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Abstract Background The tumor microenvironment (TME), including infiltrating T‐cells, is thought to play a major role in the pathogenesis and prognosis of follicular lymphoma (FL) and may contribute to its widely varied disease course. We hypothesized that programmed death‐1 inhibition may be most effective in untreated, immunocompetent FL patients. Thus, we developed a phase 2 study to evaluate the efficacy of pembrolizumab as the initial treatment for indolent B‐cell lymphoma. Methods Adults with FL or marginal zone lymphoma and an indication for treatment were eligible. Patients received pembrolizumab 200 mg IV in 21‐day cycles for up to 18 cycles, until progression or unacceptable toxicity. Early response assessment was obtained after cycle 3 with computed tomography (CT), and a fluorodeoxyglucose (FDG)‐positron emission tomography‐computed tomography (PET‐CT) was obtained after cycle 6 to determine candidacy for continuation in the study. Immunosecretome profiling was performed at baseline and on cycle 2 day 1. Results Nine patients with FL were enrolled between February 2019 and April 2021, including eight (89%) with advanced stage, seven (78%) with intermediate/high Follicular Lymphoma International Prognostic Index, and six (67%) with high‐tumor burden by Groupe d'Etude des Lymphomes Folliculaires. The best overall response rate by FDG PET‐CT was 33% (three partial metabolic responses). Three patients (33%) had stable disease, and three (33%) had progressive disease (including one patient who only had a follow‐up CT). By CT four (44%) experienced a reduction in target lesions, but all were less than partial responses. Grade 3 or higher immune‐related adverse events (IRAEs) were seen in two (22%) patients, both with transaminitis and one of whom had concurrent hypophysitis. Another patient had grade 1 pneumonitis, requiring treatment with steroids. No associations between the immunosecretome profile and clinical outcomes could be detected. Conclusion Frontline pembrolizumab for FL is associated with limited responses and a clinically significant rate of IRAEs. Alternative strategies for targeting the TME in FL should be explored.

Abstract Background Orbital decompression is recommended for TED especially in the treatment of severe, refractory cases yet there are no clear guidelines regarding the optimal surgical approach. Previously conducted surveys assessed variations in the management of TED but only amongst ophthalmologists. Our study attempts to better characterize surgical and perioperative preferences amongst otolaryngologists in the management of TED. Methods A survey was administered to the American Rhinologic Society and Canadian Society of Otolaryngology – Head and Neck Surgery via REDCap with 52 total respondents. Respondent demographic information and pre‐operative management, procedural specifics, and post‐operative management preferences were collected. Results The majority of respondents practiced in a metropolitan (82.7%), academic setting (73.1%) and received subspecialty training in Rhinology & Skull Base Surgery (88.9%). Most elected for corticosteroids (63.5%) and medical management (69.2%) prior to orbital decompression but did not use any classification system (86.5%). Orbital decompression was most often done with ophthalmology collaboration (71.2%). Removal of two bony walls (55.8%) via medial wall (97.9%) and orbital floor (72.3%) removal was most preferred. Removal of one orbital fat aspect (60.6%) via the medial fat pad was most preferred. Combined bone and fat removal (59.6%) completed via an endoscopic approach (71.2% and 97.0%, respectively) was most common. Post‐operatively, most patients were not admitted (88.4%) with saline nasal rinses (92.3%) utilized by most respondents. Conclusions This survey completed by otolaryngologists highlights several key distinctions in the preferred surgical approach during orbital decompression and the perioperative management of TED when compared to ophthalmologists and current recommendations. Level of evidence Level 4.

Abstract This study investigated the potential of different wheat varieties to influence the performance of the subsequent wheat crop. In fall 2021, a single variety of winter wheat (cv. Norwest Tandem) was planted into standing wheat stubble in plots that were previously planted to five winter wheat varieties. At harvest, yield was significantly affected by the variety that had been planted in each plot during the first year of the trial. Specifically, wheat following the variety Pritchett yielded approximately 12% more than wheat following the variety Bobtail. While planting the second crop, residue from the winter wheat variety Norwest Duet caused the no‐till plot drill to plug (accumulate large amounts of soil and crop residue in front of openers) far more than residue from the other varieties. This indicates that varieties differ in their residue management requirements. These differences could be exploited to best fit different agricultural practices. This study highlights the potential importance of varietal effects that persist in the field after the field is harvested. However, more work is needed to understand varietal differences in residue management requirements and varietal effects of the successive crop before they can be fully leveraged in wheat breeding and genetics, wheat agronomy, variety testing programs, and eventually the producer's field.

Abstract Objectives (1) To plot the trajectory of humoral and cellular immune responses to the primary (two‐dose) COVID‐19 mRNA series and the third/booster dose in B‐cell‐depleted multiple sclerosis (MS) patients up to 2 years post‐vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID‐19 infections on SARS CoV‐2‐specific immunity. Methods Sixty ocrelizumab‐treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre‐vaccination, and then 4, 12, 24, and 48 weeks post‐primary series, and 4, 12, 24, and 48 weeks post‐booster. Binding anti‐Spike antibody responses were assessed with multiplex bead‐based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live‐virus immunofluorescence‐based microneutralization assay. Spike‐specific cellular responses were assessed with IFNγ/IL‐2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)‐3 within T‐cell receptors (Adaptive Biotechnologies). A linear mixed‐effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses. Results The primary vaccination induced an 11‐ to 208‐fold increase in binding and neutralizing antibody levels and a 3‐ to 4‐fold increase in IFNγ/IL‐2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3‐ to 5‐fold increase in binding antibodies and 4‐ to 5‐fold increase in IFNγ/IL‐2, which were maintained for up to 1 year. Infections had a variable impact on immunity. Interpretation Humoral and cellular benefits of COVID‐19 vaccination in B‐cell‐depleted MS patients were sustained for up to 2 years when booster doses were administered.

Abstract Organic electrochemical transistors (OECTs) are of great interest in low‐power bioelectronics and neuromorphic computing, as they utilize organic mixed ionic‐electronic conductors (OMIECs) to transduce ionic signals into electrical signals. However, the poor environmental stability of OMIEC materials significantly restricts the practical application of OECTs. Therefore, the non‐fused planar naphthalenediimide (NDI)‐dialkoxybithiazole (2Tz) copolymers are fine‐tuned through varying ethylene glycol (EG) side chain lengths from tri(ethylene glycol) to hexa(ethylene glycol) (namely P‐XO, X = 3–6) to achieve OECTs with high‐stability and low threshold voltage. As a result, the NDI‐2Tz copolymers exhibit ambipolarity, rapid response (

Abstract Dust dynamics influence planetary atmospheres. However, the settling velocity of dust—and thus its residence time in the atmosphere—is often mispredicted. Challenging, indirect experiments involving few ideal particles revealed that dust settling velocity deviates from Stokes' law under rarefied atmospheres. While useful, such experiments are inadequate to simulate more complex scenarios, including variable particles sizes and shapes. Here, we present direct measurements of settling velocity for spherical particles under Earth‐to‐Mars atmospheric pressures using time‐resolved particle image velocimetry (TR‐PIV), and validate their robustness with existing models. Our results demonstrate that TR‐PIV provides a relatively simple approach to quantifying dust settling velocity from direct observations of over 10,000 particles, enabling systematic investigations of dust settling under realistic scenarios. Such experiments will have significant implications for our understanding of Mars' past, present, and future ‐ from providing a tool to decipher its sedimentary record to enhancing predictive capabilities of atmospheric models.

