Search Results (13)

The golden Syrian hamster (Mesocricetus auratus) is now commonly used in preclinical research for the study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the assessment of vaccines, drugs and therapeutics. Here, we show that hamsters inoculated via the intranasal route with the same infectious virus dose of prototypical SARS-CoV-2 administered in a different volume present with different clinical signs, weight loss and viral shedding, with a reduced volume resulting in reduced severity of disease similar to that obtained by a 500-fold reduction in the challenge dose. The tissue burden of the virus and the severity of pulmonary pathology were also significantly affected by different challenge inoculum volumes. These findings suggest that a direct comparison between the severity of SARS-CoV-2 variants or studies assessing the efficacy of treatments determined by hamster studies cannot be made unless both the challenge dose and inoculation volume are matched when using the intranasal route. Additionally, analysis of sub-genomic and total genomic RNA PCR data demonstrated no link between sub-genomic and live viral titres and that sub-genomic analyses do not provide any information beyond that provided by more sensitive total genomic PCR. Full article

Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide expressed in the trigeminal ganglia (TG). The TG conducts nociceptive signals in the head and may play roles in migraine. PACAP infusion provokes headaches in healthy individuals and migraine-like attacks in patients; however, it is not clear whether targeting this system could be therapeutically efficacious. To effectively target the PACAP system, an understanding of PACAP receptor distribution is required. Therefore, this study aimed to characterize commercially available antibodies and use these to detect PACAP-responsive receptors in the TG. Antibodies were initially validated in receptor transfected cell models and then used to explore receptor expression in rat and human TG. Antibodies were identified that could detect PACAP-responsive receptors, including the first antibody to differentiate between the PAC_1n and PAC_1s receptor splice variants. PAC₁, VPAC₁, and VPAC₂ receptor-like immunoreactivity were observed in subpopulations of both neuronal and glial-like cells in the TG. In this study, PAC₁, VPAC₁, and VPAC₂ receptors were detected in the TG, suggesting they are all potential targets to treat migraine. These antibodies may be useful tools to help elucidate PACAP-responsive receptor expression in tissues. However, most antibodies exhibited limitations, requiring the use of multiple methodologies and the careful inclusion of controls. Full article

Purpose: XNAT is an informatics software platform to support imaging research, particularly in the context of large, multicentre studies of the type that are essential to validate quantitative imaging biomarkers. XNAT provides import, archiving, processing and secure distribution facilities for image and related study data. Until recently, however, modern data visualisation and annotation tools were lacking on the XNAT platform. We describe the background to, and implementation of, an integration of the Open Health Imaging Foundation (OHIF) Viewer into the XNAT environment. We explain the challenges overcome and discuss future prospects for quantitative imaging studies. Materials and methods: The OHIF Viewer adopts an approach based on the DICOM web protocol. To allow operation in an XNAT environment, a data-routing methodology was developed to overcome the mismatch between the DICOM and XNAT information models and a custom viewer panel created to allow navigation within the viewer between different XNAT projects, subjects and imaging sessions. Modifications to the development environment were made to allow developers to test new code more easily against a live XNAT instance. Major new developments focused on the creation and storage of regions-of-interest (ROIs) and included: ROI creation and editing tools for both contour- and mask-based regions; a “smart CT” paintbrush tool; the integration of NVIDIA’s Artificial Intelligence Assisted Annotation (AIAA); the ability to view surface meshes, fractional segmentation maps and image overlays; and a rapid image reader tool aimed at radiologists. We have incorporated the OHIF microscopy extension and, in parallel, introduced support for microscopy session types within XNAT for the first time. Results: Integration of the OHIF Viewer within XNAT has been highly successful and numerous additional and enhanced tools have been created in a programme started in 2017 that is still ongoing. The software has been downloaded more than 3700 times during the course of the development work reported here, demonstrating the impact of the work. Conclusions: The OHIF open-source, zero-footprint web viewer has been incorporated into the XNAT platform and is now used at many institutions worldwide. Further innovations are envisaged in the near future. Full article

