bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher Relative Viral Load Excretion Determined by Normalised Threshold Crossing Value in Acute Cases infected with the B.1.1.7 Lineage VOC 202012/01 (Using S gene target failure as a Proxy) When Compared to other Circulating Lineages in Wales
Authors: Couzens Anastasia , Murrell Isa , Gifford Laura , Johns Ben , Pheasant Kathleen , Turner Luke , Evans Jonathan , Moore Catherine
Published: April 2021

Since the emergence of SARS-CoV-2, global monitoring of the virus using whole genome sequencing has identified mutations occurring across the viral genome. Whilst the majority have little impact on the virus, they are used effectively to monitor the movement of the virus globally and to inform locally on transmission chains.

In late 2020, a variant of SARS-CoV-2 (B.1.1.7 - VOC 202012/01) was identified in the UK with a distinct constellation of mutations, including in the spike gene that increased transmissibility. A deletion in spike also affected one of the screening qPCR tests being used in the UK outside of Wales, causing a failure to detect the target. This quickly became a surrogate marker for the variant to allow rapid monitoring of the virus as it seeded into new regions of the UK.

A screening study using this assay as a proxy marker, was undertaken to understand the prevalence of the variant in Wales. Secondary analysis of a screening qPCR that didn’t target the S gene and also included an endogenous control, was also performed to understand viral load excretion in those infected with the variant compared to other circulating lineages. Using a combination of analytical methods based on the Ct values of two gene targets normalised against the endogenous control, there was a difference in the excreted viral load. Those with the variant excreting more virus than those not infected with the variant. Supporting not only increased infectivity but offering a plausible reason why increased transmission was associated with this particular variant.

Whilst there are limitations in this study, the method using Ct as a proxy for viral load can be used at the population level to determine differences in viral excretion kinetics associated with different variants.
Effect of introducing interprofessional education concepts on students of various healthcare disciplines in the United Arab Emirates
Authors: Zaher Shroque , Otaki Farah , Zary Nabil , Marzouqi Amina Al , Radhakrishnan Rajan
Published: April 2021

Background

The value of interprofessional education (IPE) in nurturing healthcare professionals and shaping their professional identities and attitudes towards interdisciplinary teamwork and collaboration is established in the literature. It is an emerging concept in the Middle East and North Africa region and is new to the United Arab Emirates (UAE).

Purpose

To investigate the effect of one of the first experiences of IPE in the UAE, which was designed in alignment with the principles of the Situated Learning Theory, on students of various healthcare disciplines readiness for interprofessional learning and collaboration.

Methods

A pre-post intervention quantitative research design was adopted for this study to assess the effectiveness of the intervention in raising the level of readiness for interprofessional work among the participants. The participants included students of medicine, pharmacy, nursing, and physiotherapy. Readiness for Interprofessional Learning Scale (RIPLS) was used as the pre- and post-intervention assessments; data was analysed using SPSS.

Results

The IPE intervention under investigation significantly increased the level of readiness to engage in cross-disciplinary learning and collaboration among participating health professions’ students. In terms of the subscales, the participants’ openness to engage in teamwork was raised and their professional identity was fostered. Yet, no statistical significance around clarity of roles and responsibilities was detected.

Conclusion

IPE interventions hold the potential to significantly increase receptiveness to cross-disciplinary learning and collaboration among health professions’ students. The findings of this study encourage other universities in the MENA region to adopt IPE to improve future health professionals’ capacity to develop shared understanding and mutual respect within cross-disciplinary teams, which ultimately feed into improved quality of care and patient outcome.
Energy Insecurity Influences Urban Outdoor Air Pollution Levels during COVID-19 Lockdown in South-Central Chile
Authors: Martinez-Soto Aner , Avendaño-Vera Constanza , Boso Alex , Hofflinger Alvaro , Shupler Matthew
Published: April 2021

Introduction

In south-central Chile, outdoor air pollution primarily originates as household air pollution from wood burning for heating. The effect of COVID-19 lockdowns on ambient air pollution levels in urban south-central Chile may therefore be different from trends observed in cities where transportation and industrial emission sources dominate.

Methods

This quasi-experimental study compares hourly fine (PM2.5) and coarse (PM10) particulate matter measurements from six air monitoring stations (three reference grade beta attenuation monitors and three low-cost SPS30 sensors) in commercial and low or middle-income residential areas of Temuco and Padre Las Casas, Chile between March-September 2019 and 2020 (spanning COVID-19 lockdown).

Results

In Padre Las Casas, average outdoor PM2.5 concentrations peaked above 100 ug/m3 from 8-10 pm during winter (May-August) 2019 and 2020, when wood burning is common. During COVID-19 lockdown, average monthly ambient PM2.5 concentrations in a commercial and middle-income residential area of Temuco were up to 50% higher (12 µg/m3 to 18 µg/m3) and 59% higher (22 µg/m3 to 35 µg/m3) than 2019 levels, respectively. Conversely, PM2.5 levels decreased by up to 52% (43 µg/m3 to 21 µg/m3) in low-income neighborhoods. The night-time (8 pm-9 am) mass percent of PM10 that was PM2.5 during strict quarantine (April 2020) increased by 48% above April 2017-2019 proportions (50% to 74%) in a commercial area of Temuco.

