A protocol for scoping reviews on the role of whole-body and dedicated body-part magnetic resonance imaging for assessment of adult and juvenile idiopathic inflammatory myopathies.

Currently, standardized magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults are lacking. Therefore, we will perform a scoping review of the literature to collate and evaluate the existing semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs. The aim is to compile evidence-based information that will facilitate the future development of a universal standardized MRI scoring system for both research and clinical applications in IIM. A systematic search of electronic databases (PubMed, EMBASE, and Cochrane) will be undertaken to identify relevant articles published between January 2000 and October 2023. Data will be synthesized narratively. This scoping review seeks to comprehensively summarize and evaluate the evidence on the scanning protocols and scoring systems used in the assessment of diagnosis, disease activity, and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for the MRI assessment of skeletal muscle changes in patients with IIMs.

Heterogeneity of morphometric similarity networks in health and schizophrenia.

Introduction: Morphometric similarity is a recently developed neuroimaging phenotype of inter-regional connectivity by quantifying the similarity of a region to other regions based on multiple MRI parameters. Altered average morphometric similarity has been reported in psychotic disorders at the group level, with considerable heterogeneity across individuals. We used normative modeling to address cross-sectional and longitudinal inter-individual heterogeneity of morphometric similarity in health and schizophrenia. Methods: Morphometric similarity for 62 cortical regions was obtained from baseline and follow-up T1-weighted scans of healthy individuals and patients with chronic schizophrenia. Cortical regions were classified into seven predefined brain functional networks. Using Bayesian Linear Regression and taking into account age, sex, image quality and scanner, we trained and validated normative models in healthy controls from eleven datasets (n = 4310). Individual deviations from the norm (z-scores) in morphometric similarity were computed for each participant for each network and region at both timepoints. A z-score ≧ than 1.96 was considered supra-normal and a z-score ≦ -1.96 infra-normal. As a longitudinal metric, we calculated the change over time of the total number of infra- or supra-normal regions per participant. Results: At baseline, patients with schizophrenia had decreased morphometric similarity of the default mode network and increased morphometric similarity of the somatomotor network when compared with healthy controls. The percentage of patients with infra- or supra-normal values for any region at baseline and follow-up was low (<6%) and did not differ from healthy controls. Mean intra-group changes over time in the total number of infra- or supra-normal regions were small in schizophrenia and healthy control groups (<1) and there were no significant between-group differences. Conclusions: In a case-control setting, a decrease of morphometric similarity within the default mode network may be a robust finding implicated in schizophrenia. However, normative modeling suggests that significant reductions and changes over time of regional morphometric similarity are evident only in a minority of patients.

Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome.

Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers.

Spectrum of cutaneous lesions in a cohort of patients with neurofibromatosis type 2.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant syndrome with a predisposition to the development of central nervous system tumors, ophthalmic manifestations, and dermatological lesions. The latter are present in 70-95% of patients and can precede the evolution of other tumors. However, they are not included in the diagnostic criteria and are frequently undervalued during follow-up. METHODS: An observational cross-sectional study characterizing cutaneous lesions in a cohort of NF2 patients was carried out. Dermatological examinations were performed, and lesions were classified into neural cutaneous tumors (superficial, SNCT, and deep, DNCT), hyperpigmented patches (HyperP), and hypopigmented patches (HypoP). The Dermatology Life Quality Index (DLQI) and EQ-5D questionnaires were applied to evaluate the impact on quality of life. RESULTS: Nineteen patients with a mean age of 36 years were included. Sixteen (84%) patients had cutaneous lesions, mostly developed 10 or more years before the diagnosis. SNCT, DNCT, and HyperP showed similar frequencies (58%). HypoP were observed in only one patient. HyperP developed, on average, earlier than NCT (9.6 vs. 16.5 SNCT, 17.0 DNCT; years). The excised lesions had different histological patterns, including neurofibromas, schwannomas, and a hybrid tumor. Most patients reported a low impact of cutaneous manifestations on the quality of life (DLQI 0 or 1). CONCLUSIONS: Cutaneous lesions are frequent in NF2 and may precede the diagnosis by several years. Their identification is important to establish the diagnosis earlier and potentially reduce morbidity and mortality.

