The Epidemiology of Psychedelic Use Among United States Military Veterans.

We sought to identify patterns of psychedelic use among United States military veterans, compare demographic variables and perspectives of those who did and did not report use, and characterize benefits and adverse outcomes associated with use. Respondents (N = 426) were recruited to complete an online cross-sectional survey. Approximately one-half (51%) reported using psychedelics. Most did so for healing/treatment (70%) and/or spiritual purposes (48%), and most (85%) reported benefiting from use. Those who used psychedelics reported they would be more likely to use VA services (p < .001, d = 0.64) and to return to the VA for care (p < .001, d = 0.79) if psychedelic therapy was offered. Almost two-thirds (59%) reported adverse outcomes associated with use. Equivalent proportions rated their psychedelic experiences as beneficial among those who did (89%) and did not (81%) report adverse outcomes. Fewer adverse outcomes were associated with being older, using psilocybin, feeling prepared and confident in the reasons for use, being in a comfortable setting, and being able to "trust, let go, and be open" (Rc = 0.77; p < .001). Psychedelics may offer benefits but may also lead to adverse outcomes without proper preparation and support. Future research should examine the utility of psychedelic-based approaches for veteran mental health care.

Development of a Novel Hierarchically Biofabricated Blood Vessel Mimic Decorated with Three Vascular Cell Populations for the Reconstruction of Small-Diameter Arteries.

The availability of grafts to replace small-diameter arteries remains an unmet clinical need. Here, the validated methodology is reported for a novel hybrid tissue-engineered vascular graft that aims to match the natural structure of small-size arteries. The blood vessel mimic (BVM) comprises an internal conduit of co-electrospun gelatin and polycaprolactone (PCL) nanofibers (corresponding to the tunica intima of an artery), reinforced by an additional layer of PCL aligned fibers (the internal elastic membrane). Endothelial cells are deposited onto the luminal surface using a rotative bioreactor. A bioprinting system extrudes two concentric cell-laden hydrogel layers containing respectively vascular smooth muscle cells and pericytes to create the tunica media and adventitia. The semi-automated cellularization process reduces the production and maturation time to 6 days. After the evaluation of mechanical properties, cellular viability, hemocompatibility, and suturability, the BVM is successfully implanted in the left pulmonary artery of swine. Here, the BVM showed good hemostatic properties, capability to withstand blood pressure, and patency at 5 weeks post-implantation. These promising data open a new avenue to developing an artery-like product for reconstructing small-diameter blood vessels.

Herpes simplex virus 1 inhibits phosphorylation of RNA polymerase II CTD serine-7.

Transcriptional activity of RNA polymerase II (Pol II) is influenced by post-translational modifications of the C-terminal domain (CTD) of the largest Pol II subunit, RPB1. Herpes simplex virus type 1 (HSV-1) usurps the cellular transcriptional machinery during lytic infection to efficiently express viral mRNA and shut down host gene expression. The viral immediate-early protein ICP22 interferes with serine 2 phosphorylation (pS2) by targeting CDK9 and other CDKs, but the full functional implications of this are not well understood. Using Western blotting, we report that HSV-1 also induces a loss of serine 7 phosphorylation (pS7) of the CTD during lytic infection, requiring expression of the two immediate-early proteins ICP22 and ICP27. ICP27 has also been proposed to target RPB1 for degradation, but we show that pS2/S7 loss precedes the drop in total protein levels. Cells with the RPB1 polyubiquitination site mutation K1268R, preventing proteasomal degradation during transcription-coupled DNA repair, displayed loss of pS2/S7 but retained higher overall RPB1 protein levels later in infection, indicating this pathway is not involved in early CTD dysregulation but may mediate bulk protein loss later. Using α-amanitin-resistant CTD mutants, we observed differential requirements for Ser2 and Ser7 for the production of viral proteins, with Ser2 facilitating viral immediate-early genes and Ser7 appearing dispensable. Despite dysregulation of CTD phosphorylation and different requirements for Ser2/7, all CTD modifications tested could be visualized in viral replication compartments with immunofluorescence. These data expand the known means that HSV employs to create pro-viral transcriptional environments at the expense of host responses.IMPORTANCECells rapidly induce changes in the transcription of RNA in response to stress and pathogens. Herpes simplex virus (HSV) disrupts many processes of host mRNA transcription, and it is necessary to separate the actions of viral proteins from cellular responses. Here, we demonstrate that viral proteins inhibit two key phosphorylation patterns on the C-terminal domain (CTD) of cellular RNA polymerase II and that this is separate from the degradation of polymerases later in infection. Furthermore, we show that viral genes do not require the full "CTD code." Together, these data distinguish multiple steps in the remodeling of RNA polymerase during infection and suggest that shared transcriptional phenotypes during stress responses do not revolve around a core disruption of CTD modifications.

