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Abstract This study investigates the impact of habitual late calorie intake on glucose metabolism in adults with overweight or obesity and diet or metformin-controlled prediabetes or type 2 diabetes independently of body weight, fat mass, energy intake or diet composition. Participants (n = 26) were classified as Later Eaters (LE) if ≥45% daily calories were consumed after 5 pm and Early Eaters (EE) if not, based on daily caloric intake assessed over 2-wk. EE and LE did not differ in anthropometrics or daily energy intake, but LE consumed more carbohydrates (p = 0.038) and fats (p = 0.039) after 5 pm. Fasting glucose, insulin, and C-peptide did not differ between groups but LE exhibited higher glucose concentrations after an oral glucose tolerance test (p = 0.001), even after adjusting for body weight, fat mass, energy intake and diet composition (p

Abstract Background The Diabetes Telemedicine Mediterranean Diet (DiaTeleMed) Study is a fully remote randomized clinical trial evaluating personalized dietary management in individuals with type 2 diabetes (T2D). The study aims to test the efficacy of a personalized behavioral approach for dietary management of moderately controlled T2D, versus a standardized behavioral intervention that uses one-size-fits-all dietary recommendations, versus a usual care control (UCC). The primary outcome will compare the impact of each intervention on the mean amplitude of glycemic excursions (MAGE). Methods Eligible participants are between 21 and 80 years of age diagnosed with moderately controlled T2D (HbA1c: 6.0 to 8.0%) and managed on lifestyle alone or lifestyle plus metformin. Participants must be willing and able to attend virtual counseling sessions and log meals into a dietary tracking smartphone application (DayTwo), and wear a continuous glucose monitor (CGM) for up to 12 days. Participants are randomized with equal allocation (n = 255, n = 85 per arm) to one of three arms: (1) Personalized, (2) Standardized, or (3) UCC. Measurements occur at 0 (baseline), 3, and 6 months. All participants receive isocaloric energy and macronutrient targets to meet Mediterranean diet guidelines, in addition to 14 intervention contacts over 6 months (4 weekly then 10 biweekly) to cover diabetes self-management education. The first 4 UCC intervention contacts are delivered via synchronous videoconferences followed by educational video links. Participants in Standardized receive the same educational content as those in the UCC arm, following the same schedule. However, all intervention contacts are conducted via synchronous videoconferences, paired with Social Cognitive Theory (SCT)-based behavioral counseling, plus dietary self-monitoring of planned meals using a mobile app that provides real-time feedback on calories and macronutrients. Participants in the Personalized arm receive all elements of the Standardized intervention, in addition to real-time feedback on predicted post-prandial glycemic response (PPGR) to meals and snacks logged into the mobile app. Discussion The DiaTeleMed Study aims to address an important gap in the current landscape of precision nutrition by determining the contributions of behavioral counseling and personalized nutrition recommendations on glycemic control in individuals with T2D. The fully remote methodology of the study allows for scalability and innovative delivery of personalized dietary recommendations at a population level. Trial registration ClinicalTrials.gov NCT05046886. Registered on September 16, 2021.

Background: Although utilization of dynamic suture-button fixation for adult syndesmotic injuries has shown improved outcomes over static screw fixation, data in pediatric populations is limited. This study evaluated trends in management and identified factors influencing surgeon choice of implant for pediatric syndesmotic injuries. Methods: The Pediatric Orthopaedic Society of North America (POSNA) members were surveyed regarding syndesmotic injury implant preferences between October 2021 and May 2022. Respondents that opted out, treated ​15 years posttraining. Twenty-four percent (24/102) preferred screw versus 76% (78/102) preferring suture-button implants for syndesmotic injuries. Members >15 years posttraining were 4.7 times more likely to prefer screw implants compared to members 15 years posttraining 4.7 times more likely to prefer screw fixation to members

Abstract In forest management settings, disturbance resets forests to earlier successional stages, typically improving forage conditions for mule deer. Examining how forest disturbance influences mule deer behavior is important for guiding forest and wildlife management. We used GPS collar data collected between 2017 and 2019 from 136 adult female mule deer in three populations throughout western Montana, United States, to investigate how disturbance from burns (wildfire and prescribed fire) and timber harvest influenced three aspects of space‐use behaviors: (1) probability of migration from winter range to summer range, (2) home range (second‐order) selection by migrants on summer range, and (3) within‐home range (third‐order) selection. We hypothesized that deer would maximize use of disturbances during summer for nutritional benefits, predicting that deer with higher proportionate disturbance in their winter home range would be less likely to migrate away from those disturbances during summer. We predicted that migrants would select disturbances at the second and third orders. We found that proportionate disturbance in winter home ranges had no effect on the probability of migration. Among migrants, deer generally selected burns, timber harvests, and open‐canopy habitat at the second order in all study areas, with particularly strong selection for 6‐ to 15‐year‐old disturbances. At population levels, selection for disturbances ceased at the third order. At individual levels, however, third‐order selection for burns increased with availability, whereas selection for harvests decreased, suggesting burns may satisfy more resource needs than harvests. Our results emphasize how space‐use fidelity constrains mule deer habitat selection. During summer, adherence to migratory strategies constrains the habitat available for second‐order selection, preventing deer from exploiting disturbances that would otherwise be available had they remained resident in wintering areas. Second‐order selection then determines disturbance availability within home ranges, affecting third‐order behaviors. Although variance in selection behaviors among individuals was high, population‐level patterns were remarkably similar among study areas, suggesting these responses may be generalizable to mule deer throughout the northern Rocky Mountains. Forest management practices like timber harvest, prescribed burns, and wildfire management within higher elevation areas of summer range used by migrants could yield the greatest nutritional benefits for mule deer.

A persistent lack of juvenile recruitment in populations of the imperiled Mojave desert tortoise (Gopherus agassizii) has been attributed to artificially inflated populations of coyotes (Canis latrans) and common ravens (Corvus corax) in some areas. Subsidized by resources in the form of road-killed prey, movement corridors, or nesting perches provided by ever-expanding road and powerline networks, these “subsidized predators” threaten tortoises and other species thanks to subsidies that help support their populations in areas where they might otherwise have been less abundant. Here, we quantified the risk of predation from these subsidized predators on juvenile Mojave desert tortoises by quantifying attack rates on 3D-printed replicas. We evaluated predation risk as a function of replica size, distance from powerlines, and season—variables that can inform release strategies of head-started and translocated tortoises. We found significantly greater risk of predation from ravens in the spring than in the fall. Replica size did not significantly influence predation risk from ravens or coyotes. Replica distance from a powerline or road also did not significantly influence predation risk, supporting previous studies that have found the risk of predation can persist for up to 1.6 km from raven nesting structures. Our results support recommendations for releasing juvenile head-started and translocated tortoises in the fall and away from areas close to raven nesting structures. Our study provides insight into the interactions of prey and subsidized predators and helps guide management on potential mitigation strategies for minimizing the impacts of subsidized predators on species like the imperiled Mojave desert tortoise.

