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Determining habitat associations and co-occurrence patterns among species can provide insight into their behavior and shared roles in ecosystem function. This study used a long-term gill-net survey to investigate habitat associations and co-occurrence patterns of three predatory fishes in a large estuarine complex in the northwestern Gulf of Mexico including two top predators alligator gar (Atractosteus spatula) and bull shark (Carcharhinus leucas) and a mesopredator Atlantic stingray (Hypanus sabina). Habitat suitability models were used to assess habitat conditions under which multiple conspecifics or species co-occurred. Environmental drivers of habitat suitability differed within and across species, but salinity and temperature were the most influential variables. Intraspecific co-occurrence of both alligator gars and bull sharks were primarily observed between conspecifics of similar size in low-salinity waters, but intraspecific co-occurrence was higher for alligator gars than for bull sharks. Although sample size was low, intraspecific co-occurrence of Atlantic stingrays was frequent in open-water regions of the estuary and consisted of both juveniles and adults. Interspecific co-occurrence between alligator gars and bull sharks was primarily observed in habitats commonly used by both species, particularly in low-salinity regions of the estuary. Even though there may be confounding effects of sampling gear, interspecific co-occurrence of Atlantic stingrays with either alligator gars or bull sharks was limited, suggesting there was limited overlap in estuarine habitats or environmental conditions used by Atlantic stingrays relative to the two other species investigated. These results clarify the influence of abiotic and biotic variables on the distribution and abundance of these species and suggest potential areas where interactions between them may shape their roles as predators.

Recently, β-alanine (BA) supplementation was shown to improve cognitive function in older adults with decreased cognitive function. Mechanisms supporting these improvements have not been well defined. This study examined the effects of 10-weeks of BA supplementation on changes in circulating brain inflammatory markers, brain derived neurotrophic factor (BDNF), and brain morphology. Twenty participants were initially randomized into BA (2.4 g·d−1) or placebo (PL) groups. At each testing session, participants provided a resting blood sample and completed the Montreal cognitive assessment (MoCA) test and magnetic resonance imaging, which included diffusion tensor imaging to assess brain tissue integrity. Only participants that scored at or below normal for the MoCA assessment were analyzed (6 BA and 4 PL). The Mann-Whitney U test was used to examine Δ (POST–PRE) differences between the groups. No differences in Δ scores were noted in any blood marker (BDNF, CRP, TNF-α and GFAP). Changes in fractional anisotropy scores were significantly greater for BA than PL in the right hippocampus (p = 0.033) and the left amygdala (p = 0.05). No other differences were noted. The results provide a potential mechanism of how BA supplementation may improve cognitive function as reflected by improved tissue integrity within the hippocampus and amygdala.

Abstract Agricultural soils are increasingly undergoing inadvertent and purposeful exposures to engineered CeO2 nanoparticles (NPs), which can impact crops and root-associated microbial communities. However, interactions between NP concentration and exposure duration on plant-mediated responses of root-associated bacterial communities are not well understood. Soybeans seedlings were grown in soil with uncoated NPs added at concentrations of 0, 1 or 100 mg kg−1. Total soil exposure durations were either 190 days, starting 106 days before planting or 84 days with NP amendments coinciding with planting. We assessed plant development, bacterial diversity, differential abundance and inferred functional changes across rhizosphere, rhizoplane, and root tissue compartments. Plant non-monotonic dose responses were mirrored in bacterial communities. Most notably, effects were magnified in the rhizoplane under low-dose, short-exposures. Enriched metabolic pathways were primarily related to biosynthesis and degradation/utilization/assimilation, rather than responses to metals or oxidative stress. Our results indicate that plant-mediated bacterial responses were greater than direct NP impacts. Also, we identify needs for modeling non-monotonic legume stress responses that account for coinfection with mutualistic and parasitic bacteroids. Our findings provide new insights regarding effects of applications of soil amendments such as biosolids containing NPs or nano-enabled formulations used in cultivation of legumes and other crops.

Abstract Yellowfin tuna, Thunnus albacares, represents an important component of commercial and recreational fisheries in the Gulf of Mexico (GoM). We investigated the influence of environmental conditions on the spatiotemporal distribution of yellowfin tuna using fisheries’ catch data spanning 2012–2019 within Mexican waters. We implemented hierarchical Bayesian regression models with spatial and temporal random effects and fixed effects of several environmental covariates to predict habitat suitability (HS) for the species. The best model included spatial and interannual anomalies of the absolute dynamic topography of the ocean surface (ADTSA and ADTIA, respectively), bottom depth, and a seasonal cyclical random effect. High catches occurred mainly towards anticyclonic features at bottom depths > 1000 m. The spatial extent of HS was higher in years with positive ADTIA, which implies more anticyclonic activity. The highest values of HS (> 0.7) generally occurred at positive ADTSA in oceanic waters of the central and northern GoM. However, high HS values (> 0.6) were observed in the southern GoM, in waters with cyclonic activity during summer. Our results highlight the importance of mesoscale features for the spatiotemporal distribution of yellowfin tunas and could help to develop dynamic fisheries management strategies in Mexico and the U.S. for this valuable resource.

Abstract Antigens from viruses or immunizations can persist or are archived in lymph node stromal cells such as lymphatic endothelial cells (LEC) and fibroblastic reticular cells (FRC). Here, we find that, during the time frame of antigen archiving, LEC apoptosis caused by a second, but unrelated, innate immune stimulus such as vaccina viral infection or CpG DNA administration resulted in cross-presentation of archived antigens and boosted memory CD8 + T cells specific to the archived antigen. In contrast to ”bystander” activation associated with unrelated infections, the memory CD8 + T cells specific to the archived antigen from the immunization were significantly higher than memory CD8 + T cells of a different antigen specificity. Finally, the boosted memory CD8 + T cells resulted in increased protection against Listeria monocytogenes expressing the antigen from the immunization, but only for the duration that the antigen was archived. These findings outline an important mechanism by which lymph node stromal cell archived antigens, in addition to bystander activation, can augment memory CD8 + T cell responses during repeated inflammatory insults.

Background and objective: The tissue morphology of the intestinal surface is architecturally complex with finger-like projections called villi, and glandular structures called crypts. The ratio of villus height-to-crypt depth ratio (Vh:Cd) is used to quantitatively assess disease severity and response to therapy for intestinal enteropathies, such as celiac disease and is currently quantified manually. Given the time required, manual Vh:Cd measurements have largely been limited to clinical trials and are not used widely in clinical practice. We developed ViCE (Villus Crypt Evaluator), a user-friendly software that automatically quantifies histological parameters in standard hematoxylin and eosin-stained intestinal biopsies. Methods: ViCE is based on mathematical morphology operations and is scale and staining agnostic. It evaluates tissue orientation, identifies geometrical structure, and outputs key tissue measurements. Results: The output measurements of Vh:Cd are concordant with manual quantifications across multiple datasets. Conclusions: The underlying mathematical morphological approach for ViCE is robust, and reproducible and easily adaptable for measurement of morphological features in other tissues.