Conclusions

Wood burning for home heating was responsible for a significantly higher proportion of ambient PM2.5 pollution in commercial areas and middle-income neighborhoods of Temuco during COVID-19 lockdown, compared to winter months in 2019. Constrastingly, energy insecure households likely refrained from wood heating during lockdown, leading to PM2.5 concentration declines. To reduce the double burden of ambient air pollution and energy insecurity in south-central Chile, affordability of clean heating fuels (e.g. electricity, liquefied petroleum gas) should be a policy priority.
CERC-002, a human anti-LIGHT mAb reduces respiratory failure and death in hospitalized COVID-19 ARDS patients
Authors: Perlin David S. , Neil Garry A. , Anderson Colleen , Zafir-Lavie Inbal , Roadcap Lori , Raines Shane , Ware Carl F. , Wilkins H. Jeffrey
Published: April 2021

Background

Severe COVID-19 infection is associated with dysregulated immune response which, in a substantial minority of patients, results in cytokine release syndrome (CRS) and acute respiratory distress syndrome (ARDS). Inhibition of cytokines or cytokine-associated signal transduction is a promising strategy to ameliorate ARDS associated with CRS. We and others have previously shown that serum free LIGHT (TNFSF14) levels are markedly elevated in patients with COVID-19 pneumonia/ARDS10,11, suggesting that LIGHT neutralization may offer therapeutic benefit to COVID-19 ARDS patients.

Methods

We conducted a randomized, double-blind, placebo-controlled, multi-center, proof-of-concept clinical trial of CERC-002 in adults with mild to moderate ARDS associated with COVID-19 (n=83). Enrolled patients received a single dose of CERC-002 or placebo, in addition to standard of care that included high dose corticosteroids. The primary efficacy endpoint was alive and free of respiratory failure status through Day 28. Secondary outcomes included alive status at Day 28, free of invasive ventilation through Day 28, and serum free LIGHT levels.

Results

In patients hospitalized with COVID-19 associated pneumonia and mild to moderate (ARDS), CERC-002 increased the rate of alive and free of respiratory failure status through Day 28 as compared to placebo (83.9% vs 64.5%; p=0.044). Efficacy was highest in the prespecified subgroup of patients 60 years old and older (76.5% vs 47.1%; p=0.042), the population most vulnerable to severe complications and death with COVID-19 infection. Through both the initial 28-day and 60-day follow-up periods, reductions of approximately 50% in mortality were observed for CERC-002 compared to placebo (7.7% vs 14.3% at Day 28 and 10.8% vs 22.5% at Day 60). Importantly, this improvement was incremental to standard of care including high dose steroids and remdesivir 88.0% and 57.8%, respectively). In addition, serum LIGHT levels but not IL-6 levels were markedly reduced in patients treated with CERC-002.

Conclusions

The data presented herein demonstrate that CERC-002 markedly reduces the risk of respiratory failure and death incremental to standard of care including high dose corticosteroids and reduces LIGHT levels in patients with COVID-19 ARDS. (ClinicalTrials.gov number NCT04412057).
Understanding how Victoria, Australia gained control of its second COVID-19 wave
Authors: Trauer James M , Lydeamore Michael J , Dalton Gregory W , Pilcher David , Meehan Michael T , McBryde Emma S , Cheng Allen C , Sutton Brett , Ragonnet Romain
Published: April 2021

Victoria has been Australia’s hardest hit state by the COVID-19 pandemic, but was successful in reversing its second wave of infections through aggressive policy interventions. The clear reversal in the epidemic trajectory combined with information on the timing and geographical scope of policy interventions offers the opportunity to estimate the relative contribution of each change. We developed a compartmental model of the COVID-19 epidemic in Victoria that incorporated age and geographical structure, and calibrated it to data on case notifications, deaths and health service needs according to the administrative divisions of Victoria’s healthcare, termed clusters. We achieved a good fit to epidemiological indicators, at both the state level and for individual clusters, through a combination of time-varying processes that included changes to case detection rates, population mobility, school closures, seasonal forcing, physical distancing and use of face coverings. Estimates of the risk of hospitalisation and death among persons with disease that were needed to achieve this close fit were markedly higher than international estimates, likely reflecting the concentration of the epidemic in groups at particular risk of adverse outcomes, such as residential facilities. Otherwise, most fitted parameters were consistent with the existing literature on COVID-19 epidemiology and outcomes. We estimated a significant effect for each of the calibrated time-varying processes on reducing the risk of transmission per contact, with broad estimates of the reduction in transmission risk attributable to seasonal forcing (27.8%, 95% credible interval [95%CI] 9.26-44.7% for mid-summer compared to mid-winter), but narrower estimates for the individual-level effect of physical distancing of 12.5% (95%CI 5.69-27.9%) and of face coverings of 39.1% (95%CI 31.3-45.8%). That the multi-factorial public health interventions and mobility restrictions led to the dramatic reversal in the epidemic trajectory is supported by our model results, with the mandatory face coverings likely to have been particularly important.
Screening for diabetes and impaired glucose metabolism in Qatar: models’ development and validation
Authors: Sadek Khaled , Abdelhafez Ibrahim , Al-Hashimi Israa , Al-Shafi Wadha , Tarmizi Fatihah , Al-Marri Hissa , Alzohari Nada , Balideh Mohammad , Carr Alison
Published: April 2021

Aim

To establish two scoring models for identifying individuals at risk of developing Impaired Glucose Metabolism (IGM) and Type two Diabetes Mellitus (T2DM) in Qatari.

