Variables associated with owner perceptions of the health of their dog: Further analysis of data from a large international survey.

In a recent study (doi: 10.1371/journal.pone.0265662), associations were identified between owner-reported dog health status and diet, whereby those fed a vegan diet were perceived to be healthier. However, the study was limited because it did not consider possible confounding from variables not included in the analysis. The aim of the current study was to extend these earlier findings, using different modelling techniques and including multiple variables, to identify the most important predictors of owner perceptions of dog health. From the original dataset, two binary outcome variables were created: the 'any health problem' distinguished dogs that owners perceived to be healthy ("no") from those perceived to have illness of any severity; the 'significant illness' variable distinguished dogs that owners perceived to be either healthy or having mild illness ("no") from those perceived to have significant or serious illness ("yes"). Associations between these health outcomes and both owner-animal metadata and healthcare variables were assessed using logistic regression and machine learning predictive modelling using XGBoost. For the any health problem outcome, best-fit models for both logistic regression (area under curve [AUC] 0.842) and XGBoost (AUC 0.836) contained the variables dog age, veterinary visits and received medication, whilst owner age and breed size category also featured. For the significant illness outcome, received medication, veterinary visits, dog age and were again the most important predictors for both logistic regression (AUC 0.903) and XGBoost (AUC 0.887), whilst breed size category, education and owner age also featured in the latter. Any contribution from the dog vegan diet variable was negligible. The results of the current study extend the previous research using the same dataset and suggest that diet has limited impact on owner-perceived dog health status; instead, dog age, frequency of veterinary visits and receiving medication are most important.

Cross-sectional United Kingdom surveys demonstrate that owners and veterinary professionals differ in their perceptions of preventive and treatment healthcare needs in ageing dogs.

Perceptions of dog owners and veterinary professionals (surgeons/nurses) can influence the preventive healthcare and treatment provided to dogs, especially at the senior life-stage, when chronic diseases become more common. This study compared perceptions of healthcare of dogs as they age between dog owners and veterinary professionals. Data from two online surveys (owners: N = 633, veterinary professionals: N = 305) examined perceived need for veterinary visits and vaccinations. In addition, 48 clinical signs were rated on perceived prevalence (whether owners' dogs had experienced them) and how urgently they should seek veterinary advice. Groups were compared using descriptive statistics and chi-square. Owners most often believed a 'healthy' senior dog (>7 years) should go to the vet once a year (47% owners vs. 25% veterinary professionals, p < 0.001), compared with veterinary professionals every 6 months (39 vs. 73%). A minority (14%) of owners would just take the dog 'if they got sick' but only 2% of veterinary professionals advised this, and 16% of owners of dogs of all ages had not had any contact with their veterinary practise in the previous year. Nearly all veterinary professionals (92%) believed that senior/geriatric dogs should receive yearly vaccinations. However, 28% of owners' dogs of all ages were not vaccinated in the previous year and, of these, 33% did not believe that older dogs need vaccinations. Only 10% of dogs considered 'old' by their owners had attended a senior wellness clinic or examination, despite 14% of practises offering them. The three most common clinical signs reported by owners were slowing down on walks (57%), dental tartar (53%) and being stiff on rising (50%). Owners perceived urgency to seek veterinary care was lower if they had experienced the clinical sign before. In the current study, dog owners and veterinary professionals differed in their opinions about the need for veterinary care, suggesting new educational initiatives, and more effective communication is required.

The effect of obesity and subsequent weight reduction on cardiac morphology and function in cats.

