Computational approaches for evaluating morphological changes in the corneal stroma associated with decellularization.

Decellularized corneas offer a promising and sustainable source of replacement grafts, mimicking native tissue and reducing the risk of immune rejection post-transplantation. Despite great success in achieving acellular scaffolds, little consensus exists regarding the quality of the decellularized extracellular matrix. Metrics used to evaluate extracellular matrix performance are study-specific, subjective, and semi-quantitative. Thus, this work focused on developing a computational method to examine the effectiveness of corneal decellularization. We combined conventional semi-quantitative histological assessments and automated scaffold evaluations based on textual image analyses to assess decellularization efficiency. Our study highlights that it is possible to develop contemporary machine learning (ML) models based on random forests and support vector machine algorithms, which can identify regions of interest in acellularized corneal stromal tissue with relatively high accuracy. These results provide a platform for developing machine learning biosensing systems for evaluating subtle morphological changes in decellularized scaffolds, which are crucial for assessing their functionality.

A scalable corneal xenograft platform: simultaneous opportunities for tissue engineering and circular economic sustainability by repurposing slaughterhouse waste.

Introduction: Corneal disease is a leading cause of blindness globally that stems from various etiologies. High-throughput platforms that can generate substantial quantities of corneal grafts will be invaluable in addressing the existing global demand for keratoplasty. Slaughterhouses generate substantial quantities of underutilized biological waste that can be repurposed to reduce current environmentally unfriendly practices. Such efforts to support sustainability can simultaneously drive the development of bioartificial keratoprostheses. Methods: Scores of discarded eyes from the prominent Arabian sheep breeds in our surrounding region of the United Arab Emirates (UAE) were repurposed to generate native and acellular corneal keratoprostheses. Acellular corneal scaffolds were created using a whole-eye immersion/agitation-based decellularization technique with a widely available, eco-friendly, and inexpensive 4% zwitterionic biosurfactant solution (Ecover, Malle, Belgium). Conventional approaches like DNA quantification, ECM fibril organization, scaffold dimensions, ocular transparency and transmittance, surface tension measurements, and Fourier-transform infrared (FTIR) spectroscopy were used to examine corneal scaffold composition. Results: Using this high-throughput system, we effectively removed over 95% of the native DNA from native corneas while retaining the innate microarchitecture that supported substantial light transmission (over 70%) after reversing opacity, a well-established hallmark of decellularization and long-term native corneal storage, with glycerol. FTIR data revealed the absence of spectral peaks in the frequency range 2849 cm-1 to 3075 cm-1, indicating the effective removal of the residual biosurfactant post-decellularization. Surface tension studies confirmed the FTIR data by capturing the surfactant's progressive and effectual removal through tension measurements ranging from approximately 35 mN/m for the 4% decellularizing agent to 70 mN/m for elutes highlighting the effective removal of the detergent. Discussion: To our knowledge, this is the first dataset to be generated outlining a platform that can produce dozens of ovine acellular corneal scaffolds that effectively preserve ocular transparency, transmittance, and ECM components using an eco-friendly surfactant. Analogously, decellularization technologies can support corneal regeneration with attributes comparable to native xenografts. Thus, this study presents a simplified, inexpensive, and scalable high-throughput corneal xenograft platform to support tissue engineering, regenerative medicine, and circular economic sustainability.

Risk of hospitalization and vaccine effectiveness among COVID-19 patients in the UAE during the Delta and Omicron outbreaks.

Introduction: A rapid increase in COVID-19 cases due to the spread of the Delta and Omicron variants in vaccinated populations has raised concerns about the hospitalization risk associated with, and the effectiveness of, COVID-19 vaccines. Method: This case-control study aims to determine the hospitalization risk associated with the inactivated BBIBP-CorV (Sinopharm) and mRNA BNT162b2 (Pfizer-BionTech) vaccines, and their effectiveness reducing the rate of hospital admission between 28 May 2021 and 13 January 2022, during the Delta and Omicron outbreaks. The estimation of vaccine effectiveness of 4,618 samples was based on the number of patients hospitalized at different vaccination statuses, adjusted for confounding variables. Results: Hospitalization risk increases in patients affected with the Omicron variant if patients are aged ≤ 18 years (OR 6.41, 95% CI 2.90 to 14.17; p < 0.001), and in patients affected with the Delta variant if they are aged > 45 years (OR 3.41, 95% CI 2.21 to 5.50; p < 0.001). Vaccine effectiveness reducing the rate of hospital admission for fully vaccinated participants infected with the Delta and Omicron variants was similar for both the BBIBP-CorV (94%, 95% CI 90% to 97%; 90%, 95% CI 74% to 96%) and BNT162b2 vaccines (95%, 95% CI 61% to 99.3%; 94%, 95% CI 53% to 99%), respectively. Discussion: The BBIBP-CorV and BNT162b2 vaccines utilized in the UAE vaccination program were highly effective in reducing the rate of COVID-19-related hospitalization during the Delta and Omicron outbreaks, and further effort must be taken to achieve high vaccine coverage rates in children and adolescents in the global context to reduce the hospitalization risk associated with COVID-19 on an international scale.

