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.

Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.

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.

Participation of people living with disabilities in physical activity: a global perspective.

Approximately 1·5 billion people worldwide live with a physical, mental, sensory, or intellectual disability, about 80% of which are in low-income and middle-income countries. This Series paper provides a global overview of the prevalence, benefits, and promotion policies for physical activity for people living with disabilities (PLWD). PLWD are 16-62% less likely to meet physical activity guidelines and are at higher risk of serious health problems related to inactivity than people without disabilities. Meta-analyses have shown that physical activity has beneficial effects on cardiovascular fitness (average standardised mean difference [SMD] 0·69 [95% CI 0·31-1·01]), musculoskeletal fitness (0·59 [0·31-0·87]), cardiometabolic risk factors (0·39 [0·04-0·75]), and brain and mental health outcomes (0·47 [0·21-0·73]). These meta-analyses also show that health benefits can be achieved even with less than 150 min of physical activity per week, and suggest that some physical activity is better than none. Meta-analyses of interventions to increase physical activity for PLWD have reported effect sizes ranging from SMD 0·29 (95% CI 0·17-0·41, k=10) to 1·00 (0·46-1·53, k=10). There is increasing awareness among policy makers of the needs of PLWD for full participation in physical activity. Physical activity action plans worldwide must be adequately resourced, monitored, and enforced to truly advance the fundamental rights of PLWD to fully participate in physical activity.

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.

Characteristics and Factors Associated With Coronavirus Disease 2019 Infection, Hospitalization, and Mortality Across Race and Ethnicity.

BACKGROUND: Data on the characteristics of coronavirus disease 2019 (COVID-19) patients disaggregated by race/ethnicity remains limited. We evaluated the sociodemographic and clinical characteristics of patients across racial/ethnic groups and assessed their associations with COVID-19 outcomes. METHODS: This retrospective cohort study examined 629 953 patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large health system spanning California, Oregon, and Washington between March 1 and December 31, 2020. Sociodemographic and clinical characteristics were obtained from electronic health records. Odds of SARS-CoV-2 infection, COVID-19 hospitalization, and in-hospital death were assessed with multivariate logistic regression. RESULTS: A total of 570 298 patients with known race/ethnicity were tested for SARS-CoV-2, of whom 27.8% were non-White minorities: 54 645 individuals tested positive, with minorities representing 50.1%. Hispanics represented 34.3% of infections but only 13.4% of tests. Although generally younger than White patients, Hispanics had higher rates of diabetes but fewer other comorbidities. A total of 8536 patients were hospitalized and 1246 died, of whom 56.1% and 54.4% were non-White, respectively. Racial/ethnic distributions of outcomes across the health system tracked with state-level statistics. Increased odds of testing positive and hospitalization were associated with all minority races/ethnicities. Hispanic patients also exhibited increased morbidity, and Hispanic race/ethnicity was associated with in-hospital mortality (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.14-1.70). CONCLUSION: Major healthcare disparities were evident, especially among Hispanics who tested positive at a higher rate, required excess hospitalization and mechanical ventilation, and had higher odds of in-hospital mortality despite younger age. Targeted, culturally responsive interventions and equitable vaccine development and distribution are needed to address the increased risk of poorer COVID-19 outcomes among minority populations.

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.

Nature of the Short Rh-Li Contact between Lithium and the Rhodium ω-Alkenyl Complex [Rh(CH2CMe2CH2CH═CH2)2].

We describe the preparation of the cis-bis(η1,η2-2,2-dimethylpent-4-en-1-yl)rhodate(I) anion, cis-[Rh(CH2CMe2CH2CH═CH2)2]-, and the interaction of this species with Li+ both in solution and in the solid state. For the lithium(diethyl ether) salt [Li(Et2O)][Rh(CH2CMe2CH2CH═CH2)2], VT-NMR and 1H{7Li} NOE NMR studies in toluene-d8 show that the Li+ cation is in close proximity to the dz2 orbital of rhodium. In the solid-state structure of the lithium(12-crown-4) salt [Li(12-crown-4)2][Li{Rh(CH2CMe2CH2CH═CH2)2}2], one lithium atom is surrounded by two [Rh(CH2CMe2CH2CH═CH2)2]- anions, and in this assembly there are two unusually short Rh-Li distances of 2.48 Å. DFT calculations, natural energy decomposition, and ETS-NOCV analysis suggest that there is a weak dative interaction between the 4dz2 orbitals on the Rh centers and the 2pz orbital of the Li+ cation. The charge-transfer term between Rh and Li+ contributes only about the 1/5 of the total interaction energy, however, and the principal driving force for the proximity of Rh and Li in compounds 1 and 2 is that Li+ is electrostatically attracted to negative charges on the dialkylrhodiate anions.