Abstract DNA barcoding is commonly used for species identification. Despite this, there has not been a comprehensive assessment of the utility of DNA barcoding in crayfishes (Decapoda: Astacidea). Here we examined the extent to which local barcoding gaps (used for species identification) and global barcoding gaps (used for species discovery) exist among crayfishes, and whether global gaps met a previously suggested 10× threshold (mean interspecific difference being 10× larger than mean intra specific difference). We examined barcoding gaps using publicly available mitochondrial COI sequence data from the National Center for Biotechnology Information's nucleotide database. We created two versions of the COI datasets used for downstream analyses: one focused on the number of unique haplotypes (NH) per species, and another that focused on total number of sequences (NS; i.e., including redundant haplotypes) per species. A total of 81 species were included, with 58 species and five genera from the family Cambaridae and 23 species from three genera from the family Parastacidae. Local barcoding gaps were present in only 30 species (20 Cambaridae and 10 Parastacidae species). We detected global barcoding gaps in only four genera (Cambarus, Cherax, Euastacus, and Tenuibranchiurus), which were all below (4.2× to 5.2×) the previously suggested 10× threshold. We propose that a ~5× threshold would be a more appropriate working hypothesis for species discovery. While the NH and NS datasets yielded largely similar results, there were some discrepant inferences. To understand why some species lacked a local barcoding gap, we performed species delimitation analyses for each genus using the NH dataset. These results suggest that current taxonomy in crayfishes may be inadequate for the majority of examined species, and that even species with local barcoding gaps present may be in need of taxonomic revisions. Currently, the utility of DNA barcoding for species identification and discovery in crayfish is quite limited, and caution should be exercised when mitochondrial‐based approaches are used in place of taxonomic expertise. Assessment of the evidence for local and global barcoding gaps is important for understanding the reliability of molecular species identification and discovery, but outcomes are dependent on the current state of taxonomy. As this improves (e.g., via resolving species complexes, possibly elevating some subspecies to the species‐level status, and redressing specimen misidentifications in natural history and other collections), so too will the utility of DNA barcoding.

Abstract Impact craters that form on every planetary body provide a record of planetary surface evolution. On heavily cratered surfaces, new craters that form often overlap antecedent craters, but it is unknown how the presence of antecedent craters alters impact crater formation. We use overlapping complex crater pairs on the lunar surface to constrain this process and find that crater rims are systematically lower where they intersect antecedent crater basins. The rim morphology of the new crater depends on the depth of the antecedent crater and the degree of overlap between the craters. Our observations suggest that new craters do not always obliterate underlying topography and that transient rim collapse is altered by antecedent topography. This study represents the first formalization of the influence of antecedent topography on rim morphology and provides process insight into a common impact scenario relevant to the geology of potential Artemis landing sites.

Abstract Objectives This study aimed to compare the different respiratory rate (RR) monitoring methods used in the emergency department (ED): manual documentation, telemetry, and capnography. Methods This is a retrospective study using recorded patient monitoring data. The study population includes patients who presented to a tertiary care ED between January 2020 and December 2022. Inclusion and exclusion criteria were patients with simultaneous recorded RR data from all three methods and less than 10 min of recording, respectively. Linear regression and Bland–Altman analysis were performed between different methods. Results A total of 351 patient encounters met study criteria. Linear regression yielded an R‐value of 0.06 (95% confidence interval [CI] 0.00–0.12) between manual documentation and telemetry, 0.07 (95% CI 0.01–0.13) between manual documentation and capnography, and 0.82 (95% CI 0.79–0.85) between telemetry and capnography. The Bland–Altman analysis yielded a bias of −0.8 (95% limits of agreement [LOA] −12.2 to 10.6) between manual documentation and telemetry, bias of −0.6 (95% LOA −13.5 to 12.3) between manual documentation and capnography, and bias of 0.2 (95% LOA −6.2 to 6.6) between telemetry and capnography. Conclusion There is a poor correlation between manual documentation and both automated methods, while there is relatively good agreement between the automated methods. This finding highlights the need to further investigate the methodology used by the ED staff in monitoring and documenting RR and ways to improve its reliability given that many important clinical decisions are made based on these assessments.

Abstract Background Previous studies in dogs with degenerative mitral valve disease (DMVD) have identified altered myocardial energy metabolism and oxidation, which might contribute to cardiac hypertrophy. Diets rich in medium chain fatty acids and antioxidants are a potential means of treatment. A previous clinical study found significantly smaller left atrial diameter (LAD) and left atrium‐to‐aorta diameter ratio (LA : Ao) in dogs with subclinical DMVD fed a specially formulated diet vs control diet for 6 months. Hypothesis/Objectives A specially formulated diet will slow or arrest left heart enlargement in dogs with subclinical DMVD over 365 days. Animals One hundred twenty‐seven dogs with unmedicated subclinical DMVD; 101 dogs in the per protocol cohort. Methods Randomized double‐blinded controlled multicenter clinical trial. Results The study's primary composite outcome measure was the sum of percentage change in LAD and left ventricular internal dimension at end‐diastole (LVIDd) at day 365. In the per protocol cohort, the outcome measure increased by 8.0% (95% confidence interval [CI], 2.9%‐13.1%) in dogs receiving the test diet vs 8.8% (95% CI, 5.1%‐12.5%) in dogs receiving control diet (P = .79). Neither component of the primary outcome measure was significantly different between groups (LAD, P = .65; LVIDd, P = .92). No difference was found in mitral valve E wave velocity (P = .36) or the proportion of dogs withdrawn from the study because of worsening DMVD and heart enlargement (P = .41). Conclusions and Clinical Importance Feeding a specially formulated diet for 365 days was not associated with a significantly different rate of change of left heart size in dogs with subclinical DMVD as compared to control.

Abstract Forests contribute to numerous ecosystem functions and services and contain a large proportion of terrestrial biodiversity, but they are being negatively impaced by anthropogenic activities. Forests that have never been clear‐cut and have old growth characteristics, termed “near‐natural,” often harbor different and richer species assemblages than managed forests. Alternative management strategies may be able to balance the needs of biodiversity with the demands of forestry, but evaluation efforts are limited by the challenges of measuring biodiversity. Species richness is frequently used as a simple measure of biodiversity, but research indicates that it may not adequately capture community‐level changes. Alternatively, trait‐based measures of biodiversity may prove to be useful, but research is lacking. In this paper, we use a large dataset that includes 339 obligate saproxylic beetle species collected over a decade in the boreal region throughout southern Norway to: (1) establish if there is a difference in beetle community composition between near‐natural and managed forests; and (2) determine which measures of beetle biodiversity best indicate forest naturalness. We arranged the sites in an ordination space and tested for differences in community composition between these forest types. We also tested different measures of biodiversity to determine which were the most predictive of forest naturalness. We found a clear difference in community composition between near‐natural and managed forests. Additionally, three measures of biodiversity were most predictive of forest naturalness: proportional abundance of predators, community weighted mean (CWM) of wing length, and CWM of body roundness. The probability that a forest was near‐natural increased with the proportional abundance of predators but decreased with CWM wing length and body roundness. Although species richness was higher in near‐natural forests, the effect was not significant. Overall, our findings underscore the conservation value of near‐natural forests and highlight the potential of several measures of biodiversity for determining forest quality.

Abstract Objective This study aimed to evaluate safety (infusion‐related reactions [IRRs]) and patient satisfaction (patient‐reported outcomes [PROs]) for at‐home ocrelizumab administration for patients with multiple sclerosis (MS). Methods This open‐label study included adult patients with an MS diagnosis who had completed a ≥ 600‐mg ocrelizumab dose, had a patient‐determined disease steps score of 0 to 6 and had completed PROs. Eligible patients received a 600‐mg ocrelizumab home‐based infusion over 2 h, followed by 24‐h and 2‐week post‐infusion follow‐up calls. IRRs and adverse events (AEs) were documented during infusions and follow‐up calls. PROs were completed before and 2 weeks post infusion. Results Overall, 99 of 100 expected patients were included (mean [SD] age, 42.3 [7.7] years; 72.7% female; 91.9% White). The mean (SD) infusion time was 2.5 (0.6) hours, and 75.8% of patients completed their ocrelizumab infusion between 2 to 2.5 h. The IRR incidence rate was 25.3% (95% CI: 16.7%, 33.8%)—similar to other shorter ocrelizumab infusion studies—and all AEs were mild/moderate. In total, 66.7% of patients experienced AEs, including itch, fatigue, and grogginess. Patients reported significantly increased satisfaction with the at‐home infusion process and confidence in the care provided. Patients also reported a significant preference for at‐home infusion compared with prior infusion center experiences. Interpretation IRRs and AEs occurred at acceptable rates during in‐home infusions of ocrelizumab over a shorter infusion time. Patients reported increased confidence and comfort with the home infusion process. Findings from this study provide evidence of the safety and feasibility of home‐based ocrelizumab infusion over a shorter infusion period.

