Measuring the effect of the anti-nerve growth factor antibodies bedinvetmab and frunevetmab on quality of life in dogs and cats with osteoarthritis using a validated health-related quality of life outcome measure: an observational real-world study.

Background: Osteoarthritis causes chronic pain, impaired joint function, decreased mobility and negatively impacts quality of life (QOL). Anti-nerve growth factor antibodies bedinvetmab for dogs and frunevetmab for cats are licensed for the alleviation of osteoarthritis pain but their QOL impact is unreported. Our aim was to determine if these therapeutics improve QOL using a validated health-related QOL measure that generates scores in four domains of QOL-energetic and enthusiastic (E/E), happy and content (H/C), active and comfortable (A/C) and calm and relaxed (C/R)-in the dog and three in the cat-vitality, comfort and emotional wellbeing (EWB).

TopNEXt: automatic DDA exclusion framework for multi-sample mass spectrometry experiments.

Motivation: Liquid Chromatography Tandem Mass Spectrometry experiments aim to produce high-quality fragmentation spectra, which can be used to annotate metabolites. However, current Data-Dependent Acquisition approaches may fail to collect spectra of sufficient quality and quantity for experimental outcomes, and extend poorly across multiple samples by failing to share information across samples or by requiring manual expert input.

Results: We present TopNEXt, a real-time scan prioritization framework that improves data acquisition in multi-sample Liquid Chromatography Tandem Mass Spectrometry metabolomics experiments.

A Bayesian approach to incorporate structural data into the mapping of genotype to antigenic phenotype of influenza A(H3N2) viruses.

Surface antigens of pathogens are commonly targeted by vaccine-elicited antibodies but antigenic variability, notably in RNA viruses such as influenza, HIV and SARS-CoV-2, pose challenges for control by vaccination. For example, influenza A(H3N2) entered the human population in 1968 causing a pandemic and has since been monitored, along with other seasonal influenza viruses, for the emergence of antigenic drift variants through intensive global surveillance and laboratory characterisation. Statistical models of the relationship between genetic differences among viruses and their antigenic similarity provide useful information to inform vaccine development, though accurate identification of causative mutations is complicated by highly correlated genetic signals that arise due to the evolutionary process.

Simulated-to-real benchmarking of acquisition methods in untargeted metabolomics.

Data-Dependent and Data-Independent Acquisition modes (DDA and DIA, respectively) are both widely used to acquire MS2 spectra in untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolomics analyses. Despite their wide use, little work has been attempted to systematically compare their MS/MS spectral annotation performance in untargeted settings due to the lack of ground truth and the costs involved in running a large number of acquisitions. Here, we present a systematic comparison of these two acquisition methods in untargeted metabolomics by extending our Virtual Metabolomics Mass Spectrometer (ViMMS) framework with a DIA module.

Comprehensive genetic and functional analyses of Fc gamma receptors influence on response to rituximab therapy for autoimmunity.

Background: Rituximab is widely used to treat autoimmunity but clinical response varies. Efficacy is determined by the efficiency of B-cell depletion, which may depend on various Fc gamma receptor (FcγR)-dependent mechanisms. Study of FcγR is challenging due to the complexity of the FCGR genetic locus.

Validity and Responsiveness of the Generic Health-Related Quality of Life Instrument (VetMetrica™) in Cats With Osteoarthritis. Comparison of Vet and Owner Impressions of Quality of Life Impact.

Validity is not an inherent property of a measurement scale and so evidence for validity relating to its use for particular purposes, with defined populations and in specified contexts must be accumulated. We have published the development of a web-based, generic health-related quality of life instrument (VetMetrica™) to measure the affective impact of chronic disease in cats and provided evidence for its validity in a mixed population of cats, some of which, according to veterinary judgement, were healthy and others of which were suffering from chronic conditions likely to affect their quality of life, often with multiple co-morbidities present. The first aim of the current study was to demonstrate the construct validity of the VetMetrica™ generic instrument when used with cats suffering from osteoarthritis, by testing the hypothesis that the health-related quality of life profile of cats with different severities of osteoarthritis would differ and by demonstrating convergent validity between the health-related quality of life profile scores and independently quantified vet-assessed pain and quality of life impact scores.

Corrigendum: Development of an Early Warning System for Owners Using a Validated Health-Related Quality of Life (HRQL) Instrument for Companion Animals and Its Use in a Large Cohort of Dogs.

[This corrects the article DOI: 10.3389/fvets.2020.

Rapid Development of Improved Data-Dependent Acquisition Strategies.

