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1.
COVID-19 and the Voluntary and Community Sector in the UK: Responses, Impacts and Adaptation ; CHAP: 186-198,
Article in English | Scopus | ID: covidwho-2092930
2.
Academic Voices: A Conversation on New Approaches to Teaching and Learning in the post-COVID World ; : 269-281, 2022.
Article in English | Scopus | ID: covidwho-2035550

ABSTRACT

This chapter tells the story of 13 higher education (HE) practitioners (academics and academic developers) from 10 universities across Australia and New Zealand leveraging the COVID-19 disruption as a ‘disorienting dilemma’ that precipitated transformation from a Community of Practice (CoP) to a Community for Practice (CfP). The aim is to show how the group commenced as a CoP to ‘Talk About Teaching and Learning’ (TATAL) and support one another towards HE fellowships, and grew into a CfP that supports holistic growth that benefits each member based on their specific contexts, needs, and goals. With reflections woven throughout as evidence of transformation, the purpose of this chapter is to demonstrate how an interdisciplinary, multiuniversity group has created and nurtured a sustainable CfP. Experiential learning and reflective practice models, which are underpinned by considerations of action research and collaborative autoethnography, support and account for insights into the transformative changes. © 2022 Elsevier Ltd. All rights reserved.

3.
Clin Epigenetics ; 14(1): 94, 2022 07 23.
Article in English | MEDLINE | ID: covidwho-1957069

ABSTRACT

We recently reported the COVID-19-induced circulating leukocytes DNA methylation profile. Here, we hypothesized that some of these genes would persist differentially methylated after disease resolution. Fifteen participants previously hospitalized for SARS-CoV-2 infection were epityped one year after discharge. Of the 1505 acute illness-induced differentially methylated regions (DMRs) previously identified, we found 71 regions with persisted differentially methylated, with an average of 7 serial CpG positions per DMR. Sixty-four DMRs persisted hypermethylated, and 7 DMR persisted hypomethylated. These data are the first reported evidence that DNA methylation changes in circulating leukocytes endure long after recovery from acute illness.


Subject(s)
COVID-19 , DNA Methylation , Acute Disease , COVID-19/genetics , CpG Islands , Humans , SARS-CoV-2
4.
PubMed; 2020.
Preprint in English | PubMed | ID: ppcovidwho-333563

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The initial interaction between Transmembrane Serine Protease 2 (TMPRSS2) primed SARS-CoV-2 spike (S) protein and host cell receptor angiotensin-converting enzyme 2 (ACE-2) is a pre-requisite step for this novel coronavirus pathogenesis. Here, we expressed a GFP-tagged SARS-CoV-2 S-Ectodomain in Tni insect cells. That contained sialic acid-enriched N- and O-glycans. Surface resonance plasmon (SPR) and Luminex assay showed that the purified S-Ectodomain binding to human ACE-2 and immunoreactivity with COVID-19 positive samples. We demonstrate that bromelain (isolated from pineapple stem and used as a dietary supplement) treatment diminishes the expression of ACE-2 and TMPRSS2 in VeroE6 cells and dramatically lowers the expression of S-Ectodomain. Importantly, bromelain treatment reduced the interaction between S-Ectodomain and VeroE6 cells. Most importantly, bromelain treatment significantly diminished the SARS-CoV-2 infection in VeroE6 cells. Altogether, our results suggest that bromelain or bromelain rich pineapple stem may be used as an antiviral against COVID-19. HIGHLIGHTS: Bromelain inhibits / cleaves the expression of ACE-2 and TMPRSS2Bromelain cleaves / degrades SARS-CoV-2 spike proteinBromelain inhibits S-Ectodomain binding and SARS-CoV-2 infection.

5.
2021 IEEE CHILEAN Conference on Electrical, Electronics Engineering, Information and Communication Technologies, CHILECON 2021 ; 2021.
Article in Spanish | Scopus | ID: covidwho-1774578

ABSTRACT

COVID-19 is considered one of the largest pandemics in recent times. Predicting the number of future COVID-19 cases is extremely important for governments in order to make decisions about mobility restrictions, and for hospitals to be able to manage medical supplies, as well as health staff. Most of the predictions of COVID-19 cases are based on mathematical-epidemiological models such as the SEIR and SIR models. In our work, we propose a model of neural networks GCN-LSTM (Graph Convolutional Network - Long Short Term Memory) to predict the spatio-temporal rate incidence of COVID-19 in the Metropolitana Region, Chile. While the GCN network incorporates the spatial correlation in the nearby municipalities, the LSTM network considers the temporal correlation for the prediction over time. To interpolate the missing daily data for the network input, the use of the GAM (Generalized Additive Model) model is proposed. The results show better predictions for some municipalities with higher habitat density. © 2021 IEEE.