Abstract Infection with the apicomplexan protozoan Toxoplasma gondii can be life-threatening in immunocompromised hosts. Transmission frequently occurs through the oral ingestion of T. gondii bradyzoite cysts, which transition to tachyzoites, disseminate, and then form cysts containing bradyzoites in the central nervous system, resulting in latent infection. Encapsulation of bradyzoites by a cyst wall is critical for immune evasion, survival, and transmission. O-glycosylation of the protein CST1 by the mucin-type O-glycosyltransferase T. gondii (Txg) GalNAc-T3 influences cyst wall rigidity and stability. Here, we report X-ray crystal structures of TxgGalNAc-T3, revealing multiple features that are strictly conserved among its apicomplexan homologues. This includes a unique 2nd metal that is coupled to substrate binding and enzymatic activity in vitro and cyst wall O-glycosylation in T. gondii. The study illustrates the divergence of pathogenic protozoan GalNAc-Ts from their host homologues and lays the groundwork for studying apicomplexan GalNAc-Ts as therapeutic targets in disease.

Abstract Predators negatively affect prey outside of direct attack, and these nonconsumptive effects (NCEs) may cause over half the impacts of predators on prey populations. This “ecology of fear” framework has been extended to host–parasite interactions. The NCEs of parasites are thought to be small relative to those of predators. However, recent research shows ectoparasites exert NCEs on multiple life stages of Drosophila. In this study, we apply recent data to a matrix‐based model of fly populations experiencing infection/consumption and NCEs from an ectoparasitic mite. We found the NCEs of parasites on larvae, which are not actively parasitized, decreased the size of simulated host populations. By contrast, the NCEs on adult flies increased population size through compensatory egg production. The negative NCEs on larvae outweighed the positive effects on adults to reduce population size. This study suggests that parasitic NCEs can suppress host populations independent of infection.

Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a WHO priority pathogen. Antibody-based medical countermeasures offer an important strategy to mitigate severe disease caused by CCHFV. Most efforts have focused on targeting the viral glycoproteins. However, glycoproteins are poorly conserved among viral strains. The CCHFV nucleocapsid protein (NP) is highly conserved between CCHFV strains. Here, we investigate the protective efficacy of a CCHFV monoclonal antibody targeting the NP. We find that an anti-NP monoclonal antibody (mAb-9D5) protected female mice against lethal CCHFV infection or resulted in a significant delay in mean time-to-death in mice that succumbed to disease compared to isotype control animals. Antibody protection is independent of Fc-receptor functionality and complement activity. The antibody bound NP from several CCHFV strains and exhibited robust cross-protection against the heterologous CCHFV strain Afg09-2990. Our work demonstrates that the NP is a viable target for antibody-based therapeutics, providing another direction for developing immunotherapeutics against CCHFV.

Ionic transport is a critical property for the glass industry, since emerging applications such as sensors, batteries, and electric melting are based on the phenomenon. Short-range interactions (anion-charge carrier) have not been able to explain the total activation barrier observed experimentally, and, as such, it is critical to understand the larger role of all ions in a glass, not just the carrier and the ‘site’ ions. This research focuses on the role of network formers and their impact on diffusion in glasses, something that current models lack an explicit explanation of. Atomistic simulations with randomly generated parameters for the cation potentials and classical simulations were used to determine the diffusion coefficients and activation energies for synthetic network formers. Using this database, explainable machine learning algorithms were employed to explore network former interactions and determine which parameters are the most influential for ion diffusion. Results suggest that the bond length of the cations changes the geometry of the structure contributing the greatest to cation-modifier interactions.

Inherited retinal diseases (IRDs) are a significant contributor to visual loss in children and young adults, falling second only to diabetic retinopathy. Understanding the pathogenic mechanisms of IRDs remains paramount. Some autosomal genes exhibit random allelic expression (RAE), similar to X-chromosome inactivation. This study identifies RAE genes in IRDs. Genes in the Retinal Information Network were cross-referenced with the recent literature to identify expression profiles, RAE, or biallelic expression (BAE). Loss-of-function intolerance (LOFI) was determined by cross-referencing the existing literature. Molecular and biological pathways that are significantly enriched were evaluated using gene ontology. A total of 184 IRD-causing genes were evaluated. Of these, 31 (16.8%) genes exhibited RAE. LOFI was exhibited in 6/31 (19.4%) of the RAE genes and 18/153 (11.8%) of the BAE genes. Brain tissue exhibited BAE in 107/128 (83.6%) genes for both sexes. The molecular pathways significantly enriched among BAE genes were photoreceptor activity, tubulin binding, and nucleotide/ribonucleotide binding. The biologic pathways significantly enriched for RAE genes were equilibrioception, parallel actin filament bundle assembly, photoreceptor cell outer segment organization, and protein depalmitoylation. Allele-specific expression may be a mechanism underlying IRD phenotypic variability, with clonal populations of embryologic precursor cells exhibiting RAE. Brain tissue preferentially exhibited BAE, possibly due to selective pressures against RAE. Pathways critical for cellular and visual function were enriched in BAE, which may offer a survival benefit.

Abstract Global plastic pollution has become a major concern because of its effects on environmental and human health. A major fraction of environmental plastics is likely stored temporarily within terrestrial soils. However, even though forests represent the third most common type of land cover on Earth, almost nothing is known about plastics in forest soils. The atmospheric transport of micro- and nanoplastics provides ample opportunity for forest canopies to intercept plastic particles. These plastic particles, together with local plastic sources like litter and items used in forest management, eventually reach forest soils. In this paper we discuss the potential role of forest soils as a hub within global plastic cycles; transport processes from the atmosphere to the soil; and the integration of plastics into forest material cycles. Taken together, plastic in forests could have a major impact on sensitive ecosystems, economically important functions and global environmental plastic budgets. We also develop a roadmap for further investigation into plastics in forest soil systems.

The mere presence of predators or parasites can negatively impact the fitness of prey or hosts. Exposure to predators during an organism's development can have deleterious effects on juvenile survival and the subsequent adult stage. Currently, it is unknown if parasites have analogous impacts on host larval stages and whether these effects carry over into other subsequent life stages. However, parasites may be exerting widespread yet underestimated non-consumptive effects (NCEs). We tested if Drosophila nigrospiracula larvae avoid pupating near mite cues (caged Macrocheles subbadius) in arena experiments, and measured the rate of pupation in arenas with mites and arenas without mites. Larvae disproportionately pupated on the side of arenas that lacked mite cues. Furthermore, fewer larvae successfully pupated in arenas containing mites cues compared to arenas without mite cues. We found that ectoparasitic mites exert NCEs on Drosophila larvae, even though the larval stage is not susceptible to infection. We discuss these results in the context of parasite impacts on host population growth in an infectious world.

Duchenne muscular dystrophy is an X-linked monogenic disease caused by mutations in the dystrophin gene (DMD) characterized by progressive muscle weakness, leading to loss of ambulation and decreased life expectancy. Since the current standard of care for Duchenne muscular dystrophy is to merely treat symptoms, there is a dire need for treatment modalities that can correct the underlying genetic mutations. While several gene replacement therapies are being explored in clinical trials, one emerging approach that can directly correct mutations in genomic DNA is base editing. We have recently developed CRISPR-SKIP, a base editing strategy to induce permanent exon skipping by introducing C > T or A > G mutations at splice acceptors in genomic DNA, which can be used therapeutically to recover dystrophin expression when a genomic deletion leads to an out-of-frame DMD transcript. We now demonstrate that CRISPR-SKIP can be adapted to correct some forms of Duchenne muscular dystrophy by disrupting the splice acceptor in human DMD exon 45 with high efficiency, which enables open reading frame recovery and restoration of dystrophin expression. We also demonstrate that AAV-delivered split-intein base editors edit the splice acceptor of DMD exon 45 in cultured human cells and in vivo, highlighting the therapeutic potential of this strategy.

