Fatigue is a common symptom in various diseases, including multiple sclerosis (MS). The current standard method to assess fatigue is through questionnaires, which has several shortcomings; questionnaires are subjective, prone to recall bias, and potentially confounded by other symptoms like stress and depression. Thus, there is an unmet medical need to develop objective and reliable methods to evaluate fatigue. Our study seeks to develop an objective and ubiquitous monitoring tool for assessing fatigue. Leveraging a smartphone-based rapid tapping task, we conducted a two-week in-the-wild study with 35 MS patients. We explore the association between tapping derived metrics and perceived fatigue assessed with two standard clinical scales: fatigue severity scale (FSS) and fatigue scale for motor and cognitive function (FSMC). Our novel smartphone-based fatigue metric, mean tapping frequency, objectively ranks perceived fatigue with a mean AUCROC = .76, CI = [.71, .81] according to the FSMC, and a mean AUCROC = .81, CI = [.76, .86] according to the FSS. These results demonstrate that our approach is feasible and valid in uncontrolled environments. In this work, we provide a promising tool for objective fatigue monitoring to be used in clinical trials and routine medical care.
Microbial organisms have key roles in numerous physiological processes in the human body and have recently been shown to modify the response to immune checkpoint inhibitors1,2. Here we aim to address the role of microbial organisms and their potential role in immune reactivity against glioblastoma. We demonstrate that HLA molecules of both glioblastoma tissues and tumour cell lines present bacteria-specific peptides. This finding prompted us to examine whether tumour-infiltrating lymphocytes (TILs) recognize tumour-derived bacterial peptides. Bacterial peptides eluted from HLA class II molecules are recognized by TILs, albeit very weakly. Using an unbiased antigen discovery approach to probe the specificity of a TIL CD4+ T cell clone, we show that it recognizes a broad spectrum of peptides from pathogenic bacteria, commensal gut microbiota and also glioblastoma-related tumour antigens. These peptides were also strongly stimulatory for bulk TILs and peripheral blood memory cells, which then respond to tumour-derived target peptides. Our data hint at how bacterial pathogens and bacterial gut microbiota can be involved in specific immune recognition of tumour antigens. The unbiased identification of microbial target antigens for TILs holds promise for future personalized tumour vaccination approaches.
We describe our ongoing work on the design and implementation of a system to continuously monitor different physiological parameters in patients with multiple sclerosis (MS). We focus specifically on monitoring functions of the autonomous nervous system and activities of daily life using wearable and mobile sensors and to correlate these with important symptoms of MS, in particular, fatigue. Fatigue is a highly prevalent and debilitating symptom in MS patients. However, the underlying cause and pathogenetic mechanisms are poorly understood and consequently therapeutic interventions limited. As the first step in our research effort, we evaluate the feasibility of off-the-shelf devices to record several physiological parameters in MS patients continuously.
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