HER4 is a high-affinity dimerization partner for all EGFR/HER/ErbB family proteins.

Human epidermal growth factor receptors (HER)-also known as EGFR or ErbB receptors-are a subfamily of receptor tyrosine kinases (RTKs) that play crucial roles in cell growth, division, and differentiation. HER4 (ErbB4) is the least studied member of this family, partly because its expression is lower in later stages of development. Recent work has suggested that HER4 can play a role in metastasis by regulating cell migration and invasiveness; however, unlike EGFR and HER2, the precise role that HER4 plays in tumorigenesis is still unresolved. Early work on HER family proteins suggested that there are direct interactions between the four members, but to date, there has been no single study of all four receptors in the same cell line with the same biophysical method. Here, we quantitatively measure the degree of association between HER4 and the other HER family proteins in live cells with a time-resolved fluorescence technique called pulsed interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS). PIE-FCCS is sensitive to the oligomerization state of membrane proteins in live cells, while simultaneously measuring single-cell protein expression levels and diffusion coefficients. Our PIE-FCCS results demonstrate that HER4 interacts directly with all HER family members in the cell plasma membrane. The interaction between HER4 and other HER family members intensified in the presence of a HER4-specific ligand. Our work suggests that HER4 is a preferred dimerization partner for all HER family proteins, even in the absence of ligands.

Predicting Basketball Shot Outcome From Visuomotor Control Data Using Explainable Machine Learning.

Quiet eye (QE), the visual fixation on a target before initiation of a critical action, is associated with improved performance. While QE is trainable, it is unclear whether QE can directly predict performance, which has implications for training interventions. This study predicted basketball shot outcome (make or miss) from visuomotor control variables using a decision tree classification approach. Twelve basketball athletes completed 200 shots from six on-court locations while wearing mobile eye-tracking glasses. Training and testing data sets were used for modeling eight predictors (shot location, arm extension time, and absolute and relative QE onset, offset, and duration) via standard and conditional inference decision trees and random forests. On average, the trees predicted over 66% of makes and over 50% of misses. The main predictor, relative QE duration, indicated success for durations over 18.4% (range: 14.5%-22.0%). Training to prolong QE duration beyond 18% may enhance shot success.

The Relationship Between Loneliness, Social Isolation, and Inflammatory Bowel Disease: A Narrative Review.

BACKGROUND: There is clear evidence that loneliness and social isolation have profound health consequences. Documenting the associations of loneliness and social isolation with inflammatory bowel disease (IBD) symptoms, disease severity, and treatment outcomes could meaningfully improve health and quality of life in patients with IBD. PURPOSE: The purpose of this narrative review was to synthesize the empirical evidence on the associations of loneliness and social isolation with IBD symptoms, disease severity, and treatment outcomes. METHODS: Articles were identified through systematic database searches. Quantitative studies that enrolled patients with IBD were included if they examined one of the following outcomes: (a) loneliness or social isolation or (b) IBD-related symptoms, disease severity, or treatment outcomes. RESULTS: We identified 1,816 articles after removing duplicates. Of the 18 studies that met the inclusion criteria, 15 were cross-sectional and 3 were longitudinal. Overall, studies found that loneliness was associated with greater disease activity, functional gastrointestinal symptoms, IBD illness stigma, depressive symptoms, daily IBD symptom burden, reduced resilience, and poorer quality of life. Social isolation was associated with higher prevalence of IBD hospitalizations, premature mortality, and depression. CONCLUSIONS: Findings suggest that loneliness and social isolation are associated with poorer health and quality of life in patients with IBD. Prospective cohort studies examining the biobehavioral mechanisms accounting for the associations of loneliness and social isolation with IBD-related outcomes are needed to guide the development of psychological interventions for individuals living with IBD.

