Search

Abstract Background The pretherapeutic differentiation of subtypes of primary intracranial germ cell tumours (iGCTs), including germinomas (GEs) and nongerminomatous germ cell tumours (NGGCTs), is essential for clinical practice because of distinct treatment strategies and prognostic profiles of these diseases. This study aimed to develop a deep learning model, iGNet, to assist in the differentiation and prognostication of iGCT subtypes by employing pretherapeutic MR T2-weighted imaging. Methods The iGNet model, which is based on the nnUNet architecture, was developed using a retrospective dataset of 280 pathologically confirmed iGCT patients. The training dataset included 83 GEs and 117 NGGCTs, while the retrospective internal test dataset included 31 GEs and 49 NGGCTs. The model’s diagnostic performance was then assessed with the area under the receiver operating characteristic curve (AUC) in a prospective internal dataset (n = 22) and two external datasets (n = 22 and 20). Next, we compared the diagnostic performance of six neuroradiologists with or without the assistance of iGNet. Finally, the predictive ability of the output of iGNet for progression-free and overall survival was assessed and compared to that of the pathological diagnosis. Results iGNet achieved high diagnostic performance, with AUCs between 0.869 and 0.950 across the four test datasets. With the assistance of iGNet, the six neuroradiologists’ diagnostic AUCs (averages of the four test datasets) increased by 9.22% to 17.90%. There was no significant difference between the output of iGNet and the results of pathological diagnosis in predicting progression-free and overall survival (P = .889). Conclusions By leveraging pretherapeutic MR imaging data, iGNet accurately differentiates iGCT subtypes, facilitating prognostic evaluation and increasing the potential for tailored treatment. Graphical Abstract

BackgroundFew individuals (

Evidence is increasing for digital health programs targeting the secondary prevention of stroke. We aimed to determine the feasibility of the novel Care Assistant and support Program for people after Stroke (CAPS) or transient ischaemic attack (TIA) by combining person-centred goal setting and risk-factor monitoring through a web-based clinician portal, SMS messages, a mobile application (app), and a wearable device. We conducted a 12-week mixed-methods, open-label feasibility study. Participants (6 months–3 years after stroke or TIA, access to the internet via a smartphone/tablet) were recruited via the Australian Stroke Clinical Registry. Participants set one or two secondary prevention goals with a researcher and provided access and training in technology use. Feasibility outcomes included recruitment, retention, usability, acceptability, and satisfaction. Secondary outcomes included goal attainment, health outcomes, and program costs. Following 600 invitations, 58 responded, 34/36 (94%) eligible participants commenced the program (one withdrawal; 97% retention), and 10 were interviewed. Participants (27% female, 33% TIA) generally rated the usability of the mobile application as ‘Good’ to ‘Excellent’ (System Usability Scale). Most (94%) agreed the program helped with engagement in health self-monitoring. Overall, 52 goals were set, predominantly regarding exercise (21/52), which were the most frequently achieved (9/21). At 12 weeks, participants reported significant improvements (p < 0.05) in self-efficacy (Cohen’s d = 0.40), cardiovascular health (d = 0.71), and the mental health domain of the PROMIS GH (d = 0.63). CAPS was acceptable, with good retention and engagement of participants. Evaluation of this program in a randomised controlled trial is warranted.

