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Abstract Continued spread of chronic wasting disease (CWD) through wild cervid herds negatively impacts populations, erodes wildlife conservation, drains resource dollars, and challenges wildlife management agencies. Risk factors for CWD have been investigated at state scales, but a regional model to predict locations of new infections can guide increasingly efficient surveillance efforts. We predicted CWD incidence by county using CWD surveillance data depicting white-tailed deer (Odocoileus virginianus) in 16 eastern and midwestern US states. We predicted the binary outcome of CWD-status using four machine learning models, utilized five-fold cross-validation and grid search to pinpoint the best model, then compared model predictions against the subsequent year of surveillance data. Cross validation revealed that the Light Boosting Gradient model was the most reliable predictor given the regional data. The predictive model could be helpful for surveillance planning. Predictions of false positives emphasize areas that warrant targeted CWD surveillance because of similar conditions with counties known to harbor CWD. However, disagreements in positives and negatives between the CWD Prediction Web App predictions and the on-the-ground surveillance data one year later underscore the need for state wildlife agency professionals to use a layered modeling approach to ensure robust surveillance planning. The CWD Prediction Web App is at https://cwd-predict.streamlit.app/ .

Abstract With the persistence of the SARS-CoV-2 pandemic and the emergence of novel variants, the development of novel vaccine formulations with enhanced immunogenicity profiles could help reduce disease burden in the future. Intranasally delivered vaccines offer a new modality to prevent SARS-CoV-2 infections through the induction of protective immune responses at the mucosal surface where viral entry occurs. Herein, we evaluated a novel protein subunit vaccine formulation containing a resistin-trimerized prefusion Spike antigen (SmT1v3) and a proteosome-based mucosal adjuvant (BDX301) formulated to enable intranasal immunization. In mice, the formulation induced robust antigen-specific IgG and IgA titers, in the blood and lungs, respectively. In addition, the formulations were highly efficacious in a hamster challenge model, reducing viral load and body weight loss. In both models, the serum antibodies had strong neutralizing activity, preventing the cellular binding of the viral Spike protein based on the ancestral reference strain, the Beta (B.1.351) and Delta (B.1.617.2) variants of concern. As such, this intranasal vaccine formulation warrants further development as a novel SARS-CoV-2 vaccine.

Abstract Diffusion-weighted magnetic resonance imaging (DWI) of the musculoskeletal system has various applications, including visualization of bone tumors. However, DWI acquired with echo-planar imaging is susceptible to distortions due to static magnetic field inhomogeneities. This study aimed to estimate spatial displacements of bone and to examine whether distortion corrected DWI images more accurately reflect underlying anatomy. Whole-body MRI data from 127 prostate cancer patients were analyzed. The reverse polarity gradient (RPG) technique was applied to DWI data to estimate voxel-level distortions and to produce a distortion corrected DWI dataset. First, an anatomic landmark analysis was conducted, in which corresponding vertebral landmarks on DWI and anatomic T 2-weighted images were annotated. Changes in distance between DWI- and T 2-defined landmarks (i.e., changes in error) after distortion correction were calculated. In secondary analyses, distortion estimates from RPG were used to assess spatial displacements of bone metastases. Lastly, changes in mutual information between DWI and T 2-weighted images of bone metastases after distortion correction were calculated. Distortion correction reduced anatomic error of vertebral DWI up to 29 mm. Error reductions were consistent across subjects (Wilcoxon signed-rank p

Abstract The huge worldwide demand for vaccines targeting SARS-CoV-2 has necessitated the continued development of novel improved formulations capable of reducing the burden of the COVID-19 pandemic. Herein, we evaluated novel protein subunit vaccine formulations containing a resistin-trimerized spike antigen, SmT1. When combined with sulfated lactosyl archaeol (SLA) archaeosome adjuvant, formulations induced robust antigen-specific humoral and cellular immune responses in mice. Antibodies had strong neutralizing activity, preventing viral spike binding and viral infection. In addition, the formulations were highly efficacious in a hamster challenge model reducing viral load and body weight loss even after a single vaccination. The antigen-specific antibodies generated by our vaccine formulations had stronger neutralizing activity than human convalescent plasma, neutralizing the spike proteins of the B.1.1.7 and B.1.351 variants of concern. As such, our SmT1 antigen along with SLA archaeosome adjuvant comprise a promising platform for the development of efficacious protein subunit vaccine formulations for SARS-CoV-2.