This article explores the connection between loneliness, social isolation, and health outcomes in people with inflammatory bowel disease (IBD). While loneliness and social isolation are known to negatively impact health in other chronic diseases, their specific effects within IBD have been far less studied. This study conducted a narrative review and found that loneliness is linked to more severe IBD symptoms, including increased disease activity, greater gastrointestinal distress, and lower quality of life. Similarly, social isolation is associated with higher rates of IBD-related hospitalizations, depression, and reduced coping abilities. These findings highlight the importance of addressing loneliness and social isolation in patients with IBD. Doing so may be key to developing psychological interventions that improve the well-being and health of those living with IBD.

Mammals show faster recovery from capture and tagging in human-disturbed landscapes.

Wildlife tagging provides critical insights into animal movement ecology, physiology, and behavior amid global ecosystem changes. However, the stress induced by capture, handling, and tagging can impact post-release locomotion and activity and, consequently, the interpretation of study results. Here, we analyze post-tagging effects on 1585 individuals of 42 terrestrial mammal species using collar-collected GPS and accelerometer data. Species-specific displacements and overall dynamic body acceleration, as a proxy for activity, were assessed over 20 days post-release to quantify disturbance intensity, recovery duration, and speed. Differences were evaluated, considering species-specific traits and the human footprint of the study region. Over 70% of the analyzed species exhibited significant behavioral changes following collaring events. Herbivores traveled farther with variable activity reactions, while omnivores and carnivores were initially less active and mobile. Recovery duration proved brief, with alterations diminishing within 4-7 tracking days for most species. Herbivores, particularly males, showed quicker displacement recovery (4 days) but slower activity recovery (7 days). Individuals in high human footprint areas displayed faster recovery, indicating adaptation to human disturbance. Our findings emphasize the necessity of extending tracking periods beyond 1 week and particular caution in remote study areas or herbivore-focused research, specifically in smaller mammals.

Self-management interventions for chronic widespread pain including fibromyalgia: a systematic review and qualitative evidence synthesis.

ABSTRACT: Supporting behavioural self-management is increasingly important in the care for chronic widespread pain (CWP), including fibromyalgia. Understanding peoples' experiences of these interventions may elucidate processes and mechanisms that lead to or hinder their intended impact. We conducted a systematic review and thematic synthesis of qualitative studies exploring peoples' experiences of self-management interventions for CWP, including fibromyalgia. MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science were searched. Primary qualitative or mixed-methods studies were included if they explored people's self-management intervention experiences for their CWP, including fibromyalgia. Screening, data extraction, and critical appraisal were conducted by 2 reviewers. Data analysis was conducted through thematic synthesis. Twenty-three studies were included, mostly were rated as high or moderate quality. We developed 4 analytic themes: A multifaceted experience of the intervention, potential for transformative experience of group cohesion, a new outlook, and striving for change after the loss of support. Broadly, personalisation was perceived as beneficial and people experienced a range of emotional experiences. These appeared to support positive behavioural and cognitive changes. For most, group activities promoted acceptance and support, fostering new perspectives and improved self-management, although some found aspects of group contexts challenging. Lack of on-going support after interventions led to challenges in applying behavioural strategies, and some struggled without social support from the group. The experiences of self-management interventions for CWP reflect a complex, multifaceted process. Although many reported positive experiences, addressing issues with integration of physical activity, group dynamics and postintervention support may improve effectiveness for a broader range of people.

Lower limb coordination patterns following anterior cruciate ligament reconstruction:A longitudinal study: Longitudinal lower limb coordination patterns following ACLR.

