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Abstract Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children.

Abstract It has been established that the human gut microbiota is central to health, and, consequently, there has been a growing desire to positively modulate its composition and/or function through, for example, the use of fermented foods, prebiotics or probiotics. Here, we compare the relative impact of the daily consumption of an inulin-enriched diet (n = 10), a commercial probiotic-containing fermented milk product (FMP) (n = 10), or a traditional kefir FMP (n = 9), over a 28-day period on the gut microbiome and urine metabolome of healthy human adults. None of the treatments resulted in significant changes to clinical parameters or biomarkers tested. However, shotgun metagenomic analysis revealed that kefir consumption resulted in a significant change in taxonomy, in the form of an increased abundance of the sub-dominant FMP-associated species Lactococcus raffinolactis, which further corresponded to shifts in the urine metabolome. Overall, our results indicated that daily consumption of a single portion of kefir alone resulted in detectable changes to the gut microbiota and metabolome of consumers.

Abstract Objective Given the ability of ultrasound imaging (USI) to depict tissue‐specific morphological changes before the onset of pain and before the point of irreversible structural damage, USI could play a fundamental role in earlier detection and assessment of foot osteoarthritis (OA). The current guidelines require further refinement of anatomical landmarks to establish a standardized imaging procedure to improve the interpretability and reproducibility between studies evaluating the first metatarsophalangeal joint (MTPJ). The aims were to develop an USI acquisition procedure and grading system to examine OA features in the first MTPJ and to determine intra‐examiner and inter‐examiner reliability of a newly developed USI acquisition procedure. Design Thirty participants with first MTPJ OA confirmed radiographically with the use of the La Trobe Foot Atlas were included. An experienced sonographer applied a newly developed USI procedure to examine the following features: joint effusion, synovial hypertrophy, synovitis, joint space narrowing, osteophytes, and cartilage thickness. A semiquantitative grading system was applied to all features. A continuous measure was also examined for osteophyte size, joint space narrowing, and cartilage thickness. To determine the intra‐examiner and inter‐examiner reliability, an experienced radiologist and sonographer applied the developed grading system to the images acquired from two imaging sessions. Intra‐examiner and inter‐examiner reliability were calculated using intraclass correlation coefficients (ICCs). Results ICCs for intra‐examiner between session reliability ranged from 0.58 to 0.92 for semiquantitative grading and 0.39 to 0.94 for continuous measures. Joint effusion and osteophytes achieved the highest intra‐examiner reliability (ICC = 0.78–0.94). ICCs for session one inter‐examiner reliability ranged from 0.61 to 1.0 for semiquantitative grading; all continuous measures had an ICC of 1. ICCs for session two inter‐examiner reliability ranged from 0.55 to 1.0 for semiquantitative grading and 0.9 to 0.97 for continuous measures. Inter‐examiner reliability was good for grading joint effusion (ICC = 0.55–0.62) and was excellent for all other USI features (ICC = 0.77–1.0). Conclusion The USI acquisition procedure and grading system are reliable in evaluating first MTPJ OA features in participants with radiologically confirmed OA. The study will inform the methodological development of an ultrasound atlas for grading the degree of osteoarthritic change in the first MTPJ.

The baryon cycle is crucial for understanding galaxy formation, as gas inflows and outflows vary throughout a galaxy’s lifetime and affect its star formation rate. Despite the necessity of accretion for galaxy growth at high redshifts, direct observations of inflowing gas have proven elusive, especially at z ≳ 2. We present a spectroscopic analysis of a galaxy at redshift z = 2.45, which exhibits signs of inflow in several ultraviolet interstellar absorption lines, with no clear outflow signatures. The absorption lines are redshifted by ∼250 km s ^−1 with respect to the systemic redshift, and C iv shows a prominent inverse P-Cygni profile. Simple stellar population models suggest that this galaxy has a low metallicity (∼5% solar), with a very young starburst of age ∼4 Myr dominating the ultraviolet luminosity. The gas inflow velocity and nebular velocity dispersion suggest an approximate halo mass of order ∼10 ^11 M _⊙ , a regime in which simulations predict that bursty star formation is common at this redshift. We conclude that this system is likely in the beginning of a cycle of bursty star formation, where inflow and star formation rates are high, but where supernovae and other feedback processes have not yet launched strong outflows. In this scenario, we expect the inflow-dominated phase to be observable (e.g., with net redshifted interstellar medium absorption) for only a short timescale after a starburst onset. This result represents a promising avenue for probing the full baryon cycle, including inflows, during the formative phases of low-mass galaxies at high redshifts.

Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance of LN fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within the tumor microenvironment (TME). However, the immunomodulatory role of fibroblasts in lymphoma remains unclear. Here, by studying human and mouse DLBCL-LNs, we identified the presence of an aberrantly remodeled fibroblastic reticular cell (FRC) network expressing elevated fibroblast-activated protein (FAP). RNA-Seq analyses revealed that exposure to DLBCL reprogrammed key immunoregulatory pathways in FRCs, including a switch from homeostatic to inflammatory chemokine expression and elevated antigen-presentation molecules. Functional assays showed that DLBCL-activated FRCs (DLBCL-FRCs) hindered optimal TIL and chimeric antigen receptor (CAR) T cell migration. Moreover, DLBCL-FRCs inhibited CD8+ TIL cytotoxicity in an antigen-specific manner. Notably, the interrogation of patient LNs with imaging mass cytometry identified distinct environments differing in their CD8+ TIL-FRC composition and spatial organization that associated with survival outcomes. We further demonstrated the potential to target inhibitory FRCs to rejuvenate interacting TILs. Cotreating organotypic cultures with FAP-targeted immunostimulatory drugs and a bispecific antibody (glofitamab) augmented antilymphoma TIL cytotoxicity. Our study reveals an immunosuppressive role of FRCs in DLBCL, with implications for immune evasion, disease pathogenesis, and optimizing immunotherapy for patients.