BackgroundMobile health (mHealth) technologies, such as wearable sensors, smart health devices, and mobile apps, that are capable of supporting pregnancy care are emerging. Although mHealth could be used to facilitate the tracking of health changes during pregnancy, challenges remain in data collection compliance and technology engagement among pregnant women. Understanding the interests, preferences, and requirements of pregnant women and those of clinicians is needed when designing and introducing mHealth solutions for supporting pregnant women’s monitoring of health and risk factors throughout their pregnancy journey. ObjectiveThis study aims to understand clinicians’ and pregnant women’s perceptions on the potential use of mHealth, including factors that may influence their engagement with mHealth technologies and the implications for technology design and implementation. MethodsA qualitative study using semistructured interviews was conducted with 4 pregnant women, 4 postnatal women, and 13 clinicians working in perinatal care. ResultsClinicians perceived the potential benefit of mHealth in supporting different levels of health and well-being monitoring, risk assessment, and care provision in pregnancy care. Most pregnant and postnatal female participants were open to the use of wearables and health monitoring devices and were more likely to use these technologies if they knew that clinicians were monitoring their data. Although it was acknowledged that some pregnancy-related medical conditions are suitable for an mHealth model of remote monitoring, the clinical and technical challenges in the introduction of mHealth for pregnancy care were also identified. Incorporating appropriate health and well-being measures, intelligently detecting any abnormalities, and providing tailored information for pregnant women were the critical aspects, whereas usability and data privacy were among the main concerns of the participants. Moreover, this study highlighted the challenges of engaging pregnant women in longitudinal mHealth monitoring, the additional work required for clinicians to monitor the data, and the need for an evidence-based technical solution. ConclusionsClinical, technical, and practical factors associated with the use of mHealth to monitor health and well-being in pregnant women need to be considered during the design and feasibility evaluation stages. Technical solutions and appropriate strategies for motivating pregnant women are critical to supporting their long-term data collection compliance and engagement with mHealth technology during pregnancy.

A major technological goal in neuroscience is to enable the interrogation of individual cells across the live brain. By creating a curved glass replacement to the dorsal cranium and surgical methods for its installation, we developed a chronic mouse preparation providing optical access to an estimated 800,000–1,100,000 individual neurons across the dorsal surface of neocortex. Post-surgical histological studies revealed comparable glial activation as in control mice. In behaving mice expressing a Ca2+ indicator in cortical pyramidal neurons, we performed Ca2+ imaging across neocortex using an epi-fluorescence macroscope and estimated that 25,000–50,000 individual neurons were accessible per mouse across multiple focal planes. Two-photon microscopy revealed dendritic morphologies throughout neocortex, allowed time-lapse imaging of individual cells, and yielded estimates of >1 million accessible neurons per mouse by serial tiling. This approach supports a variety of optical techniques and enables studies of cells across >30 neocortical areas in behaving mice.

Memory T cells are vital responders to skin inflammation, but cell localization and dynamics of exchange with the bloodstream are not clear. Here the authors use parabiosis and intravital microscopy to show that CD4+memory T cells equilibrate with the circulation and cluster around hair follicles in response to CCL5-dependent responses to viral infection or contact sensitization.

Hepatitis B virus (HBV) DNA integration into the host cell genome is reportedly a major cause of liver cancer, and a source of hepatitis B surface antigen (HBsAg). High HBsAg levels can alter immune responses which therefore contributes to the progression of HBV-related disease. However, to what extent integration leads to the persistent circulating HBsAg is unclear. Here, we aimed to determine if the extent of HBV DNA integration is associated with the persistence of circulating HBsAg in people exposed to HBV. We established a digital droplet quantitative inverse PCR (dd-qinvPCR) method to quantify integrated HBV DNA in patients who had been exposed to HBV (anti-HBc positive and HBeAg-negative). Total DNA extracts from both liver resections (n = 32; 14 HBsAg-negative and 18 HBsAg-positive) and fine-needle aspirates (FNA, n = 10; 2 HBsAg-negative and 8 HBsAg-positive) were analysed. Using defined in vitro samples for assay establishment, we showed that dd-qinvPCR could detect integrations within an input of

Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections.

