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Abstract Emotion recognition shows large inter-individual variability, and is substantially affected by childhood trauma as well as modality, emotion portrayed, and intensity. While research suggests childhood trauma influences emotion recognition, it is unclear whether this effect is consistent when controlling for interrelated individual differences. Further, the universality of the effects has not been explored, most studies have not examined differing modalities or intensities. This study examined childhood trauma’s association with accuracy, when controlling for alexithymia and psychopathy traits, and if this varied across modality, emotion portrayed, and intensity. An adult sample (N = 122) completed childhood trauma, alexithymia, and psychopathy questionnaires and three emotion tasks: faces, voices, audio-visual. When investigating childhood trauma alone, there was a significant association with poorer accuracy when exploring modality, emotion portrayed, and intensity. When controlling for alexithymia and psychopathy, childhood trauma remained significant when exploring emotion portrayed, however, it was no longer significant when exploring modality and intensity. In fact, alexithymia was significant when exploring intensity. The effect sizes overall were small. Our findings suggest the importance of controlling for interrelated individual differences. Future research should explore more sensitive measures of emotion recognition, such as intensity ratings and sensitivity to intensity, to see if these follow accuracy findings.

In 2021, the World Health Organization classified isocitrate dehydrogenase (IDH) mutant gliomas as a distinct subgroup of tumors with genetic changes sufficient to enable a complete diagnosis. Patients with an IDH mutant glioma have improved survival which has been further enhanced by the advent of targeted therapies. IDH enzymes contribute to cellular metabolism, and mutations to specific catalytic residues result in the neomorphic production of D-2-hydroxyglutarate (D-2-HG). The accumulation of D-2-HG results in epigenetic alterations, oncogenesis and impacts the tumor microenvironment via immunological modulations. Here, we summarize the molecular, cellular, and clinical implications of IDH mutations in gliomas as well as current diagnostic techniques.

Previous research demonstrated the distribution of distinct microbial communities in the equine hindgut surrounding the pelvic flexure. The current study evaluated gene expression in epithelial tissues surrounding the pelvic flexure to characterize patterns that might correlate with microbial distribution. Gene expression was determined by analyzing RNA sequence data from the pelvic flexure, the left and right ventral colon, and the left and right dorsal colon. An average of 18,330 genes were expressed across the five tissues sampled. Most of the genes showed some level of expression in all five tissues. Tissue-restricted patterns of expression were also observed. Genes with restricted expression in the left ventral and left dorsal colons have communication, signaling, and regulatory functions that correlate with their known physiology. In contrast, genes expressed exclusively in the pelvic flexure have diverse functions. The ontology of genes differentially expressed between the pelvic flexure and the surrounding tissues was associated with immune functions and signaling processes. Despite being non-significant, these enrichment trends were reinforced by the functions of statistically significant expression differences between tissues of the hindgut. These results provide insight into the physiology of the equine hindgut epithelium that might influence the microbiota and its distribution.

Chronic myeloid leukemia (CML) is associated with several breakpoint regions that result in different BCR::ABL1 fusion transcripts. These include the major breakpoint region (M-BCR), minor breakpoint region (m-BCR), and mu breakpoint region (u-BCR) corresponding to p210, p190, and p230 fusion transcripts, respectively. This patient is a 38-year-old female with a new diagnosis of CML in chronic phase. A novel p210 fusion transcript splice variant was detected with qualitative reverse transcription PCR and capillary electrophoresis. Subsequent FISH study was performed, which revealed 86.5% positive for the BCR::ABL1 fusion. Quantitative real-time polymerase chain reaction (PCR) showed a negative result for the p210 fusion transcript. The variant was further characterized by Sanger sequencing. This variant is in-frame and predicted to be functional. This case illustrates the need for a combination of different testing techniques to fully characterize the rare BCR::ABL1 fusion transcripts.

Recently we found compelling evidence for a gravitational-wave background with Hellings and Downs (HD) correlations in our 15 yr data set. These correlations describe gravitational waves as predicted by general relativity, which has two transverse polarization modes. However, more general metric theories of gravity can have additional polarization modes, which produce different interpulsar correlations. In this work, we search the NANOGrav 15 yr data set for evidence of a gravitational-wave background with quadrupolar HD and scalar-transverse (ST) correlations. We find that HD correlations are the best fit to the data and no significant evidence in favor of ST correlations. While Bayes factors show strong evidence for a correlated signal, the data does not strongly prefer either correlation signature, with Bayes factors ∼2 when comparing HD to ST correlations, and ∼1 for HD plus ST correlations to HD correlations alone. However, when modeled alongside HD correlations, the amplitude and spectral index posteriors for ST correlations are uninformative, with the HD process accounting for the vast majority of the total signal. Using the optimal statistic, a frequentist technique that focuses on the pulsar-pair cross-correlations, we find median signal-to-noise ratios of 5.0 for HD and 4.6 for ST correlations when fit for separately, and median signal-to-noise ratios of 3.5 for HD and 3.0 for ST correlations when fit for simultaneously. While the signal-to-noise ratios for each of the correlations are comparable, the estimated amplitude and spectral index for HD are a significantly better fit to the total signal, in agreement with our Bayesian analysis.