Parrotfishes (family Scaridae) are important to coral reef ecosystems and highly prized by both commercial and recreational fishers in the Hawaiian Islands. Although parrotfishes are known to be strictly diurnal, our knowledge of their habitat use and movement patterns across daily timescales in tropical systems is still somewhat limited. Here, acoustic telemetry was used to determine parrotfish habitat use and movements within a coral reef seascape at Puakō, Hawai‘i. An array of acoustic receivers was deployed in a nearshore reef to track fine-scale movements of two common species: ember parrotfish (Scarus rubroviolaceus) and palenose parrotfish (Scarus psittacus). Transmitters were mounted externally on fish and tracked over a four-week period using an acoustic positioning system. Coral habitats (reef flat, fore reef) within the study area were mapped and used in conjunction with triangulated positions to characterize habitat use and movements. Findings indicated that both species commonly inhabited the fore reef habitat during the day (91.6% and 95.0% of total detections, respectively), spending limited time in the reef flat during the day and no time in this habitat at night. Activity spaces (based on 95% and 50% kernel utilization distributions) indicated that home ranges and core use of both species were significantly larger during the day than night, with daytime home ranges (mean ±1 SD) significantly greater for ember parrotfish (8,712 ± 1,991 m2) than palenose parrotfish (3,725 ± 1,254 m2). Hourly mean detections peaked during crepuscular periods for palenose parrotfish and to a lesser extent for ember parrotfish, which was linked to movements between shallower daytime (foraging) and nighttime (resting) areas. Kernel utilization distributions indicated that both species occupied similar core use areas of the seascape (overlap index > 0.5), with both intra- and interspecific overlapping distributions present. Finding from this study highlight the value of the fore reef habitat for both daytime foraging and nocturnal resting activities of ember parrotfish and palenose parrotfish. This study also affords valuable information on primary activity spaces of both species as well as overlap between these two common congeners, which is essential for developing management strategies to conserve parrotfish populations.

Patients with morbid obesity and concomitant hip or knee osteoarthritis represent a challenging patient demographic to treat as these patients often present earlier in life, have more severe symptoms, and have worse surgical outcomes following total hip and total knee arthroplasty. Previously, bariatric and metabolic surgeries represented one of the few weight loss interventions that morbidly obese patients could undergo prior to total joint arthroplasty. However, data regarding the reduction in complications with preoperative bariatric surgery remain mixed. Glucagon-like peptide receptor-1 (GLP-1) agonists have emerged as an effective treatment option for obesity in patients with and without diabetes mellitus. Furthermore, recent data suggest these medications may serve as potential anti-inflammatory and disease-modifying agents for numerous chronic conditions, including osteoarthritis. This review will discuss the GLP-1 agonists and GLP-1/glucose-dependent insulinotropic polypeptide dual agonists currently available, along with GLP-1/glucose-dependent insulinotropic polypeptide/glucagon triple agonists presently being developed to address the obesity epidemic. Furthermore, this review will address the potential problem of GLP-1-related delayed gastric emptying and its impact on the timing of elective total joint arthroplasty. The review aims to provide arthroplasty surgeons with a primer for implementing this class of medication in their current and future practice, including perioperative instructions and perioperative safety considerations when treating patients taking these medications.

Epithelial to mesenchymal transition (EMT) is a cellular process that converts epithelial cells to mesenchymal cells with migratory potential in developmental and pathological processes. Although originally considered a binary event, EMT in cancer progression involves intermediate states between a fully epithelial and a fully mesenchymal phenotype, which are characterized by distinct combinations of epithelial and mesenchymal markers. This phenomenon has been termed epithelial to mesenchymal plasticity (EMP), however, the intermediate states remain poorly described and it’s unclear whether they exist during developmental EMT. Neural crest cells (NCC) are an embryonic progenitor cell population that gives rise to numerous cell types and tissues in vertebrates, and their formation and delamination is a classic example of developmental EMT. However, whether intermediate states also exist during NCC EMT and delamination remains unknown. Through single-cell RNA sequencing of mouse embryos, we identified intermediate NCC states based on their transcriptional signature and then spatially defined their locations in situ in the dorsolateral neuroepithelium. Our results illustrate the importance of cell cycle regulation and functional role for the intermediate stage marker Dlc1 in facilitating mammalian cranial NCC delamination and may provide new insights into mechanisms regulating pathological EMP.

Purpose This study compared the recovery response of physical performance and cognitive function between high volume, low intensity (HV) and high intensity, low volume (HI) resistance training in resistance trained men. Methods Eight recreationally resistance trained men (27.8 ± 1.6 y; 85.5 ± 11.2 kg; 178.4 ± 8.3 cm), with at least one-year of resistance training experience (6.4 ± 3.9 y) participated in this cross-over design study. Participants were randomly assigned to either HV (6-sets of 15–20 repetitions at 60% of the participant’s one-repetition maximum (1RM), 1-min rest between sets) or HI (6-sets of 3–5 repetitions at 90% 1RM, 3-min rest between sets). Following a one-week recovery period, participants reported back to the laboratory and performed the other training session. Cognitive function (SCAT5), physical performance (isometric mid-thigh pull), and reactive agility measures were assessed at baseline, immediately-post (IP) and at 30- (30P) and 60-minutes post-exercise. Results Parametric analysis revealed no differences in peak force (p = 0.423), and the rate of force development at 200 ms (p = 0.827) and 250 ms (p = 0.797) between HI and HV. However, magnitude-based inference (MBI) analysis indicated that peak force was possibly decreased at 30P following HI and that reactive agility was likely negatively impacted at IP following HV. Friedman analysis indicated a significant decline (p = 0.035) in delayed memory during HV at IP and 30P. Conclusions Results of this study indicate that participants engaging in HV resistance training are more susceptible to experiencing performance declines in reaction time and cognitive function than HI training. These findings shed light on differences in physical and cognitive function recovery from HI and HV training programs.

Abstract Neuromodulation through implantable pulse generators (IPGs) represents an important treatment approach for neurological disorders. While the field has observed the success of state-of-the-art interventions, such as deep brain stimulation (DBS) or responsive neurostimulation (RNS), implantable systems face various technical challenges, including the restriction of recording from a limited number of brain sites, power management, and limited external access to the assessed neural data in a continuous fashion. To the best of our knowledge, for the first time in this study, we investigated the feasibility of recording human intracranial EEG (iEEG) using a benchtop version of the Brain Interchange (BIC) unit of CorTec, which is a portable, wireless, and externally powered implant with sensing and stimulation capabilities. We developed a MATLAB/SIMULINK-based rapid prototyping environment and a graphical user interface (GUI) to acquire and visualize the iEEG captured from all 32 channels of the BIC unit. We recorded prolonged iEEG (~ 24 h) from three human subjects with externalized depth leads using the BIC and commercially available clinical amplifiers simultaneously in the epilepsy monitoring unit (EMU). The iEEG signal quality of both streams was compared, and the results demonstrated a comparable power spectral density (PSD) in all the systems in the low-frequency band (

Abstract The centromere components cohesin, CENP-A, and centromeric DNA are essential for biorientation of sister chromatids on the mitotic spindle and accurate sister chromatid segregation. Insight into the 3D organization of centromere components would help resolve how centromeres function on the mitotic spindle. We use ChIP-seq and super-resolution microscopy with single particle averaging to examine the geometry of essential centromeric components on human chromosomes. Both modalities suggest cohesin is enriched at pericentromeric DNA. CENP-A localizes to a subset of the α-satellite DNA, with clusters separated by ~562 nm and a perpendicular intervening ~190 nM wide axis of cohesin in metaphase chromosomes. Differently sized α-satellite arrays achieve a similar core structure. Here we present a working model for a common core configuration of essential centromeric components that includes CENP-A nucleosomes, α-satellite DNA and pericentromeric cohesion. This configuration helps reconcile how centromeres function and serves as a foundation to add components of the chromosome segregation machinery.

