Artificial intelligence in the management and treatment of burns: A systematic review and meta-analyses.

INTRODUCTION AND AIM: Artificial Intelligence (AI) is already being successfully employed to aid the interpretation of multiple facets of burns care. In the light of the growing influence of AI, this systematic review and diagnostic test accuracy meta-analyses aim to appraise and summarise the current direction of research in this field. METHOD: A systematic literature review was conducted of relevant studies published between 1990 and 2021, yielding 35 studies. Twelve studies were suitable for a Diagnostic Test Meta-Analyses. RESULTS: The studies generally focussed on burn depth (Accuracy 68.9%-95.4%, Sensitivity 90.8% and Specificity 84.4%), burn segmentation (Accuracy 76.0%-99.4%, Sensitivity 97.9% and specificity 97.6%) and burn related mortality (Accuracy >90%-97.5% Sensitivity 92.9% and specificity 93.4%). Neural networks were the most common machine learning (ML) algorithm utilised in 69% of the studies. The QUADAS-2 tool identified significant heterogeneity between studies. DISCUSSION: The potential application of AI in the management of burns patients is promising, especially given its propitious results across a spectrum of dimensions, including burn depth, size, mortality, related sepsis and acute kidney injuries. The accuracy of the results analysed within this study is comparable to current practices in burns care. CONCLUSION: The application of AI in the treatment and management of burns patients, as a series of point of care diagnostic adjuncts, is promising. Whilst AI is a potentially valuable tool, a full evaluation of its current utility and potential is limited by significant variations in research methodology and reporting.

Perceptions of anonymised data use and awareness of the NHS data opt-out amongst patients, carers and healthcare staff.

BACKGROUND: England operates a National Data Opt-Out (NDOO) for the secondary use of confidential health data for research and planning. We hypothesised that public awareness and support for the secondary use of health data and the NDOO would vary by participant demography and healthcare experience. We explored patient/public awareness and perceptions of secondary data use, grouping potential researchers into National Health Service (NHS), academia or commercial. We assessed awareness of the NDOO system amongst patients, carers, healthcare staff and the public. We co-developed recommendations to consider when sharing unconsented health data for research. METHODS: A patient and public engagement program, co-created and including patient and public workshops, questionnaires and discussion groups regarding anonymised health data use. RESULTS: There were 350 participants in total. Central concerns for health data use included unauthorised data re-use, the potential for discrimination and data sharing without patient benefit. 94% of respondents were happy for their data to be used for NHS research, 85% for academic research and 68% by health companies, but less than 50% for non-healthcare companies and opinions varied with demography and participant group. Questionnaires showed that knowledge of the NDOO was low, with 32% of all respondents, 53% of all NHS staff and 29% of all patients aware of the NDOO. Recommendations to guide unconsented secondary health data use included that health data use should benefit patients; data sharing decisions should involve patients/public. That data should remain in close proximity to health services with the principles of data minimisation applied. Further, that there should be transparency in secondary health data use, including publicly available lists of projects, summaries and benefits. Finally, organisations involved in data access decisions should participate in programmes to increase knowledge of the NDOO, to ensure public members were making informed choices about their own data. CONCLUSION: The majority of participants in this study reported that the use of healthcare data for secondary purposes was acceptable when accessed by NHS. Academic and health-focused companies. However, awareness was limited, including of the NDOO. Further development of publicly-agreed recommendations for secondary health data use may improve both awareness and confidence in secondary health data use.

Health data from routine care can be pseudonymised (with a link remaining to the patient but identifying features removed) or anonymised (with identifying features removed and the link to the patient severed) and used for research and health planning; termed "secondary use". The National Health Service (NHS) is a single publicly-funded health service for the United Kingdom (UK). The NHS supports secondary data use with a National Data opt-out system. The potential benefits of data secondary use are clear but concerns have been raised. Although the Data Opt-Out is publicised, it is unclear how much public awareness there is of this scheme. We report a patient and publicly created and delivered series of activities including > 350 people; with young adults, patients, NHS staff and the public; to assess concerns, knowledge and acceptance of data sharing.Perceptions of and support for secondary health data use varied depending on who was asked (by age, gender) and their experience of health services (Staff member, patient, member of the public). Knowledge of schemes to limit secondary data use (such as the UK National Data Op-Out) was low, even among NHS staff. The main concerns of sharing health data included onward data use, the potential for discrimination and exploitation and commercial gain from data use with no benefit to patients. Despite this, most participants agreed with health data sharing with NHS, academic and commercial health-based entities. Agreed, co-created themes to increase the acceptability of health data secondary use included education about 'Opt-out' schemes, health service oversight of data use (as the most trusted partner), public and patient involvement in data sharing decisions and public transparency.