Abstract Observed links between parasites, such as ticks, and climate change have aroused concern for human health, wildlife population dynamics, and broader ecosystem effects. The one‐host life history of the winter tick (Dermacentor albipictus) links each annual cohort to environmental conditions during three specific time periods when they are predictably vulnerable: spring detachment from hosts, summer larval stage, and fall questing for hosts. We used mixed‐effects generalized linear models to investigate the drivers of tick loads carried by moose (Alces alces) relative to these time periods and across 750 moose, 10 years, and 16 study areas in the western United States. We tested for the effects of biotic factors (moose density, shared winter range, vegetation, migratory behavior) and weather conditions (temperature, snow, humidity) during each seasonal period when ticks are vulnerable and off‐host. We found that warm climatic regions, warm seasonal periods across multiple partitions of the annual tick life cycle, and warm years relative to long‐term averages each contributed to increased tick loads. We also found important effects of snow and other biotic factors such as host density and vegetation. Tick loads in the western United States were, on average, lower than those where tick‐related die‐offs in moose populations have occurred recently, but loads carried by some individuals may be sufficient to cause mortality. Lastly, we found interannual variation in tick loads to be most correlated with spring snowpack, suggesting this environmental component may have the highest potential to induce change in tick load dynamics in the immediate future of this region.

Abstract Objective HbA1c is an insensitive marker for assessing real‐time dysglycemia in obesity. This study investigated whether 1‐h plasma glucose level (1‐h PG) ≥155 mg/dL (8.6 mmol/L) during an oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) measurement of glucose variability (GV) better reflected dysglycemia than HbA1c after weight loss from metabolic and bariatric surgery. Methods This was a prospective cohort study of 10 participants with type 2 diabetes compared with 11 participants with non‐diabetes undergoing sleeve gastrectomy (SG). At each research visit; before SG, and 6 weeks and 6 months post‐SG, body weight, fasting lipid levels, and PG and insulin concentrations during an OGTT were analyzed. Mean amplitude of glycemic excursions (MAGE), a CGM‐derived GV index, was analyzed. Results The 1‐h PG correlated with insulin resistance markers, triglyceride/HDL ratio and triglyceride glucose index in both groups before surgery. At 6 months, SG caused 22% weight loss in both groups. Despite a reduction in HbA1c by 3.0 ± 1.3% in the diabetes group (p

A major challenge in the recovery of long-lived at-risk taxa like turtles is low juvenile recruitment. Head-starting—the raising of juveniles to larger sizes to improve survival—is one tool that can be used in circumstances where juvenile recruitment is limited. Due to declining populations and difficulty detecting juveniles, however, lack of knowledge of the ecology of juveniles can hinder efforts to develop and evaluate head-starting programs for many turtle species. We sought to inform recovery efforts of Mojave desert tortoises by quantifying multi-year space use and survival of head-started juveniles after release. We radio-tracked tortoises head-started under three different husbandry treatments that varied in rearing duration (from two to over six years) and whether head-starting included an indoor rearing component the first year. We compared post-release space use and survival as a function of treatment, release size, and time since release. We found that space use, including home range size and site fidelity, varied by husbandry treatment, with smaller and younger tortoises having smaller home ranges and higher site fidelity. Additionally, home range size decreased and site fidelity increased with time since release across treatments. Tortoises with an indoor-rearing component experiencing increased risk of mortality as movement increased compared to tortoises reared solely outdoors. Nevertheless, survival did not differ among treatments or with tortoise age or size. Regardless of husbandry treatment, head-started tortoises exhibited similar space-use and survival overall. Our study provides insight into juvenile tortoise behavior and head-starting as a tool for tortoise conservation.

Abstract Background As genome sequencing becomes better integrated into scientific research, government policy, and personalized medicine, the primary challenge for researchers is shifting from generating raw data to analyzing these vast datasets. Although much work has been done to reduce compute times using various configurations of traditional CPU computing infrastructures, Graphics Processing Units (GPUs) offer opportunities to accelerate genomic workflows by orders of magnitude. Here we benchmark one GPU-accelerated software suite called NVIDIA Parabricks on Amazon Web Services (AWS), Google Cloud Platform (GCP), and an NVIDIA DGX cluster. We benchmarked six variant calling pipelines, including two germline callers (HaplotypeCaller and DeepVariant) and four somatic callers (Mutect2, Muse, LoFreq, SomaticSniper). Results We achieved up to 65 × acceleration with germline variant callers, bringing HaplotypeCaller runtimes down from 36 h to 33 min on AWS, 35 min on GCP, and 24 min on the NVIDIA DGX. Somatic callers exhibited more variation between the number of GPUs and computing platforms. On cloud platforms, GPU-accelerated germline callers resulted in cost savings compared with CPU runs, whereas some somatic callers were more expensive than CPU runs because their GPU acceleration was not sufficient to overcome the increased GPU cost. Conclusions Germline variant callers scaled well with the number of GPUs across platforms, whereas somatic variant callers exhibited more variation in the number of GPUs with the fastest runtimes, suggesting that, at least with the version of Parabricks used here, these workflows are less GPU optimized and require benchmarking on the platform of choice before being deployed at production scales. Our study demonstrates that GPUs can be used to greatly accelerate genomic workflows, thus bringing closer to grasp urgent societal advances in the areas of biosurveillance and personalized medicine.

Glacier motion responds dynamically to changing meltwater inputs, but the multi-decadal response of basal sliding to climate remains poorly constrained due to its sensitivity across multiple timescales. Observational records of glacier motion provide critical benchmarks to decode processes influencing glacier dynamics, but multi-decadal records that precede satellite observation and modern warming are rare. Here we present a record of motion in the ablation zone of Saskatchewan Glacier that spans seven decades. We combine in situ and remote-sensing observations to inform a first-order glacier flow model used to estimate the relative contributions of sliding and internal deformation on dynamics. We find a significant increase in basal sliding rates between melt-seasons in the 1950s and those in the 1990s and 2010s and explore three process-based explanations for this anomalous behavior: (i) the glacier surface steepened over seven decades, maintaining flow-driving stresses despite sustained thinning; (ii) the formation of a proglacial lake after 1955 may support elevated basal water pressures; and (iii) subglacial topography may cause dynamic responses specific to Saskatchewan Glacier. Although further constraints are necessary to ascertain which processes are of greatest importance for Saskatchewan Glacier's dynamic evolution, this record provides a benchmark for studies of multi-decadal glacier dynamics.

Abstract Floodplain soilscapes act as temporary sinks in the environment and are nowadays affected by multiple contaminant accumulations and exposures, including different trace metals and plastics. Despite increasing knowledge about the occurrence and behaviour of plastics at the interface between aquatic and terrestrial systems, there are still major uncertainties about the spatial distribution of plastics, their sources and deposition, as well as spatial relationships with other contaminants. Our recent case study addresses these questions, using the example of a river system ranging from rural to urban areas. Based on a geospatial sampling approach we obtained data about soil properties, metal contents via ICP-MS analyses, and particle-based (171 μm – 52 mm) plastic contents, analysed using sodium chloride density separation, visual fluorescence identification and ATR-FTIR analysis. We found plastic contents of 0.00–35.82 p kg− 1 and zero to moderate metal enrichments. Levels of both contaminations occur in the lower range of known concentrations in floodplain soils and show a different spatial distribution along the river course and in the floodplain cross-section. Furthermore, we found that plastic enrichment occurs in the uppermost soil layers, while trace metal enrichment is equally distributed over depth, indicating different sources like flood dynamics and agricultural practice during different deposition periods. Finally, direct short to long-term anthropogenic impacts, like floodplain restoration or tillage may affect plastic enrichments, raising questions for future research directions within floodplain soilscapes.