Pulsar timing array experiments have recently uncovered evidence for a nanohertz gravitational wave background by precisely timing an ensemble of millisecond pulsars. The next significant milestones for these experiments include characterizing the detected background with greater precision, identifying its source(s), and detecting continuous gravitational waves from individual supermassive black hole binaries. To achieve these objectives, generating accurate and precise times of arrival of pulses from pulsar observations is crucial. Incorrect polarization calibration of the observed pulsar profiles may introduce errors in the measured times of arrival. Further, previous studies have demonstrated that robust polarization calibration of pulsar profiles can reduce noise in the pulsar timing data and improve timing solutions. In this paper, we investigate and compare the impact of different polarization calibration methods on pulsar timing precision using three distinct calibration techniques: the Ideal Feed Assumption (IFA), Measurement Equation Modeling (MEM), and Measurement Equation Template Matching (METM). Three NANOGrav pulsars—PSRs J1643−1224, J1744−1134, and J1909−3744—observed with the 800 MHz and 1.5 GHz receivers at the Green Bank Telescope (GBT) are utilized for our analysis. Our findings reveal that all three calibration methods enhance timing precision compared to scenarios where no polarization calibration is performed. Additionally, among the three calibration methods, the IFA approach generally provides the best results for timing analysis of pulsars observed with the GBT receiver system. We attribute the comparatively poorer performance of the MEM and METM methods to potential instabilities in the reference noise diode coupled to the receiver and temporal variations in the profile of the reference pulsar, respectively.

Pulsar timing arrays (PTAs) are designed to detect low-frequency gravitational waves (GWs). GWs induce achromatic signals in PTA data, meaning that the timing delays do not depend on radio frequency. However, pulse arrival times are also affected by radio-frequency-dependent “chromatic” noise from sources such as dispersion measure (DM) and scattering delay variations. Furthermore, the characterization of GW signals may be influenced by the choice of chromatic noise model for each pulsar. To better understand this effect, we assess if and how different chromatic noise models affect the achromatic noise properties in each pulsar. The models we compare include existing DM models used by the North American Nanohertz Observatory for Gravitational waves (NANOGrav) and noise models used for the European PTA Data Release 2 (EPTA DR2). We perform this comparison using a subsample of six pulsars from the NANOGrav 15 yr data set, selecting the same six pulsars as from the EPTA DR2 six-pulsar data set. We find that the choice of chromatic noise model noticeably affects the achromatic noise properties of several pulsars. This is most dramatic for PSR J1713+0747, where the amplitude of its achromatic red noise lowers from ${\mathrm{log}}_{10}{A}_{\mathrm{RN}}=-{14.1}_{-0.1}^{+0.1}$ to $-{14.7}_{-0.5}^{+0.3}$ , and the spectral index broadens from ${\gamma }_{\mathrm{RN}}={2.6}_{-0.4}^{+0.5}$ to ${\gamma }_{\mathrm{RN}}={3.5}_{-0.9}^{+1.2}$ . We also compare each pulsar's noise properties with those inferred from the EPTA DR2, using the same models. From the discrepancies, we identify potential areas where the noise models could be improved. These results highlight the potential for custom chromatic noise models to improve PTA sensitivity to GWs.

PINT is a pure-Python framework for high-precision pulsar timing developed on top of widely used and well-tested Python libraries, supporting both interactive and programmatic data analysis workflows. We present a new frequentist framework within PINT to characterize the single-pulsar noise processes present in pulsar timing data sets. This framework enables parameter estimation for both uncorrelated and correlated noise processes, as well as model comparison between different timing and noise models in a computationally inexpensive way. We demonstrate the efficacy of the new framework by applying it to simulated data sets as well as a real data set of PSR B1855+09. We also describe the new features implemented in PINT since it was first described in the literature.