Summary: Spiny projection neurons (SPNs) of the striatum are critical in integrating neurochemical information to coordinate motor and reward-based behavior. Mutations in the regulatory transcription factors expressed in SPNs can result in neurodevelopmental disorders (NDDs). Paralogous transcription factors Foxp1 and Foxp2, which are both expressed in the dopamine receptor 1 (D1) expressing SPNs, are known to have variants implicated in NDDs. Utilizing mice with a D1-SPN-specific loss of Foxp1, Foxp2, or both and a combination of behavior, electrophysiology, and cell-type-specific genomic analysis, loss of both genes results in impaired motor and social behavior as well as increased firing of the D1-SPNs. Differential gene expression analysis implicates genes involved in autism risk, electrophysiological properties, and neuronal development and function. Viral-mediated re-expression of Foxp1 into the double knockouts is sufficient to restore electrophysiological and behavioral deficits. These data indicate complementary roles between Foxp1 and Foxp2 in the D1-SPNs.

This study aims to develop an ambient-cured nano-engineered one-part alkali-activated materials with excellent thermal characteristics using graphene nanoplatelets (GNPs) and ternary precursors. Their compressive strength, thermal properties, microstructure, pore structure were characterised through visual observation, isothermal calorimetry, TGA, XRD, SEM/EDS and X-ray μCT after high temperature exposure to 200–800 °C. The research findings indicated high strength characteristics of the developed AAM (∼80 MPa) at ambient condition, which could further reach to approx. 100 MPa after being heated up to 400 °C. GNPs provided nucleation effects for promoting geopolymerisation and crystallisation. As observed from X-ray CT, a high extent of severe cracks initiated from the core and propagated towards the surface. From SEM/EDS analysis, high Na/Al and Na/Si ratios or low Si/Al and Ca/Si ratios highly correlated to thermal stability. Overall, the research outcomes implied the promising use of the nano-engineered AAMs for thermal energy storage (TES) at 400 °C.

BackgroundAdvances in multiple myeloma (MM) treatment have shifted the therapeutic landscape. Understanding patients' perspectives can assist physicians in helping patients make informed decisions. This study aimed to understand the patient decision-making process and gain insights into patient perspectives on B-cell maturation antigen (BCMA)-targeted therapies for MM.MethodsAn 18-question survey was completed by patients with MM enrolled in HealthTree® Cure Hub, an online portal helping patients with plasma cell dyscrasias navigate their disease.ResultsFrom October 28, 2022, to January 12, 2023, 325 patients with MM participated in the survey. The mean age (standard deviation) of the respondents was 66 (8) years; 54% were female and 90% were White. Among 218 patients with complete clinical records in the database, the median (min, max) lines of therapy (LOT) was 2 (1,16). Among 61 (28%) patients who had received ≥4 LOTs, 55 (90%) were triple-class exposed. Of the 290 patients who responded to the question about openness to new therapies, 76 (26%) were open to trying a new therapy immediately and 125 (43%) wanted more information on safety and efficacy. Most respondents reported likely or very likely to try a BCMA CAR T-cell therapy (60%) or a bispecific antibody (74%) and some needed more information to decide (16% for CAR T-cell therapy and 13% for bispecific antibody). The most requested information included efficacy, side effects (SEs), eligibility, and administration process for both CAR T-cell and bispecific therapies. When 2 therapies with the same efficacy and duration of response were offered, 69% of respondents would prefer the therapy with a lower risk of severe SEs but requires continuous dosing with no treatment-free interval, and 31% preferred a therapy given once followed by a treatment-free interval but with a potentially higher risk of severe SEs. To receive an effective therapy, the top acceptable trade-offs included frequent monitoring of SEs and initiating a new therapy in a hospital setting, and the least acceptable compromise was caregiver burden.ConclusionsThis study found a high level of openness in patients with MM to try BCMA-targeted therapies. Information on efficacy, safety, availability, and eligibility may assist patients on decision-making.

Summary: Little is known of the brain mechanisms that mediate sex-specific autism symptoms. Here, we demonstrate that deletion of the autism spectrum disorder (ASD)-risk gene, Pten, in neocortical pyramidal neurons (NSEPten knockout [KO]) results in robust cortical circuit hyperexcitability selectively in female mice observed as prolonged spontaneous persistent activity states. Circuit hyperexcitability in females is mediated by metabotropic glutamate receptor 5 (mGluR5) and estrogen receptor α (ERα) signaling to mitogen-activated protein kinases (Erk1/2) and de novo protein synthesis. Pten KO layer 5 neurons have a female-specific increase in mGluR5 and mGluR5-dependent protein synthesis. Furthermore, mGluR5-ERα complexes are generally elevated in female cortices, and genetic reduction of ERα rescues enhanced circuit excitability, protein synthesis, and neuron size selectively in NSEPten KO females. Female NSEPten KO mice display deficits in sensory processing and social behaviors as well as mGluR5-dependent seizures. These results reveal mechanisms by which sex and a high-confidence ASD-risk gene interact to affect brain function and behavior.

Background: Inpatient total hip arthroplasty (THA) and total knee arthroplasty (TKA) practices were dramatically affected in the United States in 2020 as elective surgeries were paused in response to the COVID-19 pandemic. This study sought to provide an updated estimate of inpatient total joint arthroplasty (TJA) case volumes in the United States in 2020. Methods: A retrospective cohort study was performed by identifying all adult patients who underwent primary, elective TJA from January 1st, 2017 to December 31st, 2020, using the National Inpatient Sample. Monthly and annual case volumes were reported with descriptive statistics. Baseline case volumes were established by taking the average number of monthly cases performed in 2017, 2018, and 2019. These monthly averages were compared to 2020 values. Results: From 2017 to 2019, the average case volume was 1,056,669 cases per year (41.0% THA, 59.0% TKA) and 88,055 cases per month. In 2020, 535,441 cases were identified (45.4% THA, 54.6% TKA), corresponding to a 49.3% reduction from the 2017-2019 annual average. Monthly cases decreased to 4515 in April during the “first wave” of COVID-19, corresponding to a 94.8% decrease from prior years. In June, cases rebounded to 55,520 before decreasing again in July to 50,100 during the “second wave” of COVID-19. During the “third wave,” COVID-19 cases decreased month-over-month from October through December (56.5% decrease). Conclusions: This updated estimate identified a 49.3% decrease in inpatient TJA cases in 2020 compared to prior years. This is similar to the 46.5-47.7% decrease in case volume previously reported.