Corticobasal syndrome (CBS) is a rare neurodegenerative condition characterized by four-repeat tau aggregation in the cortical and subcortical brain regions and accompanied by severe atrophy. The aim of this study was to evaluate partial volume effect correction (PVEC) in patients with CBS compared to a control cohort imaged with the 18-kDa translocator protein (TSPO) positron emission tomography (PET) tracer [¹⁸F]GE-180. Eighteen patients with CBS and 12 age- and sex-matched healthy controls underwent [¹⁸F]GE-180 PET. The cortical and subcortical regions were delineated by deep nuclei parcellation (DNP) of a 3D-T1 MRI. Region-specific subcortical volumes and standardized uptake values and ratios (SUV and SUVr) were extracted before and after region-based voxel-wise PVEC. Regional volumes were compared between patients with CBS and controls. The % group differences and effect sizes (CBS vs. controls) of uncorrected and PVE-corrected SUVr data were compared. Single-region positivity in patients with CBS was assessed by a >2 SD threshold vs. controls and compared between uncorrected and PVE-corrected data. Smaller regional volumes were detected in patients with CBS compared to controls in the right ventral striatum (p = 0.041), the left putamen (p = 0.005), the right putamen (p = 0.038) and the left pallidum (p = 0.015). After applying PVEC, the % group differences were distinctly higher, but the effect sizes of TSPO uptake were only slightly stronger due to the higher variance after PVEC. The single-region positivity of TSPO PET increased in patients with CBS after PVEC (100 vs. 83 regions). PVEC in the cortical and subcortical regions is valuable for TSPO imaging of patients with CBS, leading to the improved detection of elevated [¹⁸F]GE-180 uptake, although the effect sizes in the comparison against the controls did not improve strongly. Full article

Five effusive eruptions of Piton de la Fournaise (La Réunion) are analyzed to investigate temporal trends of erupted mass and sulfur dioxide (SO₂) emissions. Daily SO₂ emissions are acquired from three ultraviolet (UV) satellite instruments (the Ozone Monitoring Instrument (OMI), the Ozone Mapping and Profiler Suite (OMPS), and the Tropospheric Monitoring Instrument (TROPOMI)) and an array of ground-based UV spectrometers (Network for Observation of Volcanic and Atmospheric Change (NOVAC)). Time-averaged lava discharge rates (TADRs) are obtained from two automatic satellite-based hot spot detection systems: MIROVA and MODVOLC. Assuming that the lava volumes measured in the field are accurate, the MIROVA system gave the best estimation of erupted volume among the methods investigated. We use a reverse petrological method to constrain pre-eruptive magmatic sulfur contents based on observed SO₂ emissions and lava volumes. We also show that a direct petrological approach using SO₂ data might be a viable alternative for TADR estimation during cloudy weather that compromises hot spot detection. In several eruptions we observed a terminal increase in TADR and SO₂ emissions after initial emission of evolved degassed magma. We ascribe this to input of deeper, volatile-rich magma into the plumbing system towards the end of these eruptions. Furthermore, we find no evidence of volatile excess in the five eruptions studied, which were thus mostly fed by shallow degassed magma. Full article

Ponies and some horse breeds such as Andalusians exhibit an ‘easy keeper’ phenotype and tend to become obese more readily than other breeds such as Standardbreds. Various hypotheses have been proposed, including differences in appetite or metabolic efficiency. This study aimed to investigate the effect of breed on nutrient digestibility. Ponies, Standardbreds and Andalusian horses were adapted to consuming either a control fibre-based diet (n = 9), a hypercaloric cereal-rich diet (n = 12) or a hypercaloric fat-rich diet (n = 12) over 20 weeks. Total faecal collection was performed over 24 h to determine apparent total tract digestibility of gross energy, dry matter (DM), neutral detergent fibre (NDF), starch, crude protein and crude fat. There was no effect of breed on apparent digestibility for any of the nutrients studied (all p > 0.05). However, there was a significant effect of diet, with animals consuming the cereal-rich or fat-rich diets demonstrating higher digestibility of gross energy, DM, NDF and crude protein compared with those consuming the control diet (all p < 0.05). Animals adapted to the cereal-rich diet demonstrated higher digestibility of starch (p < 0.001) and animals adapted to the fat-rich diet demonstrated higher digestibility of fat (p < 0.001). This study found that horses and ponies had similar nutrient digestibility when adapted to the same diets and management conditions. Limitations included the relatively small number of animals from each breed per diet group and the short period of total faecal collection. The tendency towards increased adiposity in ponies and Andalusian-type horse breeds is more likely to reflect differences in metabolism, rather than differences in feed digestibility. Full article