Materials and Methods

A sample of 2000 individuals, from Qatar BioBank, was evaluated to determine features predictive of T2DM and IGM. Another sample of 1000 participants was obtained for external validation of the models. Several scoring models screening for T2DM were evaluated and compared to the model proposed by this study.

Results

Age, gender, waist-to-hip-ratio, history of hypertension and hyperlipidemia, and levels of educational were statistically associated with the risk of T2DM and constituted the Qatari diabetes risk score (QDRISK). Along with, the 6 aforementioned variables, the IGM model showed that BMI was statistically significant. The QDRISK performed well with an area under the curve (AUC) 0.870 and 0.815 in the development and external validation cohort, respectively. The QDRISK showed overall better accuracy and calibration compared to other evaluated scores. The IGM model showed good accuracy and calibration, AUCs 0.796 vs. 0.774 in the development and external validation cohorts, respectively.

Conclusions

This study developed a Qatari-specific risk scores to identify high risk individuals and can guide the development of a nationwide primary prevention program.
Sex and gender differences in COVID testing, hospital admission, presentation, and drivers of severe outcomes in the DC/Maryland region
Authors: Scully Eileen P. , Schumock Grant , Fu Martina , Massaccesi Guido , Muschelli John , Betz Joshua , Klein Eili Y. , West Natalie E. , Robinson Matthew , Garibaldi Brian T. , Bandeen-Roche Karen , Zeger Scott , Klein Sabra L. , Gupta Amita ,   for the JH-CROWN registry team
Published: April 2021

Structured Abstract

Background

Rates of severe illness and mortality from SARS-CoV-2 are greater for males, but the mechanisms for this difference are unclear. Understanding the differences in outcomes between males and females across the age spectrum will guide both public health and biomedical interventions.

Methods

Retrospective cohort analysis of SARS-CoV-2 testing and admission data in a health system. Patient-level data were assessed with descriptive statistics and logistic regression modeling was used to identify features associated with increased male risk of severe outcomes.

Results

In 213,175 SARS-CoV-2 tests, despite similar positivity rates (8.2%F vs 8.9%M), males were more frequently hospitalized (28%F vs 33%M). Of 2,626 hospitalized individuals, females had less severe presenting respiratory parameters and males had more fever. Comorbidity burden was similar, but with differences in specific conditions. Medications relevant for SARS-CoV-2 were used at similar frequency except tocilizumab (M>F). Males had higher inflammatory lab values. In a logistic regression model, male sex was associated with a higher risk of severe outcomes at 24 hours (odds ratio (OR) 3.01, 95%CI 1.75, 5.18) and at peak status (OR 2.58, 95%CI 1.78,3.74) among 18-49 year-olds. Block-wise addition of potential explanatory variables demonstrated that only the inflammatory labs substantially modified the OR associated with male sex across all ages.

Conclusion

Higher levels of clinical inflammatory labs are the only features that are associated with the heightened risk of severe outcomes and death for males in COVID-19.

Trial registration

NA

Funding

Hopkins inHealth; COVID-19 Administrative Supplement (HHS Region 3 Treatment Center), Office of the ASPR; NIH/NCI U54CA260492 (SK), NIH/NIA U54AG062333 (SK).
Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2
Authors: Deepak Parakkal , Kim Wooseob , Paley Michael A. , Yang Monica , Carvidi Alexander B. , El-Qunni Alia A. , Haile Alem , Huang Katherine , Kinnett Baylee , Liebeskind Mariel J. , Liu Zhuoming , McMorrow Lily E. , Paez Diana , Perantie Dana C. , Schriefer Rebecca E. , Sides Shannon E. , Thapa Mahima , Gergely Maté , Abushamma Suha , Klebert Michael , Mitchell Lynne , Nix Darren , Graf Jonathan , Taylor Kimberly E. , Chahin Salim , Ciorba Matthew A. , Katz Patricia , Matloubian Mehrdad , O’Halloran Jane A. , Presti Rachel M. , Wu Gregory F. , Whelan Sean P.J. , Buchser William J. , Gensler Lianne S. , Nakamura Mary C. , Ellebedy Ali H. , Kim Alfred H.J.
Published: April 2021

Background

Individuals with chronic inflammatory diseases (CID) are frequently treated with immunosuppressive medications that can increase their risk of severe COVID-19. While novel mRNA-based SARS-CoV-2 vaccination platforms provide robust protection in immunocompetent individuals, the immunogenicity in CID patients on immunosuppression is not well established. Therefore, determining the effectiveness of SARS-CoV-2 vaccines in the setting of immunosuppression is essential to risk-stratify CID patients with impaired protection and provide clinical guidance regarding medication management.

Methods

We conducted a prospective assessment of mRNA-based vaccine immunogenicity in 133 adults with CIDs and 53 immunocompetent controls. Blood from participants over 18 years of age was collected before initial immunization and 1-2 weeks after the second immunization. Serum anti-SARS-CoV-2 spike (S) IgG+binding, neutralizing antibody titers, and circulating S-specific plasmablasts were quantified to assess the magnitude and quality of the humoral response following vaccination.