BACKGROUND: Changes in lower limb joint coordination have been shown to increase localized stress on knee joint soft tissue-a known precursor of osteoarthritis. While 50% of individuals who undergo anterior cruciate ligament reconstruction (ACLR) develop radiographic osteoarthritis, it is unclear how underlying joint coordination during gait changes post-ACLR. The purpose of this study was twofold: to determine differences in lower limb coordination patterns during gait in ACLR individuals 2, 4, and 6 months post-ACLR and to compare the coordination profiles of the ACLR participants at each timepoint post-ACLR to uninjured matched controls. METHODS: We conducted a longitudinal assessment to quantify lower limb coordination at 3 timepoints post-ACLR and compared the ACLR coordination profiles to uninjured controls. Thirty-four ACLR (age = 21.43 ± 4.24 years, mean ± SD; 70.59% female) and 34 controls (age = 21.42 ± 3.43 years; 70.59% female) participated. The ACLR group completed 3 overground gait assessments (2,4, and 6 months post-ACLR), and the controls completed 1 assessment, at which lower limb kinematics were collected. Cross-recurrence quantification analysis was used to characterize sagittal and frontal plane ankle-knee, ankle-hip, and knee-hip coordination dynamics. Comprehensive general linear mixed models were constructed to compare between-limb and within-limb coordination outcomes over time post-ACLR and a between-group comparison across timepoints. RESULTS: The ACLR limb demonstrated a more "stuck" sagittal plane knee-hip coordination profile (greater trapping time (TT); p = 0.004) compared bilaterally. Between groups, the ACLR participants exhibited a more predictable ankle-knee coordination pattern (percent determinism (%DET); p < 0.05), stronger coupling between joints (meanline (MNLine)) across all segments (p < 0.05), and greater knee-hip TT (more "stuck"; p < 0.05) compared to the controls at each timepoint in the sagittal plane. Stronger frontal plane knee-hip joint coupling (MNLine) persisted across timepoints within the ACLR group compared to the controls (p < 0.05). CONCLUSION: The results indicate ACLR individuals exhibit a distinct and rigid coordination pattern during gait compared to controls within 6-month post-ACLR, which may have long-term implications for knee-joint health.

Functional correlation tensors in brain white matter and the effects of normal aging.

Resting state correlations between blood oxygenation level dependent (BOLD) MRI signals from voxels in white matter (WM) are demonstrably anisotropic, so that functional correlation tensors (FCT) may be used to quantify the underlying microstructure of BOLD effects in WM tracts. However, the overall spatial distribution of FCTs and their metrics in specific populations has not yet been established, and the factors that affect their precise arrangements remain unclear. Changes in WM occur with normal aging, and these may be expected to affect FCTs. We hypothesized that FCTs exhibit a characteristic spatial pattern and may show systematic changes with aging or other factors. Here we report our analyses of the FCT characteristics of fMRI images of a large cohort of 461 cognitively normal subjects (190 females, 271 males) sourced from the Open Access Series of Imaging Studies (OASIS), with age distributions of 42 y/o - 95 y/o. Group averages and statistics of FCT indices, including axial functional correlations, radial functional correlations, mean functional correlations and fractional anisotropy, were quantified in WM bundles defined by the JHU ICBM-DTI-81 WM atlas. In addition, their variations with normal aging were examined. The results revealed a dimorphic distribution of changes in FCT metrics with age, with decreases of the functional correlations in some regions and increases in others. Supplementary analysis revealed that females exhibited significant age effects on a greater number of WM areas, but the interaction between age and sex was not significant. The findings demonstrate the reproducibility of the spatial distribution of FCT metrics and reveal subtle regional changes with age.

Brain structure and activity predicting cognitive maturation in adolescence.

Cognitive abilities of primates, including humans, continue to improve through adolescence 1,2. While a range of changes in brain structure and connectivity have been documented 3,4, how they affect neuronal activity that ultimately determines performance of cognitive functions remains unknown. Here, we conducted a multilevel longitudinal study of monkey adolescent neurocognitive development. The developmental trajectory of neural activity in the prefrontal cortex accounted remarkably well for working memory improvements. While complex aspects of activity changed progressively during adolescence, such as the rotation of stimulus representation in multidimensional neuronal space, which has been implicated in cognitive flexibility, even simpler attributes, such as the baseline firing rate in the period preceding a stimulus appearance had predictive power over behavior. Unexpectedly, decreases in brain volume and thickness, which are widely thought to underlie cognitive changes in humans 5 did not predict well the trajectory of neural activity or cognitive performance changes. Whole brain cortical volume in particular, exhibited an increase and reached a local maximum in late adolescence, at a time of rapid behavioral improvement. Maturation of long-distance white matter tracts linking the frontal lobe with areas of the association cortex and subcortical regions best predicted changes in neuronal activity and behavior. Our results provide evidence that optimization of neural activity depending on widely distributed circuitry effects cognitive development in adolescence.