The global pandemic of coronavirus disease (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to an international thrust to study pathogenesis and evaluate interventions. Experimental infection of hamsters and the resulting respiratory disease is one of the preferred animal models since clinical signs of disease and virus shedding are similar to more severe cases of human COVID-19. The main route of challenge has been direct inoculation of the virus via the intranasal route. To resemble the natural infection, we designed a bespoke natural transmission cage system to assess whether recipient animals housed in physically separate adjacent cages could become infected from a challenged donor animal in a central cage, with equal airflow across the two side cages. To optimise viral shedding in the donor animals, a low and moderate challenge dose were compared after direct intranasal challenge, but similar viral shedding responses were observed and no discernible difference in kinetics. The results from our natural transmission set-up demonstrate that most recipient hamsters are infected within the system developed, with variation in the kinetics and levels of disease between individual animals. Common clinical outputs used for the assessment in directly-challenged hamsters, such as weight loss, are less obvious in hamsters who become infected from naturally acquiring the infection. The results demonstrate the utility of a natural transmission model for further work on assessing the differences between virus strains and evaluating interventions using a challenge system which more closely resembles human infection. Full article

The Deep Underground Neutrino Experiment (DUNE) is an international, world-class experiment aimed at exploring fundamental questions about the universe that are at the forefront of astrophysics and particle physics research. DUNE will study questions pertaining to the preponderance of matter over antimatter in the early universe, the dynamics of supernovae, the subtleties of neutrino interaction physics, and a number of beyond the Standard Model topics accessible in a powerful neutrino beam. A critical component of the DUNE physics program involves the study of changes in a powerful beam of neutrinos, i.e., neutrino oscillations, as the neutrinos propagate a long distance. The experiment consists of a near detector, sited close to the source of the beam, and a far detector, sited along the beam at a large distance. This document, the DUNE Near Detector Conceptual Design Report (CDR), describes the design of the DUNE near detector and the science program that drives the design and technology choices. The goals and requirements underlying the design, along with projected performance are given. It serves as a starting point for a more detailed design that will be described in future documents. Full article

TSPO-PET tracers are sensitive to a single-nucleotide polymorphism (rs6971-SNP), resulting in low-, medium- and high-affinity binders (LABs, MABs and HABS), but the clinical relevance of [¹⁸F]GE-180 is still unclear. We evaluated the impact of rs6971-SNP on in vivo [¹⁸F]GE-180 binding in a healthy brain and in pseudo-reference tissue in neuro-oncological and neurodegenerative diseases. Standardized uptake values (SUVs) of [¹⁸F]GE-180-PET were assessed using a manually drawn region of interest in the frontoparietal and cerebellar hemispheres. The SUVs were compared between the LABs, MABs and HABs in control, glioma, four-repeat tauopathy (4RT) and Alzheimer’s disease (AD) subjects. Second, the SUVs were compared between the patients and controls within their rs6971-subgroups. After excluding patients with prior therapy, 24 LABs (7 control, 5 glioma, 6 4RT and 6 AD) were analyzed. Age- and sex-matched MABs (n = 38) and HABs (n = 50) were selected. The LABs had lower frontoparietal and cerebellar SUVs when compared with the MABs and HABs, but no significant difference was observed between the MABs and HABs. Within each rs6971 group, no SUV difference between the patients and controls was detected in the pseudo-reference tissues. The rs6971-SNP affects [¹⁸F]GE-180 quantification, revealing lower binding in the LABs when compared to the MABs and HABs. The frontoparietal and cerebellar ROIs were successfully validated as pseudo-reference regions. Full article

This paper examines OpenStreetMap data quality at different stages of a participatory mapping process in seven slums in Africa and Asia. Data were drawn from an OpenStreetMap-based participatory mapping process developed as part of a research project focusing on understanding inequalities in healthcare access of slum residents in the Global South. Descriptive statistics and qualitative analysis were employed to examine the following research question: What is the spatial data quality of collaborative remote mapping achieved by volunteer mappers in morphologically complex urban areas? Findings show that the completeness achieved by remote mapping largely depends on the morphology and characteristics of slums such as building density and rooftop architecture, varying from 84% in the best case, to zero in the most difficult site. The major scientific contribution of this study is to provide evidence on the spatial data quality of remotely mapped data through volunteer mapping efforts in morphologically complex urban areas such as slums; the results could provide insights into how much fieldwork would be needed in what level of complexity and to what extent the involvement of local volunteers in these efforts is required. Full article