BACKGROUND: In people, obesity is a risk factor for cardiovascular disease, associated with systemic hypertension, cardiac remodelling and systolic and diastolic dysfunction. Weight reduction can reverse myocardial remodelling and reduce risk of subsequent cardiovascular disease. In cats, far less is known regarding the effects of obesity and subsequent weight reduction on cardiovascular morphology and function. This prospective study aimed to assess cardiac morphology and function, heart rate variability, cardiac biomarkers and body composition before and after controlled weight reduction in cats with obesity. Body composition analysis (by dual energy x-ray absorptiometry, DEXA) and cardiovascular assessment (echocardiography, systemic arterial systolic blood pressure, electrocardiography, plasma cardiac biomarkers) were performed prior to weight management in twenty cats with obesity. These investigations were repeated in eleven cats that reached target weight. RESULTS: At baseline, systemic hypertension was not documented, but the majority of cats with obesity (15 out of 19) showed echocardiographic evidence of diastolic dysfunction. Eleven of 20 cats had increased maximal end-diastolic septal or left ventricular free wall thickness (≥ 6.0 mm) at baseline. Median (interquartile range) percentage of weight lost in the cats reaching target weight was 26% (17-29%), with a median reduction in body fat mass of 45% (26-64%). Both the end-diastolic left ventricular free wall (median magnitude of change -0.85 mm, IQR -0.05 mm to -1.55 mm, P = 0.019; median percentage reduction 14.0%) and end-diastolic interventricular septum (median magnitude of change -0.5 mm, IQR -0.2 mm to -1.225 mm, P = 0.047; median percentage reduction 7.9%) thickness decreased after weight reduction. Following weight reduction, pulsed wave tissue Doppler imaging of the left ventricular free wall was consistent with improved diastolic function in 4 out of 8 cats, however there was no significant difference in overall diastolic function class. Further, there was no change in heart rate variability or cardiac biomarkers with weight reduction. CONCLUSION: An increase in left ventricular wall thickness and diastolic dysfunction were common echocardiographic features in cats with obesity within our study and may be reversible with successful weight and fat mass loss. Further studies are required to clarify the clinical consequences of these findings.

Effects of tofersen treatment in patients with SOD1-ALS in a "real-world" setting - a 12-month multicenter cohort study from the German early access program.

Background: In April 2023, the antisense oligonucleotide tofersen was approved by the U.S. Food and Drug Administration (FDA) for treatment of SOD1-amyotrophic lateral sclerosis (ALS), after a decrease of neurofilament light chain (NfL) levels had been demonstrated. Methods: Between 03/2022 and 04/2023, 24 patients with SOD1-ALS from ten German ALS reference centers were followed-up until the cut-off date for ALS functional rating scale revised (ALSFRS-R), progression rate (loss of ALSFRS-R/month), NfL, phosphorylated neurofilament heavy chain (pNfH) in cerebrospinal fluid (CSF), and adverse events. Findings: During the observation period, median ALSFRS-R decreased from 38.0 (IQR 32.0-42.0) to 35.0 (IQR 29.0-42.0), corresponding to a median progression rate of 0.11 (IQR -0.09 to 0.32) points of ALSFRS-R lost per month. Median serum NfL declined from 78.0 pg/ml (IQR 37.0-147.0 pg/ml; n = 23) to 36.0 pg/ml (IQR 22.0-65.0 pg/ml; n = 23; p = 0.02), median pNfH in CSF from 2226 pg/ml (IQR 1061-6138 pg/ml; n = 18) to 1151 pg/ml (IQR 521-2360 pg/ml; n = 18; p = 0.02). In the CSF, we detected a pleocytosis in 73% of patients (11 of 15) and an intrathecal immunoglobulin synthesis (IgG, IgM, or IgA) in 9 out of 10 patients. Two drug-related serious adverse events were reported. Interpretation: Consistent with the VALOR study and its Open Label Extension (OLE), our results confirm a reduction of NfL serum levels, and moreover show a reduction of pNfH in CSF. The therapy was safe, as no persistent symptoms were observed. Pleocytosis and Ig synthesis in CSF with clinical symptoms related to myeloradiculitis in two patients, indicate the potential of an autoimmune reaction. Funding: No funding was received towards this study.

A deep learning pipeline for automated classification of vocal fold polyps in flexible laryngoscopy.

PURPOSE: To develop and validate a deep learning model for distinguishing healthy vocal folds (HVF) and vocal fold polyps (VFP) on laryngoscopy videos, while demonstrating the ability of a previously developed informative frame classifier in facilitating deep learning development. METHODS: Following retrospective extraction of image frames from 52 HVF and 77 unilateral VFP videos, two researchers manually labeled each frame as informative or uninformative. A previously developed informative frame classifier was used to extract informative frames from the same video set. Both sets of videos were independently divided into training (60%), validation (20%), and test (20%) by patient. Machine-labeled frames were independently verified by two researchers to assess the precision of the informative frame classifier. Two models, pre-trained on ResNet18, were trained to classify frames as containing HVF or VFP. The accuracy of the polyp classifier trained on machine-labeled frames was compared to that of the classifier trained on human-labeled frames. The performance was measured by accuracy and area under the receiver operating characteristic curve (AUROC). RESULTS: When evaluated on a hold-out test set, the polyp classifier trained on machine-labeled frames achieved an accuracy of 85% and AUROC of 0.84, whereas the classifier trained on human-labeled frames achieved an accuracy of 69% and AUROC of 0.66. CONCLUSION: An accurate deep learning classifier for vocal fold polyp identification was developed and validated with the assistance of a peer-reviewed informative frame classifier for dataset assembly. The classifier trained on machine-labeled frames demonstrates improved performance compared to the classifier trained on human-labeled frames.