Portable Acceleration of CMS Computing Workflows with Coprocessors as a Service.

Computing demands for large scientific experiments, such as the CMS experiment at the CERN LHC, will increase dramatically in the next decades. To complement the future performance increases of software running on central processing units (CPUs), explorations of coprocessor usage in data processing hold great potential and interest. Coprocessors are a class of computer processors that supplement CPUs, often improving the execution of certain functions due to architectural design choices. We explore the approach of Services for Optimized Network Inference on Coprocessors (SONIC) and study the deployment of this as-a-service approach in large-scale data processing. In the studies, we take a data processing workflow of the CMS experiment and run the main workflow on CPUs, while offloading several machine learning (ML) inference tasks onto either remote or local coprocessors, specifically graphics processing units (GPUs). With experiments performed at Google Cloud, the Purdue Tier-2 computing center, and combinations of the two, we demonstrate the acceleration of these ML algorithms individually on coprocessors and the corresponding throughput improvement for the entire workflow. This approach can be easily generalized to different types of coprocessors and deployed on local CPUs without decreasing the throughput performance. We emphasize that the SONIC approach enables high coprocessor usage and enables the portability to run workflows on different types of coprocessors.

A Prevention Protocol Reduces Spinal Cord Ischemia in Patients Undergoing Branched/Fenestrated Endovascular Aortic Repair.

OBJECTIVES: Spinal cord ischemia (SCI) is a devastating complication that is associated with thoracoabdominal aortic repair, with higher risk associated with increased aortic coverage length, making patients undergoing branched/fenestrated endovascular repair(B/FEVAR) particularly vulnerable. A bundled SCI prevention protocol was previously reported to reduce SCI rates when compared to a historic cohort in a single-center study. Therefore, this analysis aims to further validate and update outcomes associated with the protocol given the routine implementation of this strategy at two institutions (University of Florida [UF] and the University of Alabama at Birmingham [UAB]) since inception. METHODS: Components of the SCI prevention protocol include selective cerebrospinal fluid (CSF) drainage, specified blood pressure parameters, transfusion goals, and selective pharmacologic adjuncts (naloxone, steroids). This protocol was routinely implemented in May 2015. Patients undergoing B/FEVAR from May 2015-December 2022 constituted the post-protocol cohort(n=402) and were compared to the pre-protocol cohort (n=160, January 2010-April 2015). The primary outcome was SCI incidence and subgroup analysis was conducted among patients deemed to be high-risk (Crawford extent I- III thoracoabdominal aneurysms (TAAA) dissection-related disease, prior aortic repair, coverage proximal to zone 5). Survival analysis was performed using Kaplan-Meier methodology. RESULTS: The pre- and post-protocol cohorts were demographically similar, though more post-protocol patients were American Society of Anesthesiology(ASA) class IV (86.1% vs. 55.0%; p<0.001). TAAA was the most common indication in both groups. CSF drain placement was more common in the post-protocol group, particularly among high-risk patients. SCI occurred in 15.9% of pre-protocol patients versus 3.0% of post-protocol patients(p<0.001). In high-risk patients, the pre- and post-protocol cohort SCI incidence was 23.2% vs. 5.0%, respectively (p<0.001). 30-day mortality was decreased in the post-protocol cohort (6.3% vs. 2.2%, p=0.02). Although the post-protocol group had a trend toward improved 1-year survival, this was not statistically significant (84.4% vs. 88.3%, log-rank p=0.35). Among SCI patients, one-year mortality was 28% and 33.3% in the pre- and post-protocol groups, respectively(p=0.46). CONCLUSION: Implementation of a bundled SCI prevention protocol significantly reduces SCI rates in B/FEVAR patients, which has now been validated at two institutions, with the most significant reductions occurring among high-risk patients. Although the overall one-year mortality difference was not significantly different between the cohorts, the high mortality rates among SCI patients highlights the importance of preventative measures.

Analysis of EGFR binding hotspots for design of new EGFR inhibitory biologics.

