Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells; increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL6 may be preferable to IL1 or TNF-α . We identified several potential mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C suggesting complement inhibitors could be used to treat the disease.

A hydrogel is a polymeric three-dimensional network structure. The applications of this material type are diversified over a broad range of fields. Their soft nature and similarity to natural tissue allows for their use in tissue engineering, medical devices, agriculture, and industrial health products. However, as the demand for such materials increases, the need to understand the material mechanics is paramount across all fields. As a result, many attempts to numerically model the swelling and drying of chemically responsive hydrogels have been published. Material characterization of the mechanical properties of a gel bead under osmotic loading is difficult. As a result, much of the literature has implemented variants of swelling theories. Therefore, this article focuses on reviewing the current literature and outlining the numerical models of swelling hydrogels as a result of exposure to chemical stimuli. Furthermore, the experimental techniques attempting to quantify bulk gel mechanics are summarized. Finally, an overview on the mechanisms governing the formation of geometric surface instabilities during transient swelling of soft materials is provided.

EBV is a direct causative agent in around 1.5% of all cancers. The oncogenic properties of EBV are related to its ability to activate processes needed for cellular proliferation, survival, migration, and immune evasion. The EBV latency program is required for the immortalization of infected B cells and involves the expression of non-coding RNAs (ncRNAs), including viral microRNAs. These ncRNAs have different functions that contribute to virus persistence in the asymptomatic host and to the development of EBV-associated cancers. In this review, we discuss the function and potential clinical utility of EBV microRNAs and other ncRNAs in EBV-associated malignancies. This review is not intended to be comprehensive, but rather to provide examples of the importance of ncRNAs.

The Flory-Rehner theoretical description of the free energy in a hydrogel swelling model can be broken into two swelling components: the mixing energy and the ionic energy. Conventionally for ionized gels, the ionic energy is characterized as the main contributor to swelling and, therefore, the mixing energy is assumed negligible. However, this assumption is made at the equilibrium state and ignores the dynamics of gel swelling. Here, the influence of the mixing energy on swelling ionized gels is quantified through numerical simulations on sodium polyacrylate using a Mixed Hybrid Finite Element Method. For univalent and divalent solutions, at initial porosities greater than 0.90, the contribution of the mixing energy is negligible. However, at initial porosities less than 0.90, the total swelling pressure is significantly influenced by the mixing energy. Therefore, both ionic and mixing energies are required for the modeling of sodium polyacrylate ionized gel swelling. The numerical model results are in good agreement with the analytical solution as well as experimental swelling tests.

Pancreatic ductal adenocarcinoma (PDAC) has a poor clinical outlook. Responses to immune checkpoint blockade are suboptimal and a much more detailed understanding of the tumor immune microenvironment is needed if this situation is to be improved. Here, we characterized tumor-infiltrating T-cell populations in patients with PDAC using cytometry by time of flight (CyTOF) and single-cell RNA sequencing (scRNAseq). T cells were the predominant immune cell subset observed within tumors. Over 30% of CD4+ T cells expressed a CCR6+CD161+ Th17 phenotype and 17% displayed an activated regulatory T-cell profile. Large populations of CD8+ tissue-resident memory (TRM) T cells were also present and expressed high levels of PD-1 and TIGIT. A population of putative tumor-reactive CD103+CD39+ T cells was also observed within the CD8+ TIL population. The expression of PD-1 ligands was limited largely to haemopoietic cells whilst TIGIT ligands were expressed widely within the tumor microenvironment. PD-L1 and CD155 were expressed within the T-cell area of ectopic lymphoid structures and colocalized with PD-1+TIGIT+ CD8+ T cells. Combinatorial anti–PD-1 and TIGIT blockade enhanced IFN secretion and proliferation of T cells in the presence of PD-1 and TIGIT ligands. As such, we showed that the PDAC microenvironment is characterized by the presence of substantial populations of TRM cells with an exhausted PD-1+TIGIT+ phenotype where dual checkpoint receptor blockade represents a promising avenue for future immunotherapy.

In this study, we have re-evaluated how EBV status influences clinical outcome. To accomplish this, we performed a literature review of all studies that have reported the effect of EBV status on patient outcome and also explored the effect of EBV positivity on outcome in a clinical trial of children with cHL from the UK. Our literature review revealed that almost all studies of older adults/elderly patients have reported an adverse effect of an EBV-positive status on outcome. In younger adults with cHL, EBV-positive status was either associated with a moderate beneficial effect or no effect, and the results in children and adolescents were conflicting. Our own analysis of a series of 166 children with cHL revealed no difference in overall survival between EBV-positive and EBV-negative groups (p = 0.942, log rank test). However, EBV-positive subjects had significantly longer event-free survival (p = 0.0026). Positive latent membrane protein 1 (LMP1) status was associated with a significantly lower risk of treatment failure in a Cox regression model (HR = 0.21, p = 0.005). In models that controlled for age, gender, and stage, EBV status had a similar effect size and statistical significance. This study highlights the age-related impact of EBV status on outcome in cHL patients and suggests different pathogenic effects of EBV at different stages of life.

Paediatric inflammatory multisystem inflammatory syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS) is a new disease with overlapping features of Kawasaki disease (KD) and toxic shock syndrome. Unbiased single cell RNA sequencing analysis of peripheral blood mononuclear cells from PIMS-TS and KD patients shows monocytes are the main source of pro-inflammatory cytokines and large changes in the frequency of classical, intermediate and non-classical monocytes occur in both diseases.

The key role of tertiary lymphoid structures in autoimmune and non-autoimmune conditions has been recently appreciated. While many of the molecular mechanisms involved in tertiary lymphoid structure (TLS) formation have been identified, their cellular sources and their temporal and spatial relationship to each other during the development of TLS remain unknown. Here we have constructed a cellular and functional map of key components involved in the formation of TLS in the minor salivary glands (SG) in humans. We have confirmed the presence of an immunofibroblast cell state and identified an undescribed immunopericyte cell state with potential immunological functions within TLS. The identification of TLS cellular and functional properties and their relevant modulators provided by this analysis provides key therapeutic cues for TLS associated conditions in autoimmunity and cancer.