Results

Compared to immunocompetent controls, a three-fold reduction in anti-S IgG titers (P=0.009) and SARS-CoV-2 neutralization (p<0.0001) were observed in CID patients. B cell depletion and glucocorticoids exerted the strongest effect with a 36- and 10-fold reduction in humoral responses, respectively (p<0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers in multivariate regression analysis (P<0.0001, P=0.0023, respectively). Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody formation and neutralization.

Conclusions

CID patients treated with immunosuppressive therapies exhibit impaired SARS-CoV-2 vaccine-induced immunity, with glucocorticoids and B cell depletion therapy more severely impeding optimal responses.
Evaluation of the performance of SARS-CoV-2 antibody assays for the longitudinal population-based study of COVID-19 spread in St. Petersburg, Russia
Authors: Barchuk Anton , Shirokov Daniil , Sergeeva Mariia , Tursun-zade Rustam , Dudkina Olga , Tychkova Varvara , Barabanova Lubov , Skougarevskiy Dmitriy , Danilenko Daria
Published: April 2021

Background

An evident geographical variation in the SARS-CoV-2 spread requires seroprevalence studies based on local tests with robust validation against already available antibody tests and neutralization assays. This report summarizes the evaluation of antibody tests used in the representative population-based serological study of SARS-CoV-2 in Saint Petersburg, Russia.

Methods

We used three different antibody tests throughout the study: chemiluminescent microparticle immunoassay (CMIA) Abbott Architect SARS-CoV-2 IgG, Enzyme-linked immunosorbent assay (ELISA) CoronaPass total antibodies test, and ELISA SARS-CoV-2-IgG-EIA-BEST. Clinical sensitivity was estimated with the SARS-CoV-2 PCR test as the gold standard and specificity in pre-pandemic sera samples using the cut-off recommended by manufacturers. Paired and unpaired serum sets were used. Measures of concordance were also calculated in the seroprevalence study sample against the microneutralization test (MNA).

Findings

Sensitivity was equal to 91.1% (95% CI: 78.8–97.5) and 90% (95% CI: 76.4–96.4) for ELISA Coronapass and ELISA Vector-Best respectively. It was equal to 63.1% (95% CI (50.2–74.7) for CMIA Abbott. Specificity was equal to 100% for all the tests. Comparison of ROCs for three tests has shown lower AUC for CMIA Abbott, but not for ELISA Coronapass and CMIA Abbott. The cutoff SC/O ratio of 0.28 for CMIA-Abbott resulted in a sensitivity of 80% at the same full level of specificity. In less than one-third of the population-based study participants with positive antibody test results, we detected neutralizing antibodies in titers 1:80 and above. There was a moderate correlation between antibody assays results and MNA.

Interpretation

Our validation study encourages the use of local antibody tests for population-based SARS-CoV-2 surveillance and sets the reference for the seroprevalence correction. Available tests are sensitive enough to detect antibodies in most individuals with previous positive PCR tests with a follow-up of more than 5 months. The Abbott Architect SARS-CoV-2 IgG’s sensitivity can be significantly improved by incorporating a new cut-off. Relying on manufacturers’ test characteristics for correction of reported prevalence estimates may introduce bias to the study results.

Funding

Polymetal International plc
Antibody response to SARS-CoV-2 mRNA vaccines in pregnant women and their neonates
Authors: Prabhu Malavika , Murphy Elisabeth A. , Sukhu Ashley C. , Yee Jim , Singh Sunidhi , Eng Dorothy , Zhao Zhen , Riley Laura E. , Yang Yawei J.
Published: April 2021

Pregnant women were excluded from initial clinical trials for COVID-19 vaccines1–2, thus the immunologic response to vaccination in pregnancy and the transplacental transfer of maternal antibodies are just beginning to be studied4–5.
High-Potency Polypeptide-based Inhibition of Enveloped-virus Glycoproteins
Authors: Ma Jianpeng , Acevedo Adam Campos , Wang Qinghua
Published: April 2021

Specific manipulation of proteins post-translationally remains difficult. Here we report results of a general approach that uses a partial sequence of a protein to efficiently modulate the expression level of the native protein. When applied to coronavirus, human immunodeficiency virus, Ebolavirus, respiratory syncytial virus and influenza virus, polypeptides containing highly conserved regions of the viral glycoproteins potently diminished expression of the respective native proteins. In the cases of coronavirus and influenza virus where multiple strains were tested, the polypeptides were equally effective against glycoproteins of other coronavirus and influenza strains with sequence identity as low as 27%, underscoring their high insensitivity to mutations. Thus, this method provides a platform for developing high-efficacy broad-spectrum anti-viral inhibitors, as well as a new way to alter expression of essentially any systems post-translationally.
“It’s possibly made us feel a little more alienated”: How people from ethnic minority communities conceptualise COVID-19 and its influence on engagement with testing
Authors: Vandrevala Tushna , Alidu Lailah , Hendy Jane , Shafi Shuja , Ala Aftab
Published: April 2021

Objectives

The cultural beliefs, practices and experiences of ethnic minority groups, alongside structural inequalities and the political economy play a critical, but overlooked role in health promotion. The current study aims to address this deficit; understanding how these groups conceptualise COVID-19, and how this influences engagement in testing, with the future aim of developing targeted communications to address the challenges of testing uptake.