Prescription medications with actionable pharmacogenomic recommendations in Veterans Health Administration patients.

Aim: To evaluate the prevalence of medications with actionable pharmacogenomic (PGx) safety and efficacy recommendations in patients receiving care from the Veterans Health Administration. Materials & methods: Outpatient prescription data from 2011 to 2021 and any documented adverse drug reactions (ADRs) were reviewed for those who received PGx testing at one Veterans Administration location between November 2019 and October 2021. Results: Among the reviewed prescriptions, 381 (32.8%) were associated with an actionable recommendation based on the Clinical Pharmacogenetics Implementation Consortium (CPIC) prescribing guidelines, with 205 (17.7%) for efficacy concerns and 176 (15.2%) for safety concerns. Among those with a documented ADR for a PGx-impacted medication, 39.1% had PGx results that aligned with CPIC recommendations. Conclusion: Medications with actionable PGx recommendations for safety and efficacy concerns are received with similar frequency, and most patients who have undergone PGx testing at the Phoenix Veterans Administration have received medications that may be impacted by PGx testing.

Partial weight reduction protocols in cats lead to better weight outcomes, compared with complete protocols, in cats with obesity.

Background: To date, there have been no studies comparing outcomes of cats with obesity following either complete or partial weight reduction protocols. Methods: Fifty-eight cats participated in this non-randomized observational cohort study, including 46 (79%) and 12 (21%) that underwent complete or partial weight reduction protocols, respectively. Weight loss outcomes, body composition changes and essential nutrient intake were compared between cats in the two groups. Results: All cats remained healthy, and those on a complete weight reduction protocol lost a median of 23% (range 10-39%) of starting body weight (SBW) over 294 days (113-967 days), whereas those undergoing partial restriction lost 25% (10-41%) over 178 days (54-512 days). Neither duration nor percentage weight loss differed between groups, but those that followed a partial weight reduction protocol lost weight at a faster rate (0.81% per week) and required fewer visits (4-19) than those that followed a complete weight reduction protocol (0.61% per week, p = 0.028; 11, 4-40 visits, p = 0.009). Further, lean tissue mass declined in cats on a complete weight reduction protocol (pre: 4.20 kg, 2.64-5.72 kg; post: 3.90 kg, 2.76-5.24 kg, p < 0.001), whereas lean tissue mass was unchanged in cats on partial weight reduction protocols (pre: 3.45 kg, 2.79-4.71 kg; post: 3.41 kg, 2.90-4.59 kg, p = 0.109). In 33 (57%) cats, median intake of selenium per day was less than NRC AI and RA recommendations, whilst intake was under FEDIAF recommendation in 42 (72%) cats. Median intake of choline per day was less than NRC MR and RA recommendations in 22 (38%) and 53 (91%) cats, respectively, whereas it was under the FEDIAF recommendation in 51 (88%) cats. In a small proportion (12-14%) of cats, phenylalanine/tyrosine and potassium were under recommendations; besides these, no other essential nutrient deficiencies were seen, and there were no differences between cats undergoing complete and partial weight reduction. Conclusion: Partial weight reduction protocols in cats lead to quicker average weight loss, with the possibility that lean tissue loss might be minimized. Such protocols might be more suitable for older cats and those with marked obesity.

The Histopathological Characteristic of Gastric Carcinoma in the Belgian Tervueren and Groenendael Dog: A Comparison of Two Classification Methods.

