Controlling the Response: Predictive Modeling of a Highly Central, Pathogen-Targeted Core Response Module in Macrophage Activation

We have investigated macrophage activation using computational analyses of a compendium of transcriptomic data covering responses to agonists of the TLR pathway, Salmonella infection, and manufactured amorphous silica nanoparticle exposure. We inferred regulatory relationship networks using this compendium and discovered that genes with high betweenness centrality, so-called bottlenecks, code for proteins targeted by pathogens. Furthermore, combining a novel set of bioinformatics tools, topological analysis with analysis of differentially expressed genes under the different stimuli, we identified a conserved core response module that is differentially expressed in response to all studied conditions. This module occupies a highly central position in the inferred network and is also enriched in genes preferentially targeted by pathogens. The module includes cytokines, interferon induced genes such as Ifit1 and 2, effectors of inflammation, Cox1 and Oas1 and Oasl2, and transcription factors including AP1, Egr1 and 2 and Mafb. Predictive modeling using a reverse-engineering approach reveals dynamic differences between the responses to each stimulus and predicts the regulatory influences directing this module. We speculate that this module may be an early checkpoint for progression to apoptosis and/or inflammation during macrophage activation

Leadership: Native Narratives on Building Strong Communities

Indigenous scholars strive to produce accessible research grounded in the daily lives of Native peoples, research that will improve their communities in meaningful and sustained ways. They also recognize that long-lasting change depends on effective leadership. Living Indigenous Leadership showcases innovative research and leadership practices from diverse nations and tribes in Canada, the United States, and New Zealand. The contributors, all women, use vibrant stories and personal narratives to offer insights into the unique nature of Indigenous leadership. --Publisher\u27s website. Dr. Carolyn Kenny is a professor of Human Development and Indigenous Studies in the PhD Program in Leadership & Change at Antioch University. Students and graduates of the PhD Program in Leadership & Change have contributed chapters in this book: Raquel D. Gutierrez, Gail Cheney, Annette Squetimkin-Anquoe, Michelle Archuletta Link to Table of Contentshttps://aura.antioch.edu/facbooks/1004/thumbnail.jp

Technology-enabled virtual ward for COVID management of the elderly and immunocompromised in Singapore: a descriptive cohort

Abstract Background To address the hospital bed demand for Delta and Omicron surges in Singapore, the National University Health System (NUHS) developed a COVID Virtual Ward to relieve bed pressures on its three acute hospitals—National University Hospital, Ng Teng Fong General Hospital, Alexandra Hospital. To serve a multilingual population, the COVID Virtual Ward featuring protocolized teleconsultation of high-risk patients, use of a vital signs chatbot, supplemented by home visits where necessary. This study aims to evaluate the safety, outcomes and utilisation of the Virtual Ward as a scalable response to COVID-19 surges. Methods This is a retrospective cohort study of all patients admitted to the COVID Virtual Ward between 23 September to 9 November 2021. Patients were defined as “early discharge” if they were referred from inpatient COVID-19 wards and “admission avoidance” if they were referred directly from primary care or emergency services. Patient demographics, utilisation measures and clinical outcomes were extracted from the electronic health record system. The primary outcomes were escalation to hospital and mortality. Use of the vital signs chatbot was evaluated by examining compliance levels, need for automated reminders and alerts triggered. Patient experience was evaluated using data extracted from a quality improvement feedback form. Results 238 patients were admitted to the COVID Virtual Ward from 23 September to 9 November, of whom 42% were male, 67.6% of Chinese ethnicity. 43.7% were over the age of 70, 20.5% were immunocompromised, and 36.6% were not fully vaccinated. 17.2% of patients were escalated to hospital and 2.1% of patients died. Patients who were escalated to hospital were more likely to be immunocompromised or to have a higher ISARIC 4C-Mortality Score. There were no missed deteriorations. All patients received teleconsults (median of 5 teleconsults per patient, IQR 3–7). 21.4% of patients received home visits. 77.7% of patients engaged with the vital signs chatbot, with a compliance rate of 84%. All patients would recommend the programme to others in their situation. Conclusions Virtual Wards are a scalable, safe and patient-centered strategy to care for high risk COVID-19 patients at home. Trial Registration NA. </jats:sec