A soluble model for synchronized rhythmic activity in ant colonies.

Synchronization is one of the most striking instances of collective behavior, occurring in many natural phenomena. For example, in some ant species, ants are inactive within the nest most of the time, but their bursts of activity are highly synchronized and involve the entire nest population. Here we revisit a simulation model that generates this synchronized rhythmic activity through autocatalytic behavior, i.e., active ants can activate inactive ants, followed by a period of rest. We derive a set of delay differential equations that provide an accurate description of the simulations for large ant colonies. Analysis of the fixed-point solutions, complemented by numerical integration of the equations, indicates the existence of stable limit-cycle solutions when the rest period is greater than a threshold and the event of spontaneous activation of inactive ants is very unlikely, so that most of the arousal of ants is done by active ants. Furthermore, we argue that the persistent oscillations observed in the simulations for colonies of finite size are due to resonant amplification of demographic noise.

Integrating brain function and structure in the study of the human attentional networks: a functionnectome study.

Attention is a heterogeneous function theoretically divided into different systems. While functional magnetic resonance imaging (fMRI) has extensively characterized their functioning, the role of white matter in cognitive function has gained recent interest due to diffusion-weighted imaging advancements. However, most evidence relies on correlations between white matter properties and behavioral or cognitive measures. This study used a new method that combines the signal from distant voxels of fMRI images using the probability of structural connection given by high-resolution normative tractography. We analyzed three fMRI datasets with a visual perceptual task and three attentional manipulations: phasic alerting, spatial orienting, and executive attention. The phasic alerting network engaged temporal areas and their communication with frontal and parietal regions, with left hemisphere dominance. The orienting network involved bilateral fronto-parietal and midline regions communicating by association tracts and interhemispheric fibers. The executive attention network engaged a broad set of brain regions and white matter tracts connecting them, with a particular involvement of frontal areas and their connections with the rest of the brain. These results partially confirm and extend previous knowledge on the neural substrates of the attentional system, offering a more comprehensive understanding through the integration of structure and function.

Measurement properties of the Inclusion Body Myositis Functional Rating Scale.

OBJECTIVES: To evaluate the validity, reliability, responsiveness and meaningful change threshold of the Inclusion Body Myositis (IBM) Functional Rating Scale (FRS). METHODS: Data from a large 20-month multicentre, randomised, double-blind, placebo-controlled trial in IBM were used. Convergent validity was tested using Spearman correlation with other health outcomes. Discriminant (known groups) validity was assessed using standardised effect sizes (SES). Internal consistency was tested using Cronbach's alpha. Intrarater reliability in stable patients and equivalence of face-to-face and telephone administration were tested using intraclass correlation coefficients (ICCs) and Bland-Altman plots. Responsiveness was assessed using a standardised response mean (SRM). An receiver operator characteristic (ROC) curve anchor-based approach was used to determine clinically meaningful IBMFRS change. RESULTS: Among the 150 patients, mean (SD) IBMFRS total score was 27.4 (4.6). Convergent validity was supported by medium to large correlations (rs modulus: 0.42-0.79) and discriminant validity by moderate to large group differences (SES=0.51-1.59). Internal consistency was adequate (overall Cronbach's alpha: 0.79). Test-retest reliability (ICCs=0.84-0.87) and reliability of telephone versus face-to-face administration (ICCs=0.93-0.95) were excellent, with Bland-Altman plots showing good agreement. Responsiveness in the worsened group defined by various external constructs was large at both 12 (SRM=-0.76 to -1.49) and 20 months (SRM=-1.12 to -1.57). In ROC curve analysis, a drop in two IBMFRS total score points was shown to represent a meaningful decline. CONCLUSIONS: When administered by trained raters, the IBMFRS is a reliable, valid and responsive tool that can be used to evaluate the impact of IBM and its treatment on physical function, with a 2-point reduction representing meaningful decline. TRIAL REGISTRATION NUMBER: NCT02753530.

Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron-BA.1 variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the United States became increasingly significant. The number of detected introductions varied from 96 and 101 for Alpha and Delta to 39 for Omicron-BA.1. Most of these introductions left a low number of descendants (<10), suggesting a limited impact on the evolution of the pandemic in Galicia. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

Contrast sensitivity is resilient to induced fast periodic defocus oscillations.

This study investigates the potential effects of periodic defocus oscillations on contrast sensitivity. Sinusoidal fluctuations at 5, 15, and 25 Hz, with defocus peak-to-valley values ranging from 0.15 to 3 D, were induced by means of a focus-tunable lens after calibrating its dynamic behavior. Monocular contrast sensitivity was measured on five young emmetropic subjects. The experimental data shows that contrast sensitivity loss due to defocus fluctuations is low for a wide range of frequencies and amplitudes. Only for the more severe case studied (25 Hz, ± 1.5 D) contrast threshold showed a clear increase in most subjects. Qualitative comparison of the empirical data with a simulation of modulation loss due to time integration of defocused retinal point spread functions, suggests a short integration time by the eye for defocus blur, around or even below a hundredth of a second.

Excitatory and inhibitory synapses show a tight subcellular correlation that weakens over development.

Neurons receive correlated levels of excitation and inhibition, a feature that is important for proper brain function. However, how this relationship between excitatory and inhibitory inputs is established during the dynamic period of circuit wiring remains unexplored. Using multiple techniques, including in utero electroporation, electron microscopy, and electrophysiology, we reveal a tight correlation in the distribution of excitatory and inhibitory synapses along the dendrites of developing CA1 hippocampal neurons. This correlation was present within short dendritic stretches (<20 µm) and, surprisingly, was most pronounced during early development, sharply declining with maturity. The tight matching between excitation and inhibition was unexpected, as inhibitory synapses lacked an active zone when formed and exhibited compromised evoked release. We propose that inhibitory synapses form as a stabilizing scaffold to counterbalance growing excitation levels. This relationship diminishes over time, suggesting a critical role for a subcellular balance in early neuronal function and circuit formation.

In vitro antiproliferative effects of Vatairea macrocarpa (Benth.) Ducke lectin on human tumor cell lines and in vivo evaluation of its toxicity in Drosophila melanogaster.

Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 µg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 µg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC50 = 3.5 µg/mL), KG1 (IC50 = 18.6 µg/mL) and K562 (102.0 µg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 µg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte - HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells.

Navigating uncertainty in maximum body size in marine metazoans.

Body size is a fundamental biological trait shaping ecological interactions, evolutionary processes, and our understanding of the structure and dynamics of marine communities on a global scale. Accurately defining a species' body size, despite the ease of measurement, poses significant challenges due to varied methodologies, tool usage, and subjectivity among researchers, resulting in multiple, often discrepant size estimates. These discrepancies, stemming from diverse measurement approaches and inherent variability, could substantially impact the reliability and precision of ecological and evolutionary studies reliant on body size data across extensive species datasets. This study examines the variation in reported maximum body sizes across 69,570 individual measurements of maximum size, ranging from <0.2 µm to >45 m, for 27,271 species of marine metazoans. The research aims to investigate how reported maximum size variations within species relate to organism size, taxonomy, habitat, and the presence of skeletal structures. The investigation particularly focuses on understanding why discrepancies in maximum size estimates arise and their potential implications for broader ecological and evolutionary studies relying on body size data. Variation in reported maximum sizes is zero for 38% of species, and low for most species, although it exceeds two orders of magnitude for some species. The likelihood of zero variation in maximum size decreased with more measurements and increased in larger species, though this varied across phyla and habitats. Pelagic organisms consistently had low maximum size range values, while small species with unspecified habitats had the highest variation. Variations in maximum size within a species were notably smaller than interspecific variation at higher taxonomic levels. Significant variation in maximum size estimates exists within marine species, and partially explained by organism size, taxonomic group, and habitat. Variation in maximum size could be reduced by standardized measurement protocols and improved meta-data. Despite the variation, egregious errors in published maximum size measurements are rare, and their impact on comparative macroecological and macroevolutionary research is likely minimal.

