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"Ibrahim, Mohammad"
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A dynamic COVID-19 immune signature includes associations with poor prognosis
Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology; others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity; while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, individual traits within this signature may collectively and individually guide treatment options; offer insights into COVID-19 pathogenesis; and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19.
A common immune signature in the blood of patients with COVID-19, who are otherwise clinically heterogeneous, sheds light into the pathogenesis and clinical progression of the disease.
Journal Article
Impact of TNF-α Inhibitors on Body Weight and BMI: A Systematic Review and Meta-Analysis
The aim of this systematic review and meta-analysis of longitudinal studies was to ascertain to effects of TNF-α inhibitor therapy on body weight and BMI.
Three databases (PubMed, OVID, and EMBASE) were systematically searched from inception to August 2018. We identified prospective, retrospective, and randomized controlled studies in adults with immune-mediated inflammatory diseases treated with TNF-α inhibitors based on pre-specified inclusion criteria. A random-effects model was used to estimate standardised mean change (SMCC).
Twenty-six longitudinal studies with a total of 1,245 participants were included in the meta-analysis. We found evidence for a small increase in body weight (SMCC = 0.24, p = .0006, 95% CI [0.10, 0.37]) and in BMI (SMCC = 0.26, p < .0001, 95% CI [0.13, 0.39]). On average, patients gained 0.90kg (SD = 5.13) under infliximab, 2.34kg (D = 5.65) under etanercept and 2.27kg (SD = 4.69) during treatment with adalimumab within the duration of the respective studies (4-104 weeks).
Our results yield further support the for the view that TNF-α inhibitors increase body weight and BMI as a potential side effect. Modulating cytokine signaling could be a future therapeutic mechanism to treat disorders associated with weight changes such as anorexia nervosa.
Journal Article
Novel NFKB2 Mutation in Early-Onset CVID
Common variable immunodeficiency (CVID) is heterogeneous, clinically, immunologically and genetically. The majority of genetic mechanisms leading to CVID remain elusive. We studied a Greek Cypriot family of non-consanguineous parents. Two children were diagnosed with CVID at an early age. Whole exome sequencing revealed 8bp deletion in the C-terminal part of NFKB2 gene associated with disease. The mutation leads to a frameshift (p.Asp865Valfs*17) altering 17 C-terminal amino acids from residue 865, and creating a premature stop-codon resulting in a truncated protein, 19 amino acids shorter than wild type (p100Δ19). We validated the results with Dye-termination sequencing and Western blot, and confirmed that the conserved residue at 866 is mutated from serine to arginine in p100Δ19, leaving the mutant protein unphosphorylated at this critical regulatory position. Consequently, NFKB2/p100 processing and nuclear translocation were abrogated. Using flow cytometry, we further demonstrated that there was a reduction in B cells (CD19+), switched memory B cells (CD27+IgD−) and T follicular helper (Tfh) cells (both CD4+CXCR5+ and CD4+CXCR5Hi) in a CVID patient with NFKB2/p100Δ19, compared to healthy controls. These data support the notion that the non-canonical NFκB pathway plays an important role in B cell differentiation and the development of Tfh cells, and may pave the way for better understanding of the pathology of CVID.
Journal Article
CXCL13 as a Biomarker of Complex Common Variable Immunodeficiency
Background
Common Variable Immunodeficiency (CVID) is a group of heterogeneous disorders with common denominators of impaired antibody production and function, and recurrent infections. Currently, prognostic biomarkers for CVID are limited. CXCL13 is a critical regulator of germinal centre responses and antibody production, with T follicular helper (Tfh) cells as a major source, and acts as a potent B cell chemoattractant. Serum levels of CXCL13 are increased in chronic inflammatory conditions and malignancy.
Objectives
We aimed to explore whether serum CXCL13 levels are altered in CVID and whether they can categorise the patients based on their clinical and immune phenotype.
Methods
We compared the serum levels of CXCL13 between CVID and healthy donors (HD) and associated them with the clinical and immune phenotype of the patients.
Results
The serum levels of CXCL13 were higher in CVID, especially in female patients, as compared to HD, and were positively correlated with the number of clinical complications in CVID and the total peripheral circulating Tfh cells (cTfh). CVID patients with higher levels of CXCL13 were more likely to have clinical complications and/or high frequency of CD21
low
B cells or low frequency of switched memory B cells.
Conclusions
CXCL13 can categorise heterogeneous patients with CVID and be used as a biomarker of complex disease.