Method

Black (African and Caribbean) and South Asian (Indian, Pakistani and Bangladeshi) community members were purposefully recruited across the UK. Fifty-seven semi-structured interviews were conducted and analysed using principles of Grounded Theory.

Results

The findings illustrate that Black and South Asian’s conceptualise COVID-19 as a disease that makes them visible to others outside their community; in having more severe risk and suffering worst consequences; resulting in fear, stigmatisation and alienation. Views about COVID-19 were embedded in cultural beliefs, relating to culturally specific ideas around disease, such as ill-health being God’s will. Challenges brought about by the pandemic were conceptualised as one of many struggles, with the saliency of the virus contextualised against life experiences. These themes and others influenced engagement with COVID-19 testing. Testing waslessabout accessing timely and effective treatment for themselves, and more about acting to protect the family and community. Testing symbolised a loss of income, anxiety and isolation, accentuated by issues of mistrust of the system, and not being valued, or being treated unfairly.

Conclusion

In tackling these challenges, we conclude that health communications should focus on counterbalancing the mistrust, alienation and stigmatisation that act as barriers to testing, with trust built using local credible sources.
Colony stimulating factor 1 signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands
Authors: Hason Martina , Mikulasova Tereza , Machonova Olga , Pombinho Antonio , van Ham Tjakko J , Irion Uwe , Nüsslein-Volhard Christiane , Bartunek Petr , Svoboda Ondrej
Published: April 2021

Macrophage colony-stimulating factor receptor (M-CSFR/CSF1R) signaling is crucial for the differentiation, proliferation, and survival of myeloid cells. Therapeutic targeting of the CSF1R pathway is a promising strategy in many human diseases, including neurological disorders or cancer. Zebrafish are commonly used for human disease modeling and preclinical therapeutic screening. Therefore, it is necessary to understand the proper function of cytokine signaling in zebrafish to reliably model human-related diseases. Here, we investigate the roles of zebrafish Csf1rs and their ligands - Csf1a, Csf1b and Il34, in embryonic and adult myelopoiesis. The proliferative effect of exogenous Csf1a on embryonic macrophages is connected to both receptors as it is diminished in bothcsf1raΔ5bpandcsf1rbΔ4bpmutants. There is no evident effect of Csf1b in zebrafish embryonic myelopoiesis. Further, we uncover an unknown role of Csf1rb in zebrafish granulopoiesis. Deregulation of Csf1rb signaling leads to failure in myeloid differentiation resulting in neutropenia throughout the whole lifespan. Surprisingly, Il34 signaling through Csf1rb seems to be of high importance as bothcsf1rbΔ4bpandil34Δ5bpdeficient zebrafish larvae lack granulocytes. Our single-cell RNA sequencing analysis of adult whole kidney marrow (WKM) hematopoietic cells suggests thatcsf1rbis expressed mainly by blood and myeloid progenitors and that the expression ofcsf1raandcsf1rbis non-overlapping. We point out differentially expressed genes important in hematopoietic cell differentiation and immune response in selected WKM populations. Our findings could improve the understanding of myeloid cell function and lead to the further study of CSF1R pathway deregulation in disease, mostly in cancerogenesis.

Key points:

csf1raandcsf1rbare indispensable for macrophage differentiation and together withcsf1aregulate embryonic macrophage fates in zebrafish

csf1rbis important for granulocyte differentiation and migration and together withil34it regulates embryonic granulocytic fates in zebrafish
ADNKA overcomes SARS-CoV2-mediated NK cell inhibition through non-spike antibodies
Authors: Fielding CA , Sabberwal P , Williamson JC , Greenwood EJD , Crozier TWM , Zelek W , Seow J , Graham C , Huettner I , Edgeworth JD , Price D , Morgan BP , Ladell K , Eberl M , Humphreys IR , Merrick B , Doores K , Wilson SJ , Lehner PJ , Wang ECY , Stanton RJ
Published: April 2021

The outcome of infection is dependent on the ability of viruses to manipulate the infected cell to evade immunity, and the ability of the immune response to overcome this evasion. Understanding this process is key to understanding pathogenesis, genetic risk factors, and both natural and vaccine-induced immunity. SARS-CoV-2 antagonises the innate interferon response, but whether it manipulates innate cellular immunity is unclear. An unbiased proteomic analysis determined how cell surface protein expression is altered on SARS-CoV-2-infected lung epithelial cells, showing downregulation of activating NK ligands B7-H6, MICA, ULBP2, and Nectin1, with minimal effects on MHC-I. This correlated with a reduction in NK cell activation, identifying a novel mechanism by which SARS-CoV2 antagonises innate immunity. Later in the disease process, strong antibody-dependent NK cell activation (ADNKA) developed. These responses were sustained for at least 6 months in most patients, and led to high levels of pro-inflammatory cytokine production. Depletion of spike-specific antibodies confirmed their dominant role in neutralisation, but these antibodies played only a minor role in ADNKA compared to antibodies to other proteins, including ORF3a, Membrane, and Nucleocapsid. In contrast, ADNKA induced following vaccination was focussed solely on spike, was weaker than ADNKA following natural infection, and was not boosted by the second dose. These insights have important implications for understanding disease progression, vaccine efficacy, and vaccine design.
The Evolutionary History of Wild, Domesticated, and FeralBrassica oleracea(Brassicaceae)
Authors: Mabry Makenzie E. , Turner-Hissong Sarah D. , Gallagher Evan Y. , McAlvay Alex C. , An Hong , Edger Patrick P. , Moore Jonathan D. , Pink David A. C. , Teakle Graham R. , Stevens Chris J. , Barker Guy , Labate Joanne , Fuller Dorian Q. , Allaby Robin G. , Beissinger Timothy , Decker Jared E. , Gore Michael A. , Pires J. Chris
Published: April 2021

