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Cell migration is critical for tissue development and regeneration but requires extracellular environments that are conducive to motion. Cells may actively generate migratory routes in vivo by degrading or remodeling their environments or instead utilize existing extracellular matrix microstructures or microtracks as innate pathways for migration. While hydrogels in general are valuable tools for probing the extracellular regulators of 3-dimensional migration, few recapitulate these natural migration paths. Here, we develop a biopolymer-based bicontinuous hydrogel system that comprises a covalent hydrogel of enzymatically crosslinked gelatin and a physical hydrogel of guest and host moieties bonded to hyaluronic acid. Bicontinuous hydrogels form through controlled solution immiscibility, and their continuous subdomains and high micro-interfacial surface area enable rapid 3D migration, particularly when compared to homogeneous hydrogels. Migratory behavior is mesenchymal in nature and regulated by biochemical and biophysical signals from the hydrogel, which is shown across various cell types and physiologically relevant contexts (e.g., cell spheroids, ex vivo tissues, in vivo tissues). Our findings introduce a design that leverages important local interfaces to guide rapid cell migration. Extracellular microinterfaces provide cells with migration tracks in vivo. Here, the authors introduce these microtracks into bicontinuous hydrogels to elicit rapid cell migration in 3-dimensional contexts.

Embedding a collective of tumor cells, i.e. a tumor spheroid, in a fibrous environment, such as a collagen network, provides an essential in vitro platform to investigate the biophysical mechanisms of tumor invasion. To predict new mechanisms, we develop a three-dimensional computational model of an embedded spheroid using a vertex model, with cells represented as deformable polyhedrons, mechanically coupled to a fiber network via active linker springs. As the linker springs actively contract, the fiber network remodels. As we tune the rheology of the spheroid and the fiber network stiffness, we find that both factors affect the remodeling of the fiber network with fluid-like spheroids densifying and radially realigning the fiber network more on average than solid-like spheroids but only for a range of intermediate fiber network stiffnesses. Our predictions are supported by experimental studies comparing non-tumorigenic MCF10A spheroids and malignant MDA-MB-231 spheroids embedded in collagen networks. The spheroid rheology-dependent effects are the result of cellular motility generating spheroid shape fluctuations. These shape fluctuations lead to emergent feedback between the spheroid and the fiber network to further remodel the fiber network. This emergent feedback occurs only at intermediate fiber network stiffness since at low fiber network stiffness, the mechanical response of the coupled system is dominated by the spheroid and for high fiber network stiffness, the mechanical response is dominated by the fiber network. We are therefore able to quantify the regime of optimal spheroid-fiber network mechanical reciprocity. Our results uncover intricate morphological-mechanical interplay between an embedded spheroid and its surrounding fiber network with both spheroid contractile strength and spheroid shape fluctuations playing important roles in the pre-invasion stages of tumor invasion.

Functional connectomics is one of the most rapidly expanding areas of neuroimaging research. Yet, concerns remain regarding the use of resting-state fMRI (R-fMRI) to characterize inter-individual variation in the functional connectome. In particular, recent findings that “micro” head movements can introduce artifactual inter-individual and group-related differences in R-fMRI metrics have raised concerns. Here, we first build on prior demonstrations of regional variation in the magnitude of framewise displacements associated with a given head movement, by providing a comprehensive voxel-based examination of the impact of motion on the BOLD signal (i.e., motion–BOLD relationships). Positive motion–BOLD relationships were detected in primary and supplementary motor areas, particularly in low motion datasets. Negative motion–BOLD relationships were most prominent in prefrontal regions, and expanded throughout the brain in high motion datasets (e.g., children). Scrubbing of volumes with FD>0.2 effectively removed negative but not positive correlations; these findings suggest that positive relationships may reflect neural origins of motion while negative relationships are likely to originate from motion artifact. We also examined the ability of motion correction strategies to eliminate artifactual differences related to motion among individuals and between groups for a broad array of voxel-wise R-fMRI metrics. Residual relationships between motion and the examined R-fMRI metrics remained for all correction approaches, underscoring the need to covary motion effects at the group-level. Notably, global signal regression reduced relationships between motion and inter-individual differences in correlation-based R-fMRI metrics; Z-standardization (mean-centering and variance normalization) of subject-level maps for R-fMRI metrics prior to group-level analyses demonstrated similar advantages. Finally, our test–retest (TRT) analyses revealed significant motion effects on TRT reliability for R-fMRI metrics. Generally, motion compromised reliability of R-fMRI metrics, with the exception of those based on frequency characteristics — particularly, amplitude of low frequency fluctuations (ALFF). The implications of our findings for decision-making regarding the assessment and correction of motion are discussed, as are insights into potential differences among volume-based metrics of motion. •Positive but not negative motion-BOLD relationships appear to be neural in origin.•Motion should always be accounted for in group-level analyses.•Global signal regression and Z-standardization mitigate motion effects.•Motion compromises test-retest reliability, and correction strategies improve.