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.

Synthesis and Characterization of Cu(II) and Mixed-Valence Cu(I)Cu(II) Clusters Supported by Pyridylamide Ligands.

A group of copper complexes supported by polydentate pyridylamide ligands H2bpda and H2ppda were synthesized and characterized. The two Cu(II) dimers [CuII2(Hbpda)2(ClO4)2] (1) and [CuII2(ppda)2(DMF)2] (2) were constructed by using neutral ligands to react with Cu(II) salts. Although the dimers showed similar structural features, the second-sphere interactions affect the structures differently. With the application of Et3N, the tetranuclear cluster (HNEt3)[CuII4(bpda)2(µ3-OH)2(ClO4)(DMF)3](ClO4)2 (3) and hexanuclear cluster (HNEt3)2[CuII6(ppda)6(H2O)2(CH3OH)2](ClO4)2 (4) were prepared under similar reaction conditions. The symmetrical and unsymmetrical arrangement of the ligand donors in ligands H2bpda and H2ppda led to the dramatic conformation difference of the two Cu(II) complexes. As part of our effort to explore mixed-valence copper chemistry, the triple-decker pentanuclear cluster [CuII3CuI2(bpda)3(µ3-O)] (5) was prepared. XPS examination demonstrated the localized mixed-valence properties of complex 5. Magnetic studies of the clusters with EPR evidence showed either weak ferromagnetic or antiferromagnetic interactions among copper centers. Due to the trigonal-planar conformation of the trinuclear Cu(II) motif with the µ3-O center, complex 5 exhibits geometric spin frustration and engages in antisymmetric exchange interactions. DFT calculations were also performed to better interpret spectroscopic evidence and understand the electronic structures, especially the mixed-valence nature of complex 5.

Traveling Material↔Semiotic Environments of Disability, Rehabilitation, and Physical Activity.

In this article, we apply narrative dialogism and new materialism to health research. We examine how material↔semiotic environments (MSEs) affect the rehabilitation process of Patrick, a man who exercised with the aim to recover from spinal cord injury. The MSEs are considered embedded subcases within the overall holistic case of Patrick. Three MSEs were identified: the hospital gym, the personal gym, and the adapted gym. These are examined using the analytical lens of assemblages. First, the mutually affecting components of each MSE are described. Second, a larger environmental assemblage is identified, which is termed exercise-is-restitution assemblage. This composite assemblage illuminates the associations between the three MSEs, and reveals how restitution resonated across time and space. The article contributes to the literature by reconceptualizing restitution. It highlights the importance of the materiality of health-related narratives, and it reveals the potential of MSE for transforming rehabilitation and improving exercise promotion and maintenance.

Overweight and obese men's experiences in a sport-based weight loss intervention for men.

In Western countries, such as Australia and the UK, a significantly greater proportion of men (relative to women) are overweight and obese, yet relatively few weight loss interventions have been developed that sufficiently target men. This lack of male-focused programming may be in part because 'traditional' weight loss programs are unappealing for what is considered a 'hard-to-reach' population. One program that appears to have such appeal for men is the MAN v FAT Football (MVFF) program, based out of the United Kingdom, which is designed for men with a body mass index of (or greater than) 27.5. MVFF encourages men's participation in a community-based weight loss program that incentivizes weight loss through participation in a football league, and since 2016 MVFF has supported the weight loss efforts of several thousand men. Using MVFF as an exemplar, our aim was to derive insight into how men experience a male-only competitive, sport-based weight loss program. We recruited twenty-seven players (Mage = 41.13, SD = 9.93), and ten coaches (Mage = 31.8, SD = 11.55) from program locations throughout the United Kingdom. Using semi-structured interviews and thematic analysis, we identified several appraisal aspects of the program that players and coaches considered important, including the appeal of sport, competition on a level playing field, being part of a team, camaraderie, accountability, men sharing issues with other men, gender-sensitized environment, likeminded and similar men, and perceptions that traditional weight loss programs are tailored towards women. Player experiences (i.e., competence and enjoyment) and functional supports in the program (e.g., player handbook, weight loss coach) were reported to drive outcomes of effective weight loss and program retention. Interventions aiming to target men may be more successful working with rather than against formulations of identity such as masculinities, and this can be achieved by tailoring program content (e.g., messaging), settings (e.g., among men sharing similar characteristics such as body-type or goals), and mode of delivery (e.g., through organized sports, and leveraging competition to drive healthy behaviours).