Gastric carcinoma is generally considered to be a rare disease in dogs, carrying a grave prognosis. However, in the Tervueren and Groenendael varieties of the Belgian Shepherd dog breed, the disease is highly prevalent. While histopathology is the gold standard for diagnosing gastric carcinoma, there is no general consensus on the methods for histological classification in these cases. Biopsies of a group of 61 dogs with confirmed gastric carcinoma (45 Tervueren and 16 Groenendael) were examined and classified according to World Health Organization (WHO) and Laurén classifications. Kaplan-Meier curves were used to compare survival between the different subtypes and simple and multiple linear regression were used to analyse the association between age of onset and breed variant, sex, neuter status, location of the tumour, inflammation score, and Laurén and WHO classifications. Mean age at diagnosis was significantly different in Groenendael (10.1 ± 2.01) and Tervueren dogs (8.5 ± 1.90). The Laurén classification resulted in 29 (48%) diffuse- and 32 (52%) intestinal-type tumours. Applying the WHO classification resulted in 30 (49%) tubular carcinoma growth patterns and 31 (51%) others. Median survival time was significantly reduced for the diffuse type as compared to the intestinal type according to the Laurén classification, with the same median survival time results for tubular compared to non-tubular subtypes according to the WHO classification (median survival time of 61 vs. 182 days, respectively). Using the WHO and Lauren classification on tumour biopsies may help the practising clinician in the prognostication of gastric carcinoma in Tervueren and Groenendael dogs.

Serum insulin concentration in dogs with insulinoma as a clinical marker for presence of metastasis at the time of diagnosis.

BACKGROUND: Information regarding serum insulin concentration in dogs newly diagnosed with insulinoma and its association with clinical stage and survival time is lacking. OBJECTIVE: Examine association between serum insulin concentration and survival and clinical disease stage in dogs with insulinoma. ANIMALS: Fifty-nine client-owned dogs with a diagnosis of insulinoma from 2 referral hospitals. METHOD: Retrospective observational study. The χ2 test was used to compare the proportion of dogs with increased insulin concentration in groups with or without metastasis at the time of diagnosis. Linear mixed-effect models were built to compare differences in insulin concentration between dogs with and without evidence of metastasis at the time of original diagnosis. Cox's proportional hazards regression and Kaplan-Meier graphs were used to evaluate the association between insulin concentration and insulin groups and survival. RESULTS: Median serum insulin concentration was 33 mIU/L (range, 8-200 mIU/L) in dogs with World Health Organization (WHO) stage I disease and 45 mIU/L (range, 12-213 mIU/L) in dogs with WHO stage II and III disease. No difference was found in the proportion of dogs with increased insulin concentration with or without metastasis (P = .09). No association was identified between insulin concentration and survival (P = .63), and between dogs grouped by insulin concentration and survival (P = .51). CONCLUSIONS AND CLINICAL IMPORTANCE: Serum insulin concentrations were not different between dogs with or without metastasis at diagnosis. The degree of insulinemia does not provide further information regarding the stage of the disease and is not associated with survival time in dogs with insulinoma.

Comparison of growth in neutered Domestic Shorthair kittens with growth in sexually-intact cats.

The first aim of these studies was to compare growth patterns of healthy kittens neutered during growth with growth standards created for sexually-intact kittens. A second aim was to clarify the impact of neutering in kittens on body composition and body shape. Study 1 was a retrospective observational study comparing median growth trajectories of healthy, client-owned domestic shorthair (DSH) kittens in optimal body condition and neutered at different ages, with previously-created growth standards from a similar, sexually-intact, population. The neuter groups contained between 3.0k and 9.3k cats. For all neuter groups in both sexes, the median growth trajectory inclined upwards after the procedure, with this being more marked in female than in male kittens. This upwards inclination was less marked for kittens neutered later during growth in both sexes, with the effect being least in kittens neutered after 28-29 weeks. Study 2 was an analysis of new body composition and zoometric data from a previously-published randomised study, comparing growth-related measures between 11 pairs of sexually-intact and neutered (at 19 weeks age) female DSH cats in a research population. Before neutering, the growth pattern in neutered kittens and sexually-intact kittens was similar, but neutered kittens were heavier by 52 weeks (mean difference in fold change vs. 10 weeks 1.34, 95-CI: 1.07-1.72), had a greater fat mass (mean difference in fold change vs. 10 weeks 1.91, 95-CI 1.09-3.21) and greater lean mass (mean difference in fold change vs. 10 weeks 1.23, 95-CI: 1.03-1.48). Abdominal girth (mean difference in fold change vs. 10 weeks 1.20, 95-CI: 1.04-1.39) and rib cage length (mean difference in fold change vs. 10 weeks 1.18, 95-CI: 1.02-1.36) were also greater, but there were no differences in other zoometric measurements. Veterinarians should consider the potential impact that neutering has on gain of adipose tissue, especially early neutering in female kittens. Bodyweight should be monitored closely during growth and especially after neutering to prevent inappropriate weight gain.