After five years of research on microplastic pollution of soils it becomes obvious that soil systems act as a reservoir for microplastics on global scales. Nevertheless, the exact role of soils within global microplastic cycles, plastic fluxes within soils and environmental consequences are so far only partly understood. Against the background of a global environmental plastic pollution, the spatial reference, spatial levels, sampling approaches and documentation practices of soil context data becomes important. Within this review, we therefore evaluate the availability of spatial MP soil data on a global scale through the application of a questionnaire applied to 35 case studies on microplastics in soils published since 2016. We found that the global database on microplastics in soils is mainly limited to agricultural used topsoils in Central Europe and China. Data on major global areas and soil regions are missing, leading to a limited understanding of soils plastic pollution. Furthermore, we found that open data handling, geospatial data and documentation of basic soil information are underrepresented, which hinders further understanding of global plastic fluxes in soils. Out of this context, we give recommendations for spatial reference and soil context data collection, access and combination with soil microplastic data, to work towards a global and free soil microplastic data hub.

Crimean-Congo hemorrhagic fever (CCHF) is a World Health Organization prioritized disease because its broad distribution and severity of disease make it a global health threat. Despite advancements in preclinical vaccine development for CCHF virus (CCHFV), including multiple platforms targeting multiple antigens, a clear definition of the adaptive immune correlates of protection is lacking. Levels of neutralizing antibodies in vaccinated animal models do not necessarily correlate with protection, suggesting that cellular immunity, such as CD8+ T cells, might have an important role in protection in this model. Using a well-established IFN-I antibody blockade mouse model (IS) and a DNA-based vaccine encoding the CCHFV M-segment glycoprotein precursor, we investigated the role of humoral and T cell immunity in vaccine-mediated protection in mice genetically devoid of these immune compartments. We found that in the absence of the B-cell compartment (µMT knockout mice), protection provided by the vaccine was not reduced. In contrast, in the absence of CD8+ T cells (CD8+ knockout mice) the vaccine-mediated protection was significantly diminished. Importantly, humoral responses to the vaccine in CD8+ T-cell knockout mice were equivalent to wild-type mice. These findings indicated that CD8+ T-cell responses are necessary and sufficient to promote protection in mice vaccinated with the M-segment DNA vaccine. Identifying a crucial role of the cellular immunity to protect against CCHFV should help guide the development of CCHFV-targeting vaccines.

Abstract Background Ischemic stroke is a leading cause of mortality worldwide, largely due to the inflammatory response to brain ischemia during post-stroke reperfusion. Despite ongoing intensive research, there have not been any clinically approved drugs targeting the inflammatory component to stroke. Preclinical studies have identified T cells as pro-inflammatory mediators of ischemic brain damage, yet mechanisms that regulate the infiltration and phenotype of these cells are lacking. Further understanding of how T cells migrate to the ischemic brain and facilitate neuronal death during brain ischemia can reveal novel targets for post-stroke intervention. Methods To identify the population of T cells that produce IL-21 and contribute to stroke, we performed transient middle cerebral artery occlusion (tMCAO) in mice and performed flow cytometry on brain tissue. We also utilized immunohistochemistry in both mouse and human brain sections to identify cell types and inflammatory mediators related to stroke-induced IL-21 signaling. To mechanistically demonstrate our findings, we employed pharmacological inhibitor anti-CXCL13 and performed histological analyses to evaluate its effects on brain infarct damage. Finally, to evaluate cellular mechanisms of stroke, we exposed mouse primary neurons to oxygen glucose deprivation (OGD) conditions with or without IL-21 and measured cell viability, caspase activity and JAK/STAT signaling. Results Flow cytometry on brains from mice following tMCAO identified a novel population of cells IL-21 producing CXCR5+ CD4+ ICOS-1+ T follicular helper cells (TFH) in the ischemic brain early after injury. We observed augmented expression of CXCL13 on inflamed brain vascular cells and demonstrated that inhibition of CXCL13 protects mice from tMCAO by restricting the migration and influence of IL-21 producing TFH cells in the ischemic brain. We also illustrate that neurons express IL-21R in the peri-infarct regions of both mice and human stroke tissue in vivo. Lastly, we found that IL-21 acts on mouse primary ischemic neurons to activate the JAK/STAT pathway and induce caspase 3/7-mediated apoptosis in vitro. Conclusion These findings identify a novel mechanism for how pro-inflammatory T cells are recruited to the ischemic brain to propagate stroke damage and provide a potential new therapeutic target for stroke.

Abstract Plastic contamination of terrestrial ecosystems and arable soils pose potentially negative impacts on several soil functions. Whereas substantial plastic contamination is now traceable in agro-landscapes, often internal-caused by the application of fertilizers such as sewage sludge, questions remain unanswered concerning what happens to the plastic after incorporation. Based on a combined surface and depth sampling approach, including density separation, fluorescence staining and ATR-FTIR or µFTIR analyses, we quantified macro- and microplastic abundance on two agricultural fields—34 years after the last sewage sludge application. By sub-dividing the study area around sludge application sites, we were able to determine spatial distribution and spreading of plastics. Past sewage sludge application led to a still high density of macroplastics (637.12 items per hectare) on agricultural soil surfaces. Microplastic concentration, measured down to 90 cm depth, ranged from 0.00 to 56.18 particles per kg of dry soil weight. Maximum microplastic concentrations were found in regularly ploughed topsoils. After 34 years without sewage sludge application, macro- and microplastic loads were significantly higher on former application areas, compared to surrounding areas without history of direct sewage application. We found that anthropogenic ploughing was mainly responsible for plastic spread, as opposed to natural transport processes like erosion. Furthermore, small-scale lateral to vertical heterogeneous distribution of macro- and microplastics highlights the need to determine appropriate sampling strategies and the modelling of macro- and microplastic transport in soils.

Predictive models are increasingly being developed and implemented to improve patient care across a variety of clinical scenarios. While a body of literature exists on the development of models using existing data, less focus has been placed on practical operationalization of these models for deployment in real-time production environments. This case-study describes challenges and barriers identified and overcome in such an operationalization for a model aimed at predicting risk of outpatient falls after Emergency Department (ED) visits among older adults. Based on our experience, we provide general principles for translating an EHR-based predictive model from research and reporting environments into real-time operation.

A growing evidence base has shown that plastics are widely distributed in soils and could have negative effects on soil functions. However, within international standards for soil description, plastics are handled so far as one part of human-made artefacts. With the ongoing plastic crisis, such a simple classification may no longer be sufficient to provide a satisfactory description of plastics in soils. Based on the latest research on plastics in soils, these foreign components can no longer be understood as relevant only for soils in urban, industrial, traffic, mining and military areas. This perspective therefore aims to suggest a possible approach towards a future and more comprehensive description of plastics in soil characterization. Based on the existing definitions within the international soil description standards, a description concept and a corresponding field guide are proposed. The proposed approach comprises a recent definition of plastics and guidelines for the description of visible plastic residues in soils during field work. Classification approaches are developed for plastics abundance and distribution as well as plastic characteristics. Furthermore, pitfalls during the description, as well as during the extraction of plastics from soils in the field, and further limitations are discussed. Basic soil description during soil surveys or soil mapping, are a strong tool of soil science to derive environmental data sets. The perspective and the field guide presented in this paper are intended to change this circumstance and enable soil scientists to describe plastic residues in soils simple, comparable and adapted to existing standards in future.

