [ABSTRACT FROM AUTHOR]

Objective: To evaluate the frequency of cell‐bound complement activation products (CB‐CAPs) as a marker of complement activation in patients with suspected systemic lupus erythematosus (SLE) and the usefulness of this biomarker as a predictor of the evolution of probable SLE into SLE as classified by the American College of Rheumatology (ACR) criteria. Methods: Patients in whom SLE was suspected by lupus experts and who fulfilled 3 ACR classification criteria for SLE (probable SLE) were enrolled, along with patients with established SLE as classified by both the ACR and the Systemic Lupus International Collaborating Clinics (SLICC) criteria, patients with primary Sjögren's syndrome (SS), and patients with other rheumatic diseases. Individual CB‐CAPs were measured by flow cytometry, and positivity rates were compared to those of commonly assessed biomarkers, including serum complement proteins (C3 and C4) and autoantibodies. The frequency of a positive multianalyte assay panel (MAP), which includes CB‐CAPs, was also evaluated. Probable SLE cases were followed up prospectively. Results: The 92 patients with probable SLE were diagnosed more recently than the 53 patients with established SLE, and their use of antirheumatic medications was lower. At the enrollment visit, more patients with probable SLE were positive for CB‐CAPs (28%) or MAP (40%) than had low complement levels (9%) (P = 0.0001 for each). In probable SLE, MAP scores of >0.8 at enrollment predicted fulfillment of a fourth ACR criterion within 18 months (hazard ratio 3.11, P < 0.01). Conclusion: Complement activation occurs in some patients with probable SLE and can be detected with higher frequency by evaluating CB‐CAPs and MAP than by assessing traditional serum complement protein levels. A MAP score above 0.8 predicts transition to classifiable SLE according to ACR criteria. [ABSTRACT FROM AUTHOR]

PDZ-containing proteins comprise one of the most widely distributed protein families playing major role in localization and membrane receptor clustering. They are hence important regulators of signal transduction in cellular pathways. Although knowledge on these proteins has increased exponentially, the existing database 'PDZBase' is limited by presence of only 339 proteins as it dates back to 2004 when very little data was available. Thus, lack of exclusive information on this protein family led us to develop PDZscape. 'PDZscape' encompasses the complete available information on 58,648 PDZ-containing proteins with their known and putative binding partners on one platform. It has a user-friendly web interface that can be easily queried with external protein identifiers. With unique integration of prominent databases including NCBI, UniProtKB, Swiss-Prot, Pubmed, PDB, STRING, IntAct, KEGG, Pfam and Protein Mutant Database, it provides detailed information on PDZ interactome apart from the customized BLAST option. Most importantly, this database encompasses the mutations and diseases associated with PDZ containing proteins manually curated by our group, thus making it a comprehensive compilation. It also features tools to query the database using sequence (PDZ-Blast) and to find if protein of interest is a PDZ-binding protein. PDZscape is freely available at http://www.actrec.gov.in:8080/pdzscape. [ABSTRACT FROM AUTHOR]

Background: Transforming growth factor-βs regulate a wide range of cellular responses by activating Smad-dependent and Smad-independent cascades. In the infarcted heart, Smad3 signaling is activated in both cardiomyocytes and interstitial cells. We hypothesized that cell-specific actions of Smad3 regulate repair and remodeling in the infarcted myocardium.Methods: To dissect cell-specific Smad3 actions in myocardial infarction, we generated mice with Smad3 loss in activated fibroblasts or cardiomyocytes. Cardiac function was assessed after reperfused or nonreperfused infarction using echocardiography. The effects of cell-specific Smad3 loss on the infarcted heart were studied using histological studies, assessment of protein, and gene expression levels. In vitro, we studied Smad-dependent and Smad-independent actions in isolated cardiac fibroblasts.Results: Mice with fibroblast-specific Smad3 loss had accentuated adverse remodeling after reperfused infarction and exhibited an increased incidence of late rupture after nonreperfused infarction. The consequences of fibroblast-specific Smad3 loss were not a result of effects on acute infarct size but were associated with unrestrained fibroblast proliferation, impaired scar remodeling, reduced fibroblast-derived collagen synthesis, and perturbed alignment of myofibroblast arrays in the infarct. Polarized light microscopy in Sirius red-stained sections demonstrated that the changes in fibroblast morphology were associated with perturbed organization of the collagenous matrix in the infarcted area. In contrast, α-smooth muscle actin expression by infarct myofibroblasts was not affected by Smad3 loss. Smad3 critically regulated fibroblast function, activating integrin-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (NOX-2) expression. Smad3 loss in cardiomyocytes attenuated remodeling and dysfunction after infarction. Cardiomyocyte-specific Smad3 loss did not affect acute infarct size but was associated with attenuated cardiomyocyte apoptosis in the remodeling myocardium, accompanied by decreased myocardial NOX-2 levels, reduced nitrosative stress, and lower matrix metalloproteinase-2 expression.Conclusions: In healing myocardial infarction, myofibroblast- and cardiomyocyte-specific activation of Smad3 has contrasting functional outcomes that may involve activation of an integrin/reactive oxygen axis. [ABSTRACT FROM AUTHOR]

