Correction: Detection of novel coronaviruses in bats in Myanmar.

[This corrects the article DOI: 10.1371/journal.pone.0230802.].

An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges.

Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph-based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly "Question-of-the-Month (QotM) Challenge" series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.

The scalable precision medicine open knowledge engine (SPOKE): a massive knowledge graph of biomedical information.

MOTIVATION: Knowledge graphs (KGs) are being adopted in industry, commerce and academia. Biomedical KG presents a challenge due to the complexity, size and heterogeneity of the underlying information. RESULTS: In this work, we present the Scalable Precision Medicine Open Knowledge Engine (SPOKE), a biomedical KG connecting millions of concepts via semantically meaningful relationships. SPOKE contains 27 million nodes of 21 different types and 53 million edges of 55 types downloaded from 41 databases. The graph is built on the framework of 11 ontologies that maintain its structure, enable mappings and facilitate navigation. SPOKE is built weekly by python scripts which download each resource, check for integrity and completeness, and then create a 'parent table' of nodes and edges. Graph queries are translated by a REST API and users can submit searches directly via an API or a graphical user interface. Conclusions/Significance: SPOKE enables the integration of seemingly disparate information to support precision medicine efforts. AVAILABILITY AND IMPLEMENTATION: The SPOKE neighborhood explorer is available at https://spoke.rbvi.ucsf.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Genome-microbiome interplay provides insight into the determinants of the human blood metabolome.

Variation in the blood metabolome is intimately related to human health. However, few details are known about the interplay between genetics and the microbiome in explaining this variation on a metabolite-by-metabolite level. Here, we perform analyses of variance for each of 930 blood metabolites robustly detected across a cohort of 1,569 individuals with paired genomic and microbiome data while controlling for a number of relevant covariates. We find that 595 (64%) of these blood metabolites are significantly associated with either host genetics or the gut microbiome, with 69% of these associations driven solely by the microbiome, 15% driven solely by genetics and 16% under hybrid genome-microbiome control. Additionally, interaction effects, where a metabolite-microbe association is specific to a particular genetic background, are quite common, albeit with modest effect sizes. This knowledge will help to guide targeted interventions designed to alter the composition of the human blood metabolome.

Moving on From the Delphi Study: The Development of a Physical Activity Training Programme Prototype Through Co-produced Qualitative Research.

This research developed from a co-produced project called Moving Social Work. The purpose of this ongoing project is to train social workers in how to promote physical activity for and to disabled people. The first stage of the project consisted of building evidence to design a training programme prototype. As part of this stage, a Delphi study was conducted to ask leading experts about what should be included in the prototype. Questionnaires were sent to participants until consensus was reached. In reflecting on the results, people involved in the study commented that there was more about the experts' opinions than percentages of agreement. Our co-production partners resolved that the Delphi was insufficient and called for detailed conversations with the experts. In response to this call, follow-up interviews with 10 experts who participated in the final questionnaire round of the Delphi were carried out. The interviews were co-produced, dyadic and data prompted. Dialogical inquiry was used to frame and co-analyse data. The results illuminate the capacity of qualitative research to justify, rectify, complicate, clarify, concretize, expand and question consensus-based evidence. The implications of the results for Moving Social Work are discussed. Beyond the empirical border of the project, wider contributions to literature are presented. As part of these, two key statements are highlighted and warranted: dialogical inquiry supports the practice of co-produced research, and Delphi studies should be followed by a Big Q qualitative study.

A biomedical open knowledge network harnesses the power of AI to understand deep human biology.

Knowledge representation and reasoning (KR&R) has been successfully implemented in many fields to enable computers to solve complex problems with AI methods. However, its application to biomedicine has been lagging in part due to the daunting complexity of molecular and cellular pathways that govern human physiology and pathology. In this article we describe concrete uses of SPOKE, an open knowledge network that connects curated information from 37 specialized and human-curated databases into a single property graph, with 3 million nodes and 15 million edges to date. Applications discussed in this article include drug discovery, COVID-19 research and chronic disease diagnosis and management.

Coronavirus and Paramyxovirus Shedding by Bats in a Cave and Buildings in Ethiopia.