Parkinson's disease or multiple system atrophy: potential separation by quantitative susceptibility mapping.

Background: Due to the absence of robust biomarkers, and the low sensitivity and specificity of routine imaging techniques, the differential diagnosis between Parkinson's disease (PD) and multiple system atrophy (MSA) is challenging. High-field magnetic resonance imaging (MRI) opened up new possibilities regarding the analysis of pathological alterations associated with neurodegenerative processes. Recently, we have shown that quantitative susceptibility mapping (QSM) enables visualization and quantification of two major histopathologic hallmarks observed in MSA: reduced myelin density and iron accumulation in the basal ganglia of a transgenic murine model of MSA. It is therefore emerging as a promising imaging modality on the differential diagnosis of Parkinsonian syndromes. Objectives: To assess QSM on high-field MRI for the differential diagnosis of PD and MSA. Methods: We assessed 23 patients (nine PDs and 14 MSAs) and nine controls using QSM on 3T and 7T MRI scanners at two academic centers. Results: We observed increased susceptibility in MSA at 3T in prototypical subcortical and brainstem regions. Susceptibility measures of putamen, pallidum, and substantia nigra reached excellent diagnostic accuracy to separate both synucleinopathies. Increase toward 100% sensitivity and specificity was achieved using 7T MRI in a subset of patients. Magnetic susceptibility correlated with age in all groups, but not with disease duration in MSA. Sensitivity and specificity were particularly high for possible MSA, and reached 100% in the putamen. Conclusion: Putaminal susceptibility measures, in particular on ultra-high-field MRI, may distinguish MSA patients from both, PD and controls, allowing an early and sensitive diagnosis of MSA.

Ultrasonographic monitoring of feline epaxial muscle height as part of an annual wellness examination to assess for the development of sarcopenia.

OBJECTIVES: The aim of this study was to determine if epaxial muscle height (EMH) could be reliably incorporated into annual routine wellness screenings, and also determine its relationship to age, body condition score (BCS), subjective muscle assessment (SMA), breed and sex in mature cats. METHODS: EMH was determined independently by three observers from ultrasonographic examinations - collected by an additional trained individual - of cats enrolled at the Feline Healthy Ageing Clinic, University of Liverpool, UK. Age, body weight, BCS and SMA data were also collected. RESULTS: A total of 92 cats were included, 35 of which had repeat ultrasonographic examinations 12 months apart. Enrolled cats were a median age of 8 years and 9 months at the time of the first measurement. Variation in the quality of ultrasonographic images collected did not affect muscle depth measurements (P = 0.974). Further, there was good intra- and inter-observer repeatability for all observations (intraclass correlation range 0.97-0.99). There was a moderate positive association between EMH and body weight (r = 0.49, P <0.001) but no association with age (r = -0.05, P = 0.680). There were also positive associations in EMH among cats with different BCSs (P = 0.001) and SMAs (thoracic spine, P = 0.021; lumbar spine, P = 0.014), but breed (P = 0.429) and sex (P = 0.187) had no effect. Finally, there was no change in EMH measurements in the paired samples (P = 0.145) or correlation between percentage weight and EMH change over 12 months. CONCLUSIONS AND RELEVANCE: The accuracy of EMH measurement using ultrasonographic imaging is good, irrespective of observer experience and provided that the ultrasonographer has some training. This suggests that ultrasonographic measurement of EMH could have a major practical impact as a non-invasive determination of muscle mass in pet cat populations. Further research is required to assess longitudinal changes in muscle mass over time in senior pet cats.

7 tricks for 7 T CEST: Improving the reproducibility of multipool evaluation provides insights into the effects of age and the early stages of Parkinson's disease.