Although artificial neural networks (ANNs) were inspired by the brain, ANNs exhibit a brittleness not generally observed in human perception. One shortcoming of ANNs is their susceptibility to adversarial perturbations—subtle modulations of natural images that result in changes to classification decisions, such as confidently mislabelling an image of an elephant, initially classified correctly, as a clock. In contrast, a human observer might well dismiss the perturbations as an innocuous imaging artifact. This phenomenon may point to a fundamental difference between human and machine perception, but it drives one to ask whether human sensitivity to adversarial perturbations might be revealed with appropriate behavioral measures. Here, we find that adversarial perturbations that fool ANNs similarly bias human choice. We further show that the effect is more likely driven by higher-order statistics of natural images to which both humans and ANNs are sensitive, rather than by the detailed architecture of the ANN. Artificial neural networks (ANNs) are vulnerable to subtle adversarial perturbations that yield misclassification errors. Here, behavioral studies demonstrate that adversarial perturbations that fool ANNs similarly bias human choice.

Crowdsourcing relies on online platforms to connect a community of users to perform specific tasks. However, without appropriate control, the behavior of the online community might not align with the platform’s designed objective, which can lead to an inferior platform performance. This paper investigates how the feedback information on a crowdsourcing platform and systematic bias of crowdsourcing workers can affect crowdsourcing outcomes. Specifically, using archival data from the online crowdsourcing platform Kaggle, combined with survey data from actual Kaggle contest participants, we examine the role of a systematic bias, namely, the salience bias, in influencing the performance of the crowdsourcing workers and how the number of crowdsourcing workers moderates the impact of the salience bias on the outcomes of contests. Our results suggest that the salience bias influences the performance of contestants, including the winners of the contests. Furthermore, the number of participating contestants may attenuate or amplify the impact of the salience bias on the outcomes of contests, depending on the effort required to complete the tasks. Our results have critical implications for crowdsourcing firms and platform designers. The online appendix is available at https://doi.org/10.1287/isre.2018.0775 .

High-Frequency (HF) radar is well suited to the surveillance of low-earth-orbit space. For large targets, a small deployable HF radar is able to match the detection performance of much larger space surveillance radar systems operating at higher frequencies. However, there are some unique challenges associated with the use of HF, including the range–Doppler coupling bias, coarse detection-level localisation, and the presence of meteor returns and other unwanted signals. This paper details the use of HF radar for space surveillance, including signal processing and radar product formation, tracking, ionospheric correction, and orbit determination. It is shown that by fusing measurements from multiple passes, accurate orbital estimates can be obtained. Included are results from recent SpaceFest trials of the Defence Science and Technology Group’s HF space surveillance radar, achieving real-time wide-area surveillance in tracking, orbit determination, and cueing of other space surveillance sensors.