The excess intake of dietary sodium is a key modifiable factor for reducing disease progression in autosomal dominant polycystic kidney disease (ADPKD). The aim of this study was to test the hypothesis that the scored salt questionnaire (SSQ; a frequency questionnaire of nine sodium-rich food types) is a valid instrument to identify high dietary salt intake in ADPKD. The performance of the SSQ was evaluated in adults with ADPKD with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m² during the screening visit of the PREVENT-ADPKD trial. High dietary sodium intake (HSI) was defined by a mean 24-h urinary sodium excretion ≥ 100 mmol/day from two collections. The median 24-h urine sodium excretion was 132 mmol/day (IQR: 112–172 mmol/d) (n = 75; mean age: 44.6 ± 11.5 years old; 53% female), and HSI (86.7% of total) was associated with male gender and higher BMI and systolic blood pressure (p < 0.05). The SSQ score (73 ± 23; mean ± SD) was weakly correlated with log₁₀ 24-h urine sodium excretion (r = 0.29, p = 0.01). Receiving operating characteristic analysis showed that the optimal cut-off point in predicting HSI was an SSQ score of 74 (area under the curve 0.79; sensitivity 61.5%; specificity 90.0%; p < 0.01). The evaluation of the SSQ in participants with a BMI ≥ 25 (n = 46) improved the sensitivity (100%) and the specificity (100%). Consumers with an SSQ score ≥ 74 (n = 41) had higher relative percentage intake of processed meats/seafood and flavourings added to cooking (p < 0.05). In conclusion, the SSQ is a valid tool for identifying high dietary salt intake in ADPKD but its value proposition (over 24-h urinary sodium measurement) is that it may provide consumers and their healthcare providers with insight into the potential origin of sodium-rich food sources. Full article

Molecularly imprinted polymers (MIPs) prepared via a semi-covalent imprinting strategy using stigmasteryl methacrylate as a polymerisable template have been evaluated by static binding methods for their ability to selectively capture other valuable phytosterol targets, including campesterol and brassicasterol. Design criteria based on molecular modelling procedures and interaction energy calculations were employed to aid the selection of the co-monomer type, as well as the choice of co-monomer:template ratios for the formation of the pre-polymerisation complex. These novel hybrid semi-covalently imprinted polymers employed N,N′-dimethylacryl-amide (N,N′-DMAAM) as the functional co-monomer and displayed specific binding capacities in the range 5.2–5.9 mg sterol/g MIP resin. Their binding attributes and selectivities towards phytosterol compounds were significantly different to the corresponding MIPs prepared via non-covalent procedures or when compared to non-imprinted polymers. Cross-reactivity studies using stigmasterol, ergosterol, cholesterol, campesterol, and brassicasterol as single analytes revealed the importance of the A-ring C-3-β-hydroxyl group and the orientational preferences of the D-ring alkyl chain structures in their interaction in the templated cavity with the N,N′-dimethylamide functional groups of the MIP. Finally, to obtain useful quantities of both campersterol and brassicasterol for these investigations, improved synthetic routes have been developed to permit the conversion of the more abundant, lower cost stigmasterol via a reactive aldehyde intermediate to these other sterols. Full article

Molecularly imprinted polymers are versatile materials with wide application scope for the detection, capture and separation of specific compounds present in complex feed stocks. A major challenge associated with their preparation has been the need to sacrifice one mole equivalent of the template molecule to generate the complementary polymer cavities that selectively bind the target molecule. Moreover, template molecules can often be difficult to synthesise, expensive or lack stability. In this study, we describe a new approach, directed at the use of synthetic selectophores, chosen as readily prepared and low cost structural analogues with recognition groups in similar three-dimensional arrangements as found in the target molecule. To validate the approach, a comparative study of selectophores related to the polyphenolic compound (E)-resveratrol has been undertaken using traditional and green chemical synthetic approaches. These molecular mimic compounds were employed as polymer templates and also as binding analytes to interrogate the recognition sites associated with the molecularly imprinted polymers. Importantly, the study confirms that the use of selectophores has the potential to confer practical advantages, including access to more efficient methods for selection and preparation of suitable template molecules with a broader range of molecular diversity, as well as delivering imprinted polymers capable of recognizing the target compound and structurally related products. Full article