The epidermal growth factor (EGF) receptor (EGFR) is activated by the binding of one of seven EGF-like ligands to its ectodomain. Ligand binding results in EGFR dimerization and stabilization of the active receptor conformation subsequently leading to activation of downstream signaling. Aberrant activation of EGFR contributes to cancer progression through EGFR overexpression/amplification, modulation of its positive and negative regulators, and/or activating mutations within EGFR. EGFR targeted therapeutic antibodies prevent dimerization and interaction with endogenous ligands by binding the ectodomain of EGFR. However, these antibodies have had limited success in the clinic, partially due to EGFR ectodomain resistance mutations, and are only applicable to a subset of patients with EGFR-driven cancers. These limitations suggest that alternative EGFR targeted biologics need to be explored for EGFR-driven cancer therapy. To this end, we analyze the EGFR interfaces of known inhibitory biologics with determined structures in the context of endogenous ligands, using the Rosetta macromolecular modeling software to highlight the most important interactions on a per-residue basis. We use this analysis to identify the structural determinants of EGFR targeted biologics. We suggest that commonly observed binding motifs serve as the basis for rational design of new EGFR targeted biologics, such as peptides, antibodies, and nanobodies.

Tissue adhesives based on chitosan for biomedical applications.

Chitosan bio-adhesives bond strongly with various biological tissues, such as skin, mucosa, and internal organs. Their adhesive ability arises from amino acid and hydroxyl groups in chitosan, facilitating interactions with tissue surfaces through chemical (ionic, covalent, and hydrogen) and physical (chain entanglement) bonding. As non-toxic, biodegradable, and biocompatible materials, chitosan bio-adhesives are a safe option for medical therapies. They are particularly suitable for drug delivery, wound healing, and tissue regeneration. In this review, we address chitosan-based bio-adhesives and the mechanisms associated with them. We also discuss different chitosan composite-based bio-adhesives and their biomedical applications in wound healing, drug delivery, hemostasis, and tissue regeneration. Finally, challenges and future perspectives for the clinical use of chitosan-based bio-adhesives are discussed.

Spatiospectral image processing workflow considerations for advanced MR spectroscopy of the brain.

Magnetic resonance spectroscopy (MRS) is one of the few non-invasive imaging modalities capable of making neurochemical and metabolic measurements in vivo. Traditionally, the clinical utility of MRS has been narrow. The most common use has been the "single-voxel spectroscopy" variant to discern the presence of a lactate peak in the spectra in one location in the brain, typically to evaluate for ischemia in neonates. Thus, the reduction of rich spectral data to a binary variable has not classically necessitated much signal processing. However, scanners have become more powerful and MRS sequences more advanced, increasing data complexity and adding 2 to 3 spatial dimensions in addition to the spectral one. The result is a spatially- and spectrally-variant MRS image ripe for image processing innovation. Despite this potential, the logistics for robustly accessing and manipulating MRS data across different scanners, data formats, and software standards remain unclear. Thus, as research into MRS advances, there is a clear need to better characterize its image processing considerations to facilitate innovation from scientists and engineers. Building on established neuroimaging standards, we describe a framework for manipulating these images that generalizes to the voxel, spectral, and metabolite level across space and multiple imaging sites while integrating with LCModel, a widely used quantitative MRS peak-fitting platform. In doing so, we provide examples to demonstrate the advantages of such a workflow in relation to recent publications and with new data. Overall, we hope our characterizations will lower the barrier of entry to MRS processing for neuroimaging researchers.