Abstract Accurate interpretation of the genetic signatures of past demographic events is crucial for reconstructing evolutionary history. Lineage fusion (complete merging, resulting in a single panmictic population) is a special case of secondary contact that is seldom considered. Here, the circumstances under which lineage fusion can be distinguished from population size constancy, growth, bottleneck, and decline were investigated. Multi‐locus haplotype data were simulated under models of lineage fusion with different divergence versus sampling lag times (D:L ratios). These pseudo‐observed datasets also differed in their allocation of a fixed amount of sequencing resources (number of sampled alleles, haplotype length, number of loci). Distinguishability of lineage fusion versus each of 10 untrue non‐fusion scenarios was quantified based on six summary statistics (neutrality tests). Some datasets were also analyzed using extended Bayesian skyline plots. Results showed that signatures of lineage fusion very closely resemble those of decline—high distinguishability was generally limited to the most favorable scenario (D:L = 9), using the most sensitive summary statistics (FS and ZnS), coupled with the optimal sequencing resource allocation (maximizing number of loci). Also, extended Bayesian skyline plots often erroneously inferred population decline. Awareness of the potential for lineage fusion to carry the hallmarks of population decline is critical.

Abstract Migratory waterfowl are an important resource for consumptive and non‐consumptive users alike and provide tremendous economic value in North America. These birds rely on a complex matrix of public and private land for forage and roosting during migration and wintering periods, and substantial conservation effort focuses on increasing the amount and quality of target habitat. Yet, the value of habitat is a function not only of a site's resources but also of its geographic position and weather. To quantify this value, we used a continental‐scale energetics‐based model of daily dabbling duck movement to assess the marginal value of lands across the contiguous United States during the non‐breeding period (September to May). We examined effects of eliminating each habitat node (32 × 32 km) in both a particularly cold and a particularly warm winter, asking which nodes had the largest effect on survival. The marginal value of habitat nodes for migrating dabbling ducks was a function of forage and roosting habitat but, more importantly, of geography (especially latitude and region). Irrespective of weather, nodes in the Southeast, central East Coast, and California made the largest positive contributions to survival. Conversely, nodes in the Midwest, Northeast, Florida, and the Pacific Northwest had consistent negative effects. Effects (positive and negative) of more northerly nodes occurred in late fall or early spring when climate was often severe and was most variable. Importance and effects of many nodes varied considerably between a cold and a warm winter. Much of the Midwest and central Great Plains benefited duck survival in a warm winter, and projected future warming may improve the value of lands in these regions, including many National Wildlife Refuges, for migrating dabbling ducks. Our results highlight the geographic variability in habitat value, as well as shifts that may occur in these values due to climate change.

Introduction Vertebral artery stenting represents a viable option in treating symptomatic vertebral artery atherosclerotic stenosis. However, its safety and efficacy in improving neurological status and reducing recurrent strokes remain to be established. Methods We systematically searched PubMed, Embase, and Cochrane databases using keywords with Boolean operators to increase search sensitivity and specificity (‘extracranial’; ‘stenting’; ‘vertebral artery’; ‘stenosis’). We included articles reporting patients > 18 years old with symptomatic extracranial vertebral artery stenoses due to atherosclerosis treated with stenting (with or without angioplasty). Those reporting patients with vertebral dissections were excluded. Patients’ characteristics, procedural details, complications, and outcomes were extracted. Estimated rates weighted for sample size were generated for each variable using fixed and random effects models. Results From 89 unique studies identified, 21 met our inclusion criteria and were included in the analysis, comprising 1499 patients with 1570 lesions. The mean age was 65 years, and 74.4% were men. The mean baseline NIHSS was 4.6. The most frequent stenosis location was the V1 segment of the vertebral artery (88.4%). Device‐related issues occurred in 1.8%. Periprocedural ischemic and hemorrhagic complications occurred in 2.1% and 1.7%, respectively. Neurological improvement post‐procedure was observed in 84.2%, and the in‐hospital mortality rate was 2.1%. During follow‐up, in‐stent stenosis >50% was observed in 12.8%, and retreatment with either re‐stenting or angioplasty was performed in 10.8%. Ischemic complications during follow‐up occurred in 5%, and the overall mortality rate was 5%. Conclusion Stenting for the treatment of atherosclerotic vertebral artery stenosis is technically feasible, associated with a high rate of neurological improvement and low short and long‐term complication rates.

Abstract Wetlands are responsible for 20%–31% of global methane (CH4) emissions and account for a large source of uncertainty in the global CH4 budget. Data‐driven upscaling of CH4 fluxes from eddy covariance measurements can provide new and independent bottom‐up estimates of wetland CH4 emissions. Here, we develop a six‐predictor random forest upscaling model (UpCH4), trained on 119 site‐years of eddy covariance CH4 flux data from 43 freshwater wetland sites in the FLUXNET‐CH4 Community Product. Network patterns in site‐level annual means and mean seasonal cycles of CH4 fluxes were reproduced accurately in tundra, boreal, and temperate regions (Nash‐Sutcliffe Efficiency ∼0.52–0.63 and 0.53). UpCH4 estimated annual global wetland CH4 emissions of 146 ± 43 TgCH4 y−1 for 2001–2018 which agrees closely with current bottom‐up land surface models (102–181 TgCH4 y−1) and overlaps with top‐down atmospheric inversion models (155–200 TgCH4 y−1). However, UpCH4 diverged from both types of models in the spatial pattern and seasonal dynamics of tropical wetland emissions. We conclude that upscaling of eddy covariance CH4 fluxes has the potential to produce realistic extra‐tropical wetland CH4 emissions estimates which will improve with more flux data. To reduce uncertainty in upscaled estimates, researchers could prioritize new wetland flux sites along humid‐to‐arid tropical climate gradients, from major rainforest basins (Congo, Amazon, and SE Asia), into monsoon (Bangladesh and India) and savannah regions (African Sahel) and be paired with improved knowledge of wetland extent seasonal dynamics in these regions. The monthly wetland methane products gridded at 0.25° from UpCH4 are available via ORNL DAAC (https://doi.org/10.3334/ORNLDAAC/2253).

Abstract Functional trait approaches are common in ecology, but a lack of clear hypotheses on how traits relate to environmental gradients (i.e., trait–niche relationships) often makes uncovering mechanisms difficult. Furthermore, measures of community functional structure differ in their implications, yet inferences are seldom compared among metrics. Community‐weighted mean trait values (CWMs), a common measure, are largely driven by the most common species and thus do not reflect community‐wide trait–niche relationships per se. Alternatively, trait–niche relationships can be estimated across a larger group of species using hierarchical joint species distribution models (JSDMs), quantified by a parameter Γ. We investigated how inferences about trait–niche relationships are affected by the choice of metric. Using deadwood‐dependent (saproxylic) beetles in fragmented Finnish forests, we followed a protocol for investigating trait–niche relationships by (1) identifying environmental filters (climate, forest age, and deadwood volume), (2) relating these to an ecological function (dispersal ability), and (3) identifying traits related to this function (wing morphology). We tested 18 hypothesized dispersal relationships using both CWM and Γ estimates across these environmental gradients. CWMs were more likely than Γ to show support for trait–niche relationships. Up to 13% of species' realized niches were explained by dispersal traits, but the directions of effects were consistent with fewer than 11%–39% of our 18 trait–niche hypotheses (depending on the metric used). This highlights the difficulty in connecting morphological traits and ecological functions in insects, despite the clear conceptual link between landscape connectivity and flight‐related traits. Caution is thus warranted in hypothesis development, particularly where apparent trait–function links are less clear. Inferences differ when CWMs versus Γ estimates are used, necessitating the choice of a metric that reflects study questions. CWMs help explain the effects of environmental gradients on community trait composition, whereas the effects of traits on species' niches are better estimated using hierarchical JSDMs.