6.
Achdout, H.; Aimon, A.; Bar-David, E.; Barr, H.; Ben-Shmuel, A.; Bennett, J.; Bilenko, V. A.; Bilenko, V. A.; Boby, M. L.; Borden, B.; Bowman, G. R.; Brun, J.; Bvnbs, S.; Calmiano, M.; Carbery, A.; Carney, D.; Cattermole, E.; Chang, E.; Chernyshenko, E.; Chodera, J. D.; Clyde, A.; Coffland, J. E.; Cohen, G.; Cole, J.; Contini, A.; Cox, L.; Cvitkovic, M.; Dias, A.; Donckers, K.; Dotson, D. L.; Douangamath, A.; Duberstein, S.; Dudgeon, T.; Dunnett, L.; Eastman, P. K.; Erez, N.; Eyermann, C. J.; Fairhead, M.; Fate, G.; Fearon, D.; Fedorov, O.; Ferla, M.; Fernandes, R. S.; Ferrins, L.; Foster, R.; Foster, H.; Gabizon, R.; Garcia-Sastre, A.; Gawriljuk, V. O.; Gehrtz, P.; Gileadi, C.; Giroud, C.; Glass, W. G.; Glen, R.; Glinert, I.; Godoy, A. S.; Gorichko, M.; Gorrie-Stone, T.; Griffen, E. J.; Hart, S. H.; Heer, J.; Henry, M.; Hill, M.; Horrell, S.; Huliak, V. D.; Hurley, M. F. D.; Israely, T.; Jajack, A.; Jansen, J.; Jnoff, E.; Jochmans, D.; John, T.; De Jonghe, S.; Kantsadi, A. L.; Kenny, P. W.; Kiappes, J. L.; Kinakh, S. O.; Koekemoer, L.; Kovar, B.; Krojer, T.; Lee, A.; Lefker, B. A.; Levy, H.; Logvinenko, I. G.; London, N.; Lukacik, P.; Macdonald, H. B.; MacLean, B.; Malla, T. R.; Matviiuk, T.; McCorkindale, W.; McGovern, B. L.; Melamed, S.; Melnykov, K. P.; Michurin, O.; Mikolajek, H.; Milne, B. F.; Morris, A.; Morris, G. M.; Morwitzer, M. J.; Moustakas, D.; Nakamura, A. M.; Neto, J. B.; Neyts, J.; Nguyen, L.; Noske, G. D.; Oleinikovas, V.; Oliva, G.; Overheul, G. J.; Owen, D.; Pai, R.; Pan, J.; Paran, N.; Perry, B.; Pingle, M.; Pinjari, J.; Politi, B.; Powell, A.; Psenak, V.; Puni, R.; Rangel, V. L.; Reddi, R. N.; Reid, S. P.; Resnick, E.; Ripka, E. G.; Robinson, M. C.; Robinson, R. P.; Rodriguez-Guerra, J.; Rosales, R.; Rufa, D.; Saar, K.; Saikatendu, K. S.; Schofield, C.; Shafeev, M.; Shaikh, A.; Shi, J.; Shurrush, K.; Singh, S.; Sittner, A.; Skyner, R.; Smalley, A.; Smeets, B.; Smilova, M. D.; Solmesky, L. J.; Spencer, J.; Strain-Damerell, C.; Swamy, V.; Tamir, H.; Tennant, R.; Thompson, W.; Thompson, A.; Tomasio, S.; Tsurupa, I. S.; Tumber, A.; Vakonakis, I.; Van Rij, R. P.; Vangeel, L.; Varghese, F. S.; Vaschetto, M.; Vitner, E. B.; Voelz, V.; Volkamer, A.; Von Delft, F. f, Von Delft, A.; Walsh, M.; Ward, W.; Weatherall, C.; Weiss, S.; White, K. M.; Wild, C. F.; Wittmann, M.; Wright, N.; Yahalom-Ronen, Y.; Zaidmann, D.; Zidane, H.; Zitzmann, N..
Embase; 2020.
Preprint in English | EMBASE | ID: ppcovidwho-330569