Bats are important hosts of zoonotic viruses with pandemic potential, including filoviruses, MERS-Coronavirus (CoV), SARS-CoV -1, and likely SARS-CoV-2. Viral infection and transmission among wildlife are dependent on a combination of factors that include host ecology and immunology, life history traits, roosting habitats, biogeography, and external stressors. Between 2016 and 2018, four species of insectivorous bats from a readily accessed roadside cave and buildings in Ethiopia were sampled and tested for viruses using consensus PCR assays for five viral families/genera. Previously identified and novel coronaviruses and paramyxoviruses were identified in 99 of the 589 sampled bats. Bats sampled from the cave site were more likely to test positive for a CoV than bats sampled from buildings; viral shedding was more common in the wet season; and rectal swabs were the most common sample type to test positive. A previously undescribed alphacoronavirus was detected in two bat species from different taxonomic families, sampling interfaces, geographic locations, and years. These findings expand knowledge of the range and diversity of coronaviruses and paramyxoviruses in insectivorous bats in Ethiopia and reinforce that an improved understanding of viral diversity and species-specific shedding dynamics is important for designing informed zoonotic disease surveillance and spillover risk reduction efforts.

Surveillance for potentially zoonotic viruses in rodent and bat populations and behavioral risk in an agricultural settlement in Ghana.

BACKGROUND: In Ghana, the conversion of land to agriculture, especially across the vegetative belt has resulted in fragmented forest landscapes with increased interactions among humans, domestic animals, and wildlife. METHODS: We investigated viruses in bats and rodents, key reservoir hosts for zoonotic viral pathogens, in a small agricultural community in the vegetation belt of Ghana. We also administered questionnaires among the local community members to learn more about people's awareness and perceptions of zoonotic disease risks and the environmental factors and types of activities in which they engage that might influence pathogen transmission from wildlife. RESULTS: Our study detected the RNA from paramyxoviruses and coronaviruses in rodents and bats, including sequences from novel viruses with unknown zoonotic potential. Samples collected from Epomophorus gambianus bats were significantly more likely to be positive for coronavirus RNA during the rainy season, when higher numbers of young susceptible individuals are present in the population. Almost all community members who responded to the questionnaire reported contact with wildlife, especially bats, rodents, and non-human primates in and around their homes and in the agricultural fields. Over half of the respondents were not aware or did not perceive any zoonotic disease risks associated with close contact with animals, such as harvesting and processing animals for food. To address gaps in awareness and mitigation strategies for pathogen transmission risks, we organized community education campaigns using risk reduction and outreach tools focused around living safely with bats and rodents. CONCLUSIONS: These findings expand our knowledge of the viruses circulating in bats and rodents in Ghana and of the beliefs, perceptions, and practices that put community members at risk of zoonotic virus spillover through direct and indirect contact with bats and rodents. This study also highlights the importance of community engagement in research and interventions focused on mitigating risk and living safely with wildlife.

Multiple early factors anticipate post-acute COVID-19 sequelae.

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

Designing a programme to train social workers on how to promote physical activity for disabled people: A Delphi study in the UK.

Recently, social workers have been identified as a key messenger group for promoting physical activity (PA) to disabled people. Also identified is the need to train social workers in PA promotion. In response, the purpose of this article is to inform the design of a training programme prototype aiming to support social workers to become active PA messengers. We conducted a three-round Delphi study to identify the essential contents and teaching methods for the programme, as well as the challenges that may jeopardise its success. Qualified experts on physical activity and health, social work, and/or disability working in the UK were invited to partake in the study. The response rates were 55% (33/60) in the first round, 79% (26/33) in the second and 77% (20/26) in the third rounds. Following the last questionnaire round, the experts reached consensus on 8 contents, 7 teaching methods and 10 challenges to success. The top three most important contents were: benefits of PA (1.05 ± 0.22), what PA means to disabled people (1.15 ± 0.36) and person-centred PA planning (1.35 ± 0.57). The most relevant teaching methods were interactive activities and discussions (1.20 ± 0.51) and case studies (1.25 ± 0.43). Blended learning (1.85 ± 0.57) was preferred to e-learning (2.20 ± 0.60) and face-to-face learning (2.10 ± 0.70). Lack of time (1.30 ± 0.46) and confidence (1.45 ± 0.59) were deemed vital challenges. However, consensus around other potential barriers such as lack of interest and commitment (1.30 ± 0.46), lack of buy in from employers (1.75 ± 0.70) and professional inertia (2.05 ± 0.67) suggest that a major challenge for long-term impact is to convince key people that social work and PA promotion make a good match. The results of this study provide a valuable starting point evidence base for PA curriculum development. Future research will delve into expert opinions using in-depth qualitative interviews. Participatory approaches including knowledge cafés will also be used to add more views of stakeholders with experiential knowledge.

