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Medicinal chemistry optimization of a previously described stilbene inhibitor of HIV-1, 5350150 (2-(2-(5-nitro-2-thienyl)vinyl)quinoline), led to the identification of the thiazole-5-carboxamide derivative (GPS491), which retained potent anti-HIV-1 activity with reduced toxicity. In this report, we demonstrate that the block of HIV-1 replication by GPS491 is accompanied by a drastic inhibition of viral gene expression (IC50 ~ 0.25 µM), and alterations in the production of unspliced, singly spliced, and multiply spliced HIV-1 RNAs. GPS491 also inhibited the replication of adenovirus and multiple coronaviruses. Low µM doses of GPS491 reduced adenovirus infectious yield ~1000 fold, altered virus early gene expression/viral E1A RNA processing, blocked viral DNA amplification, and inhibited late (hexon) gene expression. Loss of replication of multiple coronaviruses (229E, OC43, SARS-CoV2) upon GPS491 addition was associated with the inhibition of viral structural protein expression and the formation of virus particles. Consistent with the observed changes in viral RNA processing, GPS491 treatment induced selective alterations in the accumulation/phosphorylation/function of splicing regulatory SR proteins. Our study establishes that a compound that impacts the activity of cellular factors involved in RNA processing can prevent the replication of several viruses with minimal effect on cell viability.

Education for sustainable development (ESD) is considered vital to the success of the United Nations¿ sustainable development goals. Systems thinking has been identified as a core competency that must be included in ESD. However, systems thinking-orientated ESD learning tools, established methods of the assessment of sustainability skills, and formal trials to demonstrate the effectiveness of such learning tools are all lacking. This research presents a randomised controlled trial (n = 106) to investigate whether an innovative online sustainability learning tool that incorporates two factors, systems thinking and system dynamics simulation, increases the understanding of a specific sustainability problem. A further aim was to investigate whether these factors also support the transfer of knowledge to a second problem with a similar systemic structure. The effects of the two factors were tested separately and in combination using a two-by-two factorial study design. ANOVA and related inferential statistical techniques were used to analyse the effect of the factors on sustainability understanding. Cohen¿s d effect sizes were also calculated. Simulation alone was found to increase ESD learning outcomes significantly, and also to support the transfer of skills, although less significantly. Qualitative feedback was also gathered from participants, most of whom reported finding systems thinking and simulation very helpful. This research was undertaken for the PhD studies of the corresponding author at the National University of Ireland Galway (NUIG) and was supported by funding from ResponSEAble (EU Horizon 2020 project number 652643), Ireland’s Higher Education Authority and Department of Further and Higher Education, Research, Innovation and Science (through the IT Investment Fund and ComputerDISC, and the COVID-19 Costed Extension), and the NUIG PhD Write-Up Bursary. peer-reviewed

This chapter reflects on how youth, through the medium of youth-led research, can seek to influence public policy by bringing a more democratic and informed youth perspective into the policy-making arena. The chapter details the Youth as Researchers Programme Model. It outlines how the programme has supported youth, in Ireland and internationally, to undertake social research projects with their peers on issues of concern, to collectively inform policy dialogue. The chapter documents the development of the programme, including a case study of one of the early youth-led research projects set up in Ireland in response to Ireland¿s National Child and Family Agency seeking to better understand how young people facing adversity can be heard and helped. It traces the programme¿s development from its inception to the present day, when the programme is now central to UNESCO¿s global response to inform policy on supporting youth during COVID-19. Not peer reviewed 2023-06-24

The current study investigates the mental health condition of Mainland Chinese in Canada and identifies the associated sociodemographic and COVID-19-related predictors. A sample of 471 Mainland Chinese aged 18 or older completed an online survey that collected information on demographics, experience, cognition, and behaviours related to the COVID-19 pandemic and mental health condition. Mental health condition was assessed with the Depression, Anxiety, and Stress Scale-21 (DASS-21) for the depression, anxiety, and stress levels of Mainland Chinese during the pandemic. Moderate to severe depression, anxiety, and stress levels were respectively reported by 11.30%, 10.83%, and 5.10% of respondents. Univariate analysis of variance models (ANOVAs) were conducted to assess mental health condition variance as stratified by independent sociodemographic- or COVID-19-related explanatory variables, to identify possible predictors to be entered into the subsequent regression models. The regression models identified age, income level, health status, and perceived discrimination as significant sociodemographic predictors (absolute value of βs = 1.19–7.11, ps βs = 1.33–3.45, ps < 0.05) for mental health outcomes. The results shed light on our understanding of the major factors associated with the mental health condition of Mainland Chinese in Canada during the COVID-19 pandemic.