Utility of HbA1c assessment in people with diabetes awaiting liver transplantation.

AIMS: To investigate the relationship between HbA1c and glucose in people with co-existing liver disease and diabetes awaiting transplant, and in those with diabetes but no liver disease. METHODS: HbA1c and random plasma glucose data were collected for 125 people with diabetes without liver disease and for 29 people awaiting liver transplant with diabetes and cirrhosis. Cirrhosis was caused by non-alcoholic fatty liver disease, hepatitis C, alcoholic liver disease, hereditary haemochromatosis, polycystic liver/kidneys, cryptogenic/non-cirrhotic portal hypertension and α-1-antitrypsin-related disease. RESULTS: The median (interquartile range) age of the diabetes with cirrhosis group was 55 (49-63) years compared to 60 (50-71) years (P=0.13) in the group without cirrhosis. In the diabetes with cirrhosis group there were 21 men (72%) compared with 86 men (69%) in the group with diabetes and no cirrhosis (P=0.82). Of the group with diabetes and cirrhosis, 27 people (93%) were of white European ethnicity, two (7%) were South Asian and none was of Afro-Caribbean/other ethnicity compared with 94 (75%), 16 (13%), 10 (8%)/5 (4%), respectively, in the group with diabetes and no cirrhosis (P=0.20). Median (interquartile range) HbA1c was 41 (32-56) mmol/mol [5.9 (5.1-7.3)%] vs 61 (52-70) mmol/mol [7.7 (6.9-8.6)%] (P<0.001), respectively, in the diabetes with cirrhosis group vs the diabetes without cirrhosis group. The glucose concentrations were 8.4 (7.0-11.2) mmol/l vs 7.3 (5.2-11.5) mmol/l (P=0.17). HbA1c was depressed by 20 mmol/mol (1.8%; P<0.001) in 28 participants with cirrhosis but elevated by 28 mmol/mol (2.6%) in the participant with α-1-antitrypsin disorder. Those with cirrhosis and depressed HbA1c had fewer larger erythrocytes, and higher red cell distribution width and reticulocyte count. This was reflected in the positive association of glucose with mean cell volume (r=0.39) and haemoglobin level (r=0.49) and the negative association for HbA1c (r=-0.28 and r=-0.26, respectively) in the diabetes group with cirrhosis. CONCLUSION: HbA1c is not an appropriate test for blood glucose in people with cirrhosis and diabetes awaiting transplant as it reflects altered erythrocyte presentation.

Building mouse phenotype ontologies.

The structured description of mutant phenotypes presents a major conceptual and practical problem. A general model for generating mouse phenotype ontologies that involves combing a variety of different ontologies to better link and describe phenotypes is presented. This model is based on the Phenotype and Trait Ontology schema proposal and incorporates practical limitations and designing solutions in an attempt to model a testbed for the first phenotype ontology constructed in this manner, namely the mouse behavior phenotype ontology. We propose the application of such a model could provide curators with a powerful mechanism of annotation, mining and knowledge representation as well as achieving some level of free text disassociation.

Ontologies for the description of mouse phenotypes.

Ontologies are becoming increasingly important for the efficient storage, retrieval and mining of biological data. The description of phenotypes using ontologies is a particularly complex problem. We outline a schema that can be used to describe phenotypes by combining orthologous axiomatic ontologies. We also describe tools for storing, browsing and searching such complex ontologies. Central to this approach is that assays (protocols for measuring phenotypic characters) describe what has been measured as well as how this was done, allowing assays to link individual organisms to ontologies describing phenotypes. We have evaluated this approach by automatically annotating data on 600,000 mutant mice phenotypes using the SHIRPA protocol. We believe this approach will enable the flexible, extensible and detailed description of phenotypes from any organism.

Lipid-facing correlated mutations and dimerization in G-protein coupled receptors.