This study aimed to: (1) develop an integrated approach to quantifying match physical-tactical performance and (2) comprehensively examine the validity and reliability of this novel approach. Both UEFA qualified coaches and performance analysts (n = 30) participated to verify the scientific robustness of this new method. The percentage of correct responses were used to verify the validity of the integrated approach and the minimum acceptable agreement was set at 80%. Two well-trained groups of observers analysed a randomly selected English Premier League match for inter- and intra-observer reliability using the kappa statistic. A high degree of validity was demonstrated as the mean percentage of correct responses by all participants, accounting for 91.8 ± 4.3% for all, 92.2 ± 4.7% for out-of-possession, and 91.6 ± 5.7% for in-possession physical-tactical variables. Inter- and intra-observer reliability were found to be strong (κ = 0.81) to almost perfect (κ = 0.94), respectively. Additional analyses demonstrated that there was a nearly perfect correlation between data derived from the novel filter used for the present study to capture high-intensity running and those obtained from the filter of the commercial data provider (r = 0.99; P < 0.01). The data demonstrates that the integrated approach is valid and reliable regarding the quantification of physical-tactical performances. Therefore, it is now possible to unveil unique high-intensity profiles of elite players related to key tactical actions. This may help coaches and practitioners better understand the physical-tactical performances of players, as well as effectively translate physical metrics into training.

Orthopaedic and related care has the potential to present unique obstacles for patients with a range of autism manifestations. In this review, we aim to describe and analyze the literature on autistic patients’ experience within orthopaedics and closely related fields. This literature search utilized the PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature databases. Three major concepts were built into the search terms: (1) patients on the autism spectrum; (2) patient experience; and (3) movement sciences, including orthopaedics, physical medicine and rehabilitation (PM&R), occupational therapy (OT), and physical therapy (PT). Our search yielded 35 topical publications, with the major topic areas addressed as follows: (1) clinical and perioperative management, (2) therapy interventions, (3) participation in exercise and social play, (4) sensory management and accommodations, (5) caregiver/parent training and involvement in care, (6) healthcare needs and barriers to care, and (7) utilization of technology. In the current literature, there are no studies that attempt to directly assess autistic patient experience with care practices and clinical environments in orthopaedics. Rigorous, direct examination of the experience of autistic patients within clinical orthopaedic settings is urgently needed to address this gap.

Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus that causes severe hemorrhagic fever disease in humans. Currently, no licensed CCHF vaccines exist, and the protective epitopes remain unclear. Previously, we tested a DNA vaccine expressing the M-segment glycoprotein precursor gene of the laboratory CCHFV strain IbAr 10200 (CCHFV-M10200). CCHFV-M10200 provided >60% protection against homologous CCHFV-IbAr 10200 challenge in mice. Here, we report that increasing the dose of CCHFV-M10200 provides complete protection from homologous CCHFV challenge in mice, and significant (80%) protection from challenge with the clinically relevant heterologous strain CCHFV-Afg09-2990. We also report complete protection from CCHFV-Afg09-2990 challenge following vaccination with a CCHFV-Afg09-2990 M-segment DNA vaccine (CCHFV-MAfg09). Finally, we show that the non-structural M-segment protein, GP38, influences CCHF vaccine immunogenicity and provides significant protection from homologous CCHFV challenge. Our results demonstrate that M-segment DNA vaccines elicit protective CCHF immunity and further illustrate the immunorelevance of GP38.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The glioma tumor microenvironment (TME) is complex and heterogeneous, and multiple emerging and current technologies are being utilized for an improved comprehension and understanding of these tumors. Single cell analysis techniques such as single cell genomic and transcriptomic sequencing analysis are on the rise and play an important role in elucidating the glioma TME. These large datasets will prove useful for patient tumor characterization, including immune configuration that will ultimately influence therapeutic choices and especially immune therapies. In this review we discuss the advantages and drawbacks of these techniques while debating their role in the domain of glioma-infiltrating myeloid cells characterization and function.

Crimean-Congo hemorrhagic fever virus (CCHFV) is an important human pathogen. In cell culture, CCHFV is sensed by the cytoplasmic RNA sensor retinoic acid-inducible gene I (RIG-I) molecule and its adaptor molecule mitochondrial antiviral signaling (MAVS) protein. MAVS initiates both type I interferon (IFN-I) and proinflammatory responses. Here, we studied the role MAVS plays in CCHFV infection in mice in both the presence and absence of IFN-I activity. MAVS-deficient mice were not susceptible to CCHFV infection when IFN-I signaling was active and showed no signs of disease. When IFN-I signaling was blocked by antibody, MAVS-deficient mice lost significant weight, but were uniformly protected from lethal disease, whereas all control mice succumbed to infection. Cytokine activity in the infected MAVS-deficient mice was markedly blunted. Subsequent investigation revealed that CCHFV infected mice lacking TNF-α receptor signaling (TNFA-R-deficient), but not IL-6 or IL-1 activity, had more limited liver injury and were largely protected from lethal outcomes. Treatment of mice with an anti-TNF-α neutralizing antibody also conferred partial protection in a post-virus exposure setting. Additionally, we found that a disease causing, but non-lethal strain of CCHFV produced more blunted inflammatory cytokine responses compared to a lethal strain in mice. Our work reveals that MAVS activation and cytokine production both contribute to CCHFV pathogenesis, potentially identifying new therapeutic targets to treat this disease.

Pancreatic islet transplantation improves metabolic control and prevents complications in patients with brittle type 1 diabetes (T1D). However, chronic immunosuppression is required to prevent allograft rejection and recurrence of autoimmunity. Islet encapsulation may eliminate the need for immunosuppression. Here, we analyzed in parallel two microencapsulation platforms that provided long-term diabetes reversal in preclinical T1D models, alginate single and double capsules versus polyethylene glycol conformal coating, to identify benefits and weaknesses that could inform the design of future clinical trials with microencapsulated islets. We performed in vitro and in vivo functionality assays with human islets and analyzed the explanted grafts by immunofluorescence. We quantified the size of islets and capsules, measured capsule permeability, and used these data for in silico simulations of islet functionality in COMSOL Multiphysics. We demonstrated that insulin response to glucose stimulation is dependent on capsule size, and the presence of permselective materials augments delays in insulin secretion. Non-coated and conformally coated islets could be transplanted into the fat pad of diabetic mice, resulting in comparable functionality and metabolic control. Mac-2+ cells were found in conformally coated grafts, indicating possible host reactivity. Due to their larger volume, alginate capsules were transplanted in the peritoneal cavity. Despite achieving diabetes reversal, changes in islet composition were found in retrieved capsules, and recipient mice experienced hypoglycemia indicative of hyperinsulinemia induced by glucose retention in large capsules as the in silico model predicted. We concluded that minimal capsule size is critical for physiological insulin secretion, and anti-inflammatory modulation may be beneficial for small conformal capsules.

