Opposition-based sine cosine optimizer utilizing refraction learning and variable neighborhood search for feature selection.

This paper proposes new improved binary versions of the Sine Cosine Algorithm (SCA) for the Feature Selection (FS) problem. FS is an essential machine learning and data mining task of choosing a subset of highly discriminating features from noisy, irrelevant, high-dimensional, and redundant features to best represent a dataset. SCA is a recent metaheuristic algorithm established to emulate a model based on sine and cosine trigonometric functions. It was initially proposed to tackle problems in the continuous domain. The SCA has been modified to Binary SCA (BSCA) to deal with the binary domain of the FS problem. To improve the performance of BSCA, three accumulative improved variations are proposed (i.e., IBSCA1, IBSCA2, and IBSCA3) where the last version has the best performance. IBSCA1 employs Opposition Based Learning (OBL) to help ensure a diverse population of candidate solutions. IBSCA2 improves IBSCA1 by adding Variable Neighborhood Search (VNS) and Laplace distribution to support several mutation methods. IBSCA3 improves IBSCA2 by optimizing the best candidate solution using Refraction Learning (RL), a novel OBL approach based on light refraction. For performance evaluation, 19 real-wold datasets, including a COVID-19 dataset, were selected with different numbers of features, classes, and instances. Three performance measurements have been used to test the IBSCA versions: classification accuracy, number of features, and fitness values. Furthermore, the performance of the last variation of IBSCA3 is compared against 28 existing popular algorithms. Interestingly, IBCSA3 outperformed almost all comparative methods in terms of classification accuracy and fitness values. At the same time, it was ranked 15 out of 19 in terms of number of features. The overall simulation and statistical results indicate that IBSCA3 performs better than the other algorithms.

Mindfulness–based positive transformative leadership development for health organisations

Purpose>Positive transformative leadership development practices in health care are perhaps the most important pathway that, collectively, can be pursued while heading towards a post-corona virus disease 2019 world, and race towards 2030. As a practitioner paper, based on front line and leadership experience, this study aims to argue that we need transformational leaders who will go beyond knowing to practice and implementation. While the findings from research is presented from different organisations and companies, they all have something in common – people. Hence, important lessons can be extrapolated to health-related organisations in the future.Design/methodology/approach>The approach is based on practical research findings based on the literature. The approach uses real practical examples from companies and organisations to demonstrate the need for a new, radical way forward.Findings>The findings from the literature clearly indicate that mindfulness-based transformative leadership development program is a worthwhile investment for decision-makers and organisations. A new transformative leader for the future of health care needs to be developed with care with investment in that development.Research limitations/implications>Implications of this paper show that health-care organisations need to begin this journey. There is a paucity in the literature to demonstrate the implementation of mindfulness-based transformative leadership development programs.Practical implications>Organisations of the future face even greater challenges brought about by intelligent technology, new pandemics and even tighter government regulation. The time to prepare for such eventualities is now. This is not a choice but an imperative for organisations to know what to do rather than react with regret.Originality/value>There is a paucity in the health-care literature that tracks, measures, and reports on the long-term results of a mindfulness-based transformative leadership development program. This needs to be addressed, and health care should be a leader in the field of mindfulness and transformative leadership of the future.

Convergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation.

Double membrane vesicles (DMVs) serve as replication organelles of plus-strand RNA viruses such as hepatitis C virus (HCV) and SARS-CoV-2. Viral DMVs are morphologically analogous to DMVs formed during autophagy, but lipids driving their biogenesis are largely unknown. Here we show that production of the lipid phosphatidic acid (PA) by acylglycerolphosphate acyltransferase (AGPAT) 1 and 2 in the ER is important for DMV biogenesis in viral replication and autophagy. Using DMVs in HCV-replicating cells as model, we found that AGPATs are recruited to and critically contribute to HCV and SARS-CoV-2 replication and proper DMV formation. An intracellular PA sensor accumulated at viral DMV formation sites, consistent with elevated levels of PA in fractions of purified DMVs analyzed by lipidomics. Apart from AGPATs, PA is generated by alternative pathways and their pharmacological inhibition also impaired HCV and SARS-CoV-2 replication as well as formation of autophagosome-like DMVs. These data identify PA as host cell lipid involved in proper replication organelle formation by HCV and SARS-CoV-2, two phylogenetically disparate viruses causing very different diseases, i.e. chronic liver disease and COVID-19, respectively. Host-targeting therapy aiming at PA synthesis pathways might be suitable to attenuate replication of these viruses.