CARNIVORE PROTOPARVOVIRUS 1 (PARVOVIRUSES) AT THE DOMESTIC-WILD CARNIVORE INTERFACE IN INDIA.

Carnivore protoparvovirus 1 (CP1, earlier called Feline panleukopenia virus) variants such as canine parvovirus (CPV) and feline parvovirus (FPV) are significant, emerging, multihost pathogens of domestic and wild carnivores. The diversity of CP1 variants was studied between 2008 and 2014 in Wayanad, India, where flagship wildlife species such as tigers (Panthera tigris) and leopards (Panthera pardus) coexist alongside domestic carnivores, including dogs (Canis lupus familiaris) and cats (Felis catus). Using polymerase chain reaction, FPV and CPV sequences were obtained from the heart blood of a necropsied leopard individual for the first time in the world and from rectal swabs of three sympatric and clinically ill domestic dogs. CP1 amplicons were also detected in a tiger. Cross-species transmission possibilities were identified, as the closest relatives to the leopard FPV sequence were found in domestic cats from a neighboring state.

Applying Artificial Intelligence to Address the Knowledge Gaps in Cancer Care.

BACKGROUND: Rapid advances in science challenge the timely adoption of evidence-based care in community settings. To bridge the gap between what is possible and what is practiced, we researched approaches to developing an artificial intelligence (AI) application that can provide real-time patient-specific decision support. MATERIALS AND METHODS: The Oncology Expert Advisor (OEA) was designed to simulate peer-to-peer consultation with three core functions: patient history summarization, treatment options recommendation, and management advisory. Machine-learning algorithms were trained to construct a dynamic summary of patients cancer history and to suggest approved therapy or investigative trial options. All patient data used were retrospectively accrued. Ground truth was established for approximately 1,000 unique patients. The full Medline database of more than 23 million published abstracts was used as the literature corpus. RESULTS: OEA's accuracies of searching disparate sources within electronic medical records to extract complex clinical concepts from unstructured text documents varied, with F1 scores of 90%-96% for non-time-dependent concepts (e.g., diagnosis) and F1 scores of 63%-65% for time-dependent concepts (e.g., therapy history timeline). Based on constructed patient profiles, OEA suggests approved therapy options linked to supporting evidence (99.9% recall; 88% precision), and screens for eligible clinical trials on ClinicalTrials.gov (97.9% recall; 96.9% precision). CONCLUSION: Our results demonstrated technical feasibility of an AI-powered application to construct longitudinal patient profiles in context and to suggest evidence-based treatment and trial options. Our experience highlighted the necessity of collaboration across clinical and AI domains, and the requirement of clinical expertise throughout the process, from design to training to testing. IMPLICATIONS FOR PRACTICE: Artificial intelligence (AI)-powered digital advisors such as the Oncology Expert Advisor have the potential to augment the capacity and update the knowledge base of practicing oncologists. By constructing dynamic patient profiles from disparate data sources and organizing and vetting vast literature for relevance to a specific patient, such AI applications could empower oncologists to consider all therapy options based on the latest scientific evidence for their patients, and help them spend less time on information "hunting and gathering" and more time with the patients. However, realization of this will require not only AI technology maturation but also active participation and leadership by clincial experts.

First evidence of a new simian adenovirus clustering with Human mastadenovirus F viruses.

BACKGROUND: Adenoviruses play an important role as human pathogens, though most infections are believed to be asymptomatic. The over 100 human adenovirus types are classified into seven species (A-G), some of which include simian adenoviruses. Recent findings have highlighted that simian adenoviruses have a zoonotic potential and that some human adenoviruses are likely the result of relatively recent spillover events. METHODS: In order to evaluate the risks associated with primates hunted and sold as bushmeat, multiple samples from 24 freshly killed monkeys were collected in the Republic of the Congo and tested for adenovirus DNA by PCRs targeting the conserved DNA polymerase and hexon genes. RESULTS: The DNA of a novel simian adenovirus was detected in a moustached monkey (Cercopithecus cephus) by the DNA polymerase PCR, but not by the hexon PCR. The 275 nucleotide amplicon was most closely related to members of the Human mastadenovirus F species (93% HAdV-40 and 89% HAdV-41 amino acid identity), rather than to other known simian adenoviruses. CONCLUSIONS: The phylogenetic clustering with Human mastadenovirus F sequences suggests a common ancestor, more recent than the last common ancestor of humans and moustached monkeys. The findings increase concerns about the zoonotic potential of simian adenoviruses and highlight the need for more research and surveillance on the issue.

The role of the athletes' entourage on attitudes to doping.