Junín virus (JUNV), a New World arenavirus, is a rodent-borne virus and the causative agent of Argentine hemorrhagic fever. Humans become infected through exposure to rodent host secreta and excreta and the resulting infection can lead to an acute inflammatory disease with significant morbidity and mortality. Little is understood about the molecular pathogenesis of arenavirus hemorrhagic fever infections. We utilized Reverse Phase Protein Microarrays (RPPA) to compare global alterations in the host proteome following infection with an attenuated vaccine strain, Candid#1 (CD1), and the most parental virulent strain, XJ13, of JUNV in a human cell culture line. Human small airway epithelial cells were infected with CD1 or XJ13 at an MOI of 10, or mock infected. To determine proteomic changes at early timepoints (T = 1, 3, 8 and 24 h), the JUNV infected or mock infected cells were lysed in compatible buffers for RPPA. Out of 113 proteins that were examined by RPPA, 14 proteins were significantly altered following JUNV infection. Several proteins were commonly phosphorylated between the two strains and these correspond to entry and early replication events, to include p38 mitogen-activated protein kinase (MAPK), heat shock protein 27 (HSP27), and nuclear factor kappa B (NFκB). We qualitatively confirmed the alterations of these three proteins following infection by western blot analysis. We also determined that the inhibition of either p38 MAPK, with the small molecule inhibitor SB 203580 or siRNA knockdown, or HSP27, by siRNA knockdown, significantly decreases JUNV replication. Our data suggests that HSP27 phosphorylation at S82 upon virus infection is dependent on p38 MAPK activity. This work sheds light on the nuances of arenavirus replication.

Marie Linder,1 Anastasia Iliadou Nyman,2,3 Helle Kieler,1 Bengt Danielsson,2 Natalia Borg,2 Marcus Gry,2 Julius Collin2 1Centre for Pharmacoepidemiology, Karolinska Institutet, T2, Karolinska University Hospital, Stockholm, Sweden; 2The National Board of Health and Welfare, Stockholm, Sweden; 3Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenCorrespondence: Marie LinderCentre for Pharmacoepidemiology, Karolinska Institutet, T2, Karolinska University Hospital, Stockholm 171 76, SwedenTel +46 8-517 791 75Email marie.linder@ki.sePurpose: To evaluate associations between first-time use of direct oral anticoagulants or vitamin K antagonists and bleeding risk or mortality in the elderly with atrial fibrillation in a real-world setting in Sweden.Patients and Methods: The study population comprises first-time users, above age 60, of dabigatran, apixaban, rivaroxaban, or warfarin, with first atrial fibrillation occurrence within 6 months before dispensing (2012– 2016). Outcomes were gastrointestinal, any, or intracranial bleeding, and mortality. Exposure started at first dispensing of a study drug. Follow-up continued until outcome, end of drug supply, dispensing of another study drug, death or end of study (December 2016). We conducted a propensity score matched, nationwide register-based cohort study including three treatment groups: direct thrombin inhibitors, direct factor Xa inhibitors and vitamin K antagonists, each compared to the other two, focusing on subgroups of age and sex. Cox proportional hazard models adjusted for CHA2DS2VASc and HAS-BLED scores provided hazard ratios with 95% confidence intervals.Results: The matched study populations consisted of 7,264 patients for the direct thrombin inhibitors vs vitamin K antagonists comparison, 12,566 patients for the direct factor Xa inhibitors vs vitamin K antagonists comparison and 6,606 patients for the direct factor Xa inhibitors vs direct thrombin inhibitors comparison, in total 26,436 patients. Numerically high, but imprecise, hazard ratios for gastrointestinal bleeding were observed for women aged 75– 80, 80– 85, or above 85 years, eg 6.00 (1.02, 113.47) for direct thrombin inhibitors vs vitamin K antagonists. For both sexes, numerically high hazard ratios for any bleeding were observed in ages 80– 85, or above 85 years, eg 2.90 (1.01, 10.41) for direct thrombin inhibitors vs vitamin K antagonists. Numerically high HRs for intracranial bleeding were observed for women aged 75– 80 or 80– 85 years, eg 2.70 (0.65, 18.19) for direct factor Xa inhibitors vs vitamin K antagonists. Excess mortality was observed in both sexes, across age groups, for naive and experienced anticoagulant users.Conclusion: The observed increased gastrointestinal bleeding risk in first-time users of direct thrombin inhibitors or direct factor Xa inhibitors is consistent with previous studies. The possible risk of excess mortality merits further studies.Keywords: anticoagulants, arrhythmia, epidemiology, safety

Background: Achieving deep brain stimulation (DBS) dose equivalence is challenging, especially with pulse width tuning and directional contacts. Further, the precise effects of pulse width tuning are unknown, and recent reports of the effects of pulse width tuning on neural selectivity are at odds with classic biophysical studies. Methods: We created multicompartment neuron models for two axon diameters and used finite element modeling to determine extracellular influence from standard and segmented electrodes. We analyzed axon activation profiles and calculated volumes of tissue activated. Results: We find that long pulse widths focus the stimulation effect on small, nearby fibers, suppressing distant white matter tract activation (responsible for some DBS side effects) and improving battery utilization when equivalent activation is maintained for small axons. Directional leads enable similar benefits to a greater degree. Reexamining previous reports of short pulse stimulation reducing side effects, we explore a possible alternate explanation: non-dose equivalent stimulation may have resulted in reduced spread of neural activation. Finally, using internal capsule avoidance as an example in the context of subthalamic stimulation, we present a patient-specific model to show how long pulse widths could help increase the biophysical therapeutic window. Discussion: We find agreement with classic studies and predict that long pulse widths may focus the stimulation effect on small, nearby fibers and improve power consumption. While future pre-clinical and clinical work is necessary regarding pulse width tuning, it is clear that future studies must ensure dose equivalence, noting that energy- and charge-equivalent amplitudes do not result in equivalent spread of neural activation when changing pulse width.

Increasingly, eDNA is being used to infer ecological interactions. Here the authors sample eDNA over 18 months in a marine environment and use co-occurrence network analyses to infer potential interactions among organisms from microbes to mammals, testing how they change over time in response to oceanographic factors.

The objective of this study was to investigate the differences in sleep patterns among individuals with and without laboratory-confirmed SARS-CoV-2 infection. Laboratory-confirmed SARS-CoV-2 test results and self-reported measures recalling sleep habits prior to and during the pandemic were collected from May 2020 to March 2021 among 1,848 individuals in The Arizona CoVHORT Study. We used linear and logistic regression to model the association between test status, presentation of symptoms, and time since test result with sleep duration and trouble sleeping, respectively. Mixed models were used to investigate change in sleep duration prior to the pandemic compared to during the pandemic. Overall, 16.2% of the sample were SARS-CoV-2 positive, 64.3% were SARS-CoV-2 negative, and 19.5% were untested for SARS-CoV-2. Independent of SARS-CoV-2 infection status, all participants slept longer during the pandemic compared to pre-pandemic (Δ SARS-CoV-2 positive: 77.7 min, 95% CI 67.9, 87.5; Δ SARS-CoV-2 negative: 13.4 min, 95% CI 8.4, 18.3). However, SARS-CoV-2 positive participants slept 60.9 min longer (95% CI 49.1, 72.8) than SARS-CoV-2 negative participants in multivariable-adjusted models and had greater odds of trouble sleeping three or more times per week since the start of the pandemic (OR: 1.34 95% CI 1.02, 1.77) This greater odds of trouble sleeping persisted for participants who reported sleep habits > 30 days after their positive SARS-CoV-2 (OR: 2.11 95% CI 1.47, 3.03). Sleep patterns among non-hospitalized individuals with COVID-19 were altered following infection, regardless of the presentation of symptoms and time since infection.