Beyond PPE: a mixed qualitative-quantitative study capturing the wider issues affecting doctors' well-being during the COVID-19 pandemic.

The COVID-19 pandemic has brought unprecedented challenges to the medical workforce. This has put them at increased risk of burnout at a time when levels are already worryingly high in the profession, with recent studies consistently showing that around half of doctors meet the validated criteria for burnout. OBJECTIVES: To understand the wider factors influencing and impacting upon hospital doctors' well-being during the COVID-19 pandemic in England. DESIGN: Cross-sectional survey and mixed quantitative-qualitative analysis. SETTING: Acute National Health Service (NHS) Foundation Trust in England. PARTICIPANTS: An online survey was circulated in early June 2020 to all 449 doctors employed by the Trust. 242 doctors completed the survey (54% response rate). PRIMARY OUTCOME MEASURES: Questions assessed occupational details, self-reported changes in physical and mental health, satisfaction with working hours and patterns, availability of personal protective equipment (PPE), medication and facilities, communication and sought to identify areas seen as having a significant effect on doctors' well-being. RESULTS: 96% of respondents requiring PPE were able to access it. Nearly half of the respondents felt that their mental health had deteriorated since the start of the pandemic. Over a third stated that their physical health had also declined. Issues identified as having a negative impact on doctors included increased workload, redeployment, loss of autonomy, personal issues affecting family members, anxiety around recovery plans, inadequate access to changing and storage facilities and to rest areas that allow for social distancing. Doctors appreciated access to 'calm rooms' that were made available for staff, access to clinical psychology support, free drinks and free car parking on site. CONCLUSION: The emerging themes are suggestive of increased burnout risk among doctors during the COVID-19 pandemic and encompass factors well beyond shortage of PPE. Small organisational initiatives and the implementation of changes suggested by survey respondents can have a positive impact on doctors' well-being.

Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion.

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infects cells by binding to the host cell receptor ACE2 and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2, which processes the viral Spike (S) protein to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin in order to prime S protein for TMPRSS2 processing. Here we show that CRISPR-Cas9 knockout of furin reduces, but does not prevent, the production of infectious SARS-CoV-2 virus. Comparing S processing in furin knockout cells to multibasic site mutants reveals that while loss of furin substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S protein also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin in either donor or acceptor cells reduces, but does not prevent, TMPRSS2-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin promotes both SARS-CoV-2 infectivity and cell-cell spread it is not essential, suggesting furin inhibitors may reduce but not abolish viral spread.

SARS-CoV-2 Infects the Brain Choroid Plexus and Disrupts the Blood-CSF Barrier in Human Brain Organoids.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, leads to respiratory symptoms that can be fatal. However, neurological symptoms have also been observed in some patients. The cause of these complications is currently unknown. Here, we use human-pluripotent-stem-cell-derived brain organoids to examine SARS-CoV-2 neurotropism. We find expression of viral receptor ACE2 in mature choroid plexus cells expressing abundant lipoproteins, but not in neurons or other cell types. We challenge organoids with SARS-CoV-2 spike pseudovirus and live virus to demonstrate viral tropism for choroid plexus epithelial cells but little to no infection of neurons or glia. We find that infected cells are apolipoprotein- and ACE2-expressing cells of the choroid plexus epithelial barrier. Finally, we show that infection with SARS-CoV-2 damages the choroid plexus epithelium, leading to leakage across this important barrier that normally prevents entry of pathogens, immune cells, and cytokines into cerebrospinal fluid and the brain.