Tandem mass spectrometry (LC-MS/MS) is widely used to identify unknown ions in untargeted metabolomics. Data-dependent acquisition (DDA) chooses which ions to fragment based upon intensities observed in MS1 survey scans and typically only fragments a small subset of the ions present. Despite this inefficiency, relatively little work has addressed the development of new DDA methods, partly due to the high overhead associated with running the many extracts necessary to optimize approaches in busy MS facilities.

Optimisation of Scores Generated by an Online Feline Health-Related Quality of Life (HRQL) Instrument to Assist the Veterinary User Interpret Its Results.

Using methodology previously described for the dog health-related quality of life (HRQL) tool (VetMetrica™), the aim was to optimize the scores profile of a comparable feline online HRQL instrument for monitoring HRQL in cats, to assist in its interpretation. Measuring HRQL helps quantify the impact of disease and its treatment on well-being, aids clinical decision making and provides information in clinical trials. In Study 1, using data collected from previous studies, scores generated for three domains of HRQL (Vitality, Comfort, Emotional Well-being) in healthy cats were normalized using standard statistical techniques of logit transformation and -scores, such that the average healthy cat has a score of 50 in all three HRQL domains.

Development of an Early Warning System for Owners Using a Validated Health-Related Quality of Life (HRQL) Instrument for Companion Animals and Its Use in a Large Cohort of Dogs.

Preventive measures in human healthcare are recognized as a means of providing early detection of disease, however, the veterinary profession has not been as effective in communicating the benefits of preventive measures to pet owners. Readily available pet healthcare information on the internet, owners not understanding that regular health evaluations can ensure the well-being of their pets and owners confusing the signs of chronic disease with normal aging have contributed to declining numbers of veterinary visits. The use of web-based generic health-related quality of life (HRQL) measures to evaluate health status (wellness) remotely could facilitate veterinary preventive medicine.

Reflection on modern methods: generalized linear models for prognosis and intervention-theory, practice and implications for machine learning.

Prediction and causal explanation are fundamentally distinct tasks of data analysis. In health applications, this difference can be understood in terms of the difference between prognosis (prediction) and prevention/treatment (causal explanation). Nevertheless, these two concepts are often conflated in practice.

Fast parameter inference in a biomechanical model of the left ventricle by using statistical emulation.

A central problem in biomechanical studies of personalized human left ventricular modelling is estimating the material properties and biophysical parameters from clinical measurements in a timeframe that is suitable for use within a clinic. Understanding these properties can provide insight into heart function or dysfunction and help to inform personalized medicine. However, finding a solution to the differential equations which mathematically describe the kinematics and dynamics of the myocardium through numerical integration can be computationally expensive.

In Silico Optimization of Mass Spectrometry Fragmentation Strategies in Metabolomics.

Liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) is widely used in identifying small molecules in untargeted metabolomics. Various strategies exist to acquire MS/MS fragmentation spectra; however, the development of new acquisition strategies is hampered by the lack of simulators that let researchers prototype, compare, and optimize strategies before validations on real machines. We introduce Virtual Metabolomics Mass Spectrometer (ViMMS), a metabolomics LC-MS/MS simulator framework that allows for scan-level control of the MS2 acquisition process in silico.

Improving the identification of antigenic sites in the H1N1 influenza virus through accounting for the experimental structure in a sparse hierarchical Bayesian model.

Understanding how genetic changes allow emerging virus strains to escape the protection afforded by vaccination is vital for the maintenance of effective vaccines. We use structural and phylogenetic differences between pairs of virus strains to identify important antigenic sites on the surface of the influenza A(H1N1) virus through the prediction of haemagglutination inhibition (HI) titre: pairwise measures of the antigenic similarity of virus strains. We propose a sparse hierarchical Bayesian model that can deal with the pairwise structure and inherent experimental variability in the H1N1 data through the introduction of latent variables.

Optimising outputs from a validated online instrument to measure health-related quality of life (HRQL) in dogs.

Measurement of health-related quality of life (HRQL) is becoming increasingly valuable within veterinary preventative health care and chronic disease management, as well as in outcomes research. Initial reliability and validation of a 22 item shortened version of VetMetrica (VM), structured questionnaire instrument to measure HRQL in dogs via a mobile application was reported previously. Meaningful interpretation and presentation of the 4 domain scores comprising the HRQL profile generated by VM is key to its successful use in clinical practice and research.

Gaussian process emulation to accelerate parameter estimation in a mechanical model of the left ventricle: a critical step towards clinical end-user relevance.

In recent years, we have witnessed substantial advances in the mathematical modelling of the biomechanical processes underlying the dynamics of the cardiac soft-tissue. Gao et al. (Gao et al.