The present study investigated athletes' and coaches' beliefs about the role of athletes' entourage in deterring or promoting doping. Competitive athletes and coaches in Greece and Australia took part in semi-structured interviews. Our analysis of the interviews produced five main themes: coach influence, peer influence, doping stance, doping stigma, and entourage's culture. Overall, coaches and peers having a close and trusty relationship with the athletes were considered most influential with respect to doping-related decisions. The majority of the athletes held a strong anti-doping stance but could not articulate why they held this position. This inability could be ascribed to the stigmatization of doping which led to lack of knowledge and anti-doping education. Finally, an anti-doping culture in the athletes' environment was considered central to an anti-doping stance. The study findings provide valuable information towards a comprehensive understanding of the role athletes' entourage can play in shaping athletes' attitudes and decision for doping.

Posterior Hip Precautions Do Not Impact Early Recovery in Total Hip Arthroplasty: A Multicenter, Randomized, Controlled Study.

BACKGROUND: Posterior hip precautions have been routinely prescribed to decrease dislocation rates. The purpose of this study was to determine whether the absence of hip precautions improved early recovery after total hip arthroplasty via the posterolateral approach. METHODS: Patients undergoing total hip arthroplasty via the posterolateral approach at 3 centers were enrolled. Patients meeting the selection criteria were randomized to standard hip precautions (SHP) or no hip precautions (NHP) for 6 weeks following surgery. HOOS Jr, Health State visual analog score, and rate of pain scores were recorded preoperatively and in subsequent postoperative visits; dislocation episodes were also noted. Standard statistical analysis was performed. RESULTS: From 2016 to 2017, 159 patients were randomized to SHP and 154 patients were randomized to NHP. Controlling for the center at which the surgery was performed, the only difference in outcome scores between the 2 groups was at 2 weeks; the NHP group had a lower HOOS Jr score when compared to the SHP group (P = .03). There was no difference in outcome scores at any other time points when compared to preoperative assessments. In the SHP group, there were 2 recorded dislocations (1.3%) and 1 in the NHP group (0.7%; P = .62). CONCLUSION: In this multicenter, randomized, controlled study, the absence of hip precautions in the postoperative period did not improve subjective outcomes which may be explained by the self-limiting behavior of NHP patients. Furthermore, with the numbers available for the study, there was no difference in the rate of dislocation between the 2 groups.

Body Image Among Elite Rugby Union Players.

Gibson, C, Hindle, C, McLay-Cooke, R, Slater, J, Brown, R, Smith, B, Baker, D, Healey, P, and Black, K. Body image among elite rugby union players. J Strength Cond Res 33(8): 2217-2222, 2019-There is limited information on the risk of eating disorders (EDs) and body image of elite male athletes. However, research studies suggest that there are some athletes who have poor body image and they may be at increased risk of developing EDs. Therefore, the current study investigated risk of EDs, body image, and the relationship with age, in elite rugby union players during their preseason training period. This cross-sectional study was undertaken at the start of the preseason among elite rugby union players in New Zealand. Twenty-six professional rugby union players completed a 49-item questionnaire on body image and disordered eating. A "body image score" was calculated from questionnaire subscales including "drive for thinness," "bulimia," and "body dissatisfaction," with total scores above 20 indicative of poor body image. Body image scores varied from 8 to 39 out of a possible 0-100. Disordered eating behaviors were reported, including binge eating at least once a week (15%, n = 4/26), pathogenic weight control use (4%, n = 1/26), and avoidance of certain foods (77%, n = 20/26). There was a statistically significant inverse association between the bulimia subscale and age (p = 0.034). At the start of the preseason training period, many elite rugby union players experience disturbances in body image. The prevalence of disordered eating behaviors is of concern, and needs to be minimized due to the negative impact on health and performance. A focus on assessment and education of younger male rugby players may be required to reduce disordered eating patterns.

Improving Communication of Information About Physical Activity Opportunities for People With Disabilities.

One significant barrier to physical activity (PA) for people with disabilities is the lack of access to PA information. The purpose of this study was to explore how access to PA information can be improved for people with disabilities, their carers, and PA-session facilitators. To investigate the flow of PA information within a communication network, principles derived from knowledge translation were used: information audiences, messengers, methods, and effectiveness. Participants included 48 people with disabilities (34 male and 14 female; mean age 30 years), 34 carers, and 12 session facilitators. Qualitative data were analyzed using thematic analysis. Results show how communication of PA information can be improved by indicating practical value in understanding individual motivations to PA participation, including credible messengers, using multiple delivery methods, and expanding information networks. Future steps are offered, including practical implications resulting from this study to improve PA information flow within a network.