The Australian, Chinese, European, Indian, and North American pulsar timing array (PTA) collaborations recently reported, at varying levels, evidence for the presence of a nanohertz gravitational-wave background (GWB). Given that each PTA made different choices in modeling their data, we perform a comparison of the GWB and individual pulsar noise parameters across the results reported from the PTAs that constitute the International Pulsar Timing Array (IPTA). We show that despite making different modeling choices, there is no significant difference in the GWB parameters that are measured by the different PTAs, agreeing within 1 σ . The pulsar noise parameters are also consistent between different PTAs for the majority of the pulsars included in these analyses. We bridge the differences in modeling choices by adopting a standardized noise model for all pulsars and PTAs, finding that under this model there is a reduction in the tension in the pulsar noise parameters. As part of this reanalysis, we “extended” each PTA’s data set by adding extra pulsars that were not timed by that PTA. Under these extensions, we find better constraints on the GWB amplitude and a higher signal-to-noise ratio for the Hellings–Downs correlations. These extensions serve as a prelude to the benefits offered by a full combination of data across all pulsars in the IPTA, i.e., the IPTA’s Data Release 3, which will involve not just adding in additional pulsars but also including data from all three PTAs where any given pulsar is timed by more than a single PTA.

The millisecond pulsar J1713+0747 underwent a sudden and significant pulse shape change between 2021 April 16 and 17 (MJDs 59320 and 59321). Subsequently, the pulse shape gradually recovered over the course of several months. We report the results of continued multifrequency radio observations of the pulsar made using the Canadian Hydrogen Intensity Mapping Experiment and the 100 m Green Bank Telescope in a 3 yr period encompassing the shape change event, between 2020 February and 2023 February. As of 2023 February, the pulse shape had returned to a state similar to that seen before the event, but with measurable changes remaining. The amplitude of the shape change and the accompanying time-of-arrival residuals display a strong nonmonotonic dependence on radio frequency, demonstrating that the event is neither a glitch (the effects of which should be independent of radio frequency, ν ) nor a change in dispersion measure alone (which would produce a delay proportional to ν ^−2 ). However, it does bear some resemblance to the two previous “chromatic timing events” observed in J1713+0747, as well as to a similar event observed in PSR J1643−1224 in 2015.

The radio galaxy 3C 66B has been hypothesized to host a supermassive black hole binary (SMBHB) at its center based on electromagnetic observations. Its apparent 1.05 yr period and low redshift (∼0.02) make it an interesting testbed to search for low-frequency gravitational waves (GWs) using pulsar timing array (PTA) experiments. This source has been subjected to multiple searches for continuous GWs from a circular SMBHB, resulting in progressively more stringent constraints on its GW amplitude and chirp mass. In this paper, we develop a pipeline for performing Bayesian targeted searches for eccentric SMBHBs in PTA data sets, and test its efficacy by applying it to simulated data sets with varying injected signal strengths. We also search for a realistic eccentric SMBHB source in 3C 66B using the NANOGrav 12.5 yr data set employing PTA signal models containing Earth term-only as well as Earth+pulsar term contributions using this pipeline. Due to limitations in our PTA signal model, we get meaningful results only when the initial eccentricity e _0 < 0.5 and the symmetric mass ratio η > 0.1. We find no evidence for an eccentric SMBHB signal in our data, and therefore place 95% upper limits on the PTA signal amplitude of 88.1 ± 3.7 ns for the Earth term-only and 81.74 ± 0.86 ns for the Earth+pulsar term searches for e _0 < 0.5 and η > 0.1. Similar 95% upper limits on the chirp mass are (1.98 ± 0.05) × 10 ^9 and (1.81 ± 0.01) × 10 ^9 M _☉ . These upper limits, while less stringent than those calculated from a circular binary search in the NANOGrav 12.5 yr data set, are consistent with the SMBHB model of 3C 66B developed from electromagnetic observations.

We present the results of a Bayesian search for gravitational wave (GW) memory in the NANOGrav 12.5 yr data set. We find no convincing evidence for any gravitational wave memory signals in this data set. We find a Bayes factor of 2.8 in favor of a model that includes a memory signal and common spatially uncorrelated red noise (CURN) compared to a model including only a CURN. However, further investigation shows that a disproportionate amount of support for the memory signal comes from three dubious pulsars. Using a more flexible red-noise model in these pulsars reduces the Bayes factor to 1.3. Having found no compelling evidence, we go on to place upper limits on the strain amplitude of GW memory events as a function of sky location and event epoch. These upper limits are computed using a signal model that assumes the existence of a common, spatially uncorrelated red noise in addition to a GW memory signal. The median strain upper limit as a function of sky position is approximately 3.3 × 10 ^−14 . We also find that there are some differences in the upper limits as a function of sky position centered around PSR J0613−0200. This suggests that this pulsar has some excess noise that can be confounded with GW memory. Finally, the upper limits as a function of burst epoch continue to improve at later epochs. This improvement is attributable to the continued growth of the pulsar timing array.