Knowledge of the distribution of short range-order structural units in oxide glasses is important for deciphering their composition–property relations. However, measurements of the fractions of such units are often difficult and time consuming, especially for multicomponent glasses. Here, we introduce StatMechGlass, a Python-based software for calculating the short range-order structure distribution in oxide glasses based on statistical mechanics. By accounting for the enthalpic and entropic contributions to the network interactions in glass-forming melts, the atomic-scale structures of the resulting glasses can be calculated. As input, the software requires accurate interaction enthalpy values that can be supplied by the user or obtained directly by the software from experimental structure data. StatMechGlass thus enables the prediction of composition–structure relations for any oxide glass composition. When coupled with existing composition–property databases of experimental data, it enables the construction of composition–structure–property databases and models. StatMechGlass is open source and designed in a modular fashion for easy tailoring for specific needs.

Background:. Displaced supracondylar humeral fractures (SCHFs) benefit from closed reduction and percutaneous pinning. In Malawi, many SCHFs are treated nonoperatively because of limited surgical capacity. We sought to assess clinical and functional outcomes of nonoperatively treated SCHFs in a resource-limited setting. Methods:. We retrospectively reviewed all patients with SCHFs treated at Nkhotakota District Hospital (NKKDH) in Malawi between January 2014 and December 2016. Patients subsequently underwent clinical and functional follow-up assessment. Results:. We identified 182 children (54% male, mean age of 7 years) with an SCHF; 151 (83%) of the fractures were due to a fall, and 178 (98%) were extension-type (Gartland class distribution: 63 [35%] type I, 52 [29%] type II, and 63 [35%] type III). Four patients with type-I fractures were treated with an arm sling alone, and 59 were treated with straight-arm traction to reduce swelling and then splint immobilization until union. All 119 of the patients with Gartland type-II and III or flexion-type injuries were treated with straight-arm traction, manipulation under anesthesia without fluoroscopy, and then splint immobilization until union. A total of 137 (75%) of the patients were available for follow-up, at a mean of 3.9 years after injury. The Flynn functional outcome was excellent for 39 (95%) with a type-I fracture, 30 (70%) with type-II, and 14 (29%) with type-III. The Flynn cosmetic outcome was excellent for 40 (98%) with a type-I fracture, 42 (98%) with type-II, and 41 (84%) with type-III. Forty (98%) of the children with a type-I fracture, 41 (95%) with type-II, and 32 (65%) with type-III returned to school without limitation. Controlling for sex, delayed presentation, medical comorbidities, injury mechanism, and skin blistering/superinfection during traction, patients with type-II fractures were 5.82-times more likely (95% confidence interval [CI], 1.71 to 19.85) and those with type-III fractures were 9.81-times more likely (95% CI, 3.00 to 32.04), to have a clinical complication or functional limitation compared with patients with type-I fractures. Conclusions:. Nonoperative treatment of type-III SCHFs resulted in a high risk of clinical complications or functional impairment. These results illustrate the urgent need to increase surgical capacity in low-income countries like Malawi to improve pediatric fracture care. Level of Evidence:. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Biagina-Carla Farnesi,1 Francine M Ducharme,2,3 Lucie Blais,4 Johanne Collin,4 Kim L Lavoie,5,6 Simon L Bacon,1,6 Martha L McKinney,7 Sandra Peláez3,8 1Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, QC Canada; 2Departments of Pediatrics and of Social and Preventive Sciences, University of Montreal, Montreal, QC Canada; 3Research Centre, CHU Sainte-Justine, University of Montreal, Montreal, QC Canada; 4Faculty of Pharmacy, University of Montreal, Montreal, QC Canada; 5Psychology Department, University of Quebec at Montreal, Montreal, QC Canada; 6Research Center, Sacré-Cœur de Montréal Hospital, CIUSSS du Nord-de-l’Ile-de-Montréal, Montreal, QC Canada; 7CHU Ste-Justine, University of Montreal, Montreal, QC Canada; 8School of Kinesiology and Physical Activity Sciences, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada Purpose: The purpose of this study was to better understand patients’ perspective of asthma self-management by focusing on the sociocultural and medical context shaping patients’ illness representations and individual decisions. Patients and methods: We conducted a secondary analysis of semi-structured interviews carried out as part of a multicentered collective qualitative case study. In total, 24 patients, aged 2–76 years with a confirmed diagnosis of asthma (or were parents of a child), who renewed the prescription for inhaled corticosteroids in the past year, participated in this study. The thematic analysis focused on asthma-related events and experiences reported by the patients. Consistent with narrative inquiry, similar patterns were grouped together, and three vignettes representing the different realities experienced by the patients were created. Results: The comparison of experiences and events reported by the patients suggested that patients’ perceptions and beliefs regarding asthma and treatment goals influenced their self-management-related behaviors. More specifically, the medical context in which the patients were followed (ie, frame in which the medical encounter takes place, medical recommendations provided) contributed to shape their understanding of the disease and the associated treatment goals. In turn, a patient’s perception of the disease and the treatment goals influenced asthma self-management behaviors related to environmental control, lifestyle habits, and medication intake. Conclusion: Current medical recommendations regarding asthma self-management highlight the importance of the physicians’ guidance through the provision of a detailed written action plan and asthma education. These data suggest that while physicians contribute to shaping patients’ beliefs and perceptions about the disease and treatment goals, patients tend to listen to their own experience and manage the disease accordingly. Thus, a medical encounter between the patient and the physician, aiming at enhancing a meaningful conversation about the disease, may lead the patient to approach the disease in a more effective manner, which goes beyond taking preventative paths to avoid symptoms. Keywords: asthma, adherence, self-management, written action plan, patient-physician relationship, narrative inquiry

Abstract Environmental DNA (eDNA) is the DNA suspended in the environment (e.g., water column), which includes cells, gametes, and other material derived from but not limited to shedding of tissue, scales, mucus, and fecal matter. Amplifying and sequencing marker genes (i.e., metabarcoding) from eDNA can reveal the wide range of taxa present in an ecosystem through analysis of a single water sample. Metabarcoding of eDNA provides higher resolution data than visual surveys, aiding in assessments of ecosystem health. This study conducted eDNA metabarcoding of two molecular markers (cytochrome c oxidase I (COI) and 18S ribosomal RNA (rRNA) genes) to survey eukaryotic diversity across multiple trophic levels in surface water samples collected at three sites along the coral reef tract within the Florida Keys National Marine Sanctuary (FKNMS) during four research cruises in 2015. The 18S rRNA gene sequences recovered 785 genera while the COI gene sequences recovered 115 genera, with only 33 genera shared between the two datasets, emphasizing the complementarity of these marker genes. Community composition for both genetic markers clustered by month of sample collection, suggesting that temporal variation has a larger effect on biodiversity than spatial variability in the FKNMS surface waters. Sequences from both marker genes were dominated by copepods, but each marker recovered distinct phytoplankton groups, with 18S rRNA gene sequences dominated by dinoflagellates and COI sequences dominated by coccolithophores. Although eDNA samples were collected from surface waters, many benthic species such as sponges, crustaceans, and corals were identified. These results show the utility of eDNA metabarcoding for cataloging biodiversity to establish an ecosystem baseline against which future samples can be compared in order to monitor community changes.

The energy landscape of a material holds information that describes the thermodynamics and the kinetics of any process, making it valuable to understand a range of important phenomena. Mapping energy landscapes is a difficult task, with multiple approaches offering different ways to explore the landscape. In this work, we present our new software that has three techniques to explore energy landscapes in parallel, including a novel algorithm. Our software is based on a familiar framework, LAMMPS, allowing for any user of LAMMPS to quickly gain the ability to explore energy landscapes.