Diffusion-weighted magnetic resonance imaging (DWI) of the musculoskeletal system has various applications, including visualization of bone tumors. However, DWI acquired with echo-planar imaging is susceptible to distortions due to static magnetic field inhomogeneities. This study aimed to estimate spatial displacements of bone and to examine whether distortion corrected DWI images more accurately reflect underlying anatomy. Whole-body MRI data from 127 prostate cancer patients were analyzed. The reverse polarity gradient (RPG) technique was applied to DWI data to estimate voxel-level distortions and to produce a distortion corrected DWI dataset. First, an anatomic landmark analysis was conducted, in which corresponding vertebral landmarks on DWI and anatomic T2-weighted images were annotated. Changes in distance between DWI- and T2-defined landmarks (i.e., changes in error) after distortion correction were calculated. In secondary analyses, distortion estimates from RPG were used to assess spatial displacements of bone metastases. Lastly, changes in mutual information between DWI and T2-weighted images of bone metastases after distortion correction were calculated. Distortion correction reduced anatomic error of vertebral DWI up to 29 mm. Error reductions were consistent across subjects (Wilcoxon signed-rank p

Abstract We investigated the association of CA125 response with prognosis and RECIST response/progressive disease (PD) criteria in recurrent high grade serous ovarian cancer (HGSOC) patients treated with a cell cycle checkpoint kinase 1 inhibitor (CHK1i), prexasertib. 81 patients had measurable disease per RECISTv1.1, of which 72 and 70 were measurable by Gynecologic Cancer InterGroup (GCIG) CA125 response and PD criteria, respectively. Univariate and multivariate analyses showed that GCIG CA125 response (n = 32) is associated with improved progression-free survival (PFS) and overall survival (OS) compared to no GCIG CA125 response (n = 40) (median PFS 8.0 vs. 3.5 months [HR: 0.30, 95% CI: 0.18–0.51, p

Diffusion-weighted magnetic resonance imaging (DWI) of the musculoskeletal system has various applications, including visualization of bone tumors. However, DWI acquired with echo-planar imaging is susceptible to distortions due to static magnetic field inhomogeneities. This study aimed to estimate spatial displacements of bone and to examine whether distortion corrected DWI images more accurately reflect underlying anatomy. Whole-body MRI data from 127 prostate cancer patients were analyzed. The reverse polarity gradient (RPG) technique was applied to DWI data to estimate voxel-level distortions and to produce a distortion corrected DWI dataset. First, an anatomic landmark analysis was conducted, in which corresponding vertebral landmarks on DWI and anatomic T2-weighted images were annotated. Changes in distance between DWI- and T2-defined landmarks (i.e., changes in error) after distortion correction were calculated. In secondary analyses, distortion estimates from RPG were used to assess spatial displacements of bone metastases. Lastly, changes in mutual information between DWI and T2-weighted images of bone metastases after distortion correction were calculated. Distortion correction reduced anatomic error of vertebral DWI up to 29 mm. Error reductions were consistent across subjects (Wilcoxon signed-rank p < 10–20). On average (± SD), participants' largest error reduction was 11.8 mm (± 3.6). Mean (95% CI) displacement of bone lesions was 6.0 mm (95% CI 5.0–7.2); maximum displacement was 17.1 mm. Corrected diffusion images were more similar to structural MRI, as evidenced by consistent increases in mutual information (Wilcoxon signed-rank p < 10–12). These findings support the use of distortion correction techniques to improve localization of bone on DWI. [ABSTRACT FROM AUTHOR]