Background: There is growing attention to individual-level patient social needs such as unstable housing and food insecurity. Such considerations, however, have historically been the purview of public health and have not been a priority of more traditional health care delivery organizations, such as acute care hospitals., Purpose: The purpose of this study was to examine whether the presence of patient and family advisory boards (PFABs) among acute care community hospitals was associated with screening for and programs to address patient social needs., Methods: We used a secondary data set derived from the American Hospital Association's 2020 and 2021 annual surveys, along with multinomial and negative binomial regression models to assess the relationship between the presence/absence of a PFAB and the likelihood of offering and the number of areas addressed by social needs screening programs., Results: More than half (55.9%) of all responding hospitals reported having a PFAB in 2020 (55.9%) and 2021 (52.7%). The presence of a PFAB among hospitals was significantly associated with patient social needs screening, more areas addressed by programs, and more types of partners to address these needs., Conclusions: Community hospitals with a PFAB have more robust programs and partnerships to address patient social needs., Practice Implications: Hospital leaders should consider going beyond simply establishing programs to address social needs but also consider comprehensiveness of these programs to recognize the intersectionality of social needs. One way to do this is to formally establish a PFAB to help hospitals better identify and prioritize the needs in local communities and design social needs programs/solutions that are patient- and family-centric., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The viral capsid performs critical functions during HIV-1 infection and is a validated target for antiviral therapy. Previous studies have established that the proper structure and stability of the capsid are required for efficient HIV-1 reverse transcription in target cells. Moreover, it has recently been demonstrated that permeabilized virions and purified HIV-1 cores undergo efficient reverse transcription in vitro when the capsid is stabilized by addition of the host cell metabolite inositol hexakisphosphate (IP6). However, the molecular mechanism by which the capsid promotes reverse transcription is undefined. Here we show that wild type HIV-1 virions can undergo efficient reverse transcription in vitro in the absence of a membrane-permeabilizing agent. This activity, originally termed "natural endogenous reverse transcription" (NERT), depends on expression of the viral envelope glycoprotein during virus assembly and its incorporation into virions. Truncation of the gp41 cytoplasmic tail markedly reduced NERT activity, suggesting that gp41 licenses the entry of nucleotides into virions. By contrast to reverse transcription in permeabilized virions, NERT required neither the addition of IP6 nor a mature capsid, indicating that an intact viral membrane can substitute for the function of the viral capsid during reverse transcription in vitro. Collectively, these results demonstrate that the viral capsid functions as a nanoscale container for reverse transcription during HIV-1 infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jennings et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Geographically expanding and invading ticks are a global concern. The Asian longhorned tick (ALT, Haemaphysalis longicornis) was introduced to the mid-Atlantic US between 2010 and 2017 and recently invaded Ohio, an inland state. To date, ALTs in the US have been associated with livestock exsanguination and transmission of the agent of bovine theileriosis. To inform management, studies describing tick ecology and epidemiology of associated disease agents are critical. In this study, we described phenology, habitat and host associations, and tested for agents of medical and veterinary concern at the site of the first known established ALT population in Ohio, where pesticide treatment was applied in early fall 2021. In spring-fall 2022, we sampled wildlife (small mammals) and collected ticks from forest, edge, and grassland habitats. We also opportunistically sampled harvested white-tailed deer at nearby processing stations and fresh wildlife carcasses found near roads. Field-collected ALTs were tested for five agents using real-time PCR. We found that ALT nymphs emerged in June, followed by adults, and concluded with larvae in the fall. ALTs were detected in all habitats but not in wildlife. We also found a 4.88% (2/41) prevalence of Anaplasma phagocytophilum across ALT adults and nymphs. Host and habitat associations were similar to other studies in the eastern United States, but two potential differences in phenology were identified. Whether ALTs will acquire more endemic disease agents requires further investigations. Our findings provide the first evidence regarding ALT life history from the Midwest region of the United States and can inform exposure risk and guide integrated management., (© 2024 The Authors. Medical and Veterinary Entomology published by John Wiley & Sons Ltd on behalf of Royal Entomological Society.)