Aims Tissue transglutaminase (tTG) is induced in injured and remodelling tissues, and modulates cellular phenotype, while contributing to matrix cross-linking. Our study tested the hypothesis that tTG may be expressed in the pressure-overloaded myocardium, and may regulate cardiac function, myocardial fibrosis and chamber remodelling. Methods and results In order to test the hypothesis, wild-type and tTG null mice were subjected to pressure overload induced through transverse aortic constriction. Moreover, we used isolated cardiac fibroblasts and macrophages to dissect the mechanisms of tTG-mediated actions. tTG expression was upregulated in the pressure-overloaded mouse heart and was localized in cardiomyocytes, interstitial cells, and in the extracellular matrix. In contrast, expression of transglutaminases 1, 3, 4, 5, 6, 7 and FXIII was not induced in the remodelling myocardium. In vitro, transforming growth factor (TGF)-β1 stimulated tTG synthesis in cardiac fibroblasts and in macrophages through distinct signalling pathways. tTG null mice had increased mortality and enhanced ventricular dilation following pressure overload, but were protected from diastolic dysfunction. tTG loss was associated with a hypercellular cardiac interstitium, reduced collagen cross-linking, and with accentuated matrix metalloproteinase (MMP)2 activity in the pressure-overloaded myocardium. In vitro, tTG did not modulate TGF-β-mediated responses in cardiac fibroblasts; however, tTG loss was associated with accentuated proliferative activity. Moreover, when bound to the matrix, recombinant tTG induced synthesis of tissue inhibitor of metalloproteinases (TIMP)-1 through transamidase-independent actions. Conclusions Following pressure overload, endogenous tTG mediates matrix cross-linking, while protecting the remodelling myocardium from dilation by exerting matrix-preserving actions. [ABSTRACT FROM AUTHOR]

In remote sensing imagery, segmentation techniques fail to encounter multiple regions of interest due to challenges such as dense features, low illumination, uncertainties, and noise. Consequently, exploiting vast and redundant information makes segmentation a difficult task. Existing multilevel thresholding techniques achieve low segmentation accuracy with high temporal difficulty due to the absence of spatial information. To mitigate this issue, this paper presents a new Rényi's entropy and modified cuckoo search-based robust automatic multi-thresholding algorithm for remote sensing image analysis. In the proposed method, the modified cuckoo search algorithm is combined with Rényi's entropy thresholding criteria to determine optimal thresholds. In the modified cuckoo search algorithm, the Lévy flight step size was modified to improve the convergence rate. An experimental analysis was conducted to validate the proposed method, both qualitatively and quantitatively against existing metaheuristic-based thresholding methods. To do this, the performance of the proposed method was intensively examined on high-dimensional remote sensing imageries. Moreover, numerical parameter analysis is presented to compare the segmented results against the gray-level co-occurrence matrix, Otsu energy curve, minimum cross entropy, and Rényi's entropy-based thresholding. Experiments demonstrated that the proposed approach is effective and successful in attaining accurate segmentation with low time complexity. [ABSTRACT FROM AUTHOR]