Arrhythmic Mitral Valve Prolapse Phenotype: An Unsupervised Machine Learning Analysis Using a Multicenter Cardiac MRI Registry.

Purpose To use unsupervised machine learning to identify phenotypic clusters with increased risk of arrhythmic mitral valve prolapse (MVP). Materials and Methods This retrospective study included patients with MVP without hemodynamically significant mitral regurgitation or left ventricular (LV) dysfunction undergoing late gadolinium enhancement (LGE) cardiac MRI between October 2007 and June 2020 in 15 European tertiary centers. The study end point was a composite of sustained ventricular tachycardia, (aborted) sudden cardiac death, or unexplained syncope. Unsupervised data-driven hierarchical k-mean algorithm was utilized to identify phenotypic clusters. The association between clusters and the study end point was assessed by Cox proportional hazards model. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 female, 230 male) with two phenotypic clusters were identified. Patients in cluster 2 (199 of 474, 42%) had more severe mitral valve degeneration (ie, bileaflet MVP and leaflet displacement), left and right heart chamber remodeling, and myocardial fibrosis as assessed with LGE cardiac MRI than those in cluster 1. Demographic and clinical features (ie, symptoms, arrhythmias at Holter monitoring) had negligible contribution in differentiating the two clusters. Compared with cluster 1, the risk of developing the study end point over a median follow-up of 39 months was significantly higher in cluster 2 patients (hazard ratio: 3.79 [95% CI: 1.19, 12.12], P = .02) after adjustment for LGE extent. Conclusion Among patients with MVP without significant mitral regurgitation or LV dysfunction, unsupervised machine learning enabled the identification of two phenotypic clusters with distinct arrhythmic outcomes based primarily on cardiac MRI features. These results encourage the use of in-depth imaging-based phenotyping for implementing arrhythmic risk prediction in MVP. Keywords: MR Imaging, Cardiac, Cardiac MRI, Mitral Valve Prolapse, Cluster Analysis, Ventricular Arrhythmia, Sudden Cardiac Death, Unsupervised Machine Learning Supplemental material is available for this article. © RSNA, 2024.

AI Applied to Volatile Organic Compound (VOC) Profiles from Exhaled Breath Air for Early Detection of Lung Cancer.

Volatile organic compounds (VOCs) are an increasingly meaningful method for the early detection of various types of cancers, including lung cancer, through non-invasive methods. Traditional cancer detection techniques such as biopsies, imaging, and blood tests, though effective, often involve invasive procedures or are costly, time consuming, and painful. Recent advancements in technology have led to the exploration of VOC detection as a promising non-invasive and comfortable alternative. VOCs are organic chemicals that have a high vapor pressure at room temperature, making them readily detectable in breath, urine, and skin. The present study leverages artificial intelligence (AI) and machine learning algorithms to enhance classification accuracy and efficiency in detecting lung cancer through VOC analysis collected from exhaled breath air. Unlike other studies that primarily focus on identifying specific compounds, this study takes an agnostic approach, maximizing detection efficiency over the identification of specific compounds focusing on the overall compositional profiles and their differences across groups of patients. The results reported hereby uphold the potential of AI-driven techniques in revolutionizing early cancer detection methodologies towards their implementation in a clinical setting.

Clinical and biomechanical characteristics of responders and non-responders to insoles in individuals with excessive foot pronation during walking.

This study aimed to identify the clinical and biomechanical factors of subjects with excessive foot pronation who are not responsive (i.e., "non-responders") to medially wedged insoles to increase knee adduction external moment. Ankle dorsiflexion range of motion, forefoot-shank alignment, passive hip stiffness, and midfoot passive resistance of 25 adults with excessive bilateral pronation were measured. Also, lower-limb angles and external moments were computed during walking with the participants using control (flat surface) and intervention insoles (arch support and 6° medial heel wedge). A comparison between "responders" (n = 34) and "non-responders" (n = 11) was conducted using discrete and continuous analyses. Compared with the responders, the non-responders had smaller forefoot varus (p = 0.014), larger midfoot passive internal torque peak (p = 0.005), and stiffness measured by the torsimeter (p = 0.022). During walking, non-responders had lower angle peaks for forefoot eversion (p = 0.001), external forefoot rotation (p = 0.037), rearfoot eversion (p = 0.022), knee adduction (p = 0.045), and external hip rotation (p = 0.022) and higher hip internal rotation angle peak (p = 0.026). Participants with small forefoot varus alignment, large midfoot passive internal torque, stiffness, small knee valgus, hip rotated internally, and foot-toed-in during walking did not modify the external knee adduction moment ("non-responders"). Clinicians are advised to interpret these findings with caution when considering the prescription of insoles. Further investigation is warranted to fully comprehend the response to insole interventions among individuals with specific pathologies, such as patellofemoral pain and knee osteoarthritis (OA).