ABSTRACT

The COVID-19 pandemic is a stark reminder that a barren global antiviral pipeline has grave humanitarian consequences. Future pandemics could be prevented by accessible, easily deployable broad-spectrum oral antivirals and open knowledge bases that derisk and accelerate novel antiviral discovery and development. Here, we report the results of the COVID Moonshot, a fully open-science structure-enabled drug discovery campaign targeting the SARS-CoV-2 main protease. We discovered a novel chemical scaffold that is differentiated to current clinical candidates in terms of toxicity and pharmacokinetics liabilities, and developed it into orally-bioavailable inhibitors with clinical potential. Our approach leverages crowdsourcing, high throughput structural biology, machine learning, and exascale molecular simulations. In the process, we generated a detailed map of the structural plasticity of the main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. In a first for a structure-based drug discovery campaign, all compound designs (>18,000 designs), crystallographic data (>500 ligand-bound X-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2,400 compounds) for this campaign were shared rapidly and openly, creating a rich open and IP-free knowledgebase for future anti-coronavirus drug discovery.

8.
European Heart Journal ; 42(SUPPL 1):3267, 2021.
Article in English | EMBASE | ID: covidwho-1554126

ABSTRACT

Background/Introduction: SARS-CoV-2 causes life threatening COVID- 19 complications including acute coronary syndrome, venous thromboembolism, hyperinflammation and damage in multiple tissues. The SARSCoV- 2 spike protein binds cell surface receptors including angiotensinconverting enzyme 2 (ACE2) for entry into host cells to initiate infection. Host cell dipeptidyl peptidase-4 (DPP4 / CD26) is implicated as a cofactor in uptake. Recent evidence indicates expression of factors involved in SARS-CoV-2 uptake into host cells is regulated by BET proteins, epigenetic readers modulating gene expression. Apabetalone, the most clinically advanced BET inhibitor (BETi), is in phase 3 trials for cardiovascular disease (CVD) (a, b). In cultured human cardiomyocytes, apabetalone suppressed infection with SARS-CoV-2 and prevented dysfunction of cardiac organoids induced by the cytokine-storm that arises in patients with severe symptoms (c). However, anti-viral properties of apabetalone in other cell types are not known. Purpose: To examine effects of apabetalone on SARS-CoV-2 infection in cell culture via downregulated expression of cell surface receptors involved in viral entry. Cell systems used mimic initial sites of infection in the lung as well as cell types contributing to complications in late stages of infection. Methods: Gene expression was measured by real-time PCR, protein levels by immunoblot or flow cytometry, and binding of recombinant SARSCoV- 2 spike protein by flow cytometry. Infection with SARS-CoV-2 was determined in a BSL3 facility. Infectivity was quantified by determining levels of viral spike protein amongst total cells via imaging on an Operetta CLS. Results: In Calu-3, a human bronchial epithelial cell line, apabetalone dose-dependently downregulated ACE2 gene expression (up to 98%), reduced ACE2 protein levels (up to 84%) and diminished binding of SARSCoV- 2 spike protein (up to 77%, p<0.001 for all parameters). Further, apabetalone abolished infection of Calu-3 cells with live SARS-CoV-2, which was comparable to other antiviral agents. Apabetalone-driven ACE2 downregulation was also observed in extrapulmonary cell types including HepG2, Huh-7 or primary hepatocytes (up to 90%, p<0.001 for all cell types), and Vero E6, a monkey kidney epithelial cell line (up to 38%, p<0.05). DPP4/CD26, a potential cofactor for SARS-CoV-2 uptake, was also downregulated by apabetalone in Calu-3 cells (mRNA ∼65% and protein ∼40%, p<0.001), which may be synergistic with ACE2 reductions to impede SARS-CoV-2 infection. Conclusions: Apabetalone, an investigational drug for CVD, reduced cell surface receptors (ACE2 and DPP4) involved in SARS-CoV-2 uptake into host cells and dramatically attenuated SARS-CoV-2 infection/propagation in vitro. Our results suggest apabetalone can mitigate SARS-CoV-2 replication in multiple organs, which together with an established safety profile supports clinical evaluation of apabetalone to treat.