Abstract Objective To compare “hybrid immunity” (prior COVID‐19 infection plus vaccination) and post‐vaccination immunity to SARS CoV‐2 in MS patients on different disease‐modifying therapies (DMTs) and to assess the impact of vaccine product and race/ethnicity on post‐vaccination immune responses. Methods Consecutive MS patients from NYU MS Care Center (New York, NY), aged 18–60, who completed primary COVID‐19 vaccination series ≥6 weeks previously were evaluated for SARS CoV‐2‐specific antibody responses with electro‐chemiluminescence and multiepitope bead‐based immunoassays and, in a subset, live virus immunofluorescence‐based microneutralization assay. SARS CoV‐2‐specific cellular responses were assessed with cellular stimulation TruCulture IFNγ and IL‐2 assay and, in a subset, with IFNγ and IL‐2 ELISpot assays. Multivariate analyses examined associations between immunologic responses and prior COVID‐19 infection while controlling for age, sex, DMT at vaccination, time‐to‐vaccine, and vaccine product. Results Between 6/01/2021 and 11/11/2021, 370 MS patients were recruited (mean age 40.6 years; 76% female; 53% non‐White; 22% with prior infection; common DMT classes: ocrelizumab 40%; natalizumab 15%, sphingosine‐1‐phosphate receptor modulators 13%; and no DMT 8%). Vaccine‐to‐collection time was 18.7 (±7.7) weeks and 95% of patients received mRNA vaccines. In multivariate analyses, patients with laboratory‐confirmed prior COVID‐19 infection had significantly increased antibody and cellular post‐vaccination responses compared to those without prior infection. Vaccine product and DMT class were independent predictors of antibody and cellular responses, while race/ethnicity was not. Interpretation Prior COVID‐19 infection is associated with enhanced antibody and cellular post‐vaccine responses independent of DMT class and vaccine type. There were no differences in immune responses across race/ethnic groups.

Abstract Aquatic invasive species (AIS) present major ecological and economic challenges globally, endangering ecosystems and human livelihoods. Managers and policy makers thus need tools to predict invasion risk and prioritize species and areas of concern, and they often use native range climate matching to determine whether a species could persist in a new location. However, climate matching for AIS often relies on air temperature rather than water temperature due to a lack of global water temperature data layers, and predictive power of models is seldom evaluated. We developed 12 global lake (water) temperature‐derived “BioLake” bioclimatic layers for distribution modeling of aquatic species and compared “climatch” climate matching predictions (from climatchR package) from BioLake with those based on BioClim temperature layers and with a null model. We did this for 73 established AIS in the United States, training the models on their ranges outside of the United States and Canada. Models using either set of climate layers outperformed the null expectation by a similar (but modest) amount on average, but some species were occasionally found in locations with low climatch scores. Mean US climatch scores were higher for most species when using air temperature. Including additional climate layers in models reduced mean climatch scores, indicating that commonly used climatch score thresholds are not absolute but can be context specific and may require calibration based upon climate data used. Although finer resolution global lake temperature data would likely improve predictions, our BioLake layers provide a starting point for aquatic species distribution modeling. Climate matching was most effective for some species that originated at low latitudes or had small ranges. Climatch scores remain useful but limited for predicting AIS risk, perhaps because current ranges seldom fully reflect climatic tolerances (fundamental niches). Managers could consider climate matching as one of a suite of tools that can be used in AIS prioritization.

Abstract Objectives Recent research has helped define the complex pathways in sepsis, affording new opportunities for advancing diagnostics tests. Given significant advances in the field, a group of academic investigators from emergency medicine, intensive care, pathology, and pharmacology assembled to develop consensus around key gaps and potential future use for emerging rapid host response diagnostics assays in the emergency department (ED) setting. Methods A modified Delphi study was conducted that included 26 panelists (expert consensus panel) from multiple specialties. A smaller steering committee first defined a list of Delphi statements related to the need for and future potential use of a hypothetical sepsis diagnostic test in the ED. Likert scoring was used to assess panelists agreement or disagreement with statements. Two successive rounds of surveys were conducted and consensus for statements was operationally defined as achieving agreement or disagreement of 75% or greater. Results Significant gaps were identified related to current tools for assessing risk of sepsis in the ED. Strong consensus indicated the need for a test providing an indication of the severity of dysregulated host immune response, which would be helpful even if it did not identify the specific pathogen. Although there was a relatively high degree of uncertainty regarding which patients would most benefit from the test, the panel agreed that an ideal host response sepsis test should aim to be integrated into ED triage and thus should produce results in less than 30 minutes. The panel also agreed that such a test would be most valuable for improving sepsis outcomes and reducing rates of unnecessary antibiotic use. Conclusion The expert consensus panel expressed strong consensus regarding gaps in sepsis diagnostics in the ED and the potential for new rapid host response tests to help fill these gaps. These finding provide a baseline framework for assessing key attributes of evolving host response diagnostic tests for sepsis in the ED.

Abstract On 20 December 2020, after more than 2 years of quiescence at Kīlauea Volcano, Hawaiʻi, renewed volcanic activity in the summit crater caused boiling of the water lake over a period of ∼90 min. The resulting water‐rich, electrified plume rose to 11–13 km above sea level, which is among the highest plumes on record for Kīlauea. Although conventional models would infer a high mass flux from explosive magma‐water interaction, the plume was not associated with an infrasound signal indicative of “explosive” activity, nor did it produce a measurable ash‐fall deposit. We use multisensor data to characterize lava‐water interaction and plume generation during this opening phase of the 2020–21 eruption. Satellite, weather radar, and eyewitness observations revealed that the plume was rich in water vapor and hydrometeors but transported less ash than expected from its maximum height. Volcanic lightning flashes detected by ground‐based cameras were confined to freezing altitudes of the upper cloud, suggesting that the ice formation drove the electrification of this plume. The low acoustic energy from lava‐water interaction points to a weakly explosive style of hydrovolcanism. Heat transfer calculations show that the lava to water heat flux was sufficient to boil the lake within 90 min. Limited mixing of lava and water inhibited major steam explosions and fine fragmentation. Results from one‐dimensional plume modeling suggest that the models may underpredict plume height due to overestimation of crosswind air‐entrainment. Our findings shed light on an unusual style of volcanism in which weakly explosive lava‐water interaction generated an outsized plume.