The objective of the current study was to optimize the postprocessing pipeline of 7 T chemical exchange saturation transfer (CEST) imaging for reproducibility and to prove this optimization for the detection of age differences and differences between patients with Parkinson's disease versus normal subjects. The following 7 T CEST MRI experiments were analyzed: repeated measurements of a healthy subject, subjects of two age cohorts (14 older, seven younger subjects), and measurements of 12 patients with Parkinson's disease. A slab-selective, B 1 + -homogeneous parallel transmit protocol was used. The postprocessing, consisting of motion correction, smoothing, B 0 -correction, normalization, denoising, B 1 + -correction and Lorentzian fitting, was optimized regarding the intrasubject and intersubject coefficient of variation (CoV) of the amplitudes of the amide pool and the aliphatic relayed nuclear Overhauser effect (rNOE) pool within the brain. Seven "tricks" for postprocessing accomplished an improvement of the mean voxel CoV of the amide pool and the aliphatic rNOE pool amplitudes of less than 5% and 3%, respectively. These postprocessing steps are: motion correction with interpolation of the motion of low-signal offsets (1) using the amide pool frequency offset image as reference (2), normalization of the Z-spectrum using the outermost saturated measurements (3), B 0 correction of the Z-spectrum with moderate spline smoothing (4), denoising using principal component analysis preserving the 11 highest intensity components (5), B 1 + correction using a linear fit (6) and Lorentzian fitting using the five-pool fit model (7). With the optimized postprocessing pipeline, a significant age effect in the amide pool can be detected. Additionally, for the first time, an aliphatic rNOE contrast between subjects with Parkinson's disease and age-matched healthy controls in the substantia nigra is detected. We propose an optimized postprocessing pipeline for CEST multipool evaluation. It is shown that by the use of these seven "tricks", the reproducibility and, thus, the statistical power of a CEST measurement, can be greatly improved and subtle changes can be detected.

Changes in Cough Airflow and Acoustics After Injection Laryngoplasty.

OBJECTIVE/HYPOTHESIS: We explored the following hypotheses in a cohort of patients undergoing injection laryngoplasty: (1) glottic insufficiency affects voluntary cough airflow dynamics and restoring glottic competence may improve parameters of cough strength, (2) cough strength can be inferred from cough acoustic signal, and (3) glottic competence changes cough sounds and correlates with spectrogram morphology. STUDY TYPE/DESIGN: Prospective interventional study. METHODS: Subjects with glottic insufficiency secondary to unilateral vocal fold paresis, paralysis, or atrophy, and scheduled for injection laryngoplasty completed an instrumental assessment of voluntary cough airflow using a pneumotachometer and a protocolized voluntary cough sound recording. A Wilcoxon signed-rank test was used to compare the differences between pre- and post-injection laryngoplasty in airflow and acoustic measures. A Spearman rank-order correlation was used to evaluate the association between airflow and acoustic cough measures. RESULTS: Twenty-five patients (13F:12M, mean age 68.8) completed voluntary cough airflow measurements and 22 completed cough sound recordings. Following injection laryngoplasty, patients had a statistically significant decreased peak expiratory flow rise time (PEFRT) (mean change: -0.03 s, SD: 0.06, p = 0.04) and increased cough volume acceleration (mean change: 13.1 L/s2 , SD: 33.9, p = 0.03), suggesting improved cough effectiveness. Correlation of cough acoustic measures with airflow measures showed a weak relationship between PEFRT and acoustic energy (coefficient: -0.31, p = 0.04) and peak power density (coefficient: -0.35, p = 0.02). CONCLUSIONS: Our study thus indicates that injection laryngoplasty may help avert aspiration in patients with glottic insufficiency by improving cough effectiveness and that improved cough airflow measures may be tracked with cough sounds. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:S1-S14, 2023.

Linear projection-based chemical exchange saturation transfer parameter estimation.

Isolated evaluation of multiparametric in vivo chemical exchange saturation transfer (CEST) MRI often requires complex computational processing for both correction of B0 and B1 inhomogeneity and contrast generation. For that, sufficiently densely sampled Z-spectra need to be acquired. The list of acquired frequency offsets largely determines the total CEST acquisition time, while potentially representing redundant information. In this work, a linear projection-based multiparametric CEST evaluation method is introduced that offers fast B0 and B1 inhomogeneity correction, contrast generation and feature selection for CEST data, enabling reduction of the overall measurement time. To that end, CEST data acquired at 7 T in six healthy subjects and in one brain tumor patient were conventionally evaluated by interpolation-based inhomogeneity correction and Lorentzian curve fitting. Linear regression was used to obtain coefficient vectors that directly map uncorrected data to corrected Lorentzian target parameters. L1-regularization was applied to find subsets of the originally acquired CEST measurements that still allow for such a linear projection mapping. The linear projection method allows fast and interpretable mapping from acquired raw data to contrast parameters of interest, generalizing from healthy subject training data to unseen healthy test data and to the tumor patient dataset. The L1-regularization method shows that a fraction of the acquired CEST measurements is sufficient to preserve tissue contrasts, offering up to a 2.8-fold reduction of scan time. Similar observations as for the 7-T data can be made for data from a clinical 3-T scanner. Being a fast and interpretable computation step, the proposed method is complementary to neural networks that have recently been employed for similar purposes. The scan time acceleration offered by the L1-regularization ("CEST-LASSO") constitutes a step towards better applicability of multiparametric CEST protocols in a clinical context.