Human skin contains various populations of memory T cells in permanent residence and in transit. Arguably, the best characterized of the skin subsets are the CD8(+) permanently resident memory T cells (TRM) expressing the integrin subunit, CD103. In order to investigate the remaining skin T cells, we isolated skin-tropic (CLA(+)) helper T cells, regulatory T cells, and CD8(+) CD103(-) T cells from skin and blood for RNA microarray analysis to compare the transcriptional profiles of these groups. We found that despite their common tropism, the T cells isolated from skin were transcriptionally distinct from blood-derived CLA(+) T cells. A shared pool of genes contributed to the skin/blood discrepancy, with substantial overlap in differentially expressed genes between each T cell subset. Gene set enrichment analysis further showed that the differential gene profiles of each human skin T cell subset were significantly enriched for previously identified TRM core signature genes. Our results support the hypothesis that human skin may contain additional TRM or TRM-like populations.

This paper presents the results of an experimental investigation of two gesture representations (overlaying hands and cursor pointer) in a video-mediated scenario—remote collaboration on physical task. Our study assessed the relative value of the two gesture representations with respect to their effectiveness in task performance, user's satisfaction, and user's perceived quality of collaboration in terms of the coordination and interaction with the remote partner. Our results show no clear difference between these two gesture representations in the effectiveness and user satisfaction. However, when considering the perceived quality of collaboration, the overlaying hands condition was statistically significantly higher than the pointer cursor condition. Our results seem to suggest that the value of a more expressive gesture representation is not so much a gain in performance but rather a gain in user's experience, more specifically in user's perceived quality of collaborative effort.

Abstract Background Older adults with cancer are vulnerable to declines in muscle performance (e.g., strength, speed, duration of muscular contraction), which are associated with worse cancer-related outcomes. Exercise-based interventions can mitigate these declines, but evidence of their effect among older adults with myeloid malignancies receiving outpatient treatment is limited. We explore change in muscle performance among patients in a single arm pilot study of a mobile health (mHealth) exercise intervention. Methods Patients ≥ 60 years old with myeloid malignancies receiving outpatient chemotherapy completed a home-based resistance band and walking exercise program [EXercise for Cancer Patients (EXCAP)©®] delivered via a mobile application with symptom monitoring [(Geriatric Oncology-EXCAP (GO-EXCAP)] lasting 2 cycles of chemotherapy (approximately 8–12 weeks). Clinical exercise physiologists provided instruction and ongoing support. Upper and lower extremity peak torque (maximum force, newton-meters, Nm), total work (force over entire movement, Nm), and average power (speed of force, watts, W) were assessed using the BIODEX System 4 isokinetic dynamometer. Muscle activation (motor recruitment, millivolts, mV) was captured using the BTS FREEEMG 1000. We report descriptive statistics and within-patient differences from baseline to post-intervention using Wilcoxon signed rank tests (α = 0.10) and effect size (ES, Cohen’s d, 0.20 ≤ small

Abstract Background Autonomy-supporting interventions may be a prerequisite to achieve better long-term management of type 2 diabetes. Evidence suggests that the guided self-determination (GSD) method might improve haemoglobin A1c and diabetes distress in people with type 1 diabetes. The evidence of an effect of a GSD intervention compared with an attention control group in adults with type 2 diabetes is unknown. Methods/design The trial is designed as a pragmatic, investigator-initiated, dual-centre, randomised, parallel-group, assessor-blinded, superiority clinical trial of persons with type 2 diabetes. A nurse will administer GSD intervention versus an attention control. The primary outcome is diabetes distress, and secondary outcomes are quality of life, depressive symptoms, and non-serious adverse events. Exploratory outcomes are haemoglobin A1c, motivation, and serious adverse events. Participants are assessed at baseline, 5-, and 12-month follow-up. Here, we present a detailed, comprehensive plan of all statistical analyses, including methods to handle missing data, and assessments of the underlying statistical assumptions. The statistical analyses will be conducted independently by two statisticians following the present plan. Discussion To mitigate the risk of analysis bias and increase the validity of the OVEROME trial, this statistical analysis plan was developed prior to unblinding of the trial results in concordance with the Declaration of Helsinki and the Conference on Harmonization of Good Clinical Practice Guidelines. Trial registration ClinicalTrials.gov NCT 04601311. Registered on October 2020.