Understanding the evolutionary history of crops, including identifying wild relatives, helps to provide insight for designing new approaches in crop breeding efforts. CultivatedBrassica oleraceahas intrigued researchers for centuries due to its wide diversity in forms, which include cabbage, broccoli, cauliflower, kale, kohlrabi, and Brussels sprouts. Yet, the evolutionary history of this species remains understudied. With such different vegetables produced from a single species,B. oleraceais a model organism for understanding the power of artificial selection. Persistent challenges in the study ofB. oleraceainclude conflicting hypotheses regarding domestication and the identity of the closest living wild relative. Using a diversity panel of 224 accessions, which represents 14 differentB. oleraceacrop types and nine potential wild progenitor species, we integrate phylogenetic and population genetic techniques with ecological niche modeling, archaeological, and literary evidence to examine relationships among cultivars and wild relatives to clarify the origin of this horticulturally important species. Our analyses point to the Aegean endemicB. creticaas the closest living relative of cultivatedB. oleracea, supporting an origin of cultivation in the Eastern Mediterranean region. Additionally, we identify several feral lineages, suggesting that cultivated plants of this species are able to revert to a wild-like state with relative ease. By expanding our understanding of the evolutionary history inB. oleracea, these results contribute to a growing body of knowledge on crop domestication that will facilitate continued breeding efforts including adaptation to changing environmental conditions.
Pre-diabetes increases tuberculosis disease severity, while high body fat without impaired glucose tolerance is protective
Authors: Sinha Roma , Ngo Minh Dao , Bartlett Stacey , Bielefeldt-Ohmann Helle , Keshvari Sahar , Hasnain Sumaira Z. , Donovan Meg L. , Kling Jessica C. , Blumenthal Antje , Chen Chen , Short Kirsty R. , Ronacher Katharina
Published: April 2021

Type 2 diabetes (T2D) is a well-known risk factor for tuberculosis (TB), but little is known about pre-diabetes and the relative contribution of impaired glucose tolerancevs. obesity towards susceptibility to TB. Here, we developed a preclinical model of pre-diabetes and TB. Mice fed a high fat diet (HFD) for 12 weeks presented with impaired glucose tolerance and hyperinsulinemia compared to mice fed normal chow diet (NCD). Infection withM. tuberculosis(Mtb) H37Rvafter the onset of dysglycemia was associated with significantly increased lung pathology, lower concentrations of TNF-a, IFN-g, IFN-β and IL-10 and a trend towards higher bacterial burden at 3 weeks post infection. To determine whether the increased susceptibility of pre-diabetic mice to TB is reversible and is associated with dysglycemia or increased body fat mass, we performed a diet reversal experiment. Pre-diabetic mice were fed a NCD for 10 additional weeks (HFD/NCD) at which point glucose tolerance was restored, but body fat mass remained higher compared to control mice that consumed NCD throughout the entire experiment (NCD/NCD). Upon Mtb infection HFD/NCD mice had significantly lower bacterial burden compared to NCD/NCD mice and this was accompanied by restored IFN-γ responses. Our findings demonstrate that pre-diabetes increases susceptibility to TB, but a high body mass index without dysglycemia is protective. This murine model offers the opportunity to further study the underlying immunological, metabolic and endocrine mechanisms of this association.
Controlling multiple COVID-19 epidemic waves: an insight from a multi-scale model linking the behavior change dynamics to the disease transmission dynamics
Authors: Tang Biao , Zhou Weike , Wang Xia , Wu Hulin , Xiao Yanni , Tang Sanyi
Published: April 2021

COVID-19 epidemics exhibited multiple waves regionally and globally since 2020. It is important to understand the insight and underlying mechanisms of the multiple waves of COVID-19 epidemics in order to design more efficient non-pharmaceutical interventions (NPIs) and vaccination strategies to prevent future waves. We propose a multi-scale model by linking the behavior change dynamics to the disease transmission dynamics to investigate the effect of behavior dynamics on COVID-19 epidemics using the game theory. The proposed multi-scale model was calibrated and key parameters related to disease transmission dynamics and behavioral dynamics with/without vaccination were estimated based on COVID-19 epidemic data and vaccination data. Our modeling results demonstrate that the feedback loop between behavior changes and COVID-19 transmission dynamics plays an essential role in inducing multiple epidemic waves. We find that the long period of high-prevalence or persistent deterioration of COVID-19 epidemics could drive almost all population to change their behaviors and maintain the altered behaviors, however, the effect of behavior changes faded out gradually along the progress of epidemics. This suggests that it is essential not only to have persistent, but also effective behavior changes in order to avoid subsequent epidemic waves. In addition, our model also suggests the importance to maintain the effective altered behaviors during the initial stage of vaccination, and to counteract relaxation of NPIs, it requires quick and massive vaccination to avoid future epidemic waves.
Modelling vaccination capacity at mass vaccination hubs and general practice clinics
Authors: Hanly Mark , Churches Tim , Fitzgerald Oisín , Caterson Ian , MacIntyre Chandini Raina , Jorm Louisa
Published: April 2021