Abstract Changing environmental temperatures impact the physiological performance of fishes, and consequently their distributions. A mechanistic understanding of the linkages between experienced temperature and the physiological response expressed within complex natural environments is often lacking, hampering efforts to project impacts especially when future conditions exceed previous experience. In this study, we use natural chemical tracers to determine the individual experienced temperatures and expressed field metabolic rates of Atlantic bluefin tuna (Thunnus thynnus) during their first year of life. Our findings reveal that the tuna exhibit a preference for temperatures 2–4 °C lower than those that maximise field metabolic rates, thereby avoiding temperatures warm enough to limit metabolic performance. Based on current IPCC projections, our results indicate that historically-important spawning and nursery grounds for bluefin tuna will become thermally limiting due to warming within the next 50 years. However, limiting global warming to below 2 °C would preserve habitat conditions in the Mediterranean Sea for this species. Our approach, which is based on field observations, provides predictions of animal performance and behaviour that are not constrained by laboratory conditions, and can be extended to any marine teleost species for which otoliths are available.

Abstract Correlated electron materials (CEMs) host a rich variety of condensed matter phases. Vanadium dioxide (VO2) is a prototypical CEM with a temperature-dependent metal-to-insulator (MIT) transition with a concomitant crystal symmetry change. External control of MIT in VO2—especially without inducing structural changes—has been a long-standing challenge. In this work, we design and synthesize modulation-doped VO2-based thin film heterostructures that closely emulate a textbook example of filling control in a correlated electron insulator. Using a combination of charge transport, hard X-ray photoelectron spectroscopy, and structural characterization, we show that the insulating state can be doped to achieve carrier densities greater than 5 × 1021 cm−3 without inducing any measurable structural changes. We find that the MIT temperature (TMIT) continuously decreases with increasing carrier concentration. Remarkably, the insulating state is robust even at doping concentrations as high as ~0.2 e−/vanadium. Finally, our work reveals modulation-doping as a viable method for electronic control of phase transitions in correlated electron oxides with the potential for use in future devices based on electric-field controlled phase transitions.

Abstract Natural geochemical markers in the otolith of yellowfin tuna (Thunnus albacares) were used to establish nursery-specific signatures for investigating the origin of fish captured in the western Atlantic Ocean (WAO). Two classes of chemical markers (trace elements, stable isotopes) were used to first establish nursery-specific signatures of age-0 yellowfin tuna from four primary production zones in the Atlantic Ocean: Gulf of Mexico, Caribbean Sea, Cape Verde, and Gulf of Guinea. Next, mixture and individual assignment methods were applied to predict the origin of sub-adult and adult yellowfin tuna from two regions in the WAO (Gulf of Mexico, Mid Atlantic Bight) by relating otolith core signatures (corresponding to age-0 period) to baseline signatures of age-0 fish from each nursery. Significant numbers of migrants from Caribbean Sea and eastern Atlantic Ocean (EAO) production zones (Gulf of Guinea, Cape Verde) were detected in the WAO, suggesting that fisheries in this region were subsidized by outside spawning/nursery areas. Contributions from local production (Gulf of Mexico) were also evident in samples from both WAO fisheries, but highly variable from year to year. High levels of mixing by yellowfin tuna from the different production zones and pronounced interannual trends in nursery-specific contribution rates in the WAO emphasize the complex and dynamic nature of this species’ stock structure and population connectivity. Given that geographic shifts in distribution across national or political boundaries leads to governance and management challenges, this study highlights the need for temporally resolved estimates of nursery origin to refine assessment models and promote the sustainable harvest of this species.

Abstract While the accessibility of enhancers is dynamically regulated during development, promoters tend to be constitutively accessible and poised for activation by paused Pol II. By studying Lola-I, a Drosophila zinc finger transcription factor, we show here that the promoter state can also be subject to developmental regulation independently of gene activation. Lola-I is ubiquitously expressed at the end of embryogenesis and causes its target promoters to become accessible and acquire paused Pol II throughout the embryo. This promoter transition is required but not sufficient for tissue-specific target gene activation. Lola-I mediates this function by depleting promoter nucleosomes, similar to the action of pioneer factors at enhancers. These results uncover a level of regulation for promoters that is normally found at enhancers and reveal a mechanism for the de novo establishment of paused Pol II at promoters.

Abstract Background Clinical Practice Guidelines for Gulf War Illness (GWI) recommend integrative health approaches such as yoga for relief from symptoms, yet little is known about the long-term efficacy of yoga in reducing symptoms of GWI. Here, we evaluated the long-term efficacy of yoga and cognitive-behavioral therapy (CBT) chronic pain treatment in a randomized controlled trial (RCT) of 75 Veterans (57 men, 42–71 ± 7.1 years of age) with Gulf War Illness (GWI). Methods Participants received either 10 weeks of yoga or 10 weeks of CBT for chronic pain. The primary outcome measures were pain severity, and pain interference (Brief Pain Inventory-Short Form). The secondary outcome measures were fatigue, as indicated by a measure of functional exercise capacity (6-Minute Walk Test), depression, autonomic symptom severity, and quality of life. Piecewise linear mixed models were used to examine study hypotheses. Results Compared to the CBT group, yoga was associated with greater reductions in pain severity during the 6-month follow-up period (group × time interaction: b = 0.036, se = 0.014, p = .011). Although we did not find between-group differences in the other primary or secondary outcome measures during follow-up (p’s > 0.05), exploratory analyses revealed within-group improvements in pain interference, total pain (an experimental outcome variable which combines pain severity and interference), and fatigue in the yoga group (p’s

This previously undescribed species of Micropterus is described from collections in Lake Erie. The species was first recognized by the tri-colored tail of juveniles. This tri-colored tail, the presence of bold parallel lines ventral to the lateral band, and scales in the inter-radial membranes of the dorsal fin distinguish it from Micropterus nigricans. The large mouth that extends past the eye distinguishes it from Micropterus punctulatus.