Though far less obvious than direct effects (clinical disease or mortality), the indirect influences of pathogens are difficult to estimate but may hold fitness consequences. Here, we disentangle the directional relationships between infection and energetic reserves, evaluating the hypotheses that energetic reserves influence infection status of the host and that infection elicits costs to energetic reserves. Using repeated measures of fat reserves and infection status in individual bighorn sheep ( Ovis canadensis ) in the Greater Yellowstone Ecosystem, we documented that fat influenced ability to clear pathogens ( Mycoplasma ovipneumoniae ) and infection with respiratory pathogens was costly to fat reserves. Costs of infection approached, and in some instances exceeded, costs of rearing offspring to independence in terms of reductions to fat reserves. Fat influenced probability of clearing pathogens, pregnancy and over-winter survival; from an energetic perspective, an animal could survive for up to 23 days on the amount of fat that was lost to high levels of infection. Cost of pathogens may amplify trade-offs between reproduction and survival. In the absence of an active outbreak, the influence of resident pathogens often is overlooked. Nevertheless, the energetic burden of pathogens likely has consequences for fitness and population dynamics, especially when food resources are insufficient.

Cancer vaccines strive to induce robust, antigen-targeted, T-cell-mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, SQZ-PBMC-HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA-A*02+ patients. The SQZ-PBMC-HPV-101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers. Here, we present a post hoc analysis of the relationship between Posttreatment CD8+ T cell infiltration and patient outcomes. SQZ-PBMC-HPV was administered as monotherapy every 3 weeks. Tumor samples were collected pre-dose and post-dose 4 weeks after treatment start. Biomarkers including CD8, MHC-I, E6, E7, GZMB, and Ki67 were evaluated by immunohistochemistry, immunofluorescence, and RNA in situ hybridization, and were correlated with clinical response, survival, and drug product composition. Eighteen patients had paired pre- and post-dose biopsies. Six (33%) had an increase in CD8+ T cell density in tumor parenchyma between screening and C2D8. Patients with increased CD8+ T cell density had improved disease control rate (66.7% vs 16.7%) and median overall survival (606.5 days vs 170.0 days, p = 0.0078). Drug product was significantly enriched for higher T cells and lower monocytes in the increased CD8+ T cell density group. In patients with incurable HPV16+ solid tumors treated with SQZ-PBMC-HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells., (© 2024 Wiley Periodicals LLC.)

Background: Surface cleaning and disinfection is a key part of breaking the chain of transmission and reducing the risk of healthcare associated infections. However, if cleaning and disinfectant formulations are incompatible with surface materials, frequent application can cause premature failure of plastics due to environmental stress cracking (ESC). Material compatibility should be considered when selecting cleaning and disinfecting products., Aim: This study evaluated the tendency of 2-in-1 wet wipes to cause ESC in commonly found healthcare plastics., Methods: Eight ready-to-use 2-in-1 wet wipes were evaluated for their ability to cause ESC in 13 plastic surfaces in accordance with BS EN ISO-22088-3. Polymers were exposed to fluid extracted from wipes at a fixed strain of 0.5% for seven days and assessed for cracking, crazing, and tensile strength in accordance with ISO 527-2:2012., Findings: All 2-in-1 wet wipes tested contained ESC agents, although the severity of ESC varied. Products with higher pH (>8.0) were responsible for 74% of failures, with 22 of the 39 tested plastics visibly cracking. Although the primary active in all tested wipe formulations were quaternary ammonium compounds, formulations that included small/medium amines or alcohol demonstrated a greater propensity for plastic cracking., Conclusion: Each disinfectant formulation exhibits a unique spectrum of microbial efficacy and unique potential to cause surface damage. This may result in device failures and recalls that could compromise patient and staff safety. BS EN ISO-22088-3 can support material compatibility assessments of disinfectant and detergent products before they come to market., (Copyright © 2024 Gama Healthcare Ltd. Published by Elsevier Ltd.. All rights reserved.)

Background: Vagus nerve stimulation (VNS) is an established therapy for treating a variety of chronic diseases, such as epilepsy, depression, obesity, and for stroke rehabilitation. However, lack of precision and side-effects have hindered its efficacy and extension to new conditions. Achieving a better understanding of the relationship between VNS parameters and neural and physiological responses is therefore necessary to enable the design of personalized dosing procedures and improve precision and efficacy of VNS therapies., Methods: We used biomarkers from recorded evoked fiber activity and short-term physiological responses (throat muscle, cardiac and respiratory activity) to understand the response to a wide range of VNS parameters in anaesthetised pigs. Using signal processing, Gaussian processes (GP) and parametric regression models we analyse the relationship between VNS parameters and neural and physiological responses., Results: Firstly, we illustrate how considering multiple stimulation parameters in VNS dosing can improve the efficacy and precision of VNS therapies. Secondly, we describe the relationship between different VNS parameters and the evoked fiber activity and show how spatially selective electrodes can be used to improve fiber recruitment. Thirdly, we provide a detailed exploration of the relationship between the activations of neural fiber types and different physiological effects. Finally, based on these results, we discuss how recordings of evoked fiber activity can help design VNS dosing procedures that optimize short-term physiological effects safely and efficiently., Conclusion: Understanding of evoked fiber activity during VNS provide powerful biomarkers that could improve the precision, safety and efficacy of VNS therapies., (© 2024. The Author(s).)