Out-of-hospital cardiac arrest (OHCA) is a leading cause of death in the United States, and efforts have been made to develop termination of resuscitation protocols utilizing clinical criteria predictive of successful resuscitation and survival to discharge. A termination of resuscitation protocol utilizing longer resuscitation time and end-tidal carbon dioxide (EtCO2) monitoring criteria for termination was implemented for Emergency Medical Service (EMS) providers in an urban prehospital system in 2017. This study examines the effect the modified termination of resuscitation protocol had on rates of patient transport to a hospital, return of spontaneous circulation (ROSC), and survival to discharge. A retrospective analysis was performed utilizing data from the Cardiac Arrest Registry to Enhance Survival (CARES) database. A total of 1,005 prehospital cardiac arrest patients 18 years and older from 2016 through 2017 were included in the analysis. Patients with traumatic cardiac arrest or had valid do-not-resuscitate orders were excluded. Unadjusted analysis using chi-square statistics was performed, including an analysis stratified by Utstein style reporting. Adjusted analysis was also performed using logistic regression with multiple imputation for missing values. Unadjusted analysis showed a significant decrease in ROSC on emergency department (ED) arrival (30% versus 13%; P <.001) following the change in protocol. There was no significant difference in patient transport rate (62%) and a statistically non-significant decrease in overall survival (15% versus 11%). When stratified by Utstein style analysis, statistically significant decreases in ED arrival with ROSC were seen for unwitnessed asystolic, as well as bystander witnessed asystolic, pulseless electrical activity (PEA), and shockable OHCA. Adjusted analysis showed a decreased likelihood of ROSC with the protocol change (0.337; 95% CI, 0.235-0.482). The modification of termination of resuscitation protocol was not associated with a statistically significant change in transport rate or survival. A significant decrease in rate of arrivals to the ED with ROSC was seen, particularly for bystander witnessed OHCA.

Dyslipidemia is a treatable risk factor for atherosclerotic cardiovascular disease that can be addressed through lifestyle changes and/or lipid-lowering therapies. Adherence to statins can be a clinical challenge in some patients due to statin-associated muscle symptoms and other side effects. There is a growing interest in integrative cardiology and nutraceuticals in the management of dyslipidemia, as some patients desire or are actively seeking a more natural approach. These agents have been used in patients with and without established atherosclerotic cardiovascular disease. We provide an updated review of the evidence on many new and emerging nutraceuticals. We describe the mechanism of action, lipid-lowering effects, and side effects of many nutraceuticals, including red yeast rice, bergamot and others.

Deep tissue pressure ulcers, a serious clinical challenge originating in the muscle layer, are hardly detectable at the beginning. The challenge apparently occurs in aged subjects more frequently. As the ulcer propagates to the skin surface, it becomes very difficult to manage and can lead to fatal complications. Preventive measures are thus highly desirable. Although the complex pathological mechanisms have not been fully understood, prolonged and excessive physical challenges and oxidative stress are believed to be involved in the ulcer development. Previous reports have demonstrated that oxidative stress could compromise the mechanical properties of muscle cells, making them easier to be damaged when physical challenges are introduced. In this study, we used senescence accelerated (SAMP8) mice and its control breed (SAMR1) to examine the protective effects of intermittent vibration on aged and control muscle tissues during prolonged epidermal compression under 100mmHg for 6h. Results showed that an application of 35Hz, 0.25g intermittent vibration during compression decreased the compression-induced muscle breakdown in SAMP8 mice, as indicated histologically in terms of number of interstitial nuclei. The fact that no significant difference in muscle damage could be established in the corresponding groups in SAMR1 mice suggests that SAMR1 mice could better accommodate the compression insult than SAMP8 mice. Compression-induced oxidative damage was successfully curbed using intermittent vibration in SAMP8 mice, as indicated by 8-OHdG. A possible explanation is that the anti-oxidative defense could be maintained with intermittent vibration during compression. This was supported by the expression level of PGC-1-alpha, catalase, Gpx-1 and SOD1. Our data suggested intermittent vibration could serve as a preventive measure for deep tissue ulcer, particularly in aged subjects.