The Chesapeake Logperch, Percina bimaculata, is a small fish endemic to the upper Chesapeake Bay drainage with a range significantly reduced by water quality and habitat degradation. It was described by Haldeman in 1842 and 1844 from the Susquehanna River, Pennsylvania, synonymized with the Logperch (Percina caprodes) by Jordan in 1877, and redescribed by Near in 2008. It is extirpated from the Potomac River drainage and extant in a portion of its historic range within the Susquehanna River drainage of Pennsylvania and Maryland in the United States of America. We reviewed available historic field survey information and defined the likely extent of the historic distribution of P. bimaculata and its change in response to historic environmental perturbations. We performed fisheries surveys during 2004–2023 to fill data gaps and to define the current distribution and abundance in the Susquehanna River drainage within Pennsylvania. Our surveys utilized electrofishing gears, electrified benthic trawls, and seines. Our surveys targeting P. bimaculata on the Susquehanna River and tributaries from York Haven to Holtwood, Pennsylvania, combined with available fisheries surveys conducted by others, confirm it was extirpated from that portion of the drainage. We documented the continued usage of Conowingo Pond, Susquehanna River, and tributaries below Holtwood by populations known to exist in historic field surveys. These populations appear to have been stable since at least the 1960s based on historic data and our current surveys. We documented previously unknown populations in the Octoraro Creek drainage, Octoraro Reservoir, and Muddy Run Pumped Storage Facility. Habitat utilization observations during our surveys indicate that clean sand, gravel, rubble, boulders, and large woody debris are preferred substrates. In the lower Susquehanna River and two tributaries, P. bimaculata has demonstrated a plasticity of habitat usage by continuing to occur in environments converted into impoundments by dams. In these impoundments, shorelines and connections with clean tributaries containing preferred substrates appear to be important given their utilization by P. bimaculata during our surveys. It is our opinion that the Susquehanna River and tributaries above Holtwood once again constitute suitable habitats. Conservation efforts focused on reintroductions, water quality, habitat, and connectivity have the potential to increase the extent of occurrence, abundance, and security of P. bimaculata.

Abstract Floodplains provide critical ecosystem services; however, loss of natural floodplain functions caused by human alterations increase flood risks and lead to massive loss of life and property. Despite recent calls for improved floodplain protection and management, a comprehensive, global-scale assessment quantifying human floodplain alterations does not exist. We developed the first publicly available global dataset that quantifies human alterations in 15 million km2 floodplains along 520 major river basins during the recent 27 years (1992–2019) at 250-m resolution. To maximize the reuse of our dataset and advance the open science of human floodplain alteration, we developed three web-based programming tools supported with tutorials and step-by-step audiovisual instructions. Our data reveal a significant loss of natural floodplains worldwide with 460,000 km2 of new agricultural and 140,000 km2 of new developed areas between 1992 and 2019. This dataset offers critical new insights into how floodplains are being destroyed, which will help decision-makers to reinforce strategies to conserve and restore floodplain functions and habitat.

Abstract Predation and competition are among the most important factors affecting sandfish, Holothuria scabra, growth and survival in ocean‐based production systems. In this study, the potential predators and competitors of sandfish juveniles reared at two sites in the Philippines using the floating hapa ocean nursery system were assessed. A total of 26 species of potential predators and competitors from 16 different families of fishes, molluscs and crustaceans were recorded. These taxa were dominated by the opisthobranch Stylocheilus striatus at Bolinao (north–west Luzon) and the isopod Cymodoce sp. at Maliwaliw (eastern Visayas). Highest number of potential predators and competitors that recruited and/or migrated to the inside of floating hapa nets was recorded on day 23 at Bolinao and day 30 at Maliwaliw, then decreased over the 69‐day duration of the study. Mean length, absolute growth rates (AGRs) and survival of sandfish juveniles reared in floating hapas at the two sites varied during the study. AGRs were highest at 1.17 ± 0.06 mm day−1 at Bolinao, and 1 ± 0.08 mm day−1 at Maliwaliw, by days 23 and 60, respectively. Mean lengths of sandfish juveniles reared at Bolinao and Maliwaliw by the end of the study were 46.7 ± 0.15 and 58.8 ± 2.4 mm, respectively, and survival at both sites was high at 96% by the end of the study. Negative correlations were observed between the number of individual predators and competitors, and survival and growth rates of sandfish juveniles reared at Bolinao and Maliwaliw, respectively. Our results highlight the importance of predator and competitor management measures and appropriate site selection to optimize growth performance and survival of sandfish juveniles reared in ocean‐based culture production systems.

Background & aims: Humans with WNT2B deficiency have severe intestinal disease, including significant inflammatory injury, highlighting a critical role for WNT2B. We sought to understand how WNT2B contributes to intestinal homeostasis. Methods: We investigated the intestinal health of Wnt2b knock out (KO) mice. We assessed the baseline histology and health of the small intestine and colon, and the impact of inflammatory challenge using dextran sodium sulfate (DSS). We also evaluated human intestinal tissue. Results: Mice with WNT2B deficiency had normal baseline histology but enhanced susceptibility to DSS colitis because of an increased early injury response. Although intestinal stem cells markers were decreased, epithelial proliferation was similar to control subjects. Wnt2b KO mice showed an enhanced inflammatory signature after DSS treatment. Wnt2b KO colon and human WNT2B-deficient organoids had increased levels of CXCR4 and IL6, and biopsy tissue from humans showed increased neutrophils. Conclusions: WNT2B is important for regulation of inflammation in the intestine. Absence of WNT2B leads to increased expression of inflammatory cytokines and increased susceptibility to gastrointestinal inflammation, particularly in the colon.

Atlantic tarpon (Megalops atlanticus) are capable of long-distance migrations (hundreds of kilometers) but also exhibit resident behaviors in estuarine and coastal habitats. The aim of this study was to characterize the spatial distribution of juvenile tarpon and identify migration pathways of adult tarpon in the northern Gulf of Mexico. Spatial distribution of juvenile tarpon was investigated using gillnet data collected by Texas Parks and Wildlife Department (TPWD) over the past four decades. Generalized additive models (GAMs) indicated that salinity and water temperature played a significant role in tarpon presence, with tarpon occurrences peaking in the fall and increasing over the past four decades in this region. Adult tarpon caught off Texas (n = 40) and Louisiana (n = 4) were tagged with acoustic transmitters to characterize spatial and temporal trends in their movements and migrations. Of the 44 acoustic transmitters deployed, 18 of the individuals were detected (n = 16 west of the Mississippi River Delta and n = 2 east of the Mississippi River Delta). Tarpon tagged west of the Mississippi River Delta off Texas migrated south in the fall and winter into areas of south Texas and potentially into Mexico, while individuals tagged east of the delta migrated into Florida during the same time period, suggesting the presence of two unique migratory contingents or subpopulations in this region. An improved understanding of the habitat requirements and migratory patterns of tarpon inhabiting the Gulf of Mexico is critically needed by resource managers to assess the vulnerability of each contingent to fishing pressure, and this information will guide multi-state and multi-national conservation efforts to rebuild and sustain tarpon populations.