Abstract In landscape genetics, it is largely unknown how choices regarding sampling density and study area size impact inferences upon which habitat features impede vs. facilitate gene flow. While it is recommended that sampling locations be spaced no further apart than the average individual's dispersal distance, for low‐mobility species, this could lead to a challenging number of sampling locations, or an unrepresentative study area. We assessed the effects of sampling density and study area size on landscape genetic inferences for a dispersal‐limited amphibian, Plethodon mississippi, via analysis of nested datasets. Microsatellite‐based genetic distances among individuals were divided into three datasets representing sparse sampling across a large study area, dense sampling across a small study area, or sparse sampling across the same small study area. These datasets were a proxy for gene flow (i.e., the response variable) in maximum‐likelihood population effects models that assessed the nature and strength of their relationship with each of five land‐use classes (i.e., potential predictor variables). Comparisons of outcomes were based on the rank order of effect, sign of effect (i.e., gene flow resistance vs. facilitation), spatial scale of effect, and functional relationship with gene flow. The best‐fit model for each dataset had the same sign of effect for hardwood forests, manmade structures, and pine forests, indicating the impacts of these land‐use classes on dispersal and gene flow in P. mississippi are robust to sampling scheme. Contrasting sampling densities led to a different inferred functional relationship between agricultural areas and gene flow. Study area size appeared to influence the scale of effect of manmade structures and the sign of effect of pine forests. Our findings provided evidence for an influence of sampling density, study area size, and sampling effort upon inferences. Accordingly, we recommend iterative subsampling of empirical datasets and continued investigation into the sensitivities of landscape genetic analyses using simulations.

Abstract Mucosal melanoma is a rare form of melanoma which arises from melanocytes in the mucosal membranes and can be effectively treated with immune checkpoint blockade (ICB). However, response rates in mucosal melanoma are lower than those observed for cutaneous melanomas. Targeted sequencing of up to 447 genes (OncoPanel) was performed on tumors from all mucosal melanoma patients seen at the Dana‐Farber Cancer Institute from 2011 until March 2019. We identified a total of 46 patients who received ICB with both tumor‐genotype and ICB response data available. Within this cohort of patients, 16 (35%) had durable clinical benefit (DCB) to their first line of ICB. The average mutational burden/megabase was 6.23 and did not correlate with tumor response to ICB. Patients with KIT aberrations had a higher DCB rate compared with patients with wildtype KIT (71 vs. 28%), but this was not found to be statistically significant. For comparison, we analyzed tumor genotypes from an additional 50 mucosal melanoma tumors and 189 cutaneous melanoma tumors. The most frequent mutations in mucosal melanoma were in SF3B1 (27%), KIT (18%), and NF1 (17%), a pattern that is distinct from cutaneous melanomas. In addition, there were genetic differences observed based upon the site of origin of the mucosal melanoma. Our findings explore clinical features of response in patients with mucosal melanoma treated with ICB and demonstrate a low mutational burden that does not correlate with response. In addition, the lack of significant association between the genetic aberrations tested and response to ICB indicates the need for further exploration in this patient population.

Abstract Background Adopting a better understanding of how both older adults and health care providers view the community management of frailty is necessary for improving home health, especially facing the coronavirus disease 2019 (COVID‐19) pandemic. We conducted a qualitative focus group study to assess how both older adults and health care providers view frailty and virtual health care in home health. Methods Two focus groups enrolled home‐living older adults and health care professionals, respectively (n = 15). Questions targeting the use of virtual / telehealth technologies in‐home care for frail older adults were administered at audio‐recorded group interviews. Transcribed discussions were coded and analyzed using NVivo software. Results The older adult group emphasized the autonomy related to increasing frailty and social isolation and the need for transparent dissemination of health care planning. They were optimistic about remote technology‐based supports and suggested that telehealth / health‐monitoring/tracking were in high demand. Health care professionals emphasized the importance of a holistic biopsychosocial approach to frailty management. They highlighted the need for standardized early assessment and management of frailty. Conclusions The integrated perspectives provided an updated understanding of what older adults and practitioners value in home‐living supports. This knowledge is helpful to advancing virtual home care, providing better care for frail individuals with complex health care needs.

Abstract Background Cardiac magnetic resonance imaging (CMR) allows for detection of fibrosis in hypertrophic cardiomyopathy (HCM) by quantification of the extracellular volume fraction (ECV). Hypothesis/Objectives To quantify native T1 mapping and ECV in cats. We hypothesize that native T1 mapping and ECV will be significantly increased in HCM cats compared with healthy cats. Animals Seventeen healthy and 12 preclinical HCM, age‐matched, client‐owned cats. Methods Prospective observational study. Tests performed included indirect blood pressure, CBC, biochemical analysis including total thyroid, urinalysis, transthoracic echocardiogram, and CMR. Cats were considered healthy if all tests were within normal limits and a diagnosis of HCM was determined by the presence of left ventricular concentric hypertrophy ≥6 mm on echocardiography. Results There were statistically significant differences in LV mass (healthy = 5.87 g, HCM = 10.3 g, P

Abstract Longer exclusive breastfeeding duration has been associated with differences in neural development, better satiety responsiveness, and decreased risk for childhood obesity. Given hippocampus sensitivity to diet and potential role in the integration of satiety signals, hippocampus may play a role in these relationships. We conducted a secondary analysis of 149, 7–11‐year‐olds (73 males) who participated in one of five studies that assessed neural responses to food cues. Hippocampal grey matter volume was extracted from structural scans using CAT12, weight status was assessed using age‐ and sex‐adjusted body mass index (%BMIp85), and parents reported exclusive breastfeeding duration and satiety responsiveness (Children's Eating Behaviour Questionnaire). Separate path models for left and right hippocampus tested: (1) the direct effect of exclusive breastfeeding on satiety responsiveness and its indirect effect through hippocampal grey matter volume; (2) the direct effect of hippocampal grey matter volume on %BMIp85 and its indirect effect through satiety responsiveness. %BMIp85 was adjusted for maternal education, yearly income, and premature birth while hippocampal grey matter volume was adjusted for total intercranial volume, age, and study from which data were extracted. Longer exclusive breastfeeding duration was associated with greater bilateral hippocampal grey matter volumes. In addition, better satiety responsiveness and greater left hippocampal grey matter volume were both associated with lower %BMIp85. However, hippocampal grey matter volumes were not associated with satiety responsiveness. Although no relationship was found between breastfeeding and child weight status, these results highlight the potential impact of exclusive breastfeeding duration on the hippocampal structure.

Objective There are limited data on the impact of coronavirus disease 2019 (COVID‐19) on hospitalized patients with autoimmune and chronic inflammatory disease (AICID) compared with patients who do not have AICID. We sought to evaluate whether patients with AICID who have confirmed COVID‐19 presenting to the hospital are at higher risk of adverse outcomes compared with those patients without AICID who are infected with COVID‐19 and whether immunosuppressive medications impact this risk. Methods We performed a multicenter retrospective cohort study with patients presenting to five hospitals in a large academic health system with polymerase chain reaction–confirmed COVID‐19 infection. We evaluated the impact of having an AICID and class of immunosuppressive medication being used to treat patients with AICID (biologics, nonbiologic immunosuppressives, or systemic corticosteroids) on the risk of developing severe COVID‐19 defined as requiring mechanical ventilation (MV) and/or death. Results A total of 6792 patients with confirmed COVID‐19 were included in the study, with 159 (2.3%) having at least one AICID. On multivariable analysis, AICIDs were not significantly associated with severe COVID‐19 (adjusted odds ratio [aOR] 1.3, 95% confidence interval [CI]: 0.9‐1.8). Among patients with AICID, use of biologics or nonbiologic immunosuppressives did not increase the risk of severe COVID‐19. In contrast, systemic corticosteroid use was significantly associated with an increased risk of severe COVID‐19 (aOR 6.8, 95% CI: 2.5‐18.4). Conclusion Patients with AICID are not at increased risk of severe COVID‐19 with the exception of those on corticosteroids. These data suggest that patients with AICID should continue on biologic and nonbiologic immunosuppression but limit steroids during the COVID‐19 pandemic.