Is waiting for rewards good for you? No association between impulsive choice, psychopathology, and functional outcomes in a large cohort sample.

Background: A stronger preference for immediate rewards has been reported in individuals with ADHD and other disorders. However, the consistency of the associations between this preference and psychiatric conditions as well as functional outcomes have been questioned. Research on its association with longitudinal outcomes is scarce. Methods: The current study used data on a choice delay task (CDT) from a school-based cohort of Brazilian children with those at higher risk for psychiatric disorders over-sampled (n = 1917). The sample included typically developing children (n = 1379), those with ADHD (n = 213), and other disorders. The frequency of the trials where children chose a larger later reward versus a smaller sooner reward was compared for those with ADHD and typically developing children. Cross-sectionally and longitudinally, the study also evaluated whether children's preference for larger delayed rewards at baseline predicted the presence of psychiatric disorders and functional life outcomes (academic performance, alcohol use, early pregnancy, criminal conviction, BMI). Results: Children with ADHD and their typically developing peers performed similarly on the CDT. Their baseline task performance was not related to psychiatric conditions or life outcomes. Conclusions: The current results raise questions regarding the use of the CDT with diverse populations and whether a preference for larger delayed rewards is predictive of positive long-term outcomes as widely assumed.

Citizen silence: Missed opportunities in citizen science.

Citizen science is personal. Participation is contingent on the citizens' connection to a topic or to interpersonal relationships meaningful to them. But from the peer-reviewed literature, scientists appear to have an acquisitive data-centered relationship with citizens. This has spurred ethical and pragmatic criticisms of extractive relationships with citizen scientists. We suggest five practical steps to shift citizen-science research from extractive to relational, reorienting the research process and providing reciprocal benefits to researchers and citizen scientists. By virtue of their interests and experience within their local environments, citizen scientists have expertise that, if engaged, can improve research methods and product design decisions. To boost the value of scientific outputs to society and participants, citizen-science research teams should rethink how they engage and value volunteers.

Adverse Childhood Experiences and Their Relationships with Perceived Stress and Self-Care Behaviors in African American Social Work Students: Insights from a Latent Class Analysis.

Based on stress sensitization theory and stress proliferation theory, this study was designed to identify adverse childhood experience (ACE) classes and their relationships with perceived stress and self-care behaviors. Hypotheses were that (a) there would be diverse ACE classes among African American social work students; (b) the identified classes embedded in high/multiple ACEs would have greater levels of perceived stress than those in low ACEs; and (c) the identified classes embedded in high/multiple ACEs would have lower levels of self-care behaviors than those in low ACEs. Recruited from one of the South's historically Black colleges and universities, 186 African American social work students completed an online survey. Latent class analysis found three classes fit the data best: low ACEs, high divorce/abuse/neglect, and high/multiple ACEs. Students in the high divorce/abuse/neglect class had the greatest levels of perceived stress and significantly greater perceived stress levels than the low ACEs class. The low ACEs class had greater self-care behaviors than students in the other two ACEs classes. The study revealed diverse ACE classes and the effect of more ACEs on greater perceived stress and lower self-care behaviors, supporting the importance of using a range of approaches to support African American social work students with different ACEs.