COVID-19 population vaccination programs are underway globally. In Australia, the federal government has entered into three agreements for the supply of vaccines, with roll-out beginning for the highest priority groups in February 2021. Expansion of the vaccination program throughout February and March failed to meet government targets and this has been attributed to international supply issues. However, Australia has local capacity to manufacture one million doses of the AstraZeneca vaccine weekly and once fully operational this will greatly increase the national vaccination capacity. Under current plans, these vaccine doses will be distributed primarily through a network of general practices, to be joined in later phases by community pharmacies. It remains unclear whether these small distribution venues have the logistical capacity to administer vaccines at the rate they will become available. To inform this discussion, we applied stochastic queue network models to estimate the capacity of vaccination sites based on assumptions about appointment schedules, service times and available staff numbers. We specified distinct queueing models for two delivery modes: (i) mass vaccination hubs located in hospitals or sports arenas and (ii) smaller clinics situated in general practices or community pharmacies. Based on our assumed service times, the potential daily throughput for an eight hour clinic at a mass vaccination hub ranged from around 500 vaccinations for a relatively small hub to 1,400 vaccinations a day for a relatively large hub. For GP vaccination clinics, the estimated daily throughput ranged from about 100 vaccinations a day for a relatively small practice to almost 300 a day for a relatively large practice. Stress tests showed that for both delivery modes, sites with higher staff numbers were more robust to system pressures, such as increased arrivals or staff absences, and mass vaccination sites were more robust that GP clinics. Our analysis is accompanied by an interactive web-based queue simulation applet, which allows users to explore queue performance under their own assumptions regarding appointments, service times and staff availability. Different vaccine delivery modes offer distinct benefits and may be particularly appealing to specific population segments. A combination of expanded mass vaccination hubs and expanded GP vaccination is likely to achieve mass vaccination faster than either mode alone.
Towards customized studies of G-quadruplex DNA structures in live cells
Authors: Prasad Bagineni , Doimo Mara , Andréasson Måns , L’Hôte Valentin , Chorell Erik , Wanrooij Sjoerd
Published: April 2021

G-quadruplex (G4) DNA structures are implicated in central biological processes and are considered promising therapeutic targets because of their links to human diseases such as cancer. However, functional details of how, when, and why G4 DNA structures formin vivoare largely missing leaving a knowledge gap that requires tailored chemical biology studies in relevant live-cell model systems. Towards this end, we developed a synthetic platform centered around one of the most effective and selective G4 stabilizing compounds, Phen-DC3. We used a structure-based design to equip Phen-DC3 with an amine in a position that does not interfere with G4 interactions. To evaluate the power of the approach, we next used this reactive handle to conjugate a BODIPY fluorophore and a cell-penetrating peptide to Phen-DC3. The BODIPY conjugation generated a fluorescent derivative with retained G4 selectivity, G4 stabilization, and cellular effects that revealed the localization and function of Phen-DC3 in human cells. On the other hand, the cell-penetrating peptide conjugation, while retaining G4 selectivity and stabilization, increased nuclear localization and cellular effects, showcasing the potential of this approach to modulate and direct cellular uptake e.g. as delivery vehicles. The developed platform can thus generate tailored biochemical tools for the studies of G4 biology to uncover molecular details and therapeutic approaches.
Zebrafish heme oxygenase 1a is necessary for normal development and macrophage migration
Authors: Luo Kaiming , Ogawa Masahito , Ayer Anita , Britton Warwick J , Stocker Roland , Kikuchi Kazu , Oehlers Stefan H
Published: April 2021

Heme oxygenase function is highly conserved between vertebrates where it plays important roles in normal embryonic development and controls oxidative stress. Expression of the zebrafish heme oxygenase 1 genes are known to be responsive to oxidative stress suggesting a conserved physiological function. Here we generate a knockout allele of zebrafishhmox1aand characterize the effects ofhmox1aandhmox1bloss on embryonic development. We find that loss ofhmox1aorhmox1bcauses developmental defects in only a minority of embryos, in contrast toHmox1gene deletions in mice that causes loss of most embryos. Using a tail wound inflammation assay we find a conserved role forhmox1a, but nothmox1b, in normal macrophage migration to the wound site. Together our results indicate zebrafishhmox1ahas clearly a partitioned role fromhmox1bthat is more consistent with conserved functions of mammalian Heme oxygenase 1.
Enabling constrained spherical deconvolution and diffusional variance decomposition with tensor-valued diffusion MRI
Authors: Karan Philippe , Reymbaut Alexis , Gilbert Guillaume , Descoteaux Maxime
Published: April 2021