Systematic Review of the Efficacy and Safety of RSV-Specific Monoclonal Antibodies and Antivirals in Development.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection amongst all ages, causing a significant global health burden. Preventative and therapeutic options for RSV infection have long been under development, and recently, several widely-publicised vaccines targeting older adult and maternal populations have become available. Promising monoclonal antibody (mAb) and antiviral (AV) therapies are also progressing in clinical trials, with the prophylactic mAb nirsevimab recently approved for clinical use in infant populations. A systematic review on current progress in this area is lacking. We performed a systematic literature search (PubMed, Embase, Web of Science, ClinicalTrials.gov, EudraCT, ANZCTR-searched Nov 29th, 2023) to identify studies on all RSV-specific mAbs and AV therapies that has undergone human clinical trials since year 2000. Data extraction focused on outcomes related to the therapeutic efficacy and safety of the intervention on trial, and all studies were graded against the OCEBM Levels of Evidence Table. Results from 59 studies were extracted, covering efficacy and safety data on six mAbs (motavizumab, motavizumab-YTE, nirsevimab, ALX-0171, suptavumab, clesrovimab) and 12 AV therapies (ALN-RSV01, RSV604, presatovir, MDT-637, lumicitabine, IFN-α1b, rilematovir, enzaplatovir, AK0529, sisunatovir, PC786, EDP-938). Of the mAbs reviewed, nirsevimab and clesrovimab hold considerable promise. The timeline for RSV-specific AV availability is less advanced, although EDP-938 and AK0529 have reported promising phase 2 efficacy and safety data. Moving forward, passive immunisation and treatment options for RSV infection will play a significant role in reducing the health burden of RSV, complementing recent advancements in vaccine development. TRIAL REGISTRATION: PROSPERO registration: CRD42022376633.

An international, expert-based, Delphi consensus document on controversial issues in the management of abdominal aortic aneurysms.

OBJECTIVE: As a result of conflicting, inadequate or controversial data in the literature, several issues concerning the management of patients with abdominal aortic aneurysms (AAAs) remain unanswered. The aim of this international, expert-based Delphi consensus document was to provide some guidance for clinicians on these controversial topics. METHODS: A three-round Delphi consensus document was produced with 44 experts on 6 prespecified topics regarding the management of AAAs. All answers were provided anonymously. The response rate for each round was 100%. RESULTS: Most participants (42 of 44 [95.4%]) agreed that a minimum case volume per year is essential (or probably essential) for a center to offer open or endovascular AAA repair (EVAR). Furthermore, 33 of 44 (75.0%) believed that AAA screening programs are (probably) still clinically effective and cost effective. Additionally, most panelists (36 of 44 [81.9%]) voted that surveillance after EVAR should be (or should probably be) lifelong. Finally, 35 of 44 participants (79.7%) thought that women smokers should (or should probably/possibly) be considered for screening at 65 years of age, similar to men. No consensus was achieved regarding lowering the threshold for AAA repair and the need for deep venous thrombosis prophylaxis in patients undergoing EVAR. CONCLUSIONS: This expert-based Delphi consensus document provides guidance for clinicians regarding specific unresolved issues. Consensus could not be achieved on some topics, highlighting the need for further research in those areas.

The Fully Understanding Eating and Lifestyle Behaviors (FUEL) trial: Protocol for a cohort study harnessing digital health tools to phenotype dietary non-adherence behaviors during lifestyle intervention.

Objective: Lifestyle intervention can produce clinically significant weight loss and reduced disease risk/severity for many individuals with overweight/obesity. Dietary lapses, instances of non-adherence to the recommended dietary goal(s) in lifestyle intervention, are associated with less weight loss and higher energy intake. There are distinct "types" of dietary lapse (e.g., eating an off-plan food, eating a larger portion), and behavioral, psychosocial, and contextual mechanisms may differ across dietary lapse types. Some lapse types also appear to impact weight more than others. Elucidating clear lapse types thus has potential for understanding and improving adherence to lifestyle intervention. Methods: This 18-month observational cohort study will use real-time digital assessment tools within a multi-level factor analysis framework to uncover "lapse phenotypes" and understand their impact on clinical outcomes. Adults with overweight/obesity (n = 150) will participate in a 12-month online lifestyle intervention and 6-month weight loss maintenance period. Participants will complete 14-day lapse phenotyping assessment periods at baseline, 3, 6, 12, and 18 months in which smartphone surveys, wearable devices, and geolocation will assess dietary lapses and relevant phenotyping characteristics. Energy intake (via 24-h dietary recall) and weight will be collected at each assessment period. Results: This trial is ongoing; data collection began on 31 October 2022 and is scheduled to complete by February 2027. Conclusion: Results will inform novel precision tools to improve dietary adherence in lifestyle intervention, and support updated theoretical models of adherence behavior. Additionally, these phenotyping methods can likely be leveraged to better understand non-adherence to other health behavior interventions. Trial Registration: This study was prospectively registered https://clinicaltrials.gov/study/NCT05562427.