Novel Homozygous FA2H Variant Causing the Full Spectrum of Fatty Acid Hydroxylase-Associated Neurodegeneration (SPG35).

Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in FA2H and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, we present the prototypical workup of a novel FA2H variant, including clinical and in silico validation. An 18-year-old male patient presented with a history of childhood-onset progressive cognitive impairment, as well as progressive gait disturbance and lower extremity muscle cramps from the age of 15. Additional symptoms included exotropia, dystonia, and limb ataxia. Trio exome sequencing revealed a novel homozygous c.75C>G (p.Cys25Trp) missense variant in the FA2H gene, which was located in the cytochrome b5 heme-binding domain. Evolutionary conservation, prediction models, and structural protein modeling indicated a pathogenic loss of function. Brain imaging showed characteristic features, thus fulfilling the complete multisystem neurodegenerative phenotype of FAHN/SPG35. In summary, we here present a novel FA2H variant and provide prototypical clinical findings and structural analyses underpinning its pathogenicity.

Growth standard charts for monitoring bodyweight in intact domestic shorthair kittens from the USA.

The optimal growth of domesticated cats has not yet been well defined. This study first aimed to create evidence-based growth standards for healthy pet domestic shorthair (DSH) kittens, and then compare the pattern of growth curves depicted by the standards with growth patterns in other healthy DSH kittens and those with abnormal body condition. Data were derived from the clinical records of the BANFIELD® Pet Hospital (BANFIELD) network in the USA and from a research population in the UK (Waltham Petcare Science Institute, UK). A 'modelling' dataset was first created from the BANFIELD records, comprising bodyweight data from immature client-owned DSH cats that had remained healthy and in ideal body condition within the first 2.5y of life. This was used to construct growth centile curves for male and female kittens, covering the age range 8 to 78 weeks, using Generalised Additive Models for Location, Shape and Scale. Growth patterns depicted by the centile curves were compared with the growth patterns of healthy DSH kittens from both research colonies and kittens attending BANFIELD that were classified as overweight or underweight. Overall, there was a broad agreement to the growth standards with approximately half of the research population (206/507, 49%) staying within 2 centile lines of their starting centile, and upward and downward movements outside this range being roughly equally distributed. Compared with the growth standards, the 122 overweight BANFIELD kittens were heavier on average at the start of monitoring and subsequently grew more quickly with 63 (52%) crossing at least 2 standard centile lines upwards. Only 4 underweight DSH kittens were available in the BANFIELD database; compared with the standards, there was a marked initial dip in growth followed by subsequent catch-up growth and 2/4 kittens crossed 2 or more centile lines downwards at some point. Evidence-based growth standards are developed here for male and female sexually-intact DSH kittens. Crossing centiles in an upwards and downwards direction is associated with cats becoming overweight or underweight by early adulthood, respectively. Further work is required to determine whether the clinical use of these growth standards will improve the health and wellbeing of pet cats.

Recording of body weight and body condition score of cats in electronic health records from UK veterinary practices.