Diffusion tensor imaging (DTI) is widely used to extract valuable tissue measurements and white matter (WM) fiber orientations, even though its lack of specificity is now well-known, especially for WM fiber crossings. Models such as constrained spherical deconvolution (CSD) take advantage of high angular resolution diffusion imaging (HARDI) data to compute fiber orientation distribution functions (fODF) and tackle the orientational part of the DTI limitations. Furthermore, the recent introduction of tensor-valued diffusion MRI allows for diffusional variance decomposition (DIVIDE), opening the door to the computation of measures more specific to microstructure than DTI measures, such as microscopic fractional anisotropy (μFA). However, tensor-valued diffusion MRI data is not mathematically compatible with latest versions of CSD and the impacts of such atypical data on fODF reconstruction with CSD are yet to be studied. In this work, we lay down the mathematical and computational foundations of a tensor-valued CSD and use simulated data to explore the effects of various combinations of diffusion encodings on the angular resolution of extracted fOFDs. We also compare the combinations with regards to their performance at producing accurate and precise μFA with DIVIDE, and present an optimised protocol for both methods. We show that our proposed protocol enables the reconstruction of both fODFs and μFA onin vivodata.
Experimental and numerical prediction of lean blowout limits for micro gas turbine combustor
Authors: V. Kirubakaran , Bhatt David
Published: April 2021

Purpose

The lean blowout (LBO) limit of the combustor is one of the important performance parameters for any gas turbine combustor design. This study aims to predict the LBO limits of an in-house designed swirl stabilized 3kW can-type micro gas turbine combustor.

Design/methodology/approach

The experimental prediction of LBO limits was performed on 3kW swirl stabilized combustor fueled with methane for the combustor inlet velocity ranging from 1.70 m/s to 6.80 m/s. The numerical prediction of LBO limits of combustor was performed on two-dimensional axisymmetric model. The blowout limits of combustor were predicted through calculated average exit gas temperature (AEGT) method and compared with experimental predictions.

Findings

The results show that the predicted LBO equivalence ratio decreases gradually with an increase in combustor inlet velocity.

Practical implications

This LBO limits predictions will use to fix the operating boundary conditions of 3kW can-type micro gas turbine combustor. This methodology will be used in design stage as well as in the testing stage of the combustor.

Originality/value

This is a first effort to predict the LBO limits on micro gas turbine combustor through AEGT method. The maximum uncertainty in LBO limit prediction with AEGT is 6 % in comparison with experimental results.
Allocating scarce financial resources effectively through function analysis in social housing projects
Authors: Melo Luane Assunção Paiva , Oliveira Clara Beatriz Ferreira de , Melo Reymard Savio Sampaio de
Published: April 2021

Purpose

Budget constraints faced by social housing projects (SHPs) developers can lead to poor value delivery to the end-users. Without a structured method to guide the decision-making processes during product development, SHP often fails to meet user needs and aspirations. Function analysis (FA) is an essential step in a value management (VM) study. Still, FA practice in SHP has been treated with secondary importance. This paper aims to propose a method for improving FA practice in the VM process for a Brazilian SHP to achieve optimum benefits.

Design/methodology/approach

The research followed Design Science Research (DSR) in a specific single case study context, focusing on solving practical problems while contributing to theory. The method has 11 steps and guides a complete VM exercise. Its development was based on prior VM research. Focus group meetings were held to get feedback about the initial method's version to increase its relevancy and applicability in the studied context.

Findings

The proposed method suggests that scarce financial resources in SHP do not necessarily lead to low-value delivery and low-design quality. When FA is fully implemented, opportunities for cost reallocations to enhance value are identified.

Originality/value

VM prior research in construction has not provided a specific method for improving FA practice for social housing developers to enhance value in the context of scarce financial resources.
The effect of corporate social responsibility on employee advocacy behaviors: a perspective of conservation of resources
Authors: Liu Zonghua , Guo Yulang , Liao Junyun , Li Yanping , Wang Xu
Published: April 2021

Purpose

Despite past studies revealed the positive effect of corporate social responsibility (CSR) on consumer advocacy behavior, little research has paid attention to employee advocacy behavior. This research aims to examine the relationship between CSR and employee advocacy behavior, the mediating role of meaningful work as well as the moderating effect of person–supervisor fit on CSR perception – meaningful work relationship.

Design/methodology/approach

This study used 263 employee samples to examine the relationship between CSR and employee advocacy behavior and its influence mechanism. Hierarchical regression analyses and bootstrap approach were applied to analyze the data.

Findings

The results show that CSR perception is positively related to employee advocacy behavior, meaningful work mediates the link between CSR perception and employee advocacy behavior, and the strength of the relationship between CSR perception and meaningful work depends on person–supervisor fit.

Research limitations

This study only investigated the effect of perceived CSR on employee advocacy behavior, future studies should explore the alternative mediation mechanism through which external/internal CSR perception or different CSR dimensions influence employee advocacy behavior.

Practical implications

This study has practical implications for organizational managers. First, firms should undertake CSR practices and make employee interpret them in a right way. Second, meaningful work is of significance for employees and training and development, challenging jobs and job rotation are conducive to create a sense of meaning in employees’ work.

Originality/value

This study discussed how and when CSR influences employee advocacy in the Chinese context.