Genomic epidemiology and emergence of SARS-CoV-2 variants of concern in the United Arab Emirates.

Since the declaration of SARS-CoV-2 outbreak as a pandemic, the United Arab Emirates (UAE) public health authorities have adopted strict measures to reduce transmission as early as March 2020. As a result of these measures, flight suspension, nationwide RT-PCR and surveillance of viral sequences were extensively implemented. This study aims to characterize the epidemiology, transmission pattern, and emergence of variants of concerns (VOCs) and variants of interests (VOIs) of SARS-CoV-2 in the UAE, followed by the investigation of mutations associated with hospitalized cases. A total of 1274 samples were collected and sequenced from all seven emirates between the period of 25 April 2020 to 15 February 2021. Phylogenetic analysis demonstrated multiple introductions of SARS-CoV-2 into the UAE in the early pandemic, followed by a local spread of root clades (A, B, B.1 and B.1.1). As the international flight resumed, the frequencies of VOCs surged indicating the January peak of positive cases. We observed that the hospitalized cases were significantly associated with the presence of B.1.1.7 (p < 0.001), B.1.351 (p < 0.001) and A.23.1 (p = 0.009). Deceased cases are more likely to occur in the presence of B.1.351 (p < 0.001) and A.23.1 (p = 0.022). Logistic and ridge regression showed that 51 mutations are significantly associated with hospitalized cases with the highest proportion originated from S and ORF1a genes (31% and 29% respectively). Our study provides an epidemiological insight of the emergence of VOCs and VOIs following the borders reopening and worldwide travels. It provides reassurance that hospitalization is markedly more associated with the presence of VOCs. This study can contribute to understand the global transmission of SARS-CoV-2 variants.

Genome-wide association study of hospitalized COVID-19 patients in the United Arab Emirates.

BACKGROUND: The heterogeneity in symptomatology and phenotypic profile attributable to COVID-19 is widely unknown. The objective of this manuscript is to conduct a trans-ancestry genome wide association study (GWAS) meta-analysis of COVID-19 severity to improve the understanding of potentially causal targets for SARS-CoV-2. METHODS: This cross-sectional study recruited 646 participants in the UAE that were divided into two phenotypic groups based on the severity of COVID-19 phenotypes, hospitalized (n=482) and non-hospitalized (n=164) participants. Hospitalized participants were COVID-19 patients that developed acute respiratory distress syndrome (ARDS), pneumonia or progression to respiratory failure that required supplemental oxygen therapy or mechanical ventilation support or had severe complications such as septic shock or multi-organ failure. We conducted a trans-ancestry meta-analysis GWAS of European (n=302), American (n=102), South Asian (n=99), and East Asian (n=107) ancestry populations. We also carried out comprehensive post-GWAS analysis, including enrichment of SNP associations in tissues and cell-types, expression quantitative trait loci and differential expression analysis. FINDINGS: Eight genes demonstrated a strong association signal: VWA8 gene in locus 13p14·11 (SNP rs10507497; p=9·54 x10-7), PDE8B gene in locus 5q13·3 (SNP rs7715119; p=2·19 x10-6), CTSC gene in locus 11q14·2 (rs72953026; p=2·38 x10-6), THSD7B gene in locus 2q22·1 (rs7605851; p=3·07x10-6), STK39 gene in locus 2q24·3 (rs7595310; p=4·55 x10-6), FBXO34 gene in locus 14q22·3 (rs10140801; p=8·26 x10-6), RPL6P27 gene in locus 18p11·31 (rs11659676; p=8·88 x10-6), and METTL21C gene in locus 13q33·1 (rs599976; p=8·95 x10-6). The genes are expressed in the lung, associated to tumour progression, emphysema, airway obstruction, and surface tension within the lung, as well as an association to T-cell-mediated inflammation and the production of inflammatory cytokines. INTERPRETATION: We have discovered eight highly plausible genetic association with hospitalized cases in COVID-19. Further studies must be conducted on worldwide population genetics to facilitate the development of population specific therapeutics to mitigate this worldwide challenge. FUNDING: This review was commissioned as part of a project to study the host cell receptors of coronaviruses funded by Khalifa University's CPRA grant (Reference number 2020-004).