Integrating host movement and pathogen data is a central issue in wildlife disease ecology that will allow for a better understanding of disease transmission. We examined how adult female mule deer ( Odocoileus hemionus ) responded behaviorally to infection with chronic wasting disease (CWD). We compared movement and habitat use of CWD-infected deer ( n  = 18) to those that succumbed to starvation (and were CWD-negative by ELISA and IHC; n  = 8) and others in which CWD was not detected ( n  = 111, including animals that survived the duration of the study) using GPS collar data from two distinct populations collared in central Wyoming, USA during 2018-2022. CWD and predation were the leading causes of mortality during our study (32/91 deaths attributed to CWD and 27/91 deaths attributed to predation). Deer infected with CWD moved slower and used lower elevation areas closer to rivers in the months preceding death compared with uninfected deer that did not succumb to starvation. Although CWD-infected deer and those that died of starvation moved at similar speeds during the final months of life, CWD-infected deer used areas closer to streams with less herbaceous biomass than starved deer. These behavioral differences may allow for the development of predictive models of disease status from movement data, which will be useful to supplement field and laboratory diagnostics or when mortalities cannot be quickly retrieved to assess cause-specific mortality. Furthermore, identifying individuals who are sick before predation events could help to assess the extent to which disease mortality is compensatory with predation. Finally, infected animals began to slow down around 4 months prior to death from CWD. Our approach for detecting the timing of infection-induced shifts in movement behavior may be useful in application to other disease systems to better understand the response of wildlife to infectious disease., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective. In bioelectronic medicine, neuromodulation therapies induce neural signals to the brain or organs, modifying their function. Stimulation devices capable of triggering exogenous neural signals using electrical waveforms require a complex and multi-dimensional parameter space to control such waveforms. Determining the best combination of parameters (waveform optimization or dosing) for treating a particular patient's illness is therefore challenging. Comprehensive parameter searching for an optimal stimulation effect is often infeasible in a clinical setting due to the size of the parameter space. Restricting this space, however, may lead to suboptimal therapeutic results, reduced responder rates, and adverse effects. Approach . As an alternative to a full parameter search, we present a flexible machine learning, data acquisition, and processing framework for optimizing neural stimulation parameters, requiring as few steps as possible using Bayesian optimization. This optimization builds a model of the neural and physiological responses to stimulations, enabling it to optimize stimulation parameters and provide estimates of the accuracy of the response model. The vagus nerve (VN) innervates, among other thoracic and visceral organs, the heart, thus controlling heart rate (HR), making it an ideal candidate for demonstrating the effectiveness of our approach. Main results. The efficacy of our optimization approach was first evaluated on simulated neural responses, then applied to VN stimulation intraoperatively in porcine subjects. Optimization converged quickly on parameters achieving target HRs and optimizing neural B-fiber activations despite high intersubject variability. Significance. An optimized stimulation waveform was achieved in real time with far fewer stimulations than required by alternative optimization strategies, thus minimizing exposure to side effects. Uncertainty estimates helped avoiding stimulations outside a safe range. Our approach shows that a complex set of neural stimulation parameters can be optimized in real-time for a patient to achieve a personalized precision dosing., (© 2024 IOP Publishing Ltd.)