Recent research has shown forest-related emissions reported in national greenhouse gas inventories are much lower than global estimates from models summarized in Intergovernmental Panel on Climate Change reports. A substantial part of this discrepancy could be explained by conceptual differences in what is counted as part of the anthropogenic forest carbon sink and the way countries report on their forest harvesting sectors. With Canada as a case study, we used published National Inventory Report and Common Reporting Format tables to isolate emissions and removals directly associated with forestry from those associated with forests more broadly. Forestry-related factors that affect CO2 emissions and removals include tree harvesting, post-harvest forest regeneration and growth, and carbon storage in long-lived harvested wood products. We found that between 2005 and 2021, forestry in Canada represented a net source of carbon (annual mean = 90.8 Mt. CO2e), and that total area logged was a significant predictor of net forestry emissions. In contrast, Canada’s NIR reported a small net carbon sink during the same time period (annual mean = −4.7 Mt. CO2e). We show this discrepancy can be explained by Canada’s GHG reporting approach that claims GHG emissions from wildfires are natural, but GHG removals from forests at the age of commercial maturity, despite being primarily natural disturbance origin, are anthropogenic. This reporting approach may lead to climate mitigation policies that are ineffectual or detrimental to reducing net carbon in the global atmosphere.

Summary: This contribution treats linear, steady-state dynamics for a metabolic network within a growing cell. Admissible steady-state reaction fluxes are assumed to form a pointed, convex, polyhedral, conical subset of the stoichiometric null-space. A solution of the problem is defined to consist of a linear basis for the stoichiometric null-space consisting of admissible fluxes called basic pathways. The algorithm used to construct the set of basic pathways scales as a polynomial of the system size in contrast to the NP-hard algorithms employed in the traditional notions of solution named extreme pathways, elementary flux modes, MEMos, and MinSpan, and that therefore suffer from the curse of dimensionality. The basic pathways approach is applied to a metabolic network consisting of a simplified version of the TCA cycle coupled to glycolysis highlighting that each basic pathway has a readily understood chemical interpretation. Generic admissible pathways are simply expressed in terms of basic pathways.

Iron is an essential transition metal for all eukaryotic cells, and its trafficking throughout the cell is highly regulated. However, the overall cellular mechanism of regulation is poorly understood despite knowing many of the molecular players involved. Here, an ordinary-differential-equations (ODE) based kinetic model of iron trafficking within a growing yeast cell was developed that included autoregulation. The 9-reaction 8-component in-silico cell model was solved under both steady-state and time-dependent dynamical conditions. The ODE for each component included a dilution term due to cell growth. Conserved rate relationships were obtained from the null space of the stoichiometric matrix, and the reduced-row-echelon-form was used to distinguish independent from dependent rates. Independent rates were determined from experimentally estimated component concentrations, cell growth rates, and the literature. Simple rate-law expressions were assumed, allowing rate-constants for each reaction to be estimated. Continuous Heaviside logistical functions were used to regulate rate-constants. These functions acted like valves, opening or closing depending on component "sensor" concentrations. Two cellular regulatory mechanisms were selected from 134,217,728 possibilities using a novel approach involving 6 mathematically-defined filters. Three cellular states were analyzed including healthy wild-type cells, iron-deficient wild-type cells, and a frataxin-deficient strain of cells characterizing the disease Friedreich's Ataxia. The model was stable toward limited perturbations, as determined by the eigenvalues of Jacobian matrices. Autoregulation allowed healthy cells to transition to the diseased state when triggered by a mutation in frataxin, and to the iron-deficient state when cells are placed in iron-deficient growth medium. The in-silico phenotypes observed during these transitions were similar to those observed experimentally. The model also predicted the observed effects of hypoxia on the diseased condition. A similar approach could be used to solve ODE-based kinetic models associated with other biochemical processes operating within growing cells.

Ribosome biogenesis is a vital and highly energy-consuming cellular function occurring primarily in the nucleolus. Cancer cells have an elevated demand for ribosomes to sustain continuous proliferation. This study evaluated the impact of existing anticancer drugs on the nucleolus by screening a library of anticancer compounds for drugs that induce nucleolar stress. For a readout, a novel parameter termed ‘nucleolar normality score’ was developed that measures the ratio of the fibrillar center and granular component proteins in the nucleolus and nucleoplasm. Multiple classes of drugs were found to induce nucleolar stress, including DNA intercalators, inhibitors of mTOR/PI3K, heat shock proteins, proteasome, and cyclin-dependent kinases (CDKs). Each class of drugs induced morphologically and molecularly distinct states of nucleolar stress accompanied by changes in nucleolar biophysical properties. In-depth characterization focused on the nucleolar stress induced by inhibition of transcriptional CDKs, particularly CDK9, the main CDK that regulates RNA Pol II. Multiple CDK substrates were identified in the nucleolus, including RNA Pol I– recruiting protein Treacle, which was phosphorylated by CDK9 in vitro. These results revealed a concerted regulation of RNA Pol I and Pol II by transcriptional CDKs. Our findings exposed many classes of chemotherapy compounds that are capable of inducing nucleolar stress, and we recommend considering this in anticancer drug development.

Summary: Prions cause fatal neurodegenerative diseases and exhibit remarkable durability, which engenders a wide array of potential exposure scenarios. In chronic wasting disease of deer, elk, moose, and reindeer and in scrapie of sheep and goats, prions are transmitted via environmental routes and the ability of plants to accumulate and subsequently transmit prions has been hypothesized, but not previously demonstrated. Here, we establish the ability of several crop and other plant species to take up prions via their roots and translocate them to above-ground tissues from various growth media including soils. We demonstrate that plants can accumulate prions in above-ground tissues to levels sufficient to transmit disease after oral ingestion by mice. Our results suggest plants may serve as vectors for prion transmission in the environment—a finding with implications for wildlife conservation, agriculture, and public health.

Rationale and objective: To compare burnout and stressors of breast radiologists prior to and during the COVID-19 pandemic. Materials and methods: Members of the Society of Breast Imaging were emailed an IRB-approved survey in January 2021 during the COVID–19 pandemic. Survey included questions from the Maslach Burnout Inventory and specific stressors including work pace, work-life balance, care of dependents, and financial strain. Data were compared to previous surveys prior to the pandemic. Results: The response rate was 25% (261/1061) for those who opened the email. Of the respondents, 74% (194/261) were female, 82% (214/261) were white, 73% (191/261) were full time, 71% (185/261) were fellowship trained, 41% (106/261) had more than 20 years of experience, and 30% (79/261) were in academic practice.Respondents in 2021 reported frequent levels of depersonalization (2.2) and emotional exhaustion (3.4) while reporting frequent levels of personal accomplishment (5.3), a protective factor. These values were nearly identical before the pandemic in 2020: (2.2, 3.5, 5.3, respectively, p = .9). Respondents rated practicing faster than they would like as the highest stressor; however, 5 of the 6 stressors improved after the pandemic onset (p

Abstract Beetroot is a homodimeric in vitro selected RNA that binds and activates DFAME, a conditional fluorophore derived from GFP. It is 70% sequence-identical to the previously characterized homodimeric aptamer Corn, which binds one molecule of its cognate fluorophore DFHO at its interprotomer interface. We have now determined the Beetroot-DFAME co-crystal structure at 1.95 Å resolution, discovering that this RNA homodimer binds two molecules of the fluorophore, at sites separated by ~30 Å. In addition to this overall architectural difference, the local structures of the non-canonical, complex quadruplex cores of Beetroot and Corn are distinctly different, underscoring how subtle RNA sequence differences can give rise to unexpected structural divergence. Through structure-guided engineering, we generated a variant that has a 12-fold fluorescence activation selectivity switch toward DFHO. Beetroot and this variant form heterodimers and constitute the starting point for engineered tags whose through-space inter-fluorophore interaction could be used to monitor RNA dimerization.

