Digital community assets: Investigating the impact of online engagement with arts and peer support groups on mental health during COVID-19

The digitisation of mental health support has acceler- ated since the outbreak of the COVID-19 pandemic. This study investigated the impact of digital engagement with community assets on mental health during COVID- 19. Digital engagement is typically not location-bound, but the restricted movement enforced during ‘lock- downs’ meant that people were primarily accessing digital community assets from their home environ- ments. We report findings from a study utilising two creative workshops and semi-structured interviews to investigate how support operates in and through three digital community assets; an online peer support forum, a social enterprise running regular creative challenges nationally via social media and a local in-person crea- tive arts support group. The concept of ‘more or less digital’ captures the ways that people’s experiences of digital community assets extend beyond the platforms to incorporate settings of use. The analysis identifies how support is diluted through digital engagement, the value of minimal and muted forms of engagement and user-led designs for future hybrid forms of support. The article concludes by emphasising the importance of analysing digital community asset engagement in the settings of use and how such knowledge is vital for plan- ning support in a future under continual pressure to be increasingly digital

Enhanced Infection of Liver Sinusoidal Endothelial Cells in a Mouse Model of Antibody-Induced Severe Dengue Disease

SummaryDengue virus (DENV) causes disease ranging from dengue fever (DF), a self-limited febrile illness, to the potentially lethal dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). DHF/DSS usually occurs in patients who have acquired DENV-reactive antibodies prior to infection, either from a previous infection with a heterologous DENV serotype or from an immune mother. Hence, it has been hypothesized that subneutralizing levels of antibodies exacerbate disease, a phenomenon termed antibody-dependent enhancement (ADE). However, given the lack of suitable animal models for DENV infection, the mechanism of ADE and its contribution to pathology remain elusive. Here we demonstrate in mice that DENV-specific antibodies can sufficiently increase severity of disease so that a mostly nonlethal illness becomes a fatal disease resembling human DHF/DSS. Antibodies promote massive infection of liver sinusoidal endothelial cells (LSECs), resulting in increased systemic levels of virus. Thus, a subprotective humoral response may, under some circumstances, have pathological consequences

Digital community assets: Investigating the impact of online engagement with arts and peer support groups on mental health during COVID‐19

The digitisation of mental health support has accelerated since the outbreak of the COVID-19 pandemic. This study investigated the impact of digital engagement with community assets on mental health during COVID-19. Digital engagement is typically not location-bound, but the restricted movement enforced during ‘lockdowns’ meant that people were primarily accessing digital community assets from their home environments. We report findings from a study utilising two creative workshops and semi-structured interviews to investigate how support operates in and through three digital community assets; an online peer support forum, a social enterprise running regular creative challenges nationally via social media and a local in-person creative arts support group. The concept of ‘more or less digital’ captures the ways that people’s experiences of digital community assets extend beyond the platforms to incorporate settings of use. The analysis identifies how support is diluted through digital engagement, the value of minimal and muted forms of engagement and user-led designs for future hybrid forms of support. The article concludes by emphasising the importance of analysing digital community asset engagement in the settings of use and how such knowledge is vital for planning support in a future under continual pressure to be increasingly digital

HIV-1 Packaging Visualised by In-Gel SHAPE.

HIV-1 packages two copies of its gRNA into virions via an interaction with the viral structural protein Gag. Both copies and their native RNA structure are essential for virion infectivity. The precise stepwise nature of the packaging process has not been resolved. This is largely due to a prior lack of structural techniques that follow RNA structural changes within an RNA-protein complex. Here, we apply the in-gel SHAPE (selective 2'OH acylation analysed by primer extension) technique to study the initiation of HIV-1 packaging, examining the interaction between the packaging signal RNA and the Gag polyprotein, and compare it with that of the NC domain of Gag alone. Our results imply interactions between Gag and monomeric packaging signal RNA in switching the RNA conformation into a dimerisation-competent structure, and show that the Gag-dimer complex then continues to stabilise. These data provide a novel insight into how HIV-1 regulates the translation and packaging of its genome.This work was funded by an Eric Reid fund for Methodology grant from the Biochemical Society (to JCK), UK Medical Research Council, Grant/Award Number: MR/N022939/1 (to AML and JCK). AMLL is supported by the Clinical Academic Reserve and his laboratory by the NIHR Cambridge BRC (Grant RCAG/18). Research in the Kappei laboratory was supported by the National Research Foundation Singapore and the Singapore Ministry of Education under its Re-search Centres of Excellence initiative

HIV-1 Packaging Visualised by In-Gel SHAPE.

HIV-1 packages two copies of its gRNA into virions via an interaction with the viral structural protein Gag. Both copies and their native RNA structure are essential for virion infectivity. The precise stepwise nature of the packaging process has not been resolved. This is largely due to a prior lack of structural techniques that follow RNA structural changes within an RNA-protein complex. Here, we apply the in-gel SHAPE (selective 2'OH acylation analysed by primer extension) technique to study the initiation of HIV-1 packaging, examining the interaction between the packaging signal RNA and the Gag polyprotein, and compare it with that of the NC domain of Gag alone. Our results imply interactions between Gag and monomeric packaging signal RNA in switching the RNA conformation into a dimerisation-competent structure, and show that the Gag-dimer complex then continues to stabilise. These data provide a novel insight into how HIV-1 regulates the translation and packaging of its genome.This work was funded by an Eric Reid fund for Methodology grant from the Biochemical Society (to JCK), UK Medical Research Council, Grant/Award Number: MR/N022939/1 (to AML and JCK). AMLL is supported by the Clinical Academic Reserve and his laboratory by the NIHR Cambridge BRC (Grant RCAG/18). Research in the Kappei laboratory was supported by the National Research Foundation Singapore and the Singapore Ministry of Education under its Re-search Centres of Excellence initiative