Pre-exposure prophylaxis (PrEP) is an effective tool in protecting persons from acquiring HIV infection through sex or injection drug use. However, awareness and willingness to use PrEP among Black gay, bisexual, and other men who have sex with men (BMSM) remain suboptimal compared to White MSM (WMSM) in the United States. Our aims were to (1) assess the factors associated with PrEP awareness and willingness to use PrEP among MSM and (2) compare the PrEP perceptions among BMSM versus non-Black MSM. Data were drawn from two cross-sectional behavioral surveys in Baltimore, MD: Behavioral Surveillance Research (BESURE) conducted in 2017, and Safe Spaces 4 Sexual Health (SS4SH), conducted in 2018 and 2019. Descriptive statistics were used to summarize the study population. We used Poisson regression models to identify variables associated with awareness of PrEP and willingness to use PrEP. PrEP perceptions were assessed via 13 items scored on a 5-point Likert scale. Finally, we conducted a post-hoc exploratory bivariate analysis of the relationship between PrEP perception and willingness to use PrEP, stratified by race/ethnicity. A total of 261 MSM participated in this study. Many of the participants were aware of PrEP (75.1%). Factors associated with greater PrEP awareness included having greater than a high school education (aRR 1.22, 95% CI 1.04, 1.43); and earning more than $25,000 annually (aRR 1.24, 95% CI 1.08, 1.42). Participants who had received money in exchange for sex one or more times were less likely to be aware of PrEP (aRR 0.59, 95% CI 0.36, 0.95). More than half of the participants were willing to use PrEP (55.3%). In bivariate and multivariable analyses, demographic or behavioral characteristics were not significantly associated with willingness to use PrEP. Higher agreement with the following statements was associated with lower willingness to use PrEP: "Having to take a pill every day is difficult" (RR 0.89, 95% CI 0.82-0.97) and, "I am concerned about the side effects of PrEP" (RR 0.89, 95% CI 0.82-0.96), and "PrEP is for people who have riskier sex lives than I do" (RR 0.86, 95% CI 0.78-0.95). Conversely, higher willingness to use PrEP was associated with comfortable having sex without a condom (RR 1.11, 95% CI 1.02-1.21), less anxious about sex (RR 1.12, 95% CI 1.02-1.24), and my friends think that I should take PrEP (RR 1.19, 95% CI 1.07-1.32). We found BMSM compared to non-Black MSM had higher mean scores related to taking a daily pill (p = 0.041), concerns about side effects (p = 0.012), concerns about people thinking they had HIV (p = 0.001), concerns about the financial costs of PrEP (p = 0.038) and caution when dealing with healthcare organizations/medical mistrust (p = 0.019). Perceptions with a statistically significant lower score among BMSM versus non-Black MSM included statements such as, comfortable having sex without a condom (p = 0.003) and less anxious about sex (p < 0.001). We conclude HIV prevention strategies, programs, and interventions should be cognizant of PrEP perceptions that facilitate or hinder PrEP uptake in Baltimore City, MD., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Device-assisted enteroscopy (DAE) has become a well-established diagnostic and therapeutic tool for the management of small-bowel pathology. We aimed to evaluate the performance measures for DAE across the UK against the quality benchmarks proposed by the European Society of Gastrointestinal Endoscopy (ESGE)., Methods: We retrospectively collected data on patient demographics and DAE performance measures from electronic endoscopy records of consecutive patients who underwent DAE for diagnostic and therapeutic purposes across 12 enteroscopy centers in the UK between January 2017 and December 2022., Results: A total of 2005 DAE procedures were performed in 1663 patients (median age 60 years; 53% men). Almost all procedures (98.1%) were performed for appropriate indications. Double-balloon enteroscopy was used for most procedures (82.0%), followed by single-balloon enteroscopy (17.2%) and spiral enteroscopy (0.7%). The estimated depth of insertion was documented in 73.4% of procedures. The overall diagnostic yield was 70.0%. Therapeutic interventions were performed in 42.6% of procedures, with a success rate of 96.6%. Overall, 78.0% of detected lesions were marked with a tattoo. Patient comfort was significantly better with the use of deep sedation compared with conscious sedation (99.7% vs. 68.5%; P <0.001). Major adverse events occurred in only 0.6% of procedures., Conclusions: Performance measures for DAE in the UK meet the ESGE quality benchmarks, with high diagnostic and therapeutic yields, and a low incidence of major adverse events. However, there is room for improvement in optimizing sedation practices, standardizing the depth of insertion documentation, and adopting marking techniques to aid in the follow-up of detected lesions., Competing Interests: E.J. Despott has received educational and travel grants and speaker’s honoraria from Fujifilm, Aquilant, Diagmed, Laborie, and Medtronic (2007 to present); his department has received educational grants from Fujifilm, Pentax, Olympus, ERBE, Norgine, and Medtronic (2012 to present). The remaining authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: The American College of Cardiology Reduce the Risk: PCI Bleed Campaign was a hospital-based quality improvement campaign designed to reduce post-percutaneous coronary intervention (PCI) bleeding events. The aim of the campaign was to provide actionable evidence-based tools for participants to review, adapt, and adopt, depending upon hospital resources and engagement., Methods: We used data from 8 757 737 procedures in the National Cardiovascular Data Registry between 2015 and 2021 to compare patient and hospital characteristics and bleeding outcomes among campaign participants (n=195 hospitals) and noncampaign participants (n=1384). Post-PCI bleeding risk was compared before and after campaign participation. Multivariable hierarchical logistic regression was used to determine the adjusted association between campaign participation and post-PCI bleeding events. Prespecified subgroups were examined., Results: Campaign hospitals were more often higher volume teaching facilities located in urban or suburban locations. After adjustment, campaign participation was associated with a significant reduction in the rate of bleeding (bleeding: adjusted odds ratio, 0.61 [95% CI, 0.53-0.71]). Campaign hospitals had a greater decrease in bleeding events than noncampaign hospitals. In a subgroup analysis, the reduction in bleeding was noted in non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction patients, but no significant reduction was seen in patients without acute coronary syndrome., Conclusions: Participation in the American College of Cardiology Reduce the Risk: PCI Bleed Campaign was associated with a significant reduction in post-PCI bleeding. Our results underscore that national quality improvement efforts can be associated with a significant impact on PCI outcomes., Competing Interests: Dr Amin has institutional grant support (modest) from GE Healthcare and Chiesi. Dr Abbott has the following relationships with industry: research: Boston Scientific and Microport; consulting: Abbott, Medtronic, Penumbra, Shockwave, and Philips. Dr Masoudi had a contract with the American College of Cardiology for his role as the Chief Scientific Advisor, National Cardiovascular Data Registry. The other authors report no conflicts.