9.
British Journal of Surgery ; 108:136-136, 2021.
Article in English | Web of Science | ID: covidwho-1539371
10.
S Afr Med J ; 111(9): 849-851, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1404035

ABSTRACT

During the second wave of the COVID-19 pandemic in South Africa, a recurrent pattern of prolonged recovery after acute COVID-19 pneumonia, characterised by low oxygen saturation levels for >2 weeks, was observed in an intermediate-care facility in Cape Town. A case study together with a series of 12 patients is presented to illustrate this phenomenon, and two types of 'sats gap' are described, which were used by physiotherapists and doctors to monitor daily progress. We attempt to explain this prolonged recovery in terms of the possible pathophysiology, and suggest a number of learning points to guide further research.


Subject(s)
COVID-19/complications , Pneumonia, Viral/physiopathology , Aged , Female , Humans , Pneumonia, Viral/virology , Recovery of Function , South Africa
11.
Clin Epigenetics ; 13(1): 118, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1243819

ABSTRACT

BACKGROUND: There are no prior reports that compare differentially methylated regions of DNA in blood samples from COVID-19 patients to samples collected before the SARS-CoV-2 pandemic using a shared epigenotyping platform. We performed a genome-wide analysis of circulating blood DNA CpG methylation using the Infinium Human MethylationEPIC BeadChip on 124 blood samples from hospitalized COVID-19-positive and COVID-19-negative patients and compared these data with previously reported data from 39 healthy individuals collected before the pandemic. Prospective outcome measures such as COVID-19-GRAM risk-score and mortality were combined with methylation data. RESULTS: Global mean methylation levels did not differ between COVID-19 patients and healthy pre-pandemic controls. About 75% of acute illness-associated differentially methylated regions were located near gene promoter regions and were hypo-methylated in comparison with healthy pre-pandemic controls. Gene ontology analyses revealed terms associated with the immune response to viral infections and leukocyte activation; and disease ontology analyses revealed a predominance of autoimmune disorders. Among COVID-19-positive patients, worse outcomes were associated with a prevailing hyper-methylated status. Recursive feature elimination identified 77 differentially methylated positions predictive of COVID-19 severity measured by the GRAM-risk score. CONCLUSION: Our data contribute to the awareness that DNA methylation may influence the expression of genes that regulate COVID-19 progression and represent a targetable process in that setting.


Subject(s)
COVID-19/blood , COVID-19/mortality , DNA Methylation/physiology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , New York/epidemiology , Prospective Studies , SARS-CoV-2
12.
Anaesthesia ; 76(SUPPL 2):83, 2021.
Article in English | EMBASE | ID: covidwho-1093681

ABSTRACT

Basic life support (BLS) is a core training component for mental health staff. National guidance states regular training is essential to maintain confidence in providing BLS [1]. Mental health staff in Central and North West London NHS Foundation Trust (CNWL) undergo 3-yearly mandatory training. Staff feel confident in BLS skills at mandatory sessions, but feel less confident in real situations in the workplace. Simulation is an evidence-based teaching method, reflective of real-life scenarios in a safe environment, which increases participant confidence [2]. We advocate use of peer-led simulation to improve confidence in adult BLS provision in CNWL mental health staff working at St Mary's Hospital. Methods A three-part simulation course was designed by a junior doctor qualified in advanced resuscitation. Teaching was delivered over two 45-min sessions to 11 mental health nurses. A five-point scale questionnaire was used to evaluate nurse confidence in elements of BLS provision before and after sessions. Practical skills were executed on manikin, dummy equipment and an automated external defibrillator (AED). Each subsequent session was altered to suit learner needs and to incorporate changes due to COVID-19. Participants were encouraged to lead session scenarios. Results A twofold increase in mean confidence was seen in participants (41% to 96%;p < 0.001) after the initial session. No participants felt unconfident providing BLS after the session. The greatest improvement in confidence was seen in assessing the unwell patient, providing BLS and recognising anaphylaxis (64% increase). The most significant increase in participant confidence was seen in AED use (46% increase;p = 0.0001). Our second session incorporated changes in BLS provision due to COVID-19. Confidence in providing BLS and using an AED was sustained. A sevenfold increase in mean confidence was seen in providing BLS to the COVID-19 patient (11% to 78%;p < 0.001). Confidence in use of personal protective equipment increased threefold. Discussion Regular peer-led simulation training of mental health staff markedly improves their confidence in adult BLS. This may be due to reduced participant anxiety, increased team familiarity and engagement in familiar settings during training sessions. We propose yearly simulation training to refresh skills and maintain mental health staff confidence in recognising and managing acutely unwell adults in CNWL NHS Trust.

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