Task-adaptive physical reservoir computing

Reservoir computing is a neuromorphic architecture that potentially offers viable solutions to the growing energy costs of machine learning. In software-based machine learning, neural network properties and performance can be readily reconfigured to suit different computational tasks by changing hyperparameters. This critical functionality is missing in ``physical" reservoir computing schemes that exploit nonlinear and history-dependent memory responses of physical systems for data processing. Here, we experimentally present a `task-adaptive' approach to physical reservoir computing, capable of reconfiguring key reservoir properties (nonlinearity, memory-capacity and complexity) to optimise computational performance across a broad range of tasks. As a model case of this, we use the temperature and magnetic-field controlled spin-wave response of Cu$_2$OSeO$_3$ that hosts skyrmion, conical and helical magnetic phases, providing on-demand access to a host of different physical reservoir responses. We quantify phase-tunable reservoir performance, characterise their properties and discuss the correlation between these in physical reservoirs. This task-adaptive approach overcomes key prior limitations of physical reservoirs, opening opportunities to apply thermodynamically stable and metastable phase control across a wide variety of physical reservoir systems, as we show its transferable nature using above(near)-room-temperature demonstration with Co$_{8.5}$Zn$_{8.5}$Mn$_{3}$ (FeGe).Comment: Main manuscript: 14 pages, 5 figures. Supplementary materials: 13 pages, 10 figure

Task-adaptive physical reservoir computing

Reservoir computing is a neuromorphic architecture that may offer viable solutions to the growing energy costs of machine learning. In software-based machine learning, computing performance can be readily reconfigured to suit different computational tasks by tuning hyperparameters. This critical functionality is missing in 'physical' reservoir computing schemes that exploit nonlinear and history-dependent responses of physical systems for data processing. Here we overcome this issue with a 'task-adaptive' approach to physical reservoir computing. By leveraging a thermodynamical phase space to reconfigure key reservoir properties, we optimize computational performance across a diverse task set. We use the spin-wave spectra of the chiral magnet Cu2OSeO3 that hosts skyrmion, conical and helical magnetic phases, providing on-demand access to different computational reservoir responses. The task-adaptive approach is applicable to a wide variety of physical systems, which we show in other chiral magnets via above (and near) room-temperature demonstrations in Co8.5Zn8.5Mn3 (and FeGe)

Systemic immunity is required for effective cancer immunotherapy

Immune responses involve coordination across cell types and tissues. However, studies in cancer immunotherapy have focused heavily on local immune responses in the tumor microenvironment. To investigate immune activity more broadly, we performed an organism-wide study in genetically engineered cancer models using mass cytometry. We analyzed immune responses in several tissues after immunotherapy by developing intuitive models for visualizing single-cell data with statistical inference. Immune activation was evident in the tumor and systemically shortly after effective therapy was administered. However, during tumor rejection, only peripheral immune cells sustained their proliferation. This systemic response was coordinated across tissues and required for tumor eradication in several immunotherapy models. An emergent population of peripheral CD4 T cells conferred protection against new tumors and was significantly expanded in patients responding to immunotherapy. These studies demonstrate the critical impact of systemic immune responses that drive tumor rejection

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia.

Introduction: The change in bone turnover markers (BTM) in response to osteoporosis therapy can be assessed by a decrease beyond the least significant change (LSC) or below the mean of the reference interval (RI). We compared the performance of these two approaches in women treated with raloxifene. Methods: Fifty postmenopausal osteopenic women, (age 51-72y) were randomised to raloxifene or no treatment for 2 years. Blood samples were collected for the measurement of BTM. The LSC for each marker was calculated from the untreated women and the RI obtained from healthy premenopausal women (age 35-40y). Bone mineral density (BMD) was measured at the spine and hip. Results: There was a decrease in BTM in response to raloxifene treatment; percentage change at 12 weeks, CTX -39% (95% CI -48 to -28) and PINP -32% (95% CI -40 to -23) P<0.001. The proportion of women classified as responding to treatment using LSC at 12 weeks was: CTX 38%, PINP 52%, at 48 weeks CTX 60%, PINP 65%. For the RI approach; at 12 weeks CTX and PINP 38%, at 48 weeks CTX 40%, PINP 45%. There was a significant difference in the change in spine BMD in the raloxifene treated group compared to the no-treatment group at week 48; difference 0.031 g/cm2, (95% CI 0.016 to 0.046, P<0.001). Conclusions: The two approaches identified women that reached the target for treatment using BTM. Both LSC and RI criteria appear useful in identifying treatment response but the two approaches do not fully overlap and may be complementary

HVEM Signalling Promotes Colitis

Background Tumor necrosis factor super family (TNFSF) members regulate important processes involved in cell proliferation, survival and differentiation and are therefore crucial for the balance between homeostasis and inflammatory responses. Several members of the TNFSF are closely associated with inflammatory bowel disease (IBD). Thus, they represent interesting new targets for therapeutic treatment of IBD. Methodology/Principal Findings We have used mice deficient in TNFSF member HVEM in experimental models of IBD to investigate its role in the disease process. Two models of IBD were employed: i) chemical-induced colitis primarily mediated by innate immune cells; and ii) colitis initiated by CD4+CD45RBhigh T cells following their transfer into immuno-deficient RAG1-/- hosts. In both models of disease the absence of HVEM resulted in a significant reduction in colitis and inflammatory cytokine production. Conclusions These data show that HVEM stimulatory signals promote experimental colitis driven by innate or adaptive immune cells