Using logistic regression and neural networks, the aim of this study was to compare model performance when predicting player draft outcome during the 2021 AFL National Draft. Physical testing, in-game movement and technical involvements were collected from 708 elite-junior Australian Rules football players during consecutive seasons. Predictive models were generated using data from 465 players (2017 to 2020). Data from 243 players were then used to prospectively predict the 2021 AFL National Draft. Logistic regression and neural network models were compared for specificity, sensitivity and accuracy using relative cut-off thresholds from 5% to 50%. Using factored and unfactored data, and a range of relative cut-off thresholds, neural networks accounted for 73% of the 40 best performing models across positional groups and data configurations. Neural networks correctly classified more drafted players than logistic regression in 88% of cases at draft rate (15%) and convergence threshold (35%). Using individual variables across thresholds, neural networks (specificity = 79 ± 13%, sensitivity = 61 ± 24%, accuracy = 76 ± 8%) were consistently superior to logistic regression (specificity = 73 ± 15%, sensitivity = 29 ± 14%, accuracy = 66 ± 11%). Where the goal is to identify talented players with draft potential, model sensitivity is paramount, and neural networks were superior to logistic regression., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jennings et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In plants, plasmodesmata establish cytoplasmic continuity between cells to allow for communication and resource exchange across the cell wall. While plant pathogens use plasmodesmata as a pathway for both molecular and physical invasion, the benefits of molecular invasion (cell-to-cell movement of pathogen effectors) are poorly understood. To establish a methodology for identification and characterization of the cell-to-cell mobility of effectors, we performed a quantitative live imaging-based screen of candidate effectors of the fungal pathogen Colletotrichum higginsianum . We predicted C. higginsianum effectors by their expression profiles, the presence of a secretion signal, and their predicted and in planta localization when fused to green fluorescent protein. We assayed for cell-to-cell mobility of nucleocytosolic effectors and identified 14 that are cell-to-cell mobile. We identified that three of these effectors are "hypermobile," showing cell-to-cell mobility greater than expected for a protein of that size. To explore the mechanism of hypermobility, we chose two hypermobile effectors and measured their impact on plasmodesmata function and found that even though they show no direct association with plasmodesmata, each increases the transport capacity of plasmodesmata. Thus, our methods for quantitative analysis of cell-to-cell mobility of candidate microbe-derived effectors, or any suite of host proteins, can identify cell-to-cell hypermobility and offer greater understanding of how proteins affect plasmodesmal function and intercellular connectivity. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license., Competing Interests: The author(s) declare no conflict of interest.

Abstract: Bias-free content in nursing education prepares students to provide equitable care. The process of assessing content promotes the dismantling of systemic bias in health care, advancing social justice, diversity, equity, and inclusion. Unfortunately, there are no published studies to guide the evaluation of nursing curricula for the presence of bias. This innovative project aimed to identify bias in a course and develop a structure to guide the wider evaluation of the curriculum to identify and remove biased content. A modified version of the Upstate Bias Checklist was applied to a 15-week, three-semester hour, prelicensure, graduate-level nursing course., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2023 National League for Nursing.)