Background: Sepsis, a leading cause for intensive care unit admissions, causes both an acute encephalopathy and chronic brain dysfunction in survivors. A history of sepsis is also a risk factor for future development of dementia symptoms. Similar neuropathologic changes are associated with the cognitive decline of sepsis and Alzheimer's disease (AD), including neuroinflammation, neuronal death, and synaptic loss. Amyloid plaque pathology is the earliest pathological hallmark of AD, appearing 10 to 20 years prior to cognitive decline, and is present in 30% of people over 65. As sepsis is also more common in older adults, we hypothesized that sepsis might exacerbate amyloid plaque deposition and plaque-related injury, promoting the progression of AD-related pathology. Methods: We evaluated whether the brain's response to sepsis modulates AD-related neurodegenerative changes by driving amyloid deposition and neuroinflammation in mice. We induced polymicrobial sepsis by cecal ligation and puncture (CLP) in APP/PS1–21 mice, a model of AD-related β-amyloidosis. We performed CLP or sham surgery at plaque onset (2 months of age) and examined pathology 2 months after CLP in surviving mice. Results: Sepsis significantly increased fibrillar amyloid plaque formation in the hippocampus of APP/PS1–21 mice. Sepsis enhanced plaque-related astrocyte activation and complement C4b gene expression in the brain, both of which may play a role in modulating amyloid formation. CLP also caused large scale changes in the gut microbiome of APP/PS1 mice, which have been associated with a pro-amyloidogenic and neuroinflammatory state. Conclusions: Our results suggest that experimental sepsis can exacerbate amyloid plaque deposition and plaque-related inflammation, providing a potential mechanism for increased dementia in older sepsis survivors.

This study is a prospective, population-based cohort of individuals with a history of SARS-CoV-2 infection and those without past infection through multiple recruitment sources. The main study goal is to track health status over time, within the diverse populations of Arizona and to identify the long-term consequences of COVID-19 on health and well-being. A total of 2,881 study participants (16.2% with a confirmed SARS-CoV-2 infection) have been enrolled as of December 22, 2020, with a target enrollment of 10,000 participants and a planned follow-up of at least 2 years. This manuscript describes a scalable study design that utilizes a wide range of recruitment sources, leveraging electronic data collection to capture and link longitudinal participant data on the current and emerging issues associated with the COVID-19 pandemic. The cohort is built within a collaborative infrastructure that includes new and established partnerships with multiple stakeholders, including the state's public universities, local health departments, tribes, and tribal organizations. Challenges remain for ensuring recruitment of diverse participants and participant retention, although the electronic data management system and timing of participant contact can help to mitigate these problems.

Clinical presentation, outcomes, and duration of COVID-19 has ranged dramatically. While some individuals recover quickly, others suffer from persistent symptoms, collectively known as long COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Most PASC research has focused on hospitalized COVID-19 patients with moderate to severe disease. We used data from a diverse population-based cohort of Arizonans to estimate prevalence of PASC, defined as experiencing at least one symptom 30 days or longer, and prevalence of individual symptoms. There were 303 non-hospitalized individuals with a positive lab-confirmed COVID-19 test who were followed for a median of 61 days (range 30–250). COVID-19 positive participants were mostly female (70%), non-Hispanic white (68%), and on average 44 years old. Prevalence of PASC at 30 days post-infection was 68.7% (95% confidence interval: 63.4, 73.9). The most common symptoms were fatigue (37.5%), shortness-of-breath (37.5%), brain fog (30.8%), and stress/anxiety (30.8%). The median number of symptoms was 3 (range 1–20). Amongst 157 participants with longer follow-up (≥60 days), PASC prevalence was 77.1%.

In the Northern Rockies of the United States, predators like wolves (Canis lupus) and mountain lions (Puma concolor) have been implicated in fluctuations or declines in populations of game species like elk (Cervus canadensis) and mule deer (Odocoileus hemionus). In particular, local distributions of these predators may affect ungulate behavior, use of space, and dynamics. Our goal was to develop generalizable predictions of habitat selection by wolves and mountain lions across western Montana. We hypothesized both predator species would select habitat that maximized their chances of encountering and killing ungulates and that minimized their chances of encountering humans. We assessed habitat selection by these predators during summer using within-home range (3rd order) resource selection functions (RSFs) in multiple study areas throughout western Montana, and tested how generalizable RSF predictions were by applying them to out-of-sample telemetry data from separate study areas. Selection for vegetation cover-types varied substantially among wolves in different study areas. Nonetheless, our predictions of 3rd order selection by wolves were highly generalizable across different study areas. Wolves consistently selected simple topography where ungulate prey may be more susceptible to their cursorial hunting mode. Topographic features may serve as better proxies of predation risk by wolves than vegetation cover-types. Predictions of mountain lion distribution were less generalizable. Use of rugged terrain by mountain lions varied across ecosystem-types, likely because mountain lions targeted the habitats of different prey species in each study area. Our findings suggest that features that facilitate the hunting mode of a predator (i.e. simple topography for cursorial predators and hiding cover for stalking predators) may be more generalizable predictors of their habitat selection than features associated with local prey densities.

Modern ultrasound (US) imaging is increasing its clinical impact, particularly with the introduction of US-based quantitative imaging biomarkers. Continued development and validation of such novel imaging approaches requires imaging phantoms that recapitulate the underlying anatomy and pathology of interest. However, current US phantom designs are generally too simplistic to emulate the structure and variability of the human body. Therefore, there is a need to create a platform that is capable of generating well-characterized phantoms that can mimic the basic anatomical, functional, and mechanical properties of native tissues and pathologies. Using a 3D-printing technique based on stereolithography, we fabricated US phantoms using soft materials in a single fabrication session, without the need for material casting or back-filling. With this technique, we induced variable levels of stable US backscatter in our printed materials in anatomically relevant 3D patterns. Additionally, we controlled phantom stiffness from 7 to >120 kPa at the voxel level to generate isotropic and anisotropic phantoms for elasticity imaging. Lastly, we demonstrated the fabrication of channels with diameters as small as 60 micrometers and with complex geometry (e.g., tortuosity) capable of supporting blood-mimicking fluid flow. Collectively, these results show that projection-based stereolithography allows for customizable fabrication of complex US phantoms.

As the need for new modalities of energy storage becomes increasingly important, all-solid-state secondary ion batteries seem poised to address a portion of tomorrow’s energy needs. The success of such batteries is contingent on the solid-state electrolyte (SSE) meeting a set of material demands, including high bulk and interfacial ionic conductivity, processability with electrodes, electrode interfacial stability, thermal stability, etc. The demanding criteria for an ideal SSE has translated into decades of research devoted to discovering new electrolytes and modifying their structure/processing to improve their properties. While much research has focused on the electrolyte properties of polycrystalline ceramics, non-crystalline materials (glasses, amorphous solids, and partially crystallized materials) have demonstrated unique advantages in processability, stability, tunability, etc. These non-crystalline electrolytes are also fundamentally interesting for their potential contributions toward understanding ionic conduction in the solid state. In this review, we first review a decade of advances in two distinct families of non-crystalline lithium-ion electrolytes: lithium thiophosphate and lithium phosphate oxynitride. In doing so, we demonstrate two pathways for non-crystalline electrolytes to address the barriers toward development of all-solid-state batteries, viz., interfacial stability and conduction. Finally, we conclude with some discussion of the development of fundamental models of ionic conduction in the non-crystalline state, including the ongoing debate between strong and weak electrolyte theories. Collectively, these discussions make a promising case for the role of non-crystalline electrolytes in the next generation of energy storage technology.