Abstract Space travel requires high-powered, efficient rocket propulsion systems for controllable launch vehicles and safe planetary entry. Interplanetary travel will rely on energy-dense propellants to produce thrust via combustion as the heat generation process to convert chemical to thermal energy. In propulsion devices, combustion can occur through deflagration or detonation, each having vastly different characteristics. Deflagration is subsonic burning at effectively constant pressure and is the main means of thermal energy generation in modern rockets. Alternatively, detonation is a supersonic combustion-driven shock offering several advantages. Detonations entail compact heat release zones at elevated local pressure and temperature. Specifically, rotating detonation rocket engines (RDREs) use detonation as the primary means of energy conversion, producing more useful available work compared to equivalent deflagration-based devices; detonation-based combustion is poised to radically improve rocket performance compared to today’s constant pressure engines, producing up to 10 $$\%$$ % increased thrust. This new propulsion cycle will also reduce thruster size and/or weight, lower injection pressures, and are less susceptible to engine-damaging acoustic instabilities. Here we present a collective effort to benchmark performance and standardize operability of rotating detonation rocket engines to develop the RDRE technology readiness level towards a flight demonstration. Key detonation physics unique to RDREs, driving consistency and control of chamber dynamics across the engine operating envelope, are identified and addressed to drive down the variability and stochasticity observed in previous studies. This effort demonstrates an RDRE operating consistently across multiple facilities, validating this technology’s performance as the foundation of RDRE architecture for future aerospace applications.

Abstract Age-related deficits in skeletal muscle function, termed sarcopenia, are due to loss of muscle mass and changes in the intrinsic mechanisms underlying contraction. Sarcopenia is associated with falls, functional decline, and mortality. Electrical impedance myography (EIM)—a minimally invasive, rapid electrophysiological tool—can be applied to animals and humans to monitor muscle health, thereby serving as a biomarker in both preclinical and clinical studies. EIM has been successfully employed in several species; however, the application of EIM to the assessment of zebrafish—a model organism amenable to high-throughput experimentation—has not been reported. Here, we demonstrated differences in EIM measures between the skeletal muscles of young (6 months of age) and aged (33 months of age) zebrafish. For example, EIM phase angle and reactance at 2 kHz showed significantly decreased phase angle (5.3 ± 2.1 versus 10.7 ± 1.5°; p = 0.001) and reactance (89.0 ± 3.9 versus 172.2 ± 54.8 ohms; p = 0.007) in aged versus young animals. Total muscle area, in addition to other morphometric features, was also strongly correlated to EIM 2 kHz phase angle across both groups (r = 0.7133, p = 0.01). Moreover, there was a strong correlation between 2 kHz phase angle and established metrics of zebrafish swimming performance, including turn angle, angular velocity, and lateral motion (r = 0.7253, r = 0.7308, r = 0.7857, respectively, p

Abstract Certain cultivars of maize show increased tolerance to water deficit conditions by maintenance of root growth. To better understand the molecular mechanisms related to this adaptation, nodal root growth zone samples were collected from the reference inbred line B73 and inbred line FR697, which exhibits a relatively greater ability to maintain root elongation under water deficits. Plants were grown under various water stress levels in both field and controlled environment settings. FR697-specific RNA-Seq datasets were generated and used for a de novo transcriptome assembly to characterize any genotype-specific genetic features. The assembly was aided by an Iso-Seq library of transcripts generated from various FR697 plant tissue samples. The Necklace pipeline was used to combine a Trinity de novo assembly along with a reference guided assembly and the Viridiplantae proteome to generate an annotated consensus “SuperTranscriptome” assembly of 47,915 transcripts with a N50 of 3152 bp in length. The results were compared by Blastn to maize reference genes, a Benchmarking Universal Single-Copy Orthologs (BUSCO) genome completeness report and compared with three maize reference genomes. The resultant ‘SuperTranscriptome’ was demonstrated to be of high-quality and will serve as an important reference for analysis of the maize nodal root transcriptomic response to environmental perturbations.