Granulocyte-macrophage colony-stimulating factor neutralisation in patients with axial spondyloarthritis in the UK (NAMASTE): a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine overproduced in several inflammatory and autoimmune diseases, including axial spondyloarthritis. Namilumab is a human IgG1 monoclonal anti-GM-CSF antibody that potently neutralises human GM-CSF. We aimed to assess the efficacy of namilumab in participants with moderate-to-severe active axial spondyloarthritis. METHODS: This proof-of-concept, randomised, double-blind, placebo-controlled, phase 2, Bayesian (NAMASTE) trial was done at nine hospitals in the UK. Participants aged 18-75 years with axial spondyloarthritis, meeting the Assessment in SpondyloArthritis international Society (ASAS) criteria and the ASAS-defined MRI criteria, with active disease as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), were eligible. Those who had inadequately responded or had intolerance to previous treatment with an anti-TNF agent were included. Participants were randomly assigned (6:1) to receive subcutaneous namilumab 150 mg or placebo at weeks 0, 2, 6, and 10. Participants, site staff (except pharmacy staff), and central study staff were masked to treatment assignment. The primary endpoint was the proportion of participants who had an ASAS ≥20% improvement (ASAS20) clinical response at week 12 in the full analysis set (all randomly assigned participants). This trial is registered with ClinicalTrials.gov (NCT03622658). FINDINGS: From Sept 6, 2018, to July 25, 2019, 60 patients with moderate-to-severe active axial spondyloarthritis were assessed for eligibility and 42 were randomly assigned to receive namilumab (n=36) or placebo (n=six). The mean age of participants was 39·5 years (SD 13·3), 17 were women, 25 were men, 39 were White, and seven had previously received anti-TNF therapy. The primary endpoint was not met. At week 12, the proportion of patients who had an ASAS20 clinical response was lower in the namilumab group (14 of 36) than in the placebo group (three of six; estimated between-group difference 6·8%). The Bayesian posterior probability η was 0·72 (>0·927 suggests high clinical significance). The rates of any treatment-emergent adverse events in the namilumab group were similar to those in the placebo group (31 vs five). INTERPRETATION: Namilumab did not show efficacy compared with placebo in patients with active axial spondyloarthritis, but the treatment was generally well tolerated. FUNDING: Izana Bioscience, NIHR Oxford Biomedical Research Centre (BRC), NIHR Birmingham BRC, and Clinical Research Facility.

Evidence of SARS-CoV-2 Antibody in Mississippi White-Tailed Deer.

Background: Early detection and monitoring of SARS-CoV-2 infections in animal populations living in close proximity to humans is crucial for preventing reverse zoonosis of new viral strains. Evidence accumulated has revealed widespread SARS-CoV-2 infection among white-tailed deer (WTD), (Odocoileus virginianus) populations in the United States except in the southeast region. Therefore, the objective was to conduct surveillance for evidence of SARS-CoV-2 infection among WTD in Mississippi. Materials and Methods: Blood, kidney tissues, and nasal swab samples were collected in 17 counties from hunter-harvested deer during 2021-2022 and 2022-2023.Samples of kidney tissue were collected to evaluate for detecting antibody as a possible alternative to blood that is not always available from dead WTD. Nasal swab samples were tested for SARS-CoV-2 viral RNA by a RT-PCR assay. Sera and kidney tissue samples were tested for SARS-CoV-2 antibody by an enzyme-linked immunoassay (ELISA) and sera by a plaque reduction neutralization test (PRNT80). Results: The results of testing sera and kidney homogenate samples provided the first evidence of SARS-CoV-2 infection among WTD in Mississippi. The infection rate during 2021-2022 was 67% (10/15) based on the detection of neutralizing antibody by the PRNT80 and 26%(16/62) based on the testing of kidney tissue homogenates by an ELISA, and viral RNA was detected in 25% (3/12) of nasal swab samples. In 2022 to 2023, neutralizing antibody was detected in 62% (28/45) of WTD serum samples. In contrast, antibodies were not detected in 220 kidney homogenates by an ELISA nor was viral RNA detected in 220 nasal swab samples. Evidence of WTD activity was common in urban areas during the survey. Conclusion: Overall, the findings documented the first SARS-CoV-2 infection among WTD in Mississippi and showed that WTD commonly inhabited urban areas as a possible source of acquiring infection from humans infected with this virus.