A correlated mutation analysis has been performed on the aligned protein sequences of a number of class A G-protein coupled receptor families, including the chemokine, neurokinin, opioid, somatostatin, thyrotrophin and the whole biogenic amine family. Many of the correlated mutations are observed flanking or neighbouring conserved residues. The correlated residues have been plotted onto the transmembrane portion of the rhodopsin crystal structure. The structure shows that a significant proportion of the correlated mutations are located on the external (lipid-facing) region of the helices. The occurrence of these highly correlated patterns of change amongst the external residues suggest that they are sites for protein-protein interactions. In particular, it is suggested that the correlated residues may be involved in either large conformational changes, the formation of heterodimers or homodimers (which may be domain swapped) or oligomers required for activation or internalization. The results are discussed in the light of the subtype-specific heterodimerization observed for the chemokine, opioid and somatostatin receptors.

Chemical markup, XML and the World-Wide Web. 3. Toward a signed semantic chemical web of trust.

We describe how a collection of documents expressed in XML-conforming languages such as CML and XHTML can be authenticated and validated against digital signatures which make use of established X.509 certificate technology. These can be associated either with specific nodes in the XML document or with the entire document. We illustrate this with two examples. An entire journal article expressed in XML has its individual components digitally signed by separate authors, and the collection is placed in an envelope and again signed. The second example involves using a software robot agent to acquire a collection of documents from a specified URL, to perform various operations and transformations on the content, including expressing molecules in CML, and to automatically sign the various components and deposit the result in a repository. We argue that these operations can used as components for building what we term an authenticated and semantic chemical web of trust.

JChemTidy: a tool for converting chemical Web document collections to an XHTML representation.

A robot-based procedure is described for traversing a collection of hyperlinked documents written in HTML and converting these to the XML-compliant and well-formed XHTML representation. Transcluded chemical content invoked using or HTML calls are converted to the XHTML recommended

In recent years there has been an increasing number of reports describing G protein-coupled receptor (GPCR) dimerization and heterodimerization. However, the evidence on the nature of the dimers and their role in GPCR activation is inconclusive. Consequently, we present here a review of our computational studies on G protein-coupled receptor dimerization and domain swapping. The studies described include molecular dynamics simulations on receptor monomers and dimers in the absence of ligand, in the presence of an agonist, and in the presence of an antagonist (or more precisely an inverse agonist). Two distinct sequence-based approaches to studying protein interfaces are also described, namely correlated mutation analysis and evolutionary trace analysis. All three approaches concur in supporting the proposal that the dimerization interface includes transmembrane helices 5 and 6. These studies cannot distinguish between domain swapped dimers and contact dimers as the models used were restricted to the helical part of the receptor. However, it is proposed that for the purpose of signalling, the domain swapped dimer and the corresponding contact dimer are equivalent. The evolutionary trace analysis suggests that every GPCR family and subfamily (for which sufficient sequence data is available) has the potential to dimerize through this common functional site on helices 5 and 6. The evolutionary trace results on the G protein are briefly described and these are consistent with GPCR dimerization. In addition to the functional site on helices 5 and 6, the evolutionary trace analysis identified a second functional site on helices 2 and 3. Possible roles for this site are suggested, including oligomerization.

Dimerization and domain swapping in G-protein-coupled receptors: a computational study.

In recent years there has been an increasing number of reports describing G protein-coupled receptor (GPCR) dimerization and heterodimerization. However, the evidence on the nature of the dimers and their role in GPCR activation is inconclusive. Consequently, we present here a review of our computational studies on G protein-coupled receptor dimerization and domain swapping. The studies described include molecular dynamics simulations on receptor monomers and dimers in the absence of ligand, in the presence of an agonist, and in the presence of an antagonist (or more precisely an inverse agonist). Two distinct sequence-based approaches to studying protein interfaces are also described, namely correlated mutation analysis and evolutionary trace analysis. All three approaches concur in supporting the proposal that the dimerization interface includes transmembrane helices 5 and 6. These studies cannot distinguish between domain swapped dimers and contact dimers as the models used were restricted to the helical part of the receptor. However, it is proposed that for the purpose of signalling, the domain swapped dimer and the corresponding contact dimer are equivalent. The evolutionary trace analysis suggests that every GPCR family and subfamily (for which sufficient sequence data is available) has the potential to dimerize through this common functional site on helices 5 and 6. The evolutionary trace results on the G protein are briefly described and these are consistent with GPCR dimerization. In addition to the functional site on helices 5 and 6, the evolutionary trace analysis identified a second functional site on helices 2 and 3. Possible roles for this site are suggested, including oligomerization.