Abstract Discrimination of pain intensity using machine learning (ML) and electroencephalography (EEG) has significant potential for clinical applications, especially in scenarios where self-report is unsuitable. However, existing research is limited due to a lack of external validation (assessing performance using novel data). We aimed for the first external validation study for pain intensity classification with EEG. Pneumatic pressure stimuli were delivered to the fingernail bed at high and low pain intensities during two independent EEG experiments with healthy participants. Study one (n = 25) was utilised for training and cross-validation. Study two (n = 15) was used for external validation one (identical stimulation parameters to study one) and external validation two (new stimulation parameters). Time–frequency features of peri-stimulus EEG were computed on a single-trial basis for all electrodes. ML training and analysis were performed on a subset of features, identified through feature selection, which were distributed across scalp electrodes and included frontal, central, and parietal regions. Results demonstrated that ML models outperformed chance. The Random Forest (RF) achieved the greatest accuracies of 73.18, 68.32 and 60.42% for cross-validation, external validation one and two, respectively. Importantly, this research is the first to externally validate ML and EEG for the classification of intensity during experimental pain, demonstrating promising performance which generalises to novel samples and paradigms. These findings offer the most rigorous estimates of ML’s clinical potential for pain classification.

Abstract Much of the United States Atlantic coastline continues to undergo subsidence due to post glacial settlement and ground water depletion. Combined with eustatic sea level rise (SLR), this contributes to an increased rate of relative SLR. In this work, we utilize the ADvanced CIRCulation model to project storm surges across coastal North Carolina. Recent hurricanes Irene and Matthew are simulated considering SLR and subsidence estimates for 2100. Relative to present day conditions, storm surge susceptible regions increase by 27% (Irene) to 40% (Matthew) due to subsidence. Combined with SLR (+ 74 cm), results suggest more than a doubling of areal flood extent for Irene and more than a three-fold increase for Hurricane Matthew. Considering current regional population distributions, this translates to an increase in at-risk populations of 18% to 61% due to subsidence. Even further, exposed populations are projected to swell relative to Matthew and Irene baseline simulations (8200 and 28,500) by more than 70,000 in all SLR scenarios (79,400 to 133,600). While increases in surge inundation are driven primarily by SLR in the region, there remains a substantial contribution due to vertical land movement. This outlines the importance of exploring spatially variable land movement in surge prediction, independent of SLR.

Diffusion-weighted magnetic resonance imaging (DWI) of the musculoskeletal system has various applications, including visualization of bone tumors. However, DWI acquired with echo-planar imaging is susceptible to distortions due to static magnetic field inhomogeneities. This study aimed to estimate spatial displacements of bone and to examine whether distortion corrected DWI images more accurately reflect underlying anatomy. Whole-body MRI data from 127 prostate cancer patients were analyzed. The reverse polarity gradient (RPG) technique was applied to DWI data to estimate voxel-level distortions and to produce a distortion corrected DWI dataset. First, an anatomic landmark analysis was conducted, in which corresponding vertebral landmarks on DWI and anatomic T 2 -weighted images were annotated. Changes in distance between DWI- and T 2 -defined landmarks (i.e., changes in error) after distortion correction were calculated. In secondary analyses, distortion estimates from RPG were used to assess spatial displacements of bone metastases. Lastly, changes in mutual information between DWI and T 2 -weighted images of bone metastases after distortion correction were calculated. Distortion correction reduced anatomic error of vertebral DWI up to 29 mm. Error reductions were consistent across subjects (Wilcoxon signed-rank p < 10 -20 ). On average (± SD), participants' largest error reduction was 11.8 mm (± 3.6). Mean (95% CI) displacement of bone lesions was 6.0 mm (95% CI 5.0-7.2); maximum displacement was 17.1 mm. Corrected diffusion images were more similar to structural MRI, as evidenced by consistent increases in mutual information (Wilcoxon signed-rank p < 10 -12 ). These findings support the use of distortion correction techniques to improve localization of bone on DWI., (© 2022. The Author(s).)