Abstract The world is still struggling in controlling and containing the spread of the COVID-19 pandemic caused by the SARS-CoV-2 virus. The medical conditions associated with SARS-CoV-2 infections have resulted in a surge in the number of patients at clinics and hospitals, leading to a significantly increased strain on healthcare resources. As such, an important part of managing patients with SARS-CoV-2 infections within the clinical workflow is severity assessment, which is often conducted with the use of chest x-ray (CXR) images. In this work, we introduce COVID-Net CXR-S, a convolutional neural network for predicting the airspace severity of a SARS-CoV-2 positive patient based on a CXR image of the patient's chest. More specifically, we leveraged transfer learning to transfer representational knowledge gained from over 16,000 CXR images from a multinational cohort of over 15,000 patient cases into a custom network architecture for severity assessment. Experimental results with a multi-national patient cohort curated by the Radiological Society of North America (RSNA) RICORD initiative showed that the proposed COVID-Net CXR-S has potential to be a powerful tool for computer-aided severity assessment of CXR images of COVID-19 positive patients. Furthermore, radiologist validation on select cases by two board-certified radiologists with over 10 and 19 years of experience, respectively, showed consistency between radiologist interpretation and critical factors leveraged by COVID-Net CXR-S for severity assessment. While not a production-ready solution, the ultimate goal for the open source release of COVID-Net CXR-S is to act as a catalyst for clinical scientists, machine learning researchers, as well as citizen scientists to develop innovative new clinical decision support solutions for helping clinicians around the world manage the continuing pandemic.

Background: The current pandemic of COVID-19 has changed the way health information is distributed through online platforms. These platforms have played a significant role in informing patients and the public with knowledge that has changed the virtual world forever. Simultaneously, there are growing concerns that much of the information is not credible, impacting patient health outcomes, causing human lives, and tremendous resource waste. With the increasing use of online platforms, patients/the public require new learning models and sharing medical knowledge. They need to be empowered with strategies to navigate disinformation on online platforms.Methods and Design: To meet the urgent need to combat health “misinformation,” the research team proposes a structured approach to develop a quality benchmark, an evidence-based tool that identifies and addresses the determinants of online health information reliability. The specific methods to develop the intervention are the following: (1) systematic reviews: two comprehensive systematic reviews to understand the current state of the quality of online health information and to identify research gaps, (2) content analysis: develop a conceptual framework based on established and complementary knowledge translation approaches for analyzing the existing quality assessment tools and draft a unique set of quality of domains, (3) focus groups: multiple focus groups with diverse patients/the public and health information providers to test the acceptability and usability of the quality domains, (4) development and evaluation: a unique set of determinants of reliability will be finalized along with a preferred scoring classification. These items will be used to develop and validate a quality benchmark to assess the quality of online health information.Expected Outcomes: This multi-phase project informed by theory will lead to new knowledge that is intended to inform the development of a patient-friendly quality benchmark. This benchmark will inform best practices and policies in disseminating reliable web health information, thus reducing disparities in access to health knowledge and combat misinformation online. In addition, we envision the final product can be used as a gold standard for developing similar interventions for specific groups of patients or populations.

Patients with COPD may be at an increased risk for severe illness from COVID-19 because of ACE2 upregulation, the entry receptor for SARS-CoV-2. Chronic exposure to cigarette smoke, the main risk factor for COPD, increases pulmonary ACE2. How ACE2 expression is controlled is not known but may involve HuR, an RNA binding protein that increases protein expression by stabilizing mRNA. We hypothesized that HuR would increase ACE2 protein expression. We analyzed scRNA-seq data to profile ELAVL1 expression in distinct respiratory cell populations in COVID-19 and COPD patients. HuR expression and cellular localization was evaluated in COPD lung tissue by multiplex immunohistochemistry and in human lung cells by imaging flow cytometry. The regulation of ACE2 expression was evaluated using siRNA-mediated knockdown of HuR. There is a significant positive correlation between ELAVL1 and ACE2 in COPD cells. HuR cytoplasmic localization is higher in smoker and COPD lung tissue; there were also higher levels of cleaved HuR (CP-1). HuR binds to ACE2 mRNA but knockdown of HuR does not change ACE2 protein levels in primary human lung fibroblasts (HLFs). Our work is the first to investigate the association between ACE2 and HuR. Further investigation is needed to understand the mechanistic underpinning behind the regulation of ACE2 expression.