Journal Article
Student satisfaction and academic efficacy during online learning with the mediating effect of student engagement: A multi-country study
The COVID-19 pandemic caused unprecedented changes to educational institutions, forcing their closure and a subsequent shift to online education to cater to student learning requirements. However, successful online learning depends on several factors and may also vary between countries. As such, this cross-sectional study sought to investigate how engagement of university students, a major driver of online learning, was influenced by course content, online interaction, student acceptance, and satisfaction with online learning, as well as self-efficacy across nine countries (China, India, Iran, Italy, Malaysia, Portugal, Serbia, Turkey, and the United Arab Emirates) during the COVID-19 pandemic. Using a questionnaire-based approach, data collected from 6,489 university students showed that student engagement was strongly linked to perception of the quality of the course content and online interactions (p < .001). The current study also indicated that online interactions are a major determinant of academic efficacy but only if mediated by engagement within the online learning context. A negative correlation between student engagement and satisfaction with online learning was found, demonstrating the importance of students being engaged behaviorally, emotionally, and cognitively to feel satisfied with learning. Academic efficacy and student satisfaction were explained by course content, online interaction, and online learning acceptance, being mediated by student engagement. Student satisfaction and, to a lesser degree academic efficacy, were also associated with online learning acceptance. Overall, the structural equation model was a good fit for the data collected from all nine countries (CFI = .947, TLI = .943; RMSEA = .068; SRMR = .048), despite differences in the percentage variations explained by each factor (no invariance), likely due to differences in levels of technology use, learning management systems, and the preparedness of teachers to migrate to full online instruction. Despite limitations, the results of this study highlight the most important factors affecting online learning, providing insight into potential approaches for improving student experiences in online learning environments.
Journal Article
The role of safety in modal choice and shift: A transport expert perspective in the state of Victoria (Australia)
Previous research showed differences in the exposure to risk from using different modes of transport and that modal choice can significantly impact road safety outcomes. Though, a modal shift to a safer mode is not commonly discussed as part of road safety strategies.
This study aimed to explore the perspectives of transport policymakers about the role of safety in modal choice and if it can be one of the main factors for modal choice and shift.
Seven semi-structured interviews were conducted with transport experts from government (n = 5) and private (n = 2) organisations in the state of Victoria. Interview transcripts were analysed using a thematic approach to identify the key perspectives of the experts.
Overall, the analyses indicated uncertainty of the ability to use safety in modal choice as a road safety strategy and identified two main issues; 1) the perceived limited role that safety plays in people's modal choice, and 2) that safety is perceived to be a barrier to modal choice and modal shift towards public and active travel. Experts suggested that when considering transport modes other factors such as convenience, availability, speed, cost, trip purpose and income are more influential than safety in modal choice. They also suggested that safety might play a role within the chosen mode, but not in choosing between modes, such as considering safety features when purchasing a car after deciding to drive a car. It was also stated that safety could act as a barrier preventing people from choosing sustainable transport modes of public transport and active travel.
Theoretically, it is argued that safety and mobility cannot be traded against each other, and that mobility becomes a function of safety, not vice-versa. However, our findings indicated that the transport experts did not believe that safety is the main factor in the modal choice process. Transport experts believed users choose their mode of transport mainly to achieve mobility benefits without necessarily considering how safe is their choice as a differentiator factor. While the shift to a safer mode of transport would help improve road safety outcomes, further investigations are needed to inform how can we influence the consideration of safety as the main factor in modal choice and removing barriers to using the relatively safest available mode of transport.
Journal Article
Properties and Applications of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Biocomposites
Polyhydroxyalkanoates (PHAs) are biopolyesters accumulated by microorganisms as intracellular storage materials and they have attracted attention as “green plastic” alternatives to their petrochemical counterparts. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PHBV, is one of the most studied members of the PHAs family, with numerous applications. PHBV has three main features, biodegradability, biocompatibility and it is a biobased polymer (biosynthesis starting from renewable resources). These three features altogether qualify PHBV as a very promising polymer that has great potential to replace conventional non-degradable polymers, and to play a significant rule in the circular economy concept. However, PHBV has some prominent disadvantages that limit its wide utilization for commercial use, these drawbacks are mainly weak mechanical properties, low thermal stability, difficult processability and considerable hydrophobicity. In order to overcome the properties issues, to produce materials with more desirable features and to engineer purpose-specific PHBV-based systems, much research has been focused on improving its properties by forming composites and to utilize these produced composites for a wide spectrum of very promising applications. The purpose of the current work is to compile and classify the research accomplished in the field of PHBV biocomposites and their applications in different disciplines. It was found that many different types of nanofillers, natural fibers, agricultural waste, clay, silicate, wood and cellulose derived natural materials have been successfully incorporated into PHBV matrix. The resultant biocomposites were characterized, tested and found promising to be utilized in a wide spectrum of applications, namely packaging, tissue engineering and drug delivery systems. The potential benefits of PHBV-based biocomposites make a strong case for research into this area. Therefore, further research works need to be conducted in order to find new PHBV biocomposite materials for advanced applications.
Journal Article