OBJECTIVES: The aim of this study was to determine how frequently body weight, body condition score (BCS) and terms pertaining to weight status are recorded in the electronic health records (EHRs) of veterinary practices in the UK, as well as to examine the variables affecting recording and associated with body weight, where recorded. METHODS: Data recorded in EHRs were searched in two 3-month periods in 2019 and 2020. For each visit, variables including type and time of consultation, signalment, recording of body weight, recording of BCS, weight (kg), BCS value and whether an overweight or weight-loss term was used in free text were recorded. Linear mixed-effects models were created to examine associations between body weight and variables, while mixed-effects logistic regression was used to determine associations between the same variables and weight or BCS recording. RESULTS: The statistical data set comprised 129,076 visits from 129,076 cats at 361 practices. Weight was recorded at most (95.2%) visits, BCS was recorded at only 22.5% of visits, and terms associated with weight loss and overweight status were recorded in 10.0% and 7.2% of free-text records, respectively. Where BCS was recorded, approximately one-third of cats had an overweight score (8.0% of total visits). Using either an overweight term (P <0.001) or weight-loss term (P <0.001) was associated with increased odds of body weight being recorded, while being an out-of-hours (P <0.001) or non-routine consultation (P <0.001) were associated with decreased odds. Increasing age (P <0.001), using a weight-loss term (P <0.001) and using an overweight term (P <0.001) were associated with increased odds of BCS being recorded, while being a non-routine consultation (P <0.001) was associated with decreased odds. Recording BCS was negatively associated with recording body weight and vice versa. CONCLUSIONS AND RELEVANCE: Cats are regularly weighed in UK practice, but BCS is less frequently recorded, and both are less often recorded in non-routine consultations. To improve both the treatment and assessment of health and nutrition in cats, veterinary professionals should record body weight and BCS concurrently at every consultation.

Automatic classification of informative laryngoscopic images using deep learning.

Objective: This study aims to develop and validate a convolutional neural network (CNN)-based algorithm for automatic selection of informative frames in flexible laryngoscopic videos. The classifier has the potential to aid in the development of computer-aided diagnosis systems and reduce data processing time for clinician-computer scientist teams. Methods: A dataset of 22,132 laryngoscopic frames was extracted from 137 flexible laryngostroboscopic videos from 115 patients. 55 videos were from healthy patients with no laryngeal pathology and 82 videos were from patients with vocal fold polyps. The extracted frames were manually labeled as informative or uninformative by two independent reviewers based on vocal fold visibility, lighting, focus, and camera distance, resulting in 18,114 informative frames and 4018 uninformative frames. The dataset was split into training and test sets. A pre-trained ResNet-18 model was trained using transfer learning to classify frames as informative or uninformative. Hyperparameters were set using cross-validation. The primary outcome was precision for the informative class and secondary outcomes were precision, recall, and F1-score for all classes. The processing rate for frames between the model and a human annotator were compared. Results: The automated classifier achieved an informative frame precision, recall, and F1-score of 94.4%, 90.2%, and 92.3%, respectively, when evaluated on a hold-out test set of 4438 frames. The model processed frames 16 times faster than a human annotator. Conclusion: The CNN-based classifier demonstrates high precision for classifying informative frames in flexible laryngostroboscopic videos. This model has the potential to aid researchers with dataset creation for computer-aided diagnosis systems by automatically extracting relevant frames from laryngoscopic videos.

Aging in Cats: Owner Observations and Clinical Finding in 206 Mature Cats at Enrolment to the Cat Prospective Aging and Welfare Study.

Two hundred and six cats, aged between 7 and 10 years, from the North-west of the UK, were enrolled in a cat aging and welfare study to determine the frequency of age-related conditions and associations with husbandry, owner observations of physical appearance, activity and behavior. This is the largest study to date of mature cats that includes data from an owner questionnaire and clinical examinations. At enrolment, owners frequently reported physical changes (53%), behavioral changes (47%), changes to eating patterns (41%), and activity changes (40%) in their mature cats. On physical examination, 45% cats were in overweight condition and 12% were obese. A heart murmur was detected in 29% cats, whilst indirect systolic blood pressure (SBP) was >160 mmHg in 5% cats. Dental disease was present in 54% cats and was associated with a matted hair coat (P = 0.01), increased sleeping (P = 0.02), absence of gray hairs (P = 0.03), and increased irritability to other pets (P = 0.04). Abnormalities were evident in 58% of cats that allowed an orthopedic examination (OE) to be performed. These cats were older than cats with a normal OE (P = 0.01), and abnormal OE findings were associated with a matted coat (P = 0.03) and increased grooming (P = 0.04). Aazotaemia was present in 10% cats, and this was associated with cats being observed to "sniff their food and then walk away" (P = 0.04). Hyperthyroidism was diagnosed in 3% cats, who were older (P = 0.02), had a leaner BCS (P = 0.02) and lesser blood creatinine concentrations (P = 0.01). Hyperthyroid cats were also more likely to have increased liver enzyme activity and increased SBP (P = <0.001) compared with non-hyperthyroid cats. Of the 176 cats where all clinical assessments were conducted, only 12% had no evidence of any disease. Clinical abnormalities are commonly identified when thorough, clinical assessments are performed in mature pet cats visiting primary care practice.