Orbivirus RNA in a Banana Serotine (Afronycteris nanus) Bat in the Republic of the Congo.

Orbiviruses are arthropod borne viruses of vertebrates, with some of them being important pathogens of veterinary, conservation and economic importance, while others are occasionally associated with human disease. Some apparently bat specific orbiviruses have been detected, but little is known about their distribution and diversity. We thus sampled and screened 52 bats living in the Congo Basin, and detected RNA indicative of a novel orbivirus in a single banana serotine (Afronycteris nanus) by PCR. The detected RNA clusters with epizootic haemorrhagic disease virus, bluetongue virus, and others. The findings highlight the need for more studies into arbovirus presence and diversity in bat species.

Integrated analysis of plasma and single immune cells uncovers metabolic changes in individuals with COVID-19.

A better understanding of the metabolic alterations in immune cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may elucidate the wide diversity of clinical symptoms experienced by individuals with coronavirus disease 2019 (COVID-19). Here, we report the metabolic changes associated with the peripheral immune response of 198 individuals with COVID-19 through an integrated analysis of plasma metabolite and protein levels as well as single-cell multiomics analyses from serial blood draws collected during the first week after clinical diagnosis. We document the emergence of rare but metabolically dominant T cell subpopulations and find that increasing disease severity correlates with a bifurcation of monocytes into two metabolically distinct subsets. This integrated analysis reveals a robust interplay between plasma metabolites and cell-type-specific metabolic reprogramming networks that is associated with disease severity and could predict survival.

The Physical Activity Messaging Framework (PAMF) and Checklist (PAMC): International consensus statement and user guide.

Effective physical activity messaging plays an important role in the pathway towards changing physical activity behaviour at a population level. The Physical Activity Messaging Framework (PAMF) and Checklist (PAMC) are outputs from a recent modified Delphi study. This sought consensus from an international expert panel on how to aid the creation and evaluation of physical activity messages. In this paper, we (1) present an overview of the various concepts within the PAMF and PAMC, (2) discuss in detail how the PAMF and PAMC can be used to create physical activity messages, plan evaluation of messages, and aid understanding and categorisation of existing messages, and (3) highlight areas for future development and research. If adopted, we propose that the PAMF and PAMC could improve physical activity messaging practice by encouraging evidence-based and target population-focused messages with clearly stated aims and consideration of potential working pathways. They could also enhance the physical activity messaging research base by harmonising key messaging terminologies, improving quality of reporting, and aiding collation and synthesis of the evidence.

σ-Donation and π-Backdonation Effects in Dative Bonds of Main-Group Elements.

The nature of donor-acceptor interactions is important for the understanding of dative bonding and can provide vital insights into many chemical processes. Here, we have performed a computational study to elucidate substantial differences between different types of dative interactions. For this purpose, a data set of 20 molecular complexes stabilized by dative bonds was developed (DAT20). A benchmark study that considers many popular density functionals with respect to accurate quantum chemical interaction energies and geometries revealed two different trends between the complexes of DAT20. This behavior was further explored by means of frontier molecular orbitals, extended-transition-state natural orbitals for chemical valence (ETS-NOCV), and natural energy decomposition analysis (NEDA). These methods revealed the extent of the forward and backdonation between the donor and acceptor molecules and how they influence the total interaction energies and molecular geometries. A new classification of dative bonds is suggested.

Training Healthcare Professionals on How to Promote Physical Activity in the UK: A Scoping Review of Current Trends and Future Opportunities.

What physical activity (PA) training do current and future healthcare professionals (HCPs) receive in the UK? How is PA training delivered to them? The present scoping review looks at existing evidence to respond these questions. Seven databases were searched: Medline, SportDISCUS, PsycINFO, EMBASE, CINAHL, Cochrane Review Database, and Web of Science. Grey literature sources and key stakeholders were consulted. Studies were screened for inclusion, data were extracted and charted, and findings were synthesised according to the two research questions. Of the 3535 identified studies, 25 were included. The results show that no standardised approach was used to deliver PA promotion in HCPs training. PA training content was chiefly underpinned by an epidemiological approach. Online delivery of content predominated in continuing professional development training, whereas in undergraduate healthcare curriculum, delivery strategies varied. Overall, the process of embedding PA in HCPs' curriculum and culture is ongoing. In addition to highlighting what is present within healthcare education, this study identifies further opportunities. Potential avenues include extending PA promotion into other workforces, including social workers.