Abstract Background Pain management is a critical component of comprehensive postsurgical care, as it influences patient safety and outcomes, and inadequate control has been associated with the development of chronic pain syndromes. Despite recent improvements, the management of postoperative pain following total knee arthroplasty (TKA) remains a challenge. The use of opioid-sparing, multimodal analgesic regimens has broad support, but there is a paucity of high-quality evidence regarding optimal postoperative protocols and novel approaches are needed. Dextromethorphan stands out among both well-studied and emerging pharmacological adjuncts for postoperative pain due its robust safety profile and unique pharmacology. The purpose of this study is to evaluate the efficacy of multi-dose dextromethorphan for postoperative pain control following TKA. Methods This is a single-center, multi-dose, randomized, double-blinded, placebo-controlled trial. A total of 160 participants will be randomized 1:1 to receive either 60 mg oral dextromethorphan hydrobromide preoperatively, as well as 30 mg 8 h and 16 h postoperatively, or matching placebo. Outcome data will be obtained at baseline, during the first 48 h, and the first two follow-up visits. The primary outcome measure will be total opioid consumption at 24 h postoperatively. Secondary outcomes related to pain, function, and quality of life will be evaluated using standard pain scales, the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR) questionnaire, the Patient-Reported Outcomes Measurement Information System (PROMIS-29) questionnaire, and clinical anchors. Discussion This study has a number of strengths including adequate power, a randomized controlled design, and an evidence-based dosing schedule. As such, it will provide the most robust evidence to date on dextromethorphan utilization for postoperative pain control following TKA. Limitations include not obtaining serum samples for pharmacokinetic analysis and the single-center study design. Trial registration This trial has been registered on the National Institute of Health’s ClinicalTrials.gov (NCT number: NCT05278494). Registered on March 14, 2022.

Abstract Background Non-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects of 4 Gy total body irradiation (TBI) at the molecular level out to 28 days and at the cytogenetic level out to 56 days after exposure. We combine the global transcriptomic and proteomic responses in peripheral whole blood to assess the impact of acute TBI exposure at extended times post irradiation. Results The overall mRNA response in the first week reflects a strong inflammatory reaction, infection response with neutrophil and platelet activation. At 1 week, cell cycle arrest and re-entry processes were enriched among mRNA changes, oncogene-induced senescence and MAPK signaling among the proteome changes. Influenza life cycle and infection pathways initiated earlier in mRNA and are reflected among the proteomic changes during the first week. Transcription factor proteins SRC, TGFβ and NFATC2 were immediately induced at 1 day after irradiation with increased transcriptional activity as predicted by mRNA changes persisting up to 1 week. Cell counts revealed a mild / moderate hematopoietic acute radiation syndrome (H-ARS) reaction to irradiation with expected lymphopenia, neutropenia and thrombocytopenia that resolved within 30 days. Measurements of micronuclei per binucleated cell levels in cytokinesis-blocked T-lymphocytes remained high in the range 0.27–0.33 up to 28 days and declined to 0.1 by day 56. Conclusions Overall, we show that the TBI 4 Gy dose in NHPs induces many cellular changes that persist up to 1 month after exposure, consistent with damage, death, and repopulation of blood cells.

Coordinating management of groundwater, surface water, and irrigated crops is fundamental economically for many arid and semi-arid regions. This paper examines conjunctive water management for agriculture using hydro-economic optimization modeling. The analysis is integrated across two timescales: a two-stage stochastic decadal model for managing annual and perennial crops spanning dry and wet years and a far-horizon dynamic program embedding the decadal model into a longer groundwater policy setting. The modeling loosely represents California’s San Joaquin Valley and has insights for many irrigated arid and semi-arid regions relying on groundwater with variable annual hydrology. Results show how conjunctive water management can stabilize crop decisions and improve agricultural profitability across different water years by pumping more in dry years and increasing recharging groundwater in wetter years. Using groundwater as a buffer for droughts allows growing more higher-value perennial crops, which maximizes profit even with water-scarce conditions. Nevertheless, ending overdraft in basins with declining groundwater for profit-maximizing farming reduces annual crops to maintain more profitable perennial crops through droughts. Results are affected by economic discount rates and future climates. Operating and opportunity costs from forgone annual crops can reduce aquifer recharge early in regulatory periods.

A long-standing goal of amyloid research has been to characterize the structural basis of the rate-determining nucleating event. However, the ephemeral nature of nucleation has made this goal unachievable with existing biochemistry, structural biology, and computational approaches. Here, we addressed that limitation for polyglutamine (polyQ), a polypeptide sequence that causes Huntington’s and other amyloid-associated neurodegenerative diseases when its length exceeds a characteristic threshold. To identify essential features of the polyQ amyloid nucleus, we used a direct intracellular reporter of self-association to quantify frequencies of amyloid appearance as a function of concentration, conformational templates, and rational polyQ sequence permutations. We found that nucleation of pathologically expanded polyQ involves segments of three glutamine (Q) residues at every other position. We demonstrate using molecular simulations that this pattern encodes a four-stranded steric zipper with interdigitated Q side chains. Once formed, the zipper poisoned its own growth by engaging naive polypeptides on orthogonal faces, in a fashion characteristic of polymer crystals with intramolecular nuclei. We further show that self-poisoning can be exploited to block amyloid formation, by genetically oligomerizing polyQ prior to nucleation. By uncovering the physical nature of the rate-limiting event for polyQ aggregation in cells, our findings elucidate the molecular etiology of polyQ diseases.

Microvillus inclusion disease (MVID), caused by loss-of-function mutations in the motor protein myosin Vb (MYO5B), is a severe infantile disease characterized by diarrhea, malabsorption, and acid/base instability, requiring intensive parenteral support for nutritional and fluid management. Human patient–derived enteroids represent a model for investigation of monogenic epithelial disorders but are a rare resource from MVID patients. We developed human enteroids with different loss-of function MYO5B variants and showed that they recapitulated the structural changes found in native MVID enterocytes. Multiplex immunofluorescence imaging of patient duodenal tissues revealed patient-specific changes in localization of brush border transporters. Functional analysis of electrolyte transport revealed profound loss of Na+/H+ exchange (NHE) activity in MVID patient enteroids with near-normal chloride secretion. The chloride channel–blocking antidiarrheal drug crofelemer dose-dependently inhibited agonist-mediated fluid secretion. MVID enteroids exhibited altered differentiation and maturation versus healthy enteroids. γ-Secretase inhibition with DAPT recovered apical brush border structure and functional Na+/H+ exchange activity in MVID enteroids. Transcriptomic analysis revealed potential pathways involved in the rescue of MVID cells including serum/glucocorticoid-regulated kinase 2 (SGK2) and NHE regulatory factor 3 (NHERF3). These results demonstrate the utility of patient-derived enteroids for developing therapeutic approaches to MVID.