Abstract Globally, many insect populations are declining, prompting calls for action. Yet these findings have also prompted discussion about sampling methods and interpretation of long‐term datasets. As insect monitoring and research efforts increase, it is critical to quantify the effectiveness of sampling methods. This is especially true if sampling biases of different methods covary with climate, which is also changing over time. We assess the effectiveness of two types of flight intercept traps commonly used for beetles, a diverse insect group responsible for numerous ecosystem services, under different climatic conditions in Norwegian boreal forest. One of these trap designs includes a device to prevent rainwater from entering the collection vial, diluting preservatives and flushing out beetles. This design is compared to a standard trap. We ask how beetle capture rates vary between these traps, and how these differences vary based on precipitation levels and beetle body size, an important species trait. Bayesian mixed models reveal that the standard and modified traps differ in their beetle capture rates, but that the magnitude and direction of these differences change with precipitation levels and beetle body size. At low rainfall levels, standard traps catch more beetles, but as precipitation increases the catch rates of modified traps overtake those of standard traps. This effect is most pronounced for large‐bodied beetles. Sampling methods are known to differ in their effectiveness. Here, we present evidence for a less well‐known but likely common phenomenon—an interaction between climate and sampling, such that relative effectiveness of trap types for beetle sampling differs depending on precipitation levels and species traits. This highlights a challenge for long‐term monitoring programs, where both climate and insect populations are changing. Sampling methods should be sought that eliminate climate interactions, any biases should be quantified, and all insect datasets should include detailed methodological metadata.

Abstract Previously thought to be nothing more than cellular debris, extracellular vesicles (EVs) are now known to mediate physiological and pathological functions throughout the body. We now understand more about their capacity to transfer nucleic acids and proteins between distant organs, the interaction of their surface proteins with target cells, and the role of vesicle‐bound lipids in health and disease. To date, most observations have been made in reductionist cell culture systems, or as snapshots from patient cohorts. The heterogenous population of vesicles produced in vivo likely act in concert to mediate both beneficial and detrimental effects. EVs play crucial roles in both the pathogenesis of diseases, from cancer to neurodegenerative disease, as well as in the maintenance of system and organ homeostasis. This two‐part review draws on the expertise of researchers working in the field of EV biology and aims to cover the functional role of EVs in physiology and pathology. Part I will outline the role of EVs in normal physiology.

Abstract Past work shows that processing information in relation to the self improves memory which is known as the self‐reference effect in memory. Other work suggests that transcranial direct current stimulation (tDCS) can also improve memory. Given recent research on self‐reference context memory effects (improved memory for contextual episodic details associated with self‐referential processing), we were interested in examining the extent stimulation might increase the magnitude of the self‐reference context memory effect. In this investigation, participants studied objects superimposed on different background scenes in either a self‐reference or other‐reference condition while receiving either active or sham stimulation to the dorsal medial prefrontal cortex (dmPFC), a cortical region known to support self‐reference context memory effects. Participants then completed a memory test that assessed item memory (have you seen this object before?) and context memory (with which background scene was this object paired?). Results showed a self‐reference context memory effect driven by enhanced memory for stimuli processed in the self‐reference compared to the other‐reference condition across all participants (regardless of stimulation condition). tDCS, however, had no effect on memory. Specifically, stimulation did not increase the magnitude of the self‐reference context memory effect under active compared to sham stimulation. These results suggest that stimulation of the dmPFC at encoding may not add to the memory benefits induced by self‐referential processing suggesting a boundary condition to tDCS effects on memory.

Objective Risk aversion is a personality trait influential to decision making in medicine. Little is known about how emergency department (ED) clinicians differ in their attitudes toward risk taking. Methods We conducted a cross‐sectional survey of practicing ED clinicians (physicians and advanced practice clinicians [APCs]) in Massachusetts using the following 4 existing validated scales: the Risk‐Taking Scale (RTS), Stress from Uncertainty Scale (SUS), the Fear of Malpractice Scale (FMS), and the Need for (Cognitive) Closure Scale (NCC). We used Cronbach's α to assess the reliability of each scale and performed multivariable linear regressions to analyze the association between the score for each scale and clinician characteristics. Results Of 1458 ED clinicians recruited for participation, 1116 (76.5%) responded from 93% of acute care hospitals in Massachusetts. Each of the 4 scales demonstrated high internal consistency reliability with Cronbach's αs ranging from 0.76 to 0.92. The 4 scales also were moderately correlated with one another (0.08 to 0.54; all P

Objective We hypothesize that Smad3 is a master regulator of fibrosis in the vocal folds (VFs) and RNA‐based therapeutics targeting Smad3 hold therapeutic promise. Delivery remains challenging. We previously described a novel synthetic peptoid oligomer, lipitoid L0, complexed with siRNA to improve stability and cellular uptake. An advantage of these peptoids, however, is tremendous structural and chemical malleability to optimize transfection efficiency. Modifications of L0 were assayed to optimize siRNA‐mediated alteration of gene expression. Methods In vitro, Smad3 knockdown by various lipitoid variants was evaluated via quantitative real‐time polymerase chain reaction in human VF fibroblasts. Cytotoxicity was quantified via colorimetric assays. In vivo, a rabbit model of VF injury was employed to evaluate the temporal dynamics of Smad3 knockdown following injection of the L0‐siRNA complex. Results In vitro, similar reductions in Smad3 expression were established by all lipitoid variants, with one exception. Sequence variants also exhibited similar nontoxic characteristics; no statistically significant differences in cell proliferation were observed. In vivo, Smad3 expression was significantly reduced in injured VFs following injection of L0‐complexed Smad3 siRNA at 1 day postinjection. Qualitative suppression of Smad3 expression persisted to 3 days following injury, but did not achieve statistical significance. Conclusions In spite of the chemical diversity of these peptoid transfection reagents, the sequence variants generally provided consistently efficient reductions in Smad3 expression. L0 yielded effective, yet temporally limited knockdown of Smad3 in vivo. Peptoids may provide a versatile platform for the discovery of siRNA delivery vehicles optimized for clinical application. Level of Evidence NA

Abstract Background Angiotensin‐converting enzyme 2 (ACE2) is a homologue of angiotensin‐converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1‐9 and 1‐7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II. Hypothesis Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs. Animals Forty‐nine dogs with and 34 dogs without heart disease. Methods Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed. Results Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1‐12.1) as compared to control (2.2 mU/mg; IQR, 1.8‐3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1‐7, in dogs with CHF (486.7 pg/mL; IQR, 214.2‐1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4‐45.1; P

Abstract The etiology of anemia in adults is often multifactorial. This case highlights an uncommon combination of causes of anemia and the importance of a diagnostic workup guided by a patient's unique history, risk factors, and laboratory findings.

Abstract Low‐angle subduction has been shown to have a profound impact on subduction processes. However, the mechanisms that initiate, drive, and sustain flat‐slab subduction are debated. Within all subduction zone systems, metamorphic dehydration reactions within the down‐going slab have been hypothesized to produce seismicity, and to produce water that fluxes melting of the asthenospheric wedge leading to arc magmatism. In this work, we examine the role hydration plays in influencing slab buoyancy and the geometry of the downgoing oceanic plate. When water is introduced to the oceanic lithosphere, it is incorporated into hydrous phases, which results in lowered rock densities. The net effect of this process is an increase in the buoyancy of the downgoing oceanic lithosphere. To better understand the role of water in low‐angle subduction settings, we model flat‐slab subduction in Alaska, where the thickened oceanic lithosphere of the Yakutat oceanic plateau is subducting beneath the continental lithosphere. In this work, we calculate the thermal conditions and stable mineral assemblages in the slab crust and mantle in order to assess the role that water plays in altering the density of the subducting slab. Our slab density results show that a moderate amount of hydration (1–1.5 wt% H2O) in the subducting crust and upper lithospheric mantle reduces slab density by 0.5%–0.8% relative to an anhydrous slab, and is sufficient to maintain slab buoyancy to 300–400 km from the trench. These models show that water is a viable factor in influencing the subduction geometry in Alaska, and is likely important globally.

Abstract Fusarium crown rot (FCR) of winter wheat (Triticum aestivum L.), caused by Fusarium pseudograminearm and Fusarium culmorum, is a yield‐limiting disease in arid wheat‐producing areas of the inland Pacific Northwest. Foliar fungicide applications and currently available seed treatments do not control FCR. Alternative crops that provide a rotational benefit to reduce disease are not economically feasible. Major‐gene resistance is unavailable, but there is preliminary evidence that some wheat and barley (Hordeum vulgare L.) cultivars are more resistant than others. We followed up on preliminary work by growing 14 varieties of winter wheat, planted with in‐furrow FCR inoculum, in 2018 and 2019 in Morrow County, Oregon—one of the world's driest wheat producing regions. Two barley cultivars were added to the experiment during the second year of research. Evaluations of cultivar resistance were made by conducting aboveground visual assessments by counting whiteheads, prematurely senesced wheat heads that are indicative of FCR infection. Whitehead count information was correlated with yield and grain volume weight data. Maximum whitehead counts were measured in plots of the FCR‐susceptible check cultivar ‘Stephens’. There was no evidence of a cultivar‐specific relationship between whitehead count and corresponding values for yield and grain volume weight. There was limited evidence that some cultivars have the capacity to compensate for effects of disease.

Abstract Introduction The interaction between isoflavones and the gut microbiota has been highlighted as a potential regulator of obesity and diabetes. In this study, we examined the interaction between isoflavones and a shortened activity photoperiod on the gut microbiome. Methods Male mice were exposed to a diet containing no isoflavones (NIF) or a regular diet (RD) containing the usual isoflavones level found in a standard vivarium chow. These groups were further divided into regular (12L:12D) or short active (16L:8D) photoperiod, which mimics seasonal changes observed at high latitudes. White adipose tissue and genes involved in lipid metabolism and adipogenesis processes were analysed. Bacterial genomic DNA was isolated from fecal boli, and 16S ribosomal RNA sequencing was performed. Results NIF diet increased body weight and adipocyte size when compared to mice on RD. The lack of isoflavones and photoperiod alteration also caused dysregulation of lipoprotein lipase (Lpl), glucose transporter type 4 (Glut‐4) and peroxisome proliferator‐activated receptor gamma (Pparg) genes. Using 16S ribosomal RNA sequencing, we found that mice fed the NIF diet had a greater proportion of Firmicutes than Bacteroidetes when compared to animals on the RD. These alterations were accompanied by changes in the endocrine profile, with lower thyroid‐stimulating hormone levels in the NIF group compared to the RD. Interestingly, the NIF group displayed increased locomotion as compared to the RD group. Conclusion Together, these data show an interaction between the gut bacterial communities, photoperiod length and isoflavone compounds, which may be essential for understanding and improving metabolic health.

Abstract Research was conducted to determine the tolerance of 11 grass species used in minimal‐to‐no‐mow turf areas to three postemergence herbicides applied at one‐ and twofold the maximum label rates in 2018 and 2019. Grasses were transplanted into field plots in West Lafayette, IN, in 2018 and 2019, allowed time to establish (∼1−2 mo), and then either treated with one application of quinclorac, sethoxydim, and topramezone at two rates or not treated. All 11 grass species had acceptable tolerance (≤20% injury) to quinclorac applied at 0.845 kg acid equivalent (a.e.) ha–1. Quinclorac at 1.69 kg a.e. ha–1 produced moderate injury (≥21% injury) on only little bluestem [Schizachyrium scoparium (Michx.) Nash.], prairie dropseed [Sporobolus heterolepis (A. Gray) A. Gray], and switchgrass (Panicum virgatum L.). Strong creeping red fescue (Festuca rubra L. ssp. rubra Gaudin), which had ≤5% injury from all three herbicides, exhibited the greatest tolerance among grass species tested. With the exception of strong creeping red fescue, sethoxydim significantly injured all other grass species. Injury from topramezone varied among grass species and herbicide rates. Grasses tolerant (≤20% injury) to topramezone at both rates were big bluestem (Andropogon gerardii Vitman), broomsedge bluestem (Andropogon virginicus L.), indiangrass [Sorghastrum nutants (L.) Nash], strong creeping red fescue, and tall fescue [Festuca arundinacea Schreb.; syn. Schedonorus arundinaceus (Schreb.) Dumort., nom. cons.]. Tolerance among species was variable to quinclorac, sethoxydim, and topramezone, and thus turf managers should first identify desired grass species prior to herbicide application.

Abstract Stable isotopes 13C and 15N are often used in lake ecosystems to assess energy sources and trophic positions, respectively. However, δ13C and δ15N are also influenced by internal biogeochemical processes in epilimnetic and hypolimnetic habitats in lakes, but the extent to which biogeochemical processing mediates isotope values between these two habitats, and whether these patterns are influenced by lake productivity is not known. We sampled δ13C and δ15N in epilimnetic mussels, Chaoborus, cisco (Coregonus artedi), and seston and zooplankton in the epilimnia and hypolimnia of 22 Minnesota (USA) lakes ranging from oligotrophic to eutrophic. We also measured lake temperature–oxygen profiles and light levels to assess factors influencing isotope patterns. Isotope samples were baseline‐corrected using epilimnetic mussels in each lake (sample—mussel) to control for watershed‐level differences in isotope values. Results showed δ13C in epilimnetic and hypolimnetic zooplankton, hypolimnetic seston, Chaoborus, and cisco became more depleted in δ13C relative to epilimnetic mussels in low‐productivity lakes where light penetrated into the hypolimnion, while epilimnetic seston δ13C stayed similar to mussel δ13C in all lakes. This pattern was likely due to hypolimnetic phytoplankton in clearwater lakes incorporating more respired CO2, which is depleted in δ13C, and subsequently passing depleted δ13C values up the food chain. Results also showed habitat differences in δ15N with epilimnetic and hypolimnetic zooplankton, hypolimnetic seston, Chaoborus, and cisco becoming more enriched relative to epilimnetic mussels in low‐productivity lakes with higher O2 levels in the hypolimnion, while epilimnetic seston δ15N remained similar to mussel values. The δ15N pattern is consistent with the idea that denitrification and microbial degradation enriched hypolimnetic seston relative to epilimnetic seston in low nutrient lakes, while enhanced epilimnetic primary production enriched epilimnetic δ15N seston relative to hypolimnetic seston in high nutrient lakes. Our results indicate isotopic differences between epilimnetic and hypolimnetic organisms that change along productivity gradients and suggest that microbial processes and the light regime are important drivers.

ABSTRACT Interactions between people and American black bears (Ursus americanus) have been increasing throughout the United States, with negative interactions becoming a major management challenge for wildlife agencies. To monitor the number, location, and severity of these conflicts, wildlife agencies typically rely on voluntary public reports. Although trends in voluntary reports are commonly assumed to reflect actual trends in human–bear interactions, recent research suggests an individual's likelihood of reporting interactions may be biased, influenced by attitudes toward the species and its management, previous experiences with wildlife, or demographic factors. During 2012, we used a mail survey of residents in the vicinity of Durango, Colorado, USA, (n = 1,667) to explore the relative importance of tolerance for black bears, satisfaction with bear management, personal experience with bears, and demographic traits as predictors of a resident's decision to report interactions to the authorities. We found that residents’ experiences with bears were most important in predicting reporting behavior, followed closely by attitudes related to tolerance for bears, and satisfaction with management; demographic factors had relatively little influence. Respondents were more likely to report when they had seen black bears near their homes, had been threatened by bears, were intolerant of bears, dissatisfied with management, and were female. Although several variables in our analyses were influential in explaining reporting behavior, the overall predictive power of our models was low (R2 = 0.17), suggesting future investigations of reporting behavior should include a broader set of covariates. Our results indicate that public reports represent a biased measure of human–bear interactions, and management agencies should either account for bias, or collect different types of interaction data, when assessing patterns of bear activity. © 2018 The Wildlife Society.

ABSTRACT Geospatial tools have become a critical component to most wildlife studies and management questions. With a diversity of approaches available, current and future wildlife professionals deserve guidance on the most important tools to answer these questions. Younger professionals may be expected to know a separate set of skills from those required further on in their career. We conducted an online survey and a year‐long search of job advertisements to identify the most important geospatial approaches, techniques, programs, and ancillary skills for wildlife professionals. We provide the results of these 2 efforts so that wildlife professionals interested in geospatial tools can prioritize those most valued in our field. Habitat modeling and home range analysis were the 2 highest‐ranked tools. Highly ranked programs included ArcGIS, R, Google Earth, and Geospatial Modeling Environment. We suggest that wildlife professionals should have a geospatial program they are comfortable with and be conversant with the major approaches (e.g., habitat modeling, home range analysis, remote sensing, and mobile mapping) but need not be experts in each field. Younger professionals should focus on the “big picture” tools such as ArcGIS, while professionals further in their career are expected to have some expertise in multiple areas, including knowledge of current and emerging trends. © 2017 The Wildlife Society.

Newts can regenerate amputated limbs and cardiac tissue, unlike mammals which lack broad regenerative capacity. Several signaling pathways involved in cell proliferation, differentiation and survival during newt tissue regeneration have been elucidated, however the factors that coordinate signaling between cells, as well as the conservation of these factors in other animals, are not well defined. Here we report that media conditioned by newt limb explant cells (A1 cells) protect mammalian cardiomyocytes from oxidative stress-induced apoptosis. The cytoprotective effect of A1-conditioned media was negated by exposing A1 cells to GW4869, which suppresses the generation of extracellular vesicles (EVs). A1-EVs are similar in diameter (~100–150 nm), structure, and share several membrane surface and cargo proteins with mammalian exosomes. However, isolated A1-EVs contain significantly higher levels of both RNA and protein per particle than mammalian EVs. Additionally, numerous cargo RNAs and proteins are unique to A1-EVs. Of particular note, A1-EVs contain numerous mRNAs encoding nuclear receptors, membrane ligands, as well as transcription factors. Mammalian cardiomyocytes treated with A1-EVs showed increased expression of genes in the PI3K/AKT pathway, a pivotal player in survival signaling. We conclude that newt cells secrete EVs with diverse, distinctive RNA and protein contents. Despite ~300 million years of evolutionary divergence between newts and mammals, newt EVs confer cytoprotective effects on mammalian cardiomyocytes.

The way in which the genome of a multicellular organism can orchestrate the differentiation of trillions of cells and many organs, all from a single fertilized egg, is the subject of intense study. Different cell types can be defined by the networks of genes they express. This differential expression is regulated at the epigenetic level by chromatin modifications, such as DNA and histone methylation, which interact with structural and enzymatic proteins, resulting in the activation or silencing of any given gene. While detailed mechanisms are emerging on the role of different chromatin modifications and how these functions are effected at the molecular level, it is still unclear how their deposition across the epigenomic landscape is regulated in different cells. A raft of recent evidence is accumulating that implicates long noncoding RNAs (lncRNAs) in these processes. Most genomes studied to date undergo widespread transcription, the majority of which is not translated into proteins. In this review, we will describe recent work suggesting that lncRNAs are more than transcriptional "noise", but instead play a functional role by acting as tethers and guides to bind proteins responsible for modifying chromatin and mediating their deposition at specific genomic locations. We suggest that lncRNAs are at the heart of developmental regulation, determining the epigenetic status and transcriptional network in any given cell type, and that they provide a means to integrate external differentiation cues with dynamic nuclear responses through the regulation of a metastable epigenome. Better characterization of the lncRNA-protein "interactome" may eventually lead to a new molecular toolkit, allowing researchers and clinicians to modulate the genome at the epigenetic level to treat conditions such as cancer.

BackgroundInfusion of allogeneic cardiosphere‐derived cells (allo‐CDCs) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. However, the long‐term effects of allo‐CDCs have not been assessed. We performed a placebo‐controlled pivotal study for long‐term evaluation, as well as shorter‐term mechanistic studies. Methods and ResultsMinipigs underwent 1.5‐hour mid‐left anterior descending balloon occlusion followed by reperfusion and were randomized to receive intracoronary allo‐CDCs or vehicle 30 minutes postreperfusion. Left ventriculography (LVG) demonstrated preserved ejection fraction (EF) and attenuation of LV remodeling in CDC‐treated pigs. Pigs underwent cardiac magnetic resonance imaging (MRI) and LVG 1 hour and 8 weeks after therapy to evaluate efficacy. MRI showed improvement of EF and attenuation of LV remodeling immediately after allo‐CDC infusion. In addition, allo‐CDCs improved regional function and decreased hypertrophy 2 months post‐treatment. Histological analysis revealed increased myocardial salvage index, enhanced vascularity, sustained reductions in infarct size/area at risk and scar transmurality, and attenuation of collagen deposition in the infarct zone of allo‐CDC‐treated pigs at 2 months. Allo‐CDCs did not evoke lymphohistiocytic infiltration or systemic humoral memory response. Short‐term experiments designed to probe mechanism revealed antiapoptotic effects of allo‐CDCs on cardiomyocytes and increases in cytoprotective macrophages, but no increase in overall inflammatory cell infiltration 2 hours after cell therapy. ConclusionsAllo‐CDC infusion postreperfusion is safe, improves cardiac function, and attenuates scar size and remodeling. The favorable effects persist for at least 2 months after therapy. Thus, cellular postconditioning confers not only acute cardioprotection, but also lasting structural and functional benefits.

Pediatric traumatic brain injury (TBI) and autism spectrum disorder (ASD) are two serious conditions that affect youth. Recent data, both preclinical and clinical, show that pediatric TBI and ASD share not only similar symptoms but also some of the same biologic mechanisms that cause these symptoms. Prominent symptoms for both disorders include gastrointestinal problems, learning difficulties, seizures, and sensory processing disruption. In this review, we highlight some of these shared mechanisms in order to discuss potential treatment options that might be applied for each condition. We discuss potential therapeutic and pharmacologic options as well as potential novel drug targets. Furthermore, we highlight advances in understanding of brain circuitry that is being propelled by improved imaging modalities. Going forward, advanced imaging will help in diagnosis and treatment planning strategies for pediatric patients. Lessons from each field can be applied to design better and more rigorous trials that can be used to improve guidelines for pediatric patients suffering from TBI or ASD.

The purpose of this paper is to provide the biomedical imaging community with details of a new high resolution contrast imaging approach referred to as “acoustic angiography.” Through the use of dual-frequency ultrasound transducer technology, images acquired with this approach possess both high resolution and a high contrast-to-tissue ratio, which enables the visualization of microvascular architecture without significant contribution from background tissues. Additionally, volumetric vessel-tissue integration can be visualized by using b-mode overlays acquired with the same probe. We present a brief technical overview of how the images are acquired, followed by several examples of images of both healthy and diseased tissue volumes. 3D images from alternate modalities often used in preclinical imaging, contrast-enhanced micro-CT and photoacoustics, are also included to provide a perspective on how acoustic angiography has qualitatively similar capabilities to these other techniques. These preliminary images provide visually compelling evidence to suggest that acoustic angiography may serve as a powerful new tool in preclinical and future clinical imaging.

Prostatic stromal hyperplasia with atypia (PSHA) is a rare histologic finding diagnosed incidentally on prostate biopsies, transurethral resection specimens, and radical prostatectomy specimens. PSHA has a bizarre histologic appearance and these lesions often raise concern for sarcoma; however, their clinical course is indolent and does not include extraprostatic progression. We discuss a case of PHSA discovered on prostate biopsy performed for an abnormal digital rectal examination and review the literature on this rare pathologic finding.