Cet article s’appuie sur mon lien avec les fils à coudre et explore comment le défi en ligne 2020 Massive Microscopic Sensemaking (MMS) a contribué à un enchevêtrement émergent de l’espace-temps lié à COVID-19, à l’enseignement et à la recherche sur l’apprentissage médical en obstétrique, et à la réflexion plus approfondie de mon doctorat . Il explore les processus affirmatifs mis en œuvre pendant les périodes d’anxiété, lorsque mes pensées se frayaient un chemin à travers des espaces intermédiaires avec des moments et des matériaux différents qui étaient génératifs et productifs. J’explique mes mouvements rhizomatiques qui saignent à travers les séparations conventionnelles et les hypothèses de délimitation. Je m’appuie sur le réalisme agential de Karen Barad pour théoriser l’émergence de relations créatives avec des artefacts astucieux mis en scène avec des étudiants de premier cycle en médecine, avec des participants au projet MMS et avec mon propre doctorat en période de tension. This article draws on my connection with sewing threads, and explores how the 2020 Massive Microscopic Sensemaking (MMS) online challenge contributed to an emergent entanglement of timespacemattering related to COVID-19, teaching and researching medical learning in obstetrics, and thinking further with my PhD. It explores affirmative processes enacted during times of anxiety, when my thoughts needled through in-between spaces with different times and materials that were generative and productive. I explain my rhizomatic movements that bleed through conventional separations and boundary-making assumptions. I draw on Karen Barad’s agential realism to theorize the emergence of creative relationalities with artful artifacts enacted with medical undergraduate students, with participants in the MMS project, and with my own PhD during times of tension.

L’article explore l’écoute médiatisée du point de vue de l’intimité pendant les premières semaines de la pandémie de coronavirus. Le cadre théorique s’appuie sur la littérature, sur l’écoute et la présence dans des environnements médiatisés, l’engagement du public et l’intimité en tant que connexions significatives. Méthodologiquement, l’étude est une ethnographie connective, les données ont été collectées par autoethnographie collaborative. Nos données montrent que l’écoute était une stratégie de perception individuelle du monde extérieur et un moyen de former une connectivité. Le filetage entre différents écrans sur les plates-formes numériques a provoqué l’effondrement de contextes publics et privés et, à travers ces derniers, des types particuliers d’intimité sont apparus. Lorsque la position des mères universitaires est souvent celle d’une “connaisseuse”, la crise grave les oblige à rechercher de manières réceptives de savoir, comme une écoute attentive des autres. L’écoute est un moyen de former l’appartenance et la compréhension, mais à partir d’une position silencieuse. Cela suggère que nous devrions accorder plus d’attention aux présences silencieuses et aux publics, dans les environnements médiatisés contemporains. This article explores mediated listening from the perspective of intimacy during the first weeks of the coronavirus pandemic. The theoretical frame builds on the literature on listening and presence in mediated environments, audience engagement, and intimacy as meaningful connections. Methodologically, the study is connective ethnography, and the data was collected by collaborative autoethnography. Our data show that listening was an individual sensemaking strategy of the outside world and a means to form connectedness. Threading between different screens on digital platforms caused the collapse of public and private contexts, and through these, particular types of intimacy arose. When the position of academic mothers is often that of a ‘knower,’ the severe crisis compels them to look for receptive ways of knowing, such as careful listening of others. Listening is a means to form belonging and understanding, but from a silent position. We should pay more attention to the silent presences and audiences in contemporary mediated environments.

La pandémie COVID-19 a occasionné une cruelle pédagogie au sujet du néolibéralisme. Le néolibéralisme incarne un processus présentant de multiples facettes selon lesquelles après les années mi-1970, le compromis Fordiste post-1945 a été graduellement transformé en un ordre mondial qui privilégiait la rivalité ou concurrence dans le monde des affaires comme pratique quotidienne et philosophie de règle. Cet ordre d’affaire fut empêtré dans une crise organique depuis 2007-8. Ceci a révélé progressivement le statut problématique du néolibéralisme en lien non seulement avec la pratique démocratique mais surtout avec la survie de notre espèce. Cet article se centre surtout sur les manières dont la pandémie a mis en lumière non seulement les contradictions au coeur du néolibéralisme, mais elle présage également leur impact grandissant. La pandemia de Covid-19 acarrea una pedagogía cruel en relación al neoliberalismo. El neoliberalismo encarna un proceso multifacético en el que el compromiso Fordista pos-1945 fue gradualmente transformado después de mediados de los años de 1970 en un mundo que privilegia la competición de los negocios como práctica diaria y como filosofía dominante. Este orden ha sido enmarañado en una “crisis orgánica” desde 2007-8, la que ha revelado progresivamente el status problemático del neoliberalismo con respecto no solo a la práctica de la democracia sino a la sobrevivencia de la especie humana. Este artículo discute específicamente las maneras en que la pandemia ha iluminado no sólo las contradicciones centrales del neoliberalismo sino presagia su intensificación y amplio impacto. The Covid-19 pandemic entailed a cruel pedagogy with regard to neoliberalism. Neoliberalism embodies a multifaceted process whereby the post-1945 Fordist compromise was gradually transformed, after the mid-1970s, into a world order privileging business competition, both as a daily practice and a philosophy of rule. This order has been enmeshed in an “organic crisis” since 2007-08, which has progressively revealed neoliberalism’s problematic status in relation not only to the practice of democracy, but to the survival of the species. This article focuses specifically on the ways in which the pandemic has not only illuminated neoliberalism’s core contradictions, but portends their intensification and widening impact.