Abstract In the United States, citizens and policymakers heavily rely upon Environmental Protection Agency mandated regulatory networks to monitor air pollution; increasingly they also depend on low‐cost sensor networks to supplement spatial gaps in regulatory monitor networks coverage. Although these regulatory and low‐cost networks in tandem provide enhanced spatiotemporal coverage in urban areas, low‐cost sensors are located often in higher income, predominantly White areas. Such disparity in coverage may exacerbate existing inequalities and impact the ability of different communities to respond to the threat of air pollution. Here we present a study using cost‐constrained multiresolution dynamic mode decomposition (mrDMDcc) to identify the optimal and equitable placement of fine particulate matter (PM2.5) sensors in four U.S. cities with histories of racial or income segregation: St. Louis, Houston, Boston, and Buffalo. This novel approach incorporates the variation of PM2.5 on timescales ranging from 1 day to over a decade to capture air pollution variability. We also introduce a cost function into the sensor placement optimization that represents the balance between our objectives of capturing PM2.5 extremes and increasing pollution monitoring in low‐income and nonwhite areas. We find that the mrDMDcc algorithm places a greater number of sensors in historically low‐income and nonwhite neighborhoods with known environmental pollution problems compared to networks using PM2.5 information alone. Our work provides a roadmap for the creation of equitable sensor networks in U.S. cities and offers a guide for democratizing air pollution data through increasing spatial coverage of low‐cost sensors in less privileged communities.

This article introduces a current-mode multiphase digital transmitter with a single-footprint transformer-based asymmetric Doherty output network. The proposed multiphase architecture overcomes the bandwidth expansion associated with the polar power amplifier (PA), while still achieving relatively constant output power and drain efficiency (DE) profiles. Additionally, to achieve efficiency enhancement in deep power back-off (PBO), and to simultaneously achieve a compact form factor, an asymmetric series Doherty output matching network using a transformer-within-transformer structure is also proposed. A proof-of-concept eight-phase digital transmitter using the proposed single-footprint Doherty network is implemented in a general-purpose 65-nm CMOS process. The transmitter achieves more than 20-dBm output power $(P_{\mathrm{ out}})$ and more than 31% DE from 4.5 to 6.7 GHz. At 8-dB PBO, it achieves a DE of 23% and 24% at 6.5 and 7.0 GHz, which corresponds to a $1.76\times $ and $1.93\times $ improvement compared to normalized class B PA, respectively. The transmitter also achieves a 21% DE and an average $P_{\mathrm{ out}}$ of 14 dBm with an r.m.s. error vector magnitude $({\mathrm{ EVM}}_{\mathrm{ rms}})$ of 4.1% for a 20-MSym/s 64-quadrature amplitude modulation waveform at 6.5 GHz.

Abstract Background The early detection and management of uncontrolled cardiovascular risk factors among prediabetes patients can prevent cardiovascular disease (CVD). Prediabetes increases the risk of CVD, which is a leading cause of death in the United States. CVD clinical decision support (CDS) in primary care settings has the potential to reduce cardiovascular risk in patients with prediabetes while potentially saving clinicians time. The objective of this study is to understand primary care clinician (PCC) perceptions of a CDS system designed to reduce CVD risk in adults with prediabetes. Methods We administered pre-CDS implementation (6/30/2016 to 8/25/2016) (n = 183, 61% response rate) and post-CDS implementation (6/12/2019 to 8/7/2019) (n = 131, 44.5% response rate) independent cross-sectional electronic surveys to PCCs at 36 randomized primary care clinics participating in a federally funded study of a CVD risk reduction CDS tool. Surveys assessed PCC demographics, experiences in delivering prediabetes care, perceptions of CDS impact on shared decision making, perception of CDS impact on control of major CVD risk factors, and overall perceptions of the CDS tool when managing cardiovascular risk. Results We found few significant differences when comparing pre- and post-implementation responses across CDS intervention and usual care (UC) clinics. A majority of PCCs felt well-prepared to discuss CVD risk factor control with patients both pre- and post-implementation. About 73% of PCCs at CDS intervention clinics agreed that the CDS helped improve risk control, 68% reported the CDS added value to patient clinic visits, and 72% reported they would recommend use of this CDS system to colleagues. However, most PCCs disagreed that the CDS saves time talking about preventing diabetes or CVD, and most PCCs also did not find the clinical domains useful, nor did PCCs believe that the clinical domains were useful in getting patients to take action. Finally, only about 38% reported they were satisfied with the CDS. Conclusions These results improve our understanding of CDS user experience and can be used to guide iterative improvement of the CDS. While most PCCs agreed the CDS improves CVD and diabetes risk factor control, they were generally not satisfied with the CDS. Moreover, only 40–50% agreed that specific suggestions on clinical domains helped patients to take action. In spite of this, an overwhelming majority reported they would recommend the CDS to colleagues, pointing for the need to improve upon the current CDS. Trial registration: NCT02759055 03/05/2016.

Abstract The Bowfin (Amia calva), as currently recognized, represents the sole living member of the family Amiidae, which dates back to approximately 150 Ma. Prior to 1896, 13 species of extant Bowfins had been described, but these were all placed into a single species with no rationale or analysis given. This situation has persisted until the present day, with little attention given to re-evaluation of those previously described nominal forms. Here, we present a phylogenomic analysis based on over 21,000 single nucleotide polymorphisms (SNPs) from 94 individuals that unambiguously demonstrates the presence of at least two independent evolutionary lineages within extant Amia populations that merit species-level standing, as well as the possibility of two more. These findings not only expand the recognizable species diversity in an iconic, ancient lineage, but also demonstrate the utility of such methods in addressing previously intractable questions of molecular systematics and phylogeography in slowly evolving groups of ancient fishes.

Abstract Microscopic organisms are often overlooked in traditional diversity assessments due to the difficulty of identifying them based on morphology. Metabarcoding is a method for rapidly identifying organisms where Environmental DNA (eDNA) is used as a template. However, legacy DNA is problematically detected from organisms no longer in the environment during sampling. Environmental RNA (eRNA), which is only produced by living organisms, can also be collected from environmental samples and used for metabarcoding. The aim of this study was to determine differences in community composition and diversity between eRNA and eDNA templates for metabarcoding. Using mesocosms containing field-collected communities from an estuary, RNA and DNA were co-extracted from sediment, libraries were prepared for two loci (18S and COI), and sequenced using an Illumina MiSeq. Results show a higher number of unique sequences detected from eRNA in both markers and higher α-diversity compared to eDNA. Significant differences between eRNA and eDNA for all β-diversity metrics were also detected. This study is the first to demonstrate community differences detected with eRNA compared to eDNA from an estuarine system and illustrates the broad applications of eRNA as a tool for assessing benthic community diversity, particularly for environmental conservation and management applications.