Objective: To reach consensus concerning which ultrasound imaging features should be assessed and graded, and what ultrasound imaging procedure should be performed when examining osteoarthritic change in the first metatarsophalangeal joint. Design: An online Delphi study was conducted over four iterative rounds with 16 expert health professionals. Items were scored from 0 to 100 (0 ​= ​not at all important; 100 ​= ​extremely important). Consensus was defined based upon an item receiving a median score of ≥70% acceptance. Items receiving median score of ≤50% were rejected. Items considered ambiguous (median score 51%–69% of acceptance) were assessed in an additional round. A final round determined the content validity of items through calculation of the content validity ratio and content validity index. Results: Sixteen items were deemed essential, which included osteophytes graded dichotomously, cartilage damage graded continuously, synovitis and joint space narrowing graded on a semiquantitative scale. The panel deemed essential that the first metatarsophalangeal joint start in a neutral position, then move through range of motion for both dorsal and plantar scanning, orientating the probe in longitudinal and in transverse, whilst using first metatarsal head and proximal phalanx as anatomical landmarks. A supine body position was only deemed essential for a dorsal scan and a neutral foot/ankle position was only rated essential for a plantar scan. The content validity index of the 16 essential items was 0.19. Conclusion: The consensus exercise has identified the essential components the ultrasound imaging acquisition procedure should encompass when examining first metatarsophalangeal joint osteoarthritis.

Abstract Low back pain (LBP) is the leading contributor to years lived with disability, and imposes an enormous burden on individuals and on health-care systems. General practitioners and physiotherapists are generally the front-line health professionals dealing with patients with LBP, and have a key role in minimising its effect. Here we review six key issues associated with LBP including its effects, diagnosis and management in primary care, and highlight the importance of the biopsychosocial model and matched care for patients with LBP.

Abstract Objectives Temporal and global changes in research utilising imaging to assess foot osteoarthritis is currently unknown. This study aimed to undertake a bibliometric analysis of published research to: (1) identify the imaging modalities that have been used to evaluate foot osteoarthritis; (2) explore the temporal changes and global differences in the use of these imaging modalities; and (3) to evaluate performance related to publication‐ and citation‐based metrics. Methods A literature search was conducted using Scopus to identify studies which had used imaging to assess foot osteoarthritis. Extracted data included publication year, imaging modality, citations, affiliations, and author collaboration networks. Temporal trends in the use of each imaging modality were analysed. Performance analysis and science mapping were used to analyse citations and collaboration networks. Results 158 studies were identified between 1980 and 2021. Plain radiography was the most widely used modality, followed by computed tomography, magnetic resonance imaging (MRI) and ultrasound imaging (USI), respectively. The number of published studies increased over time for each imaging modality (all P ≥ 0.018). The most productive country was the United States of America (USA), followed by the United Kingdom and Australia. International authorship collaboration was evident in 57 (36.1%) studies. The average citation rate was 23.4 per study, with an average annual citation rate of 2.1. Conclusions Published research employing imaging to assess foot osteoarthritis has increased substantially over the past four decades. Although plain radiography remains the gold standard modality, the emergence of MRI and USI in the past two decades continues to advance knowledge and progress research in this field.

In this study, the degradation of wood pellets and dry roasted coffee beans in a pneumatic conveyor was evaluated for high-speed impacts. The change in particle size and generation of fine particles were used as an indicating parameter for the degradation. A four-bends industrial scale conveying system was used for the degradation study in lean phase pneumatic conveying. The effects of operating parameters on the degradation were investigated, including the conveying velocity of particles and particle concentration. The experimental results showed that the degradation and the fines generation increased with an increase in particle velocity. An opposite trend was observed with an increased solid concentration in the pipeline. It was found that the two types of wood pellets traveled at different particle velocities with the same operating conditions, which resulted in significant differences in the degradation. Compared to the wood pellets, roasted coffee beans were found to travel at air velocity. In conclusion, the degradation in a pneumatic conveying system is complex and challenging to evaluate because there are many influential factors, such as the type of materials, equipment, and operation conditions. Early assessments in a laboratory will be beneficial to evaluate the degradation at all controlled operative conditions.

A 35-year-old female with positive anamnesis of COVID-19 infection presented with a seven-day history of headache along with tingling and numbness involving the right lower limb and visual disturbance on the right side of her vision. Magnetic resonance imaging (MRI) of the brain and C-spine were consistent with acute demyelinating lesions. However, the MAGNIMS criteria for a multiple sclerosis diagnosis were not met, and, subsequently, a diagnosis of clinically isolated syndrome (CIS) was made. At 12 months, the patient showed new inflammatory lesions in the right frontal lobe and at the septocallosal interface, a lesion of the right hemi-cord at C3, and subsequent development of vertigo and unsteadiness and signs consistent with a brainstem/cerebellar relapse. On the basis of clinical and radiological criteria in the 2017 McDonald criteria